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NATIONAL DRUG FORMULAR AND ESSENTIAL DRUG LIST ACT
ARRANGEMENT OF SECTIONS
1. National Drug Formulary and Essential Drugs List.
2. Prohibition of importation, etc., of drugs not in the List.
3. Importation, etc., of drugs not in the List.
4. Establishment of Review Committee and membership.
5. Functions of Review Committee.
6. Tenure of office of members of the Review Committee.
7. Pharmaceutical companies, etc.
8. Offences and penalties.
9. Monitoring of the List.
10. Removal of drug from the List.
11. Information for guidance of medical practitioners, etc.
13. Short title.
First Schedule: The Essential Drugs List
Second Schedule: The Drug Formulary Index
NATIONAL DRUG FORMULARY AND ESSENTIAL DRUGS LIST ACT
An Act to prescribe a National Drug Formulary and Essential Drugs List and to prohibit importation into and manufacture in Nigeria of any drug not in the List.
[1989 No. 43.]
[13th December, 1989] [Commencement.]
1. National Drug Formulary and Essential Drugs List
There is hereby prescribed for the Federal Republic of Nigeria a National Drug Formulary and Essential Drugs List as specified in the First Schedule to this Act (hereinafter referred to as “the List”).
2. Prohibition on importation, etc., of drugs not in the List
No person shall import into, advertise, display for sale, sell or manufacture in Nigeria any drug which is not contained in the List.
3. Importation, etc., of drugs not in the List
(1) Notwithstanding the provisions of section 1 of this Act, where the Minister is satisfied that it is necessary to import or manufacture any drug not in the List on the following grounds that—
(a) the drug is a cure for—
(i) any uncommon disease; or
(ii) a disease requiring highly specialised skill for diagnosis and treatment; or
(b) there is intolerance or lack of response to the common drugs listed;
(c) a drug of greater activity than the one in the List was not included in the List due to insufficient experience with it under local conditions, he may, on the recommendation of the appropriate body, permit the importation or manufacture of such drug and the inclusion of such drug in the List.
4. Establishment of Review Committee and membership
(1) For the purposes of the implementation of the List, there is hereby established the National Drug Formulary and Essential Drug List Review Committee (hereinafter referred to as “the Review Committee”).
(2) The Review Committee shall consist of the following members to be appointed by the Minister, that is—
(a) two clinical pharmacologists, one of who shall be the chairman;
(b) the Director of Food and Drugs Administration and Control in the Federal Ministry of Health;
(c) the Director of Hospital Services and Training in the Federal Ministry of Health;
(d) the Director of Primary Health Care Programme in the Federal Ministry of Health;
(e) four heads of pharmacy departments appointed from State Ministries of Health so however that not more than one shall be appointed from any one particular State on zonal rotation;
(f) one representative of the Pharmaceutical Society of Nigeria;
(g) one representative of the Nigerian Medical Association;
(h) one representative of the Pharmaceutical Manufacturers Association of Nigeria; and
(i) two medical practitioners appointed by the Minister.
5. Functions of the Review Committee
The Review Committee shall, from time to time, review the List and advise the Minister on any addition to or deletion from the List, as may be necessary.
6. Tenure of office of members of the Review Committee
(1) The tenure of office of members of the Review Committee, other than those appointed from the Federal Ministry of Health, shall be three years.
(2) A member of the Review Committee shall be eligible for reappointment for a further period of three years.
7. Pharmaceutical companies, etc.
A pharmaceutical company or firm or any other body (corporate or un-incorporate) may make representation to the Review Committee on any drug or formulation not in the List which it considers to be necessary for essential health care and it shall be expedient for the Review Committee to consider such representation.
8. Offences and penalties
(1) Any person who contravenes the provisions of section 2 of this Act shall be guilty of an offence and liable, on conviction, to a fine of N100,000 or to imprisonment for a term not exceeding five years.
(2) Where an offence under this Act is committed by a body corporate, every director or person in authority in that body corporate shall be held liable.
9. Monitoring of the List
There shall be established in the Department of Food and Drugs Administration and Control in the Ministry, a Secretariat, which shall be responsible for the monitoring and implementation of the List.
10. Removal of drug from the List
Notwithstanding the provisions of section 5 of this Act, the Minister may remove any drug from the List where it has been established to his satisfaction that the drug in question is no longer safe for use.
11. Information for guidance of medical practitioners, etc.
The Drug Formulary contained in the Second Schedule to this Act shall serve as information guidance to medical practitioners, pharmacists and other users of the information specified therein.
In this Act, unless the context otherwise requires—
“Appropriate body” means the National Drug Formulary and Essential Drug List Review Committee established by section 4 of this Act;
“Essential drugs” means drugs that satisfy the health care needs of the majority of the population;
“Minister” means the Minister charged with responsibility for health matters and
“Ministry” shall be construed accordingly.
13. Short title
This Act may be cited as the National Drug Formulary and Essential Drugs List Act.
The Essential Drugs List General information for use of the Formulary. Introduction.
The Main (General) List
The Primary Health Care List
The Drug Formulary Index
I. Guidance on prescribing.
2. Emergency treatment of poisoning.
3. Classified notes on drugs and preparations.
1. Central nervous system drugs.
2. Anaesthetic drugs.
3. Cardiovascular system drugs.
5. Blood and nutrition.
6. Respiratory system drugs.
7. Gastrointestinal system drugs.
8. Endocrine system drugs.
9. Anti-Infective drugs.
10. Dermatological drugs.
11. Drugs acting on the eye.
12. Drugs acting on the ear, nose and throat.
13. Dental drugs.
14. Drugs for musculoskeletal and joint diseases.
15. Drugs used in allergic disorders.
17. Drugs used for cancer chemotherapy.
18. Immunological products.
19.Diagnostic agents. 4. Formulary section. Index.
FIRST SCHEDULE [Section 1.]
General information for use of the Formulary
A. ARRANGEMENT OF INFORMATION
This National Drug Formulary and Essential Drugs List is divided into two parts. Part I is the Essential Drugs List and Part IT, is the Drug Formulary.
Part I, the Essential Drugs List, is divided into two sections: The first section or main section contains the general List of essential drugs, numbering 204 different drug entities. The second section contains a small List of 31 drugs for the primary health care level.
Part II is divided into four chapters.
Chapter 3, the Classified Notes on Drugs and Preparations, is divided into nineteen sections according to main pharmacological divisions or to main drug treatment areas.
Chapter 4, the Formulary section, is an extension of Chapter 3, containing the different dosage form presentations, strengths and the compositions of drug preparations described in Chapter 3.
It also covers the formulations of extemporaneous preparations which are in common use and can be readily prepared in pharmacies.
An index of names of drugs and preparations is included for quick reference in the book.
B. CLASSIFIED NOTES ON DRUGS
1. The formulary provides drug information for the drugs selected in the only Essential Drugs List. However, other drugs in common use but not included in the Essential Drugs List are mentioned.
2. The pharmaco-therapeutic notes included under the main pharmacological divisions, therapeutic and sub-therapeutic groups, are intended to provide a quick reference guide to doctors, pharmacists, nurses, etc., on the use of the various groups of drugs in the Essential Drugs List. These short notes are not meant to replace the consultation of appropriate text- books, etc., for more broad-based information.
3. The notes are followed by the selected drugs and their elevant drug information (dosage forms, pharmacological properties, uses, adverse effects, dosage, etc.). Again, these prescribing and dispensing information are considered to be very important, concise, and by no means inclusive of all possible information relating to the indications, adverse and side effects, etc., of many drugs.
C. DRUG TITLES
Drug titles are given in their pharmacopoeial or non-proprietary (generic) names in both the Formulary and the Essential Drugs List, except in the case of Diagnostic Agents (Chapter 3, section 19) where, for practical purposes, the proprietary names of certain products have also been included. Details of the drug dosage formulations and common extemporaneous preparations are given in Chapter 4, the Formulary section.
THE SELECTION OF ESSENTIAL DRUGS
“Essential drugs” have been defined by The World Health Organisation (WHO) as those drugs that satisfy the health care needs of the majority of the population. They should there- fore be available at all times in adequate amounts and in the appropriate dosage forms at all levels of the health care delivery system of the country. Their selection is based on the most common local diseases. The concept of essential drugs was approved by the World Health Assembly in 1975, and in 1977 the World Health Organisation produced its first model list of essential drugs. Since then more than eighty countries, practically all in the Third World, have adopted lists of essential drugs based on the WHO model list.
As emphasised by the World Health Organisation an essential drugs list only indicates priorities in drug needs. Tt does not mean that no other drugs are useful and exclusion does not necessarily imply rejection.
The need for an Essential Drugs List
In recent years there has been a big increase in the number of drugs marketed, but this increase has not been matched by a proportional improvement in health. If anything, the indis- criminate use of multiple drugs in treatment has led to a big increase in the frequency of drug- induced diseases.
The present situation is that drugs are procured with little regard to the needs and priori- ties of health care in the country. Availability of drugs in the health care system is largely a response to the sales promotional activities of manufacturers and distributors. Such pressures lead to a proliferation of available drugs which bear little relation to the actual needs of the population. The result is the present situation in which the basic drug needs of a large percent- age of the population cannot be satisfactorily met by the available drugs. There is therefore need for a change to a system in which, as far as the public sector of the health care system is concerned, priority is given to drugs proven to be therapeutically effective, to be reasonably safe and to satisfy the health needs of the population. These are the so called “essential” drugs.
Having accepted the Alma Ata declaration of health for all by the year 2000, making health care accessible to the entire population has become a major concern of the government, and the primary health care programme is designed to make the attainment of the goal of health for all possible.
One of the essential elements of primary health care is the provision of essential drugs.
Drugs occupy a unique position in health care. They make health care credible because they can cure diseases, relieve symptoms and alleviate suffering. The psychological satisfaction produced by drugs creates a favourable environment on which the preventive and education elements of health care can be built with consequent further improvement in health. It is obvi- ous, therefore, that the present situation in which regular availability of the most needed drugs cannot be ensured is not conducive to the attainment of the goal of health for all. On the other hand, the successful application of the essential drugs concept will go a long way towards improving the availability of the most needed drugs in Nigerian health care delivery system.
Criteria for selection
In selecting this list of essential drugs the Federal Ministry of Health was guided by the following principles-
1. The drugs in an essential drugs list should satisfy the health care needs of the great major- ity of the people at all levels of health care delivery.
2. They should be drugs for which there is sufficient evidence of efficacy and safety from controlled clinical studies and from experience in general use.
3. The preferred dosage forms are those which have a reasonable shelf-life and are able to withstand adverse environmental conditions unavoidable in the distribution chain. For exam- ple, tablets and capsules are probably more stable under our prevailing ambient temperatures than mixtures, syrups and elixirs. Except in infants, where specific paediatric formulations are indispensable, convenient paediatric doses can be achieved from the use of a wide range of dosage strengths of tablets (e.g. aspirin tablets, 75 mg., 100 mg., 300 mg., 500 mg., 600 mg.) or of scored tablets.
4. They should be drugs for which quality certification can be readily obtained from local institutions, or from the country of origin or through the auspices of the World Health Organi- sation.
5. They should be drugs that can either be manufactured locally using locally produced or imported raw materials or that can be imported in bulk, cheaply.
6. The drugs have been selected, as much as possible, in their generic names.
7. Where there is a large number of drugs in a particular therapeutic group (e.g. anti- hypertensives), preference is given to the drugs for which there is local experience with regard to efficacy and safety.
8. When one drug has been named in a particular chemical group containing a variety of structural analogues (e.g. thiazide diuretics), other members of the group can be substituted for the named drug. Factors which may determine the choice of product in this instance in- clude comparative cost, frequency of administration, ease of procurement and availability of desired dosage forms.
9. Selection of one member of a pharmacodynamic group (e.g, beta-adrenoceptor blockers, direct vasodilators, non-steroidal anti-inflammatory drugs) does not preclude the use of other drugs in the same group, provided they satisfy the requirements for safety and efficacy.
10. Single component drug formations are, as a rule, preferred to fixed-dosage drug combi- nations since individualisation of dosage in therapy is often difficult or impossible with the latter. However, in some instances, a fixed-dosage drug combination meets the requirements of a given clinical situation and has clearly-defined advantages in efficacy, safety and comp- liance, over separately administered single drugs. Such fixed-dosage combinations have been included in the List.
11. Drugs and preparations with unproven or doubtful therapeutic effect, even when hallowed by long usage, have not been selected. For this reason remedies like throat lozenges, expectorants, tonics, gripe water and enzyme mixtures are not in the List.
12. Drugs with known serious side effects but with acceptable risk/benefit ratio because of the severity of the conditions for which they are used, have been included in the expectation that their procurement, storage, distribution and use would be subject to the usual medico- legal and ethical constraints associated with such drugs.
Deficiencies of an Essential Drugs List
Although, if carefully selected, an Essential Drugs List should satisfy the needs of the vast majority of the population, it is clear that it will not provide the needs of every person. Situations which the Essential Drugs List may not cover include-
1. Uncommon diseases, especially where the drug treatment is still subject to frequent changes.
2. Diseases requmng highly specialised skills and facilities for diagnosis and treatment. These, as a rule, will be encountered only in tertiary health care institutions.
3. Instances where less popular drugs may need to be used due either to lack of response or intolerance to the commoner drugs listed. Patients in this kind of situation often need to be evaluated in tertiary health care centres.
4. Drugs of probably greater activity than the ones selected but for which experience in the field and particularly under local conditions is not sufficiently convincing to be listed. The high cost of a drug still under patent may make its selection untenable even when there is lo- cal evidence of its comparability with, or even advantage over, selected ones.
Expected advantages of an Essential Drugs List
Experience from other countries which have operated an essential drugs policy over the past few years has demonstrated a number of advantages-
1. There will be a reduction in the number of drugs deployed in the health care system. This will make easier the administrative processes involved in procurement, storage and distribu- tion.
2. With the limited number of drugs and the use of generic rather than proprietary names, it would be easy to provide concise, accurate and comprehensive information in the form of a national formulary on all the drugs in the Essential Drugs List.
3. It should be a lot easier for prescribers to familiarise themselves with the pharmacological properties of the prescribed drugs, thus improving the quality of drug treatment.
4. Drug utilisation in the various sectors of the health care system can easily be monitored. True quantitive requirements can therefore be determined. Knowledge of this should stimulate local pharmaceutical industries in the production of needed drugs in the right amounts.
5. It should be easier for the Federal Ministry of Health to formulate strategies for the evaluation of the quality of drugs and for the inspection of factories for compliance with the guidelines for good manufacturing practices.
6. It should be relatively easy for local committees, especially in the tertiary health care in- stitutions, to meet the needs of the various specialities and unusual clinical situations not cov- ered by the National Drug Formulary and Essential Drugs List.
Finally, this Essential Drugs List contains 205 different drugs including a few fixed combination products. Drugs which are useful in more than one therapeutic area have recurred in the list, but counted only once. The drugs are shown with the pharmaceutical dosage forms and strengths in which they should be available. An index of the drugs is included for easy reference.
This Essential Drugs List should be reviewed and updated biennially.
The Main (General) List
Name of Drug Route of Administration, Dosage Forms and Strengths
1.1 General Anaesthetics and Oxygen
Ether, Anaesthetic …………………………..Inhalation, liquid in bottle of 500 m1.
Halothane ………………………………………Inhalation, liquid in bottle of 250 m1.
Nitrous Oxide ………………………………..Inhalation, Medicinal gas
Oxygen …………………………………………Inhalation, Medicinal gas
Thiopenotone Sodium ……………………..Powder for I.V. Injection
0.5 g. and 1.0 g. in ampoules
1.2 Premedication Drugs
Atropine ………………………………………..Injection, 1 mg. (Sulphate) in I m1. ampoule
Diazepam …………………………………….. Injection, IO mg. in 2 m1. ampoule
1.3 Adjuncts of General Anaesthesia
Neostigmine …………………………………..Injection, 2.5 mg. (Methylsulphate)/m!. in I ml. ampoule
Suxamethonium ……………………………..Injection, 50 mg. (Chloride)/m1. in 2 ml. ampoule
*Pancuronium ………………………………..Injection, 2 mg. (8romide)/ml. in 2 m1. ampoule
* Representing the therapeutic group.
Name of Drug Route of Administration, Dosage Forms and Strengths
1. 4 Local Anaesthetics
Lignocaine ………………………………….Injection, I % and 2% (Hydrochloride) in via Injection, 1% and 2% (Hydrochloride) plus Adrenaline I :200,000 in vial
Topical, 2-4% (Hydrochloride)
Dental Cartridges, 2% plus Adrenaline I in 80,000
2. ANALGESICS, ANTIPYRETICS AND NON-STEROIDAL ANTI-INFLAMATORY DRUGS
2.1 Narcotic Analgesics
Morphine …………………………………….Injection, 10 mg. (Sulphate or Hydrochloride) in I ml. ampoule
Pethidine …………………………………… Injection, 50 mg. and 100 mg. (Hydrochloride) in 1 ml. and 2 ml. ampoules respectively
Pethilorfan …………………………………. Injection, Pethidine 50 mg. (Hydrochloride) plus Levallorphan 0.625 mg. (Tartrate per ml. in 1 or 2 ml. ampoule
2.2 Narcotic Antagonists
Naloxone ………Injection, 0.4 mg. (hydrochloride) in I ml. ampoule
2.3 Non-Narcotic Analgesics and Antipyretics
Acetylsalicylic Acid ……………………. Tablets, 75 mg. and 300 mg.
Paracetamol…………… …………………..Tablets, 500 mg.
Syrup, 125 mg. per 5 ml.
2.4 Non-Steroidal Anti-inflammatory Drugs
Allopurinol …………………………………Tablet, 100 mg.
Colchicine ………………………………….Tablet, 0.5 mg.
*Ibuprofen ………………………………….Tablet, 200 mg.
Chlorpheniramine ………………. Injection, 10 mg. (Maleate) inl ml. ampoule Tablet, 4 mg. (Maleate)
Syrup, 2 mg. per 5 ml.
* Representing the therapeutic group.
Name of Drug Route of Administration, Dosage Forms and Strengths
Promethazine ………………………………Injection, 2 mg. and 50 mg. (Hydrochloride) in I and 2 ml. ampoules respectively
Tablet, 2 mg. (Hydrochloride)
Syrup, 5 mg. per 5 ml.
Adrenaline ………………………………..Injection, I mg. (Bitarattre) in I ml. ampoule
4.1 Non-specific (General) Antidote
Charcoal, Activitated ……………………Powder
4.2 Specific Antidotes
Atropine ……………………………………. Injection, I mg. (Sulphate) in I ml. ampoule
Desferrioxamine ………………………….Injection, 500 mg.
(Mesylate) in vial Dimercaprol………………………………. Injection, 50 mg./ml. in 2 ml. ampoules
Naloxone ……………………………………Injection, 40 mg. (Hydrochloride) in 1 mL ampoule
Protamine Sulphate ……………………..Injection, 10 mg./ml. in 5 ml. ampoule
Vitamin K I (Phytomenadione) ……..Injection, 10 mg./ml. in 5 ml. ampoule
5. ANTI-CONVULSANTS (ANTI-EPILEPTICS)
Diazepam …………………………………..Injection, 5 mg./ml. in 2 ml. ampoules
Ethosuximide ……………………………..Tablet or Capsule, 250 mg.
Phenobarbitone …………Tablets, 30 mg. and 60 mg. Syrup, 15 mg.
Phenytoin Sodium ……………………….Tablets or Capsules 50 mg. and 100 mg.
6. ANTI-INFECTIVE DRUGS
Metronidazole …………………………….Tablet, 200 mg.
Mebendazole ………………………………Tablet, 100 mg.
Niclosamide ……………………………….Tablet, Chewable, 500 mg.
Piperazine …………………………………..Tablet, 500 mg. (Adipate or Citrate) Elixir or Syrup, 500 mg./5 ml.
Name of Drug Route of Administration, Dosage Forms and Strengths
6. ANTI-INFECTIVE DRUGS
6.2 Anthelmintics – cont.
Pyrantel …………………………………….. Tablet, 125 mg.
Syrup, 125 mg./5 rnl.
Thiabendazole ……………………………. Tablet, Chewable, 500 mg.
Syrup, 100 mg./5 ml.
6.3 Anti-filaria! Drugs
Diethylcarbamazine ……………………. Tablet, 50 mg. (Citrate)
Injection, powder in I g. vial
6.4 Anti-schistosomal Drugs
Metrifonate ……………………………….. Tablet, 100 mg.
Oxamniquine ……………………………… Capsule, 250 mg.
Praziquantel ………………………………. Tablet, 600 mg.
6.5 Anti-trypanosoma! Drugs
Melarsoprol ……………………………….. Injection, 3.6% solution
Pontamidine ………………………………. Injection, powder, 200 mg.
Suramine …………………………………… Injection, powder in I g. vial
6.6 Anti-malarial Drugs
Chloroquine ………………………………. Tablet, 150 mg. base (Phosphate or Sulphate) Syrup, 50 mg. base/5 rnl. (Phosphate or Sulphate)
Injection, 200 mg. in 5 rnl. ampoules
Pyrimethamine ……………………………Tablet, 12.5 mg. and 25 mg.
Pyrimethamine plus Sulphadoxine …Tablet, 25 mg. Phyrimethamine plus 500 mg. Sulpha- doxine
Syrup, 25 mg. Pyrimethamine plus 500 mg. Sulpha- doxine/5 ml.
Injection, 10 mg. Pyrimethamine plus 200 mg. Sulpha- doxine in 2.5 ml. ampoules
6.7 Anti-flagellate Drugs
Metronidazole …………………………….Tablet, 200 mg.
Tinidazole …………………………………..Tablet, 500 mg.
Name of Drug Route of Administration, Dosage Forms and Strengths
6. ANTI-INFECTIVE DRUGS
6.8 Anti-bacterial Drugs
• Ampicillin ………………………………..Capsules, 250 mg. and 500 mg.
Powder for Oral suspension, 125 mg./5 mJ.
Injection, powder in 250 mg. and 500 mg. vials (Sodium salt)
Benzyl Penicillin …………………………Injection, powder in 0.6 g. (1 million units) vial
‘Chloraphenicol …………………………..Capsule, 250 mg.
Syrup, 125 mg./5 ml. Injection, powder in I g. vial
Cloxacillin ………………………………….Capsule, 250 mg.
Syrup, 125 mg./5 ml.
Injection, powder in 250 mg. and 500 mg. vials
Fortified Procaine Penicillin ………….Injection, powder in 400,000 units vials containing: Pro- caine Penicillin 300,000 units (300 mg.) and Benzyl Peni- cillin 100,000 units (60 mg.)
•Phthalylsulphathiazole ………………..Tablet, 500 mg.
•Sulphadimidine ………………………….Tablet, 500 mg.
Syrup, 500 mg./5 ml.
Co-trimoxazole ……………………………Tablets, 400 mg. sulphamethoxazole plus 80 mg. Tri- methoprim, and 100 mg. Sulphamethoxazole plus 20 mg. Trimethoprim
Syrup, 200 mg. Sulphamethoxazole plus 40 mg. Tri- methoprim in 5 ml.
•Tetracycline………………………………. Tablet or Capsule, 250 mg. (Hydrochloride)
Gentamicin ………………………………… Injection, 80 mg. in 2 ml. vial, 10 mg. in 2 ml. vial
Metronidazole ……………………………. Injection, 500 mg./l 00 ml.
Nitrofurantoin ……………………………..Tablets, 50 mg. and 100 mg.
6.9 Anti-leprosy Drugs
Clofazimine ………………………………..Capsule, 100 mg.
‘Dapsone …………………………………….Tablets, 50 mg. and 100 mg.
Rifampicin ., ……………………………….Capsule, 300 mg.
*Representing the therapeutic group. *Restricted use.
Name of Drug Route of Administration, Dosage Forms and Strengths
6. ANTI-INFECTIVE DRUGS
10 Anti-tuberculosis Drugs
Isoniazid ……………………………………. Tablet, 100 mg.
Rifampicin ………………………………… Capsules, 150 mg. and 300 mg.
Streptomycin ……………………………….Injection in I g. and 5 g. (sulphate) vials
Thiacetazone plus Isoniazid …………. Tablets, Thiacetazone 50 rug. plus Isoniazid 100 rng., and Thiacetazone 150 rng. plus Isoniazid 300 mg.
6.1 I Systemic Anti-fungal Drugs
Griseofulvin ………………………………. Tablet, 125 mg.
7. ANTI-MIGRAINE DRUG
Ergotamine ………………………………… Tablet,2 rng, (Tartrate)
8. ANTI-NEOPLASTlC AND IMMUNOSUPPRESSIVE DRUGS
Actinomycin D …………………………….Injection, powder in 0.5 mg. vial
Adriamycin (Doxorubicin) …………… Injection, powder in 10 mg. and 50 mg. vials (as Hydro-
Bleomycin …………………………………. Injection, powder in 15 mg. vial (as Sulphate)
Busulphan …………………………………. Tablet,2 rng.
Chlorambucil…………………………….. Tablets, 2 rng, and 5 mg.
Cyclophosphamide Injection, powder in 100 rng, and 500 mg. vials Tablets, 25 mg, and 50 mg,
6-Mercaptopurine ……………………….. Tablet, 50 mg.
Methotrexate Injection, powder in 50 mg. vial Tablet, 2.5 mg.
•Prednisolone ……………………………..Tablet, 5 mg.
•Stilboestrol ………………………………..Tablets, I mg. and 5 mg.
9. ANTI-PARKINSONISM DRUGS
Tablets, 2 mg. and 5 mg.
Biperiden Injection, 5 mg./ml. (Lactate) in 1 ml. ampoule Tablet, 2 rng, (Hydrochloride)
Levodopa …………………………………..Tablet, or Capsule, 250 mg.
Levodopa plus Carbiopa ………………Tablets, Levodopa 100 rng. plus Carbidopa 10 mg., and Levodopa 250 mg. plus Carbidopa 25 mg.
* Representing the therapeutic group.
Name of Drug Route of Administration, Dosage Forms and Strengths
10. BLOOD DRUGS
10.1 Anti-anaemia Drugs
Ferrous Salts Tablet, equivalent to 60 mg. iron as fumarate, gluconate or stipuphate Mixresulphate Mixture, 400 mg.l 5 ml. of Fer- ric Ammonium Citrate
Folic acid ………………………………….. Tablet, 5 mg.
Heparin ……………………………………..Injection, 1000 units/ml. and 25,000 units/ml. in 5 ml. ampoules
Warfarin Sodium ……………………….. Tablet, 5 mg.
10.3 Plasma Substitute
Dextran 70 ………………………………….Injection, solution 6%
10.4 Plasma Fraction for specific use
Human Albumin …………………………Injection, solution 20%
11. CARDIOVASCULAR DRUGS
11.1 Anti-anginal Drugs
•Glyceryl Trinitrate ……………………..Tablet, Sublingual, 0.5 mg.
•Propranolol ……………………………….Tablets, 10 mg. and 40 mg. (Hydrochloride) Injection, 1 mg. (Hydrochloride) in I ml. ampoule
11.2 Anti-arrhythmic Drugs
Lignocaine ………………………………….Injection, 20 mg.lml. (Hydrochloride) in 5 ml. ampoule
•Propranolol ……………………………….Tablets, 10 mg. and 40 mg. (Hydrochloride) Injection, 1 mg. (Hydrochloride) in I ml. ampoule
11.3 Anti-hypertensive Drugs
•Bendrofluazide …………………………..Tablet, 5 mg.
•Hydralazine ……………………………….Injection, 20 mg. in I ml. ampoule
Methyldopa ………………………………..Tablet, 250 mg. and 500 mg.
•Prazosin …………………………………….Tablet, 1 mg., 2 mg. and 5 mg.
•Propranolol . ……………………………..Tablet, 40 mg. and 80 mg.
•Representing the therapeutic group.
Name of Drug Route of Administration, Dosage Forms and Strengths
11. CARDIOVASCULAR DRUGS
I 1.4 Cardiac Glycoside
Digoxin …………………………………….Tablet, 0.25 mg.
Oral Solution, 0.05 mg./ml.
Injection, 0.25 mg./ml. in 2 ml. ampoule
12. DERMATOLOGICAL DRUGS
12.1 Anti-infective Drug
Neomycin plus Bacitracin Ointment and Cream, 5 mg. Neomycin sulphate plus 500 units Bacitracin zinc per g. of ointment in 5 g. and 30 g. tubes
Dusting Powder, 0.5% Neomycin sulphate plus 250 units Bacitracin zinc per g.
12.2 Anti-inflammatory Drug
Betamethasone ……………………………Ointment or Cream, 0.1 % (Valerate)
Calamine plus Zinc oxide ……………..Lotion
12.4 Dusting Powder
Zinc, Starch and Talc …………………..Dusting Powder, containing zinc oxide 25% Starch 25% and Purified Talc. (Sterilised) 50%
Benzoic Acid plus Salicylic Acid Ointment or Cream, 6% plus 3% respectively
*Clotrimazole ……………………………..Ointment or Cream, I % Spray, I % in aerosol Pessary, 100 mg.
*Nystatin ……………………………………Oral Suspension, 100,000 units/rnl. Pessary, 100,000 units/pessary
12.6 Keratolytic Drug
Salicylic Acid ……………………………..Solution, topical, 12% in flexible collodion
12.7 Scabicide and Pediculicide
Benzyl Benzoate …………………………Emulsion, 25%
*Bendrotluazide ………………………….Tablet, 2.5 mg.
*Frusemide …………………………………Tablet, 40 mg.
Injection, 10 mg./ml.
*Representing the therapeutic group.
Name of Drug Route of Administration, Dosage Forms and Strengths
14. GASTRO-INTESTINAL DRUGS
Aluminium Hydroxide ……………….. Tablet, 500 mg.
Mixture, 320 mg./5 m1.
Magnesium Hydroxide ……………….. Tablet, 500 mg.
Mixture, 250 mg./5 m1.
Magnesium Trisilicate ………………… Tablet, 500 mg.
Mixture, 250 mg./5 m1.
*Chlorpromazine ……………………….. Tablets, 25 mg. and 50 mg.
Injection, 25 mg./m1. in 2 ml. ampoule
Promethazine …………………………….. Tablets, 10 mg. and 25 mg. (Hydrochloride) Syrup, 5 mg. (Hydrochloride)/5 ml.
Injection, 25 mg. (Hydrochloride)/mI. in 2 ml. ampoule
Lignocaine plus Betamesthsone …….Ointment, Cream, Suppository
Hyoscine N-butylbromide …………….Tablet, 10 mg.
Injection, 20 mg./m1. in 1 ml. ampoule
Bisacodyl …………………………………… Tablet, 5 mg.
Suppository, 10 mg.
Magnesium Hydroxide …………………Mixture
14.6.1 Symptomatic Relief
Kaolin with or without morphine ….. Mixture
14.6.2 Replacement Fluid
Oral Rehydration Salts ……………………Contained in Sachets, for 1 litre of water-
Glucose (Dextrose) ……………..20 g.
Potassium Chloride …………….1.5 g.
Sodium Bicarbonate/Citrate …2.5 g.
Sodium Chloride ………………..3.5 g.
* Representing the therapeutic group.
Name of Drug Route of Administration, Dosage Forms and Strengths
14. GASTRO-INTESTINAL DRUGS
14.7 Gastric and Peptic Ulcer Drugs
Tablet, 200 mg.
Tablet, 150 mg.
15. HORMONES AND SYNTHETIC SUBSTITUTES
15.1 Adrenal Hormones and Synthetic Substitutes
Dexamethasone …………………………….. Tablets, 0.5 mg. and 4 mg.
Injection, 2 ml./ml. in 2 rnl. ampoule
Hydrocortisone …………………………….. Injection, powder in 100 mg. vial, (as Sodium Succi- nate)
Prednisolone ………………………………… Tablets, I mg. and 5 mg.
Testosterone …………………………………. Injection, 200 mg. (Enantate) in I ml. ampoule, and 25 mg. (Propionate) in I ml. ampoule
Insulin Zinc Suspension (Lente) Injection, 40 and 80 units/ml.
*’Ethinyloestradiol …………………………Tablets, 0.01 mg. and 0.02 mg.
Soluble Insulin ……………………………… Injection, 40 and 80 units/ml.
*Chlorpropamide ……………………………Tablet, 250 mg.
Metformin …………………………………….Tablet, 500 mg.
Thyroid Hormones and Antagonists
Laevothyroxine ……………………………..Tablets, 0.05 mg. and 0.1 mg. (Sodium salt)
*Representing the therapeutic group. ‘See formulary section for composition.
Name of Drug Route of Administration, Dosage Forms and Strengths
15. HORMONES AND SYNTHETIC SUBSTITUTES
Carbimazole ………………………………….Tablet, 5 mg.
Iodine plus Potassium Iodide …………..Solution, containing 5% Iodine and 10% Potassium. Io- dide in purified water
15.6 Oral Contraceptives
Laevonorgestrel ………………………… Tablet, 0.03 mg. Ethinyloestradiol plus 0.15 mg. Laevo- norgestrel
Norethisterone ……………………………Tablet, 0.05 mg. Ethinyloestradiol plus 1 mg. Norethis- terone
15.7 Ovulation Inducer
Clomiphene …………………………………..Tablet, 50 mg. (Citrate)
*Norethisterone ……………………………..Tablet, 5 mg.
16. OPHTHALMOLOGICAL DRUGS
16.1 Anti-infective Drugs
Chloramphenicol…………………… Eye-drops, 0.5% Ointment, 1 %
Sulphacetamide …………………….Eye-drops, 30%, Ointment, 10%
Chlortetracycline ……………………………Eye Ointment, 1 %
16.2 Anti-inflammatory Drugs
*Betamethasone ……………………..Eye-drops and Ointment, 0.1 %
Oxyphenbutazone …………………………..Eye Ointment, 10%
Tetrahydrozoline ……………………………Eye-drops, 0.05%
16.3 Local Anaesthetic
Amethocaine …………………………………Eye-drops, 0.5% and 1 % (Hydrochloride)
16.4 Miotics and Anti-glaucoma Drugs
Pilocarpine ……………………………………Eye-drops, 1 %, 2%, 3% and 4%
Physostigmine ……………………………….Eye-drops, 0.25% and 0.5%
*Representing the therapeutic group.
Name of Drug Route of Administration, Dosage Forms and Strengths
16. OPHTHALMOLOGICAL DRUGS
Homatropine …………………………………. Eye-drops, 1% and 2%
Tropicamide …………………………………. Eye-drops, 0.5% and 1%
16.6 Systemic Drug
Acetazolamide ……………………………….Tablet, 250 mg.
17. OXYTOCICS Tablet, 0.5 mg.
Injection, 0.5 mg./ml. in I ml. ampoule Injection, 5 and 10 units/ml.
18. PSYCHOTHERAPEUTIC DRUGS
*Amitriptyline ……………………………….Tablets, 25 mg. and 50 mg. (Hydrochloride)
*Chlorpromazine ……………………………Tablets, 25 mg. 50 mg. and 100 mg. (Hydrochloride) Syrup, 25 mg./5 rnl. (Hydrochloride)
Injection, 25mg./ml. (Hydrochloride) in 2 ml. ampoule
*Diazepam …………………………………….Tablets, 2 mg. and 5 mg.
Syrup, 2 mg./5 rnl.
Injection, 5 mg./ml. in 2 ml. ampoule
Fluphenazine ………………………………… Injection, 25 mg. (Deoanoate or Enantate) in I ml. am- poule
HaJoperiodol …………………………………Tablets, 1.5 mg. and 5 mg.
Injection, 2 mg./ml. and 5 mg./ml.
*Nitrazepam ………………………………….Tablet or Capsule, 5 mg.
19. RESPIRATORY TRACT DRUGS
19.1 Anti-asthmatic Drugs
Andrenalin …………………………………… Injection, S.c. I mg./ml. in I ml. ampoules
Aminophyline ………………………………. Injection, 25 mg./ml. in 10 ml. ampoules
Beclomethasone …………………………….Oral inhalation, Aerosol, 0.05 mg. (Dipropionate) per dose
Hydrocortisone …………………………………. Injection, 100 mg. vial
*Representing the therapeutic group.
Name of Drug Route of Administration, Dosage Forms and Strengths
19. RESPIRATORY TRACT DRUGS-Continued
19.1 Anti-asthmatic Drugs=coin.
Ketotifen ……………………………………… Tablet or Capsule, I mg. Syrup, I mg./5 ml.
*Salbutamol …………………………………. Tablets, 2 mg. and 4 mg. Syrup, 2 mg./5 ml., Inhalation, metered aerosol 0.1 mg. per dose
Ephedrine plus Hydroxyzine plus
Theophylline …………………………….. Tablet or Syrup, containing: Ephedrine 25 mg., Hy- droxyzine 10 mg., Theophylline 30 mg. per tablet or per 5 ml. syrup
*Codeine …………………………………………………………………………………………………………………. Tablet, 10 mg. (Phosphate) Syrup, 5 mg. (Phosphate)/5 ml.
20. PREPARATIONS FOR CORRECTING WATER, ELECTROLYTE AND ACID-BASE DISTURBANCES
20.1 Oral Rehydration Salts
Oral Rehydration Salts ……………………Contained in Sachets, for I litre of water-
Glucose (Dextrose) ………………….. 20 g.
Potassium Chloride …………………. 1.5 g.
Sodium Bicarbonate/Citrate ……… 2.5 g.
Sodium Chloride …………………….. 3.5 g.
Potassium Chloride ………………………..Tablet, slow release, 600 mg. Oral Solution
20.2 Parenteral Preparations
Glucose ………………………………………..Injection, 5% isotonic; 50% hypertonic
Glucose with Sodium Chloride ………..Injection, 4.3% Glucose with 0.18% Sodium Chloride
Potassium Chloride ………………………..Injection, 10% in 10 ml. ampoules
Sodium Bicarbonate ……………………….Injection, 1.4% isotonic
Sodium Chloride ……………………………Injection, 0.9% (Normal Strength) 0.45% (Half Normal Strength)
Sodium Lactate Compound Injection, solution
Water for Injection …………………………Injection, 2 rnl., 5 rnl. and J 0 ml. ampoules
21.1 Sera and Immunoglobulins
Anti-Dvlmrnunoglobulin (Human) …..Injection, 0.25 mg./ml.
Anti-rabies Hyper-immune (Serum)… Injection, 1000 units in 5 rnl. ampoule
Anti-snake Venom …………………………Injection, Polyvalent, in 10 and 20 ml. ampoules
Tetanus Antitoxin …………………………. Injection, 50,000 units in vial and 1,500 unitslml. in I ml. ampoules
Name of Drug Route of Administration, Dosage Forms and Strengths
2 I. IMMUNOLOGICALS
21.2 Vaccines (All vaccines should comply with the WHO Require- ments for Biological Substances)-
For Universal Immunisation
B.C.G. vaccine (dried) …………………….Injection
Tetanus vaccine ……………………………..Injection
Measles vaccine ……………………………..Injection
Poliomyelitis (live attenuated) vaccine Oral Solution
Tetanus vaccine …………………………….. Injection
Yaccines for Specific Indications
Cholera vaccine ……………………………. Injection
Meningococcal vaccine ………………….. Injection
Rabies vaccine ……………………………… Injection
Yellow fever vaccine …………………….. Injection
+Benzoin ……………………………………… Compound Tincture of: Chlorhexidine Solution, 5% (Gluconate), for dilution
Solution 5% (Eluconate) for dilution Solution, 5%
Solution, Different Preparations
23. VITAMINS AND MINERALS
Retinol (Vitamin A) …………………….
Tablets or Capsules, 1.5 mg. (5,000 units) 7.5 mg. (25,000) units
Thiamine (Vitamin B I) …………………..Tablets, 25 mg. and 50 mg. injection, 25 mg./ml. in I ml. ampoule
Pyridoxine (Vitamin B6) …………………Tablet. 10 mg.
Vitamin B Complex ……………………….Tablet, containing: Nicotinamide, 20 rng.; Thiamine, 5 rng.; Riboflavine, 2 rng.; Pyridoxine, 2 mg.
Ascorbic Acid (Vitamin C) ……………..Tablets, 100 mg. and 500 mg.
Ergocalciferol (Vitamin D) ……………..Tablets or Capsules. 0.25 mg. (10,000 units) 1.25 mg. (50,000 units)
+ See Formulary section for composition.
Name of Drug Route of Administration, Dosage Forms and Strengths
24. EAR, NOSE AND THROAT DRUGS
24.1 Ear – Anti-Infective
Chloramphenicol ……………………………Eardrops, 5%
24.2 Combined Anti-infective and Anti-inflammatory Drugs
Hydrocortisone plus Neomycin ………..(Acetate) plus Neomycin 0.5% (Sulphate)
Hydrocortisone plus Oxytetracycline
plus Polymyxin B……………………… Eardrops, Hydrocortisone 1.5% (Acetate) plus Oxytetra- cycline 0.5% (Hydrochloride) plus Polymyxin B. 0.119% (Sulphate)
24.3 Removal of Ear Wax
Glycerol plus Sodium Bicarbonate ….. Eardrops, Containing: 5 g. Sodium Bicarbonate and 30 m1. Glycerol in 100 ml. solution
24.4 Nose – Anti-allergic and Nasal Decongestants
Antazoline plus Naphazoline …………..Nasal Drops or Spray, containing: 0.5% Antazoline plus 0.025% Naphazoline
25. DENTAL DRUGS
+Benzocaine ………………………………….Lozenges, 10 mg.
Lignocaine …………………………………….Dental Cartridges, 2% with I :80,000 Adrenaline
26. PERITONEAL DIALYSIS SOLUTIONS
Intraperitoneal Dialysis Solution of
appropriate composition ………………Parenteral Solution
27. DIAGNOSTIC AGENTS
27.1 Diabetes mellitus
Glucose Oxidase Reagent ……………….Cellulose Strips Clinistix (R) Dextrositix (R)
27.2 Gastric Function
Histamine Phosphate ………………………Injection, 2.75 mg. (Phosphate) per m1. in I ml. ampoule
Pentagastrin …………………………………..Injection, 0.25 mg. per m1. in 2 m1. ampoule
+ See Formulary section for composition.
Name of Drug Route of Administration, Dosage Forms and Strengths
27. DIAGNOSTIC AGENTS
Edrophonium …………………………. Injection, 10 mg. (Chloride) in I ml. ampoule Tensilon (R)
Eye-drops, 2% (Sodium salt)
27.5 Radio-contrast Media
27.5.1 ALimentary tract
+Barium Sulphate ………….. .
Suspension, 75-100% v/w
*Iopanoic Acid ……………………………… Tablet, 500 mg. Telepaque (R)
Meglumine lodipamide Injection, 52% in 20 ml. ampoule Biligrafin (R) Chloro- grafin (R)
Meglumine Diatrizoate …………………Injection, 60% in 20 ml. ampoule Urogatin (R)
Sodium Diatrizoate ……………………..Injection, 50% in 20 ml. ampoule Hypaque (R)
Meglumine lothalamate ………………….. Injection, 60% in 20 ml. ampoule Conray (R)
Sodium Iothalarnate ………………………. Injection, 80% in 20 ml. ampoule Agio-Conray (R)
lophendylate …………………………………. Injection, I ml. and 3 ml. ampoules Myodil (R)
ESSENTIAL DRUGS FOR PRIMARY HEALTH CARE [Section 2.]
For many patients in Nigeria, particularly those living in rural areas, but also, to some extent, those living in urban areas, the health care centre of first contact is usually staffed by health workers other than doctors. These so-called primary health workers have a responsibil- ity for treating a wide variety of endemic diseases and managing acute symptoms and emer- gencies without immediate recourse to specialist medical advice. These health workers are also sometimes involved in the implementation of nationally organised health care programmes in the fields of immunisation, family planning, material and child health, and control of communicable and endemic diseases.
*Representing the therapeutic group.
Most primary health workers are authorised to dispense a limited range of drugs at their own discretion for common, self-limiting conditions or common endemic diseases, and to provide maintenance treatment to chronically ill patients under the remote control of a doctor. It is important that these workers are able to appreciate the significance of serious acute symptoms and able to make informed intervention when necessary, or arrange for a referral to hospital as safely as possible. It is also important that these workers keep strictly within the limits of their competence.
A subsidiary List of Essential Drugs for Primary Health Care has been compiled with the above consideration in mind. The selected drugs would vary from one health centre to another depending on the competence of available personnel and the local disease pattern, but within the entire List it should be possible to satisfy the requirements of most primary health centres.
In the case of nationally organised health care programmes like the Expanded Pro- gramme on Immunisation, Family Planning, etc., both the selection of the drugs and the crite- ria for their administration would be determined within the context of the centrally-directed programme, and the personnel involved should be given adequate instructions of how to use them on a safe and rational basis.
The Primary Health Care List
Anaesthetics Local …………………………Lignocaine, topical, injections
Analgesics …………………………………….Acetylsalicylic acid, tablet, Paracetamol, tablet
Anti-Allergies ………………………………..Chlorpheniramine, tablet, syrup,
Antidote ………………………………………..Charcoal, Activated, powder
Anti-Convulsant Drug …………………….Diazepam, injection
Anti-Infective Drugs ………………………Chloroquine, tablet, syrup, injection Metronidazole, tablet
Piperazine, tablet, syrup
Pyrontel, tablet, syrup Sulphadimidine, tablet, syrup
Drugs, Affecting Blood ………………….. Iron, tablets, mixtures Folic acid, tablet
Dermatological Drugs …………………….Neomycin plus Bacitracin, dusting powder Calamine Lotion
Benzoic acid plus Salicylic acid, ointment, cream
Gastrointestinal Drugs …………………….Magnesium Trisilicate Compound, tablet, mixture Lignocaine plus Betamethasone, ointment, cream suppository
Hyoscine N-buytlbromide, tablet
Hormones ……………………………………..Oral Contraceptives
Ophthalmological Drug …………………..Chlortetracycline, eye ointment
Oxytocic ……………………………………….Ergometrine, tablet, injection
Respiratory Tract Drug ………………….. Ephedrine plus Hydroxyzine plus Theophylline, tablet
Water/Electrolyte Balance ………………Oral Rehydration Salts
Immunologicals ……………………………..Anti-snake Venom, injection
Tetanus Antitoxin, (ATS), injection
Tetanus Vaccine, injection
BCG Vaccine, injection
OPT Vaccine, injection
Poliomyelitis Vaccine, oral solution
Antiseptics …………………………………….Chlorhexidine, solution
*The types of oral contraceptives distributed under primary health care programme will be deter- mined by the prevailing National Family Planning Policy.
SECOND SCHEDULE [Section 11.]
The Drug Formulary
Guidance on prescribing
1. Prescription writing
A medical prescription should contain essentially the following- I. I Name, sex and address of patient.
1.2 Age of patient.
1.3 The name and dosage form of the drug.
1.4 The dose, frequency and duration of administration.
1.5 The date of prescription. If a prescription is presented for dispensing several weeks after it was written, the prescriber should be consulted for advice before dispensing. The clini- cal situation might have changed in the interval and the prescription might no longer be ap- propriate.
1.6 Name, signature and address of the prescriber.
Names of drugs are best written out in full and quantities should be stated in the Metric System. Accepted abbreviations are-
gram ……………………………………………………………………… g.
milligram . …………………………………………………………….. mg.
microgam ……………………………………………………………….. mg. litre …………………………………………………………………………. l.
To avoid unnecessary errors in dispensing, when the dose is less than one gram, it should be written in milligram, e.g. 100 mg. and not 0.1 g.
For household measures, a drop is about 0.05 ml., a teaspoonful about 5 ml. and a stan- dard drinking glass about 250 ml. In order to avoid confusion, especially to the illiterate, doc- tors and pharmacists are advised to demonstrate normal size models of a teaspoon and drink- ing glass to patients requiring these measures. “Tablespoonful” should be avoided altogether since it is usually confused with “dessertspoonful”.
2. Quantities of preparations
The following List is a useful guide to quantities to be dispensed when not specified- 2.1 Liquid Preparations
Adult mixtures (l0 ml. dose) ………………………………………………………..200 ml. (20 doses) 300 ml. (30 doses)
Paediatric mixtures (5 ml. dose) …………………………………………………. 50 ml. (10 doses)
Elixirs and Linctuses (5 ml. dose) 50 ml. (10 doses) 100 ml. (20 doses) 150 ml. (30 doses)
Ear, eye and nasal drops (0.05 ml. per drop) ………………………………….. 10 ml.
Gargles, mouth washes and eye lotions ………………………………………….200 ml.
Inhalations and sprays ……………………………………………..25 ml.
Liniments ………………………………………………………….. 100 ml.
2.2 Dermatological Preparations
Creams and Ointments Lotions
Face ……………………………….. 5-15 g……………………… 100 ml.
Both hands and feet ……………. 25-50 g……………………. 200 ml.
Both arms or both legs ……………100-200 g………………… 200 ml.
Body.. ……………………………. 200 g……….. …………….. 500 ml.
Groins and genitalia ……………….15-25 g……………………. 100 ml.
Dusting powders ………………………………………………..50-100 g.
Hydrocortisone, prednisolone and other corticosteroid preparations should be applied sparingly. Their ointments are usually available in 5 and 15 g. containers, and lotions in 20 ml. containers.
3. Prescribing for children
In their response to drugs, children very often differ from adults, and this fact should be borne in mind when prescribing for children. The doses of liquid preparations and pleasantly tasting mixtures that are particularly appealing to children are given in the formulary, when- ever possible, for different age groups, for example: up to I year; 1 to 5 years and 6 to 12 years. In other instances, it is advisable to take the weight into consideration when determin- ing doses for children.
GENERAL WARNING.-Parents should be warned to keep all medicines out of the reach of children in order to avoid accidental poisoning.
4. Prescribing for the elderly
Particular care should be taken in prescribing for the elderly. As a rule treatment should be initiated at a lower dosage level than in younger patients and side effects should be care- fully looked for and not misinterpreted as new manifestations of the disease.
Elderly patients in general tend to be forgetful and this may result in inadvertent over- dosage by the patient. Drugs with low therapeutic index, e.g. digoxin, should therefore be prescribed with caution; doses should be as low as possible and the quantity of drugs supplied at a time should be small.
5. Supplying Schedule 1, Part III poisons
The Schedule I, Part III poisons are available to patients on prescription only. The group includes such classes of drugs as antibiotics, sulphonamides, barbiturates, hormones, steroids, and arsenicals. The law requires that prescriptions for these classes of drugs shall be in writ- ing, signed by the prescriber and must include his name and address as well as those of the patient. In addition, the total amount of medicine supplied and the dose to be taken must be stated. If the prescriber is a dentist, the prescription must also bear the words “For Dental Treatment Only”.
The prescription must not be dispensed more than once unless so indicated by the pre- scriber. There must be noted, on the prescription, the name and address of the pharmacist and the date on which the prescription is dispensed. The dispensed prescription must be retained for a period of two years and kept on the premises of which it was dispensed in such a manner as to be readily available for inspection.
6. Prescribing dangerous drugs and other controlled substances The law requires that-
(i) the prescription must be written by hand, in ink or otherwise so as to be indelible, dated and signed by a registered medical practitioner or dentist with his usual signature and address;
(ii) the name and address of the patient must be specified and the total quantity
of drugs to be supplied indicated;
(iii) the prescription must not be for the use of the prescriber;
(iv) dentists must mark their prescriptions “For Dental Treatment Only”;
(v) the Federal Ministry of Health may authorise and issue an official form for use in giving prescriptions for dangerous drugs. In that case a prescription for these drugs shall only be given on such forms.
7. Emergency supply of dangerous drugs and poisons towards theatres and out-patients departments
The pharmacist must supply these only upon a written order signed by a doctor, dentist or the nursing sister in-charge of the ward, theatre or out-patient department.
A requisition shall be marked in the dispensary to show that the supply has been made and shall be filed by the pharmacist and a copy or note of the requisition shall be kept by the nursing sister in-charge.
The containers must be labelled with a distinguishing mark indicating that the drugs are to be stored in a cupboard reserved solely for the storage of Dangerous Drugs and Poisons.
A record must be kept by the nursing sister in-charge, from which there can be traced during the two years after the date of the supply, the names and quantities of the poisons, the names and addresses of the patients and the names of the prescribers.
Special record books to be used for this purpose are obtainable from the Federal Medical Stores, Federal Ministry of Health, Oshodi, Lagos.
8. Drugs of dependence addiction
Narcotic analgesics, sedatives, hypnotics, tranquillisers, antidepressants and almost all drugs prescribed for their action on the central nervous system are capable of producing a state of dependence in subjects to whom they are administered repeatedly in sufficient dosage. The type of dependence, its severity, symptoms and the presence or absence of withdrawal symptoms will be characteristic of the drug being used.
All substances controlled under the Dangerous Drugs Act (DDA: Cap. D I – Laws of Nigeria) are capable of causing dependence. Similarly, all powerful new analgestics should be prescribed with care even though they are not on the DDA List. The risk of dependence varies with the personality of the patient concerned, and as there is no really reliable way to deter- mine such individual risks, it is best to be circumspect about these drugs and patients to whom they are given.
The prescriber should be aware of the patient who-
(i) demands “his usual prescription”;
(ii) claims to obtain better relief from self-increased dosage, and who has found it necessary to buy more drugs, in between visits.
The prescribing of all such drugs calls for caution. It must be ensured that the amount obtained by the patient at anyone time and the frequency of renewal of supplies are in agreement with the prescriber’s good clinical judgement, especially where medical, dental and other health care workers are involved.
Dependent patients are usually insistent and coercive. They resort to all sorts of methods to obtain supply, e.g. consulting more than one doctor, fabricating stories to substantiate demands and forging prescriptions. They may even resort to stealing the drugs. To guard against these risks-
(i) lock up all prescription forms;
(ii) draw a diagonal line across the blank part of the form under the prescrip- tion;
(iii) write the quantity in words when prescribing drugs prone to abuse; (iv) add initials against altered items on prescriptions;
(v) double check by writing on both the prescription card and in the clinical notes. Appropriate records should also be kept where necessary, e.g. in the pharmacy, wards, casualty, etc.
8.1 Prevention and Treatment.-Treatment of drug dependence is extremely difficult and frustrating. It is essential, for success, that the patient be motivated to desire treatment which usually requires special skills and facilities. It is therefore THE DUTY OF THE DOC- TOR TO AVOID, SO FAR AS IS POSSIBLE, THE PRODUCTION OF NEW CASES OF DRUG DEPENDENCE. This he can do by paying rigorous attention to the points above, and by only prescribing dependence-producing drugs when essential, (e.g. not prescribing pethi- dine just to induce sleep in the absence of pain or merely to keep a psychotic patient quiet). In incurable and terminal conditions associated with considerable pain, morphine and similar analgesics should, of course, not be withheld. On the other hand, in hypochondriasis, neurosis, etc., prolonged treatment with these centrally active drugs should not be regarded as a substi- tute for psychiatric care.
Emergency treatment of poisoning
1. General measures
In the treatment of acute poisoning, success depends largely on a combination of speed and commonsense as well as on the poison, the amount taken and the time which has elapsed. The principles of treatment may be outlined as follows-
1.1 Identification of the poison.- This will help if it is immediately possible, but if not, no time should be wasted as successful treatment may not depend on specific antidotes.
1.2 Removal of the Poison-
1.2.1 External.-Skin contamination by chemicals can lead to systemic poisoning.
Contaminated clothes should be stripped off and the skin washed with soap and water, sodium bicarbonate, vinegar or alcohol as appropriate.
1.2.2 Internal.-If poison has been swallowed, removal should be by-
(i) emesis; in conscious patients only; this is induced by inserting two fingers into the back of the throat or if this fails, by giving a cup of tepid water in which two teaspoonfuls of salt have been dissolved or by administration of an emetic;
(ii) gastric aspiration or lavage especially if patient will not vomit. The fluid obtained should be kept for analysis. Special care should be exercised in patients with corrosive poisoning, in alcoholics, in patients who have had gastric surgery, and in the elderly.
W ARNING.-If patient has swallowed paraffin (kerosene) or other petroleum distillates, emetics and lavage should not be used since attempts to remove them are likely to introduce some into the lungs where they are more damaging than in the gut. In the deeply unconscious patient, lavage should only be undertaken after protecting the lungs by insertion of a cuffed endotracheal tube.
1.3 Prevention offurther absorption of the poison that cannot be removed.
(a) From puncture site.-Use of tourniquet is recornmeded; e.g. for snake bites. Cb) From the gut-
(i) specific antidotes which combine chemically with the poison are useful, e.g. use of alkalis to neutralise acid;
(ii) non-specific antidotes, mostly demulcents, e.g. raw eggs, milk, kaolin, flour and activated charcoal are useful.
1.4 Promotion of excretion of the poison.-Elimination of drugs that are excreted by the kidney is promoted by good urine volume which can be achieved by giving maximum safe
amounts of fluid and a diuretic. Sometimes, alteration of urinary pH can be particularly help- ful, as in the excretion of acidic drugs, e.g. sulphonamides, barbiturates, salicylates (alkaline urinary pH enhances), and excretion of basic drugs, e.g. chloroquine, ephedrine, pethidine (acidic urinary pH enhances).
2. Notes on some common poisonings
2.1 Acetylsalicylic acid.- The main features of poisoning are nausea with or without vomiting, epigastric pain, dizziness, mental confusion, visual disturbances, profuse perspira- tion, rapid and feeble pulse, hyperventilation.
Treatment.–Consists of early and repeated gastric lavage with water, and forced alka- line diuresis. In children with very severe poisoning, exchange transfusion may be performed.
2.2 Corrosive Adds.-(Including hydrochloric acid, nitric acid, sulphuric acid). There is a corrosion of the lips, mouth and tongue, pain in the digestive tract, intense thirst dysphagia, nausea and vomiting, rapid and feeble pulse, clammy skin, shallow and difficult respiration, collapse and convulsions.
Treatment.–Consists of administration of milk of magnesia, lime water, or soap solu- tion, followed by milk, egg albumen or olive oil, and morphine (for pain). Alkaline carbonaest (chalk, magnesium carbonate, sodium carbonate, etc), may be used in emergency but are bet- ter avoided in poisoning by concentrated acids since they liberate carbon dioxide which, may cause gastric distension and perhaps perforation. Stomach tubes or emetics should also be avoided.
2.3 Alkalis.-(Including caustic potash, caustic soda, strong ammonia, etc). There is pain in the mouth, throat and abdomen, swollen lips and tongue, vomiting, diarrhoea, cold and clammy skin, rapid and weak pulse, and shock.
Treatment.–Consists of administration of vinegar or lemon juice or solutions of citric or tartaric acid to neutralise the alkali; followed with milk, olive oil, or egg albumen and mor- phine for pain. Emetics and gastric lavage are best avoided.
2.4 Amphetamines and allied drugs.-Patient is flushed and excitable and may become delirious and violent, there may also be convulsions and coma.
Treatment.–Consists of gastric lavage followed by chlorpromazine 25-100 mg. intra- muscularly. In severe cases, forced chorid diuresis is required.
2.5 Tricyclic antidepressants.-(e.g. imipramine, nortriptyline, and amitriptyline).
Symptoms of poisoning include dry mouth, mydriasis, hypotensive collapse, convulsions, tachycardia, bradycardia and cardiac arrest.
Treatment.-Consists of gastric lavage and saline catharsis if there is not coma. ECG monitoring is essential. Acidosis is treated with MI6 soidum lactate, 20 ml. per kg body weight administered by slow intravenous infusion. The convulsion is treated with diazepam 10 mg. i.v. or i.m. repeated four-hourly. Cardiac effects may be controlled by pyridostigmine 1 mg. intravenously or propranolol 1 mg. intravenously repeated several times. Reduced doses are necessary for children.
2.6 Barbiturates and other sedatives.- There is giddiness, mental confusion, ataxia, de- lirium, coma, marked fall in blood pressure, depression of respiration, increase or decrease in body temperature, moderately dilated pupils, absence of corneal reflex, cyanosis and renal failure.
Treatment.–Consists of emesis, gastric lavage, artificial respiration, administration of oxygen and dextrose saline (i. v.).
Forced diuresis may be considered especially in severe poisoning due to long-acting bar- biturates.
2.7 Bleaching solution.-(lncluding sodium hypochlorite solution and hypochlorous acid). Inhalation of the fumes causes severe pulmonary irritation with coughing and choking followed by pulmonary oedema. Ingestion causes irritation and corrosion of mucous surfaces, oedema of the pharynx and larynx, nausea and vomiting.
Treatment.-Involves removing the bleaching solutions from the skin by washing with water. Ingested solution is removed by gastric lavage or emesis using sodium bicarbonate solution (I in 40). This is followed by sodium sulphate 30G and sodium bicarbonate 8G in 25 ml. of water and a cathartic. Acid antidotes should not be used.
2.8 Boric Acid.-In acute poisoning, the symptoms, which develop slowly, beginning about eight hours after ingestion, are nausea and vomiting, diarrhoea and prostration leading to convulsions. Increasing shock, accompanied by subnormal temperature and cold sweat eventually leads to collapse.
Absorption of boric acid through continual use as ointment, lotion or powder, produces slight but cumulative effects.
Infants are particularly susceptible and even the cleansing of the nipples of nursing mothers with solutions of boric acid can have disastrous results. Boric acid powder should never be applied undiluted to infants and the proportion in dusting powders should into exceed 5%.
Treatment.-Poisoning with boric acid is treated by the administration of oxygen and artifical respiration to relieve respiratory difficulty. Emergency treatment of acute poisoning as a result of ingestion is by emesis or gastric lavage. The patient should be kept warm and quiet and given hot coffee or milk.
2.9 Carbolic acid.-(Including other phenols, Iysol, creosote, etc.). Symptoms are whit- ened lips and mouth, burning pain occurring from the mouth to the stomach, constricted pu- pils, cold and clammy skin, subnormal temperature, feeble pulse, contracted and rigid abdo- men and urine which turns black on standing. Accidental poisoning may occur also by skin absorption.
Treatment.-Consists of gastric lavage with a copious quantity of water to which lime water is added. Milk, egg albumen or other demulcent are given later; artificial respiration may be necessary.
If contamination is external, it is advisable to remove clothing and to wash the skin im- mediately with glycerine or alcohol.
2.10 Kerosene and petroleum products.-These cause restlessness with ataxia, coughing and choking of rapid onset with nausea, vomiting and diarrhoea. Drowsiness may develop. In severe cases, dyspnoea, cyanosis and pyrexia may occur, especially if inhalation and ingestion have taken place together.
Treatment.-It is advisable not to induce vomiting as the aspiration of even 1.0 ml. of any of these products into the lungs can lead to pneumonitis. Their absorption can be slowed down by giving 250 rnl. of liquid paraffin orally. Antibiotics are indicated in full doses for prohylaxis against peumonia.
2.11 Iron Salts.-Iron poisoning occurs mainly among children who swallow the tablets that have been left within their reach. The symptoms of poisoning are gastrointestinal irrita- tional pallor, a feeling of cold, retching, vomiting, drowsiness and restlessness.
Treatment.- There must be intensive and specific therapy as mortality is always high.
The effective antidote is desferrioxamine which produces an inactive chelate with iron. Eme- sis is induced as soon as possible and the stomach washed out with sodium bicarbonate solu- tion I %. A solution of 109. desferrioxamine in 50 rnl. water should be left in the stomach. Where treatment has been delayed for severe poisoning, desferrioxamine should be infused
intravenously at the rate of 15mg per kg body weight per hour to a maximum of 80 mg. per kg. body weight in 24 hours.
2.12 Snakes Bites.-Venomous snakes are included in four families, the Hydrophidae (sea snakes), the Elapidae, and Colubridae and the Viperidae. The venom of sea snakes is predominantly myotoxic, that of colubrides is neutrotoxic and that of viperides are haemo- toxic and neurotoxic. The venoms contain proteolytic, haemolytic and cytolytic, enzymes. The most poisonous African snakes are Viperidae: Bitis (arientis, gabonica, nasicornisi, Echis carinatus and Causus rhombeatus; and Elapida: Naja (melanoleuca nigricollis, haje), Den- drapis (angusticeps, jamesoni, viridis) and Sepedon haemachates – spitting cobra.
The effects of snakes bite on man depend on the variety of snake, the site of the bite, the state of health of the snake and the efficiency and duration of the bite. Fortunately, most bites do not allow the venomous snake enough time to discharge a full dose of its poison and so victims have minimal or no poisoning. If instead of the venom being injected subcutaneously as usually occurs, the fang penetrates a vein, so that the injection is intravenous, very severe poisoning or instant death usually results.
Anti-snake venom.-Due to the variety of poisonous snakes with individual venoms in Africa, and in the usual circumstances where the offending snake cannot be caught for identi- fication, polyvalent anti-venom sera are preferred to specific antisera.
Medical treatment of snake bite.-It is necessary to give firm reassurance to the victim.
Tourniquet should be applied to the site of bite to delay absorption and spread of venom. The site of the bite should be wiped and covered with cloth or dressing.
Only symptomatic treatment is required for victims who show little or no clinical evi- dence of poisoning. It is however advisable to give anti-venom because there may be delayed reaction. Dosage: 20-100 rnl. Polyvalent antisnake venom i.v.
A subcutaneous trial dose of 0.2 ml. anti-venom should be given and the patient ob- served for signs of anaphylaxis for 30-minutes before the therapeutic dose is injected. If this is not practicable, the administration of ml. 1 of 1 : 1000 adrenaline instranmuscularly given at the same time, to lessen the risk of anaphylaxis is strongly recommended.
It is however best to check the manufacturer’s literature before use.
Classified notes on drugs and preparations
1. Central nervous system drugs
Drugs acting on the central nervous system are discussed under the following headings-
1.2 Anti-migraine Drugs.
1.3 Hypnotics and Sedatives.
1.4 Anti-convulsants (Antiepileptics). 1.5 Anti-depressants.
1.6 Anti-psychotics (Major tranquillisers). 1.7 Anti-parkinsonism Drugs.
1.1 Analgesics.-There are two main types of analgestics, namely narcotic and non-
narcotic analgesics. Drugs in this sub-section are discussed under the following headings-
1.1.1 Narcotic Analgesics.
1.1.2 Narcotic Antagonists.
1.1.3 Non-narcotic Analgesics.
1.1.1 Narcotic Analgesics.
These are powerful drugs which act on the opioid receptors in the brain and they are used for severe pain from any site including the viscera. They include the following-
Dosage form.-Injection 10 mg.lml., usually as sulphate or hydrochloride.
Pharmacological properties.-Binds to opioid receptors and its main actions are in the CNS. Its analgesic effect is usually accompanied by sedation and mental detachment or euphoria. After subcutaneous injection analgesia starts within fifteen minutes and lasts for about six hours. It depresses respiration and causes nausea and vomiting. It increases the tone of intestinal muscles.
Uses.-Most valuable narcotic analgesic against severe pain, e.g. post-surgery and post-
trauma, 10-20mg s.c. or i.m. 6 hourly-
Preoperative medication, 10-20 mg. s.c;
Left ventricular failure and pulmonary oedema, 4-10 mg. i.v. slowly; Terminal pain of caner, 10-20 mg. 4 hourly;
Cough and diarrhoea.
Precautions and Contraindications.-Avoid in labour because it causes respiratory de- pression in the new-born; in asthma and chronic bronchitis. Do not give i.v. unless a narcotic antagonist is readily available.
Adverse Reactiol1s.-Nausea, vomiting, constipation, respiratory depression, apnoea, hypotension, peripheral circulatory collapse, allergic reactions, tolerance and addiction.
Dosage.-By subcutaneous or intramuscular injection, 10-20 mg. Children’s dose must be reduced proportionately.
Doses may be repeated 4 to 6 hourly.
Overdosage.-Symptoms and Signs: Acute overdosage leads to respiratory depression with pin-point pupils, coma and death. Treat with O.4mg naloxone given i.v. every 3 minutes for 3 doses after establishing a patent airway. Chronic abuse leads to addiction. Tolerance does not usually develop to its miotic and constipating effects. Withdrawal symptoms include lacrimation, rhinorrhoea, yawning and sweating, occurring within 8-12 hours of the last dose. After about 12-14 hours the addict falls into a “yen” sleep from which he wakes, becoming more restless. Then there is mydriasis, anorexia, goose flesh, irritability and tremor. After about 48-72 hours there is insomnia, coryza, depression, sweating, tachycardia, vomiting, goose flesh, abdominal cramps, pains in bones and muscles and kicking movements with ejaculation in men and orgasm in women. Terminally there is dehydration, ketosis and shock. Treatment is by methadone substitution after rehydration.
Dosage form.-Injection, 50 mg. and 100 mg. in I ml. and 2 ml. ampoules respectively. Mode of action.-Narcotic analgesic.
Pharmacological properties.-Binds to opioid receptors and its main actions are in the CNS. After oral administration the onset of analgesic effect is within 10 minutes and peak effect is reached in about I hour. Duration of analgesic effect is shorter than that of morphine, being about 2 to 4 hours. It is less spasmogenic than morphine.
Uses.-Deep-seated pain, e.g. post-surgery, trauma, and labour pain; preoperative medication.
Precautions.-Use cautiously during labour because it crosses the placental barrier and may produce respiratory depression in the newborn. Often used as pethilorfan (pethidine and levallorphan) in obstetric analgesia. In head injury respiratory depression and elevation of CSF pressure may be masked.
Adverse reactions.-Nausea, vomiting, respiratory depression, sedation, hypotension especially when given intravenously, drug dependence and addiction.
Drug interactions.-With MAO inhibitors it produces excitation, delirium, hyperpyrexia and convulsions. Chlorpromazine and tricyclic antidepressants potentiate its respiratory de- pression. Promethazine and chlorpromazine increase pethidine induced sedation. Ampheta- mine enhances its analgesic effect.
Dosage.-50-100 mg. intramuscularly, every 3-4 hours; oral dose is 50-100 mg.; chil- dren’s dose must be reduced proportionately.
Overdosage.-Acute overdosage leads to respiratory depression with dilated pupils.
Treat with 0.4 mg. naloxone intravenously, given every 3 minutes for 3 doses. Chronic drug abuse leads to addiction. There is tolerance to respiratory depression but excitatory effect in- cluding hallucinations and convulsions may occur. Withdrawal sysmptoms develop more rapidly and are of shorter duration than those of morphine. They consist of yawning, lacrima- tion, sweating, restlessness, diarrhoea and vomiting.
It is a combination of pethidine and levallorphan tartrate-a narcotic antagonist. The combination reduces the respiratory depression produced by pethidine whose analgesic effect is enhanced.
Uses.-Analgesic during labour, to reduce the risk of respiratory depression in the new-
Minor surgery as an adjunct to nitrous oxide anaesthesia; Post-operative pain especially in chronic bronchitis.
Dosage.-Injection, 50 mg. pethidine hydrochloride plus 0.625 mg. levallorphan tartrate per ml., i.m., 2-4 m\. every 3-4 hours.
Others.-Other narcotic analgesics in common use are: Codeine, Dihydrocodeine, Leverphanol and Pentazocine.
1.1.2 Narcotic Antagonists
Dosage form.-Injection, 0.4 mg./m\. in 1 ml. ampoules. Mode of action.-Narcotic antagonist.
Pharmacological properties.-Antagonises all three sub-types of opioid receptors, but it is more potent in antagonising supraspinal analgesia, respiratory depression, euphoria, and physical dependence than sedation, miosis, dysphoria, hallucination and vasomotor stimula- tion.
Uses.-Opioid induced respiratory depression; Diagnosis of physical dependence.
Precautions.-May precipitate withdrawal symptoms from opioids, pentazocine, butor- phanol and nalbuphine.
Dosage.–O.4-0.8 mg. intravenously or intramuscularly. In neonates with respiratory de- pression. 0.01 mg./kg. into umbilical vein.
Other.-Other commonly used narcotic antagonists are- Levallorphan and Nalorphine.
1.1.3 Non-narcotic Analgesics
ACETYLSALICYLIC ACID Dosageform.-Tablets, 300 rng., 75 mg.
Mode of action.-Inhibitor of prostaglandin synthetase.
Pharmacological properties.-Analgesic, antipyretic and anti-inflammatory. It is useful for pain of low intensity which it relieves by both a peripheral and a CNS effect. It may cause gastric ulceration or exacerbate peptic ulcer. It reduces platelet aggregation and prolongs bleeding time. Small dose decrease and large doses increase urate excretion.
Uses.-Analgesic of choice for headache and mild musculo-skeletal pain; Dysmenorrhoea, neuralgia, myalgia, antipyretic;
Acute rheumatic fever; Rheumatoid arthritis; Banter’s syndrome;
Prohylaxis of coronary artery disease, myocardial infarcton, and post-operative deep vein thrombosis;
Patent ductus arteriosus in neonates.
Precautions.–Contraindicated in peptic ulcer. Caution in asthma and in impaired renal or hepatic function.
Adverse reactions.-Gastronintestinal irritation, peptic ulcer, gastrointestinal blood loss may be asymptomatic; increased bleeding time, bronchospasm, tinnitus, vertigo, mental con- fusion, rashes, angioneurotic oedema, myocarditis, blood dyscrasias, particularly thrombocy- topenia.
Dosage.-Analgesic and natipyretic dose: 300 mg./1 g., orally every 4-6 hours. Chil- dren, 10-20 mg./kg. every 6 hours, but not to exceed a total daily dose of 3.6 g. Acute rheu- matic fever: I g. 4-6 hourly. Children, 80-120 mg./kg. daily in divided doses. Continue full doses for 2 weeks after symptoms disappear; then tail off over 7-10 days. Rheumatoid Arthri- tis: 3.6-8 g. daily in divided doses.
Overdosage.-See Emergency Treatment of Poisoning (Chapter 2).
Dosage forms.- Tablet, 500 mg.; Elixir and Syrup, 125 mg./5 ml. Mode of action.-Non-narcotic analgesic.
Pharmacological properties.-Analgesic and antipyretic, but with only a week anti- intlammatoryaction.
Uses.-Mild to moderate pain including headache, toothache, myalgias, neuralgias, dysmenorrhoea, musculo-sketetal pain associated with arthritis, fever due to bacterial and viral infections. Useful in patients in whom aspirin is contraindicated.
Precautions.-Patient should not exceed maximum recommended dose of 4.0 g. daily or use for more than 10 days without advice or supervision by doctor.
Adverse reactions.-Haematological (rare), but may cause anaemia, neutropenia, leuco- penia, thrombocytopenia or pancytopenia. Hypersensitivity (rare) skin rashes, mucosal le- sions, laryngeal oedema and drug fever.
Dosage.-Adult: 0.5-1 g., 4-6 hourly up to 4.0 g. daily.
Child: Up to 1 year, 60-120 mg.; 1-5 years, 125-250 mg. 6-12 years, 250-500 mg.;
These doses may be repeated 4-6 hourly when necessary.
Overdosage.-Early: nausea, vomiting, malaise, sweating. Late: (48-72 hours after in- gestion)-Signs and Symptoms: Clinical and laboratory evidence of hepatotoxicity. Right hypochondrial pain and tenderness, increased SGOT, SGPT, Serum bilirubin and prothrombin time and hypoglycaemia.
Treatment.-Gastric aspiration to remove contents, gastric lavage. Determine serum level of drug and liver function tests within 4 hours. Give acetylcysteine (within 24 hours only), orally in a loading dose of 140mg/kg followed by 70 mg./kg. every 4 hours for 17 doses. Dosage is terminated if plasma levels show that risk of liver damage is low.
1.2 Anti-Migraine Drugs.-Most migraine attacks are mild and can be treated with aspi- rin or paracetamol. However, since peristalsis is usually reduced during migraine attack the amount of drug absorbed may not be enough to control an attack. Drugs may be used for the treatment of acute attacks or prophylasis or migraine.
ERGOTAMINE Dosage form.- Tablet, 2 mg. as the tartrate.
Mode of action.-It constricts the cranical arteries. Pharmacological properties.-Relieves migraine headache. Uses.-Treatment of migraine.
Precautions.-Contraindicated in injections, marked atherosclerosis, coronary artery disease, thromondophlebitis, Raynaud’s or Busrger’s syndrome, pregnancy, severe liver or kidney disease.
Adverse reactions.-headache, nausea, vomiting, repeated doses may cause ergotism with gangrene of extremities and mental derangement.
Dosage.-Oral for acute attack, 1-2 mg. at the onset of attack, repeated every 30 minutes if necessary until a total of 6mg has been taken. No more than 10 mg. per week.
Overdosage.-Symptoms and Signs.-Vomiting, diarrhoea, thirst, tingling, itching and coldness of skin and extremities, weak pulse, gangrene of extremities, dizziness, depression, convulsion, hemiplegia, fixed miosis, anginal pain, tachycardia or bradycardia, and elevated or lowered blood pressure.
Treatment.-Withdrawal of drug, symptomatic treatment with vasodilators, anti- coagulants, and lower molecular weight dextran.
Other.-Other anti-migraine drugs are clonidine and pizotifen.
1.3 Hypnotics and Sedatives
1.3.1 Anxiolytics.-Benzodiazepines are the most widely prescribed anxiolytics. Their use should be limited to those whose anxiety interferes with work, leisure or family relation- ship. Treatment should be limited to short periods because tolerance develops within four months of continuous use. Dependence and addiction are more likely in patient with personal- ity disorders, history of alcoholism or drug abuse.
Dosage forms.- Tablet, 2.5 mg. Injection, 5 mg./ml. in 2 ml. ampoule and 10 ml. vials.
Syrup, 2 mg./5 ml.
Mode of action.-Minor tranquilliser of the beuzodiazepine group.
Pharmacological properties.-Anxiolytic with hypnotic effect. It increases seizure and is a centrally acting muscle relaxant.
Uses.-Tension and anxiety states; Moderate to severe psychoneurosis; Acute alcohol withdrawal syndrome; Preoperative medication;
Status epilepticus or severe recurrent convulsive seizures; Tetanus;
Skeletal muscle spasm prior to endoscopic procedures.
Precautions.-Care in glaucoma unless patient is receiving appropriate therapy. Habit forming and addiction liable. Additive effect with alcohol and other CNS depressants. Con- sciousness may be impaired, therefore patient should not drive or operate hazardous machin- ery. Abrupt discontinuation of long term treatment should be avoided because of barbiturate- like withdrawal syndrome. Should be prescribed in only small quantities to potential suicidal patients. Intravenous use may result in phlebitis and venous thrombosis; must be given slowly, not faster than Smg per minute. Apnoea or cardiac arrest may occur in the elderly or debili- tated. May increase frequency and or severity of grand mal seizures. Abrupt withdrawal may also precipitate convulsion.
Adverse reactions.-Drowsiness, fatigue, ataxia (particularly in the elderly), confusion, dry mouth, headache. Cardiac and respiratory depression; hypersensitivity reactions; pain and venous thrombosis from i.v. injection.
Drug interactions.-Additive with CNS depressants like alcohol, narcotic analgesics and sedative hypnotics. Increased CNS effects with MAO inhibitors and other anti-depressants.
Dosage.-Adults, oral: 2-10 mg., 2-4 times daily. By i.m. or i. v., S-IO mg. start, and then 3-4 hourly. For status epilepticus, S-IO mg. i.m. or i.v. slowly every 10-IS minutes up to 30 mg.; repeat 2-4 hours later if needed. Children’s doses must be reduced appropriately.
Overdosage.-Symptoms and signs-Drowsiness, confusion, diminished reflexes, coma and hypotension. It has a wide margin of safety. Serious sequale are rare unless alcohol or other CNS depressants are also taken.
Treatment.-Empty stomach by gastric lavage. General supportive measures. Lv. tluids.
Hypotention may be treated with noradrenaline.
NITRAZEPAM Dosage form.-Tablet or capsule, S mg.
Mode of action.-Benzodiazepine. Pharmacological properties.-Depresses CNS. Uses.-Mainly as hypnotic.
Precautions.-Care in acute or chronic pulmonary insufficiency. Discontinue gradually
after long term use.
Adverse reactions.-Depresses respiration.
Drug interactions.-Additive with alcohol and other CNS depressants. Dosage.-5-IO mg.
Overdosage.-Symptoms, signs and treatment as for diazepam.
1.3.2• Barbiturates.-These are becoming obsolete as sedatives and hypnotics have been largely replaced by benzodiazephines, This is because the barbiturates are more hazardous in use; they cause paradoxical excitement in children, confusion in the elderly, interact dangerously with other drugs and alcohol, are liable to abuse and are often used in self
poisoning. They have therefore not been included as hypnotics or sedatives in the Essential Drugs List.
Others.-Other hypnotics which are still sometimes used are Chloralhydrate and Paral- dehyde.
l.4 Anti-Convulsants (Anti-Epileptics)
1.4.1 Barbiturates.-Having fallen into disfavour as sedative-hypnotics, the barbiturates are now more used as anti-convulsants. Most barbiturates have anti-convulsant properties. However, it is those with low anti-convulsant: hypnotic ratio that are used as anti-convulsants,
Dosage forms.- Tablets, 30 and 60 mg., Syrup, 15 mg./5 rnl. Mode of action.-CNS depressant.
Pharmacological properties.-Sedative, hypnotic and anti-convulsant pylorospasm, nausea and vomiting; hypnotic, anti-convulsant in tetanus, eclampsia, cerebral haemorrhage, poisoning by convulsant drugs and in status epilepticus; to antagonise unwanted stimulant effects of anti-asthma drugs e.g. ephedrine and theophylline; neonatal hyperbilirubinaemia and kernicterus.
Precautions.-Addiction liable; has largely been replaced by bensodiazephines as seda- tive and hypnotic because of abuse liability and frequent use in drug poisoning; contra-indi- cated in acute intermittent porphyria or porphyria variegata.
Adverse reactions.-Drowsiness, hangover effect, impaired mental and physical facul- ties, paradoxical excitement, irritability, myalgic pain in the neck, shoulder, girdle and upper limbs.
Drug interactions.-Severe CNS depression when used with alcohol and other CNS de- pressants. Potentiated by isoniazid, MAO inhibitors. Accelerates metabolism or corticoste- roidids, oral contraceptives, oral anti-coagulants, digitoxin, phenytoin, testosterone, sulphadi- methoxine, and tricyclic anti-depresants. Accelerated metabolism of Vitamin D may cause hypocalcaemia in the elderly.
Dosage.-Anti-convulsant, 30-60 mg., 2 to 3 times daily; Status epilepticus: injection, 200 mg. by i.m. or i.v.; Hypnotic: 60-200 mg.;
Children’s doses reduced appropriately.
Overdosage.-Symptoms and Signs-Moderate intoxication which resembles alcoholic inebriation; severe intoxication results in coma, depressed respiration, positive Banbinski re- sponse; pupils initially constricted and reacting to light but later become dilated; hypertension, shock, barbiturate bullae, hypothermia and renal failure.
Treatment.-General supportive measures include maintenance of patient airway, gastric lavage taking care to avoid aspiration of gastric contents, maintenance of circulation; forced diuresis, haemodialysis or haemoperfusion for renal failure.
PHENYTOIN SODIUM Dosage form.-Tablets, 50 mg., 100 mg. Capsules, 50 mg., 100 mg.
Mode of action.-Limits development of seizure activity and reduces spread of seizure. Pharmacological properties.-Exerts anti-epileptic action without causing general de-
pression of CNS.
Uses.-I. Grand mal epilepsy.
2. Partial seizures.
3. Cardiac arrhythmias.
Precautions.-Breast-feeding females; change over from other drugs should be made cautiously; avoid sudden withdrawal. Drug interactions.-Potentiates effect of chloramphenicol, cirnetidine, cotrimoxazole, diazepam, dicoumarol, disulfiram, izoniazid, phenylbutazone, sulphaphenazole, sulphinpyra- zone and sultahiame. Transient potentiation of aspirin and sodium valpuate.
Adverse reactions.-Nausea, vomiting, confusion, dizziness, headache, tremor, insomnia occur commonly. Ataxia, slurred speech, nystagmus and blurred vision are signs of overdos- age. Rare side effects include skin rashes, coarse face, acne, hirsutism, fever, hepatitis, lupus erythematosus, erythema multi forme, lymphadenopathy, gum hyperplasia and tenderness, folate deficiency rnegalobiastic anaemia, leucopenia, thrombocytopenia, agranulocytosis and aplastic anaemaia.
Dosage.-Grand mal and psychomotor epilepsies: Orally 100 mg. 3 times daily initially; may be increased to 200 mg. 3 times daily; maintenance dose, 100 mg. 3 to 4 times daily to achieve a therapeutic serum level of 10-20 ug./ml. i.v. 100-250 mg., then 100-200 mg. i.m., 4- 6 hourly for seizures associated with neuro-surgery.
Overdosage.-Symptoms and Signs-Nystagmus, ataxia, dysarthria, coma, fixed pupils, hypertension, respiratory depression, apnoea, death.
Treatment.-Gastric lavage, and symptomatic treatment. Haemodialysis. 1.4.3 Succinimides
ETHOSUXIMDE Dosage from.- Tablets or Capsules, 250 mg.
Mode of action.-Elevates seizure threshold induced by electroshock and pentylene-
Pharmacological properties.-Prevents spread of epileptic focus. Uses.-Absence seizures (petit mal).
Precautions.-May precipitate grand mal seizures if used alone for a patient with mixed type of epilepsy; may impair mental activity. Caution in liver and kidney function impairment. Abrupt withdrawal may precipitate petimal status.
Adverse reactions.-Anorexia, nausea, vomiting, epigastric pain, diarhoea, blood dys- crasias (ieukopenia, agranulocytosis, aplastic anaemia), drowsiness, headache, dizziness, hic- coughs ataxia, allergic reactions, urticaria, Stevens-Johnson syndrome, hirsutism, myopia, vaginal bleeding and systemic lapus erthematosus.
Drug Interactions.-High doses of tricyclic anti-depressants and anti-psychotics induce seizures.
Dosage.-500 mg. daily initially, increasing every 4-7 days to 1.5 g. daily in 3 divided doses. Child (3-6 years), 250 mg. daily initially, increasing every 4-7 days to 1.5 g. daily in di vided doses.
Overdosage.-Symptoms and Signs-As in adverse reactions. Treatment.-Gastric lavage and symptomatic treatment.
See Anxiolytics, 1.3.1
1.4.5 Others.-Other widely used anti-convulsant drugs are carbamazepine, paradehy- ede Sodium valprote.
1.5.1 Tricyclic Anti-depressants
AMITRIPTYLINE Dosage form.- Tablet 25, 50 mg.
Mode of action.-Prevents the re-uptake of noradrenaline and other catecholamines into central and peripheral stores.
Pharmacological properties.-Elevates depressed mode and has prominent anti- cholinergic properties; may also induce sedation.
Uses.-Depression, especially endogenous depression.
Precautions.-Do not use concurrently with MAO inhibitors, wait at least two weeks after stopping the latter. Caution in elderly males and those with urinary retention or glau- coma. Caution in coronary artery disease since it can produce tachycardia and cardiac ar- rhythmias. May increase psychotic symptoms in schizophrenic patients and shift manic de- pressive patients to manic phase. Avoid dispensing large quantities to potentially suicidal pa- tients. Stop drug several days before elective surgery. Caution in hepatic dysfunction, thyroid dysfunction and those with history of epilepsy.
Adverse reactions.-Tachycardia, palpitation, hypertenstion, hypotension, myocardial infection, arrhythnmias, stroke, confusion, disorientation, delusions, hallucinations, insomnia, nightmares, paraesthesiae, peripheral neuropathy, tinnitus, ataxia, dry mouth, blurred vision, cycoplegia, increased intraocular pressure, constipation, urinary retention, blood gdyscrasias anorexia, nausea, vomiting, diarrhoea, parotid swelling, black tongue, impairment of liver function, gynaecomastia, testicular swelling (males), breast enlargement and glactorrhoea (females), increased or decreased libido, skin rash, urticaria, oedema of face and tongue, sweating, mydriasis, urinary frequency, alopecia, weight gain or weight loss and drowsiness.
Drug Interactions.-Reduces anti-hypertensive effect of guanethidine; causes severe hy- pertension and hyperpyrexia with sympathomimetics; causes convulsions and excitability with MAO inhibitors.
Dose.-25 mg. 3 times daily, increase to 50 mg. 3 times daily. Effect may not manifest for three weeks.
Overdosage.-Symptoms and Signs-Drowsiness, tachycardia, hypothermia, arrhyth- mias, mydriasis, convulsions, coma, hyperreflexia, rigidity, hyperpyrexia and vomiting.
Treatment.-Gastric lavage; activated charcoal, 20-30 g. 4-6 hourly for 48 hours.
Symptomatic management viz-
(i) tachcardia and arrhythmias-give neostigmine, pyridostigmine or pro- pranolol;
(ii) congestive heart failure-give digitalis;
(iii) convulsions-give diazepam, or inhalation anaesthetics (not barbiturates);
N.B.-Dialysis not effective because of extensive tissue binding. Other tricyclic anti- depressants including imipramine, desimipramine and nortriptyline can be used in place of amitriotyline.
1.5.2 Monoamine-Oxidase Inhibitors (MAO/’s).-These are no longer recommended because of the risk of very severe adverse reactions.
1.6 Anti-Psychotics (Major Tranquillisers) 1.6.1 Phenothizines
Dosage form.- Tablet, 25, 50, 100 mg.;
Capsules, 30, 75, 150, 200, 300 mg.; Injections, 25 mg./ml. in 2 ml. ampoules.; Syrup, 25 mg./5 ml.
Mode of action.-Major tranquilliser.
Pharmacological properties.-Experts neuroleptic syndrome, i.e. suppresses spontane- ous movements and complex behaviour while spinal reflexes and nociceptive avoidance be- haviours remain intact. It causes disinterest in environment and little display of emotion. There is slowness in response to external stimuli and drowsiness but patient is easily roused, capable of giving appropriate answers to direct questions, and has intact intellectual function. It reduces agitation in psychotic patients. Also has anti-emetic, anti-histamine, anti-adrenergic, anti-cholinergic properties.
Uses.- I. Psychotic disorders.
2. Aggressiveness in disturbed children.
3. Excessive anxiety and agitation.
4. Nausea and vomiting–drug or disease induced.
5. Intractable hiccough.
6. Acute intermittent porphyria.
7. Preoperative restlessness and apprehension.
8. Post-operative medication.
10. Mild alcohol withdrawal symptoms.
11. Cancer pain and other severe pain.
Precautions.-Contra indicated in marrow depression and hypersensitivity to phenothi- azines. Impairs mental activity, therefore patient should not operate hazardous machines. Caution in liver and cardiovascular diseases and those taking atropine-like drugs or exposed to heat and organophophorus insecticides. Abrupt withdrawal after prolonged use may cause withdrawal symptoms including nausea, vomiting, dizziness and tremulousness.
Adverse reactions.-Drowsiness, dizziness, faintness, Parkinsonism, hyperrefleria, tar- dive dyskineia, psychotic symptoms, catatonic states, cerebral oedema and grand mal or petit mal seizures. Blood dyacrasias, postural hypotension, tachycardia, cholesatic jaundice, aller- gic reactions, skin pigmentation, lupus erythematosus, breast engorgement and lactation (fe- males), gynaecomastia, amenorhoea, glycosuria, hyperglycaemia, hypolycaemia, lens opaci- ties, particulate deposits in lens and cornea, retinitis pigmentosa, dry mouth, nasal congestion, constipation, urinary retention, miosis, mydriasis, increased appetite, weight gain, oedema, fever, hyperpyrexia and lupuserythernatosus-like syndrome.
Drugs interactions.-Increased CNS depression with alcoholic anaesthetics, barbitu- rates, narcotics and other CNS depressants; reduces hypotention with noradrenaline; reduces
the anti-hypertensive effect of guanethidine; potentiates atropine-like drugs, but the latter re- duces plasma level; antacids containing aluminium and magnesium reduce absorption; MOA inhibitors and tricyclic anti-depressants potentiate sedation and anti-muscarinic effects.
Dosage form.-Oral: 10 mg.-25 mg., 3 or 4 times daily, increased every 3 days by 25-50 mg./day to maximum of 200-800 mg. daily in divided doses.
Injection: 25 mg. i.m. start repeated I hour later if needed, then orally 25 mg.-50 mg. 3 times daily.
Child, oral: 0.5 mg./kg. every 4-6 hours.
Overdosage.-Symptoms and signs-CNS depression, somnolence, coma, hypotension, extrapyramidal symptoms, agitation, restlessness, dry mouth, fever, convulsions, arrhythmias.
Treatment.-Gastric lavage and symptomatic treatment. For extrapyramidal symptoms use Biperiden; for shock use standard measures and phenylephrine when necessary. Dialysis not helpful.
Dosage form.-Injection, 25 mg. (Decanoate or Enanthate) in I ml. ampoule. Mode of action.-Phenothiazine.
Pharmacological properties.-As for chlorpromazine. Uses.-Psychotic disorders.
Precautions.-Contraindicated in severe CNS depression, coma subcortical brain dam- age, liver disease, blood dyscrasias, allergy to phenothiazines. May impair mental and physi- cal judgement; must be tailed off to prevent withdrawal symptoms.
Adverse reactions.-As for chlorpromazine, but there usually are anorexia, nausea, sali- vation, polyuria, sweating, bladder paralysis and faceal impaction, cholestatic jaundice, flare up of psychotic behaviour, sudden death.
Dose.-Injection: Decanoate: 12.5-25 mg. subcutaneously, or i.m. every 4-6 weeks; Enanthate. 25 mg. s.c. or i.m. every 1-3 weeks.
Overdose.-Symptoms and Signs-As for chlorpromazine.
Treatment.-Gastric lavage and symptomatic treatment. But to combat hypotension do not use adrenaline, use noradrenaline.
HALOPERIDOL Dosage forms.-Tablet, l.5 mg. and 5 rng.;
Injections, 5 mg./ml. in I ml. ampoules; 2 mg./ml.; 5 mg./ml. in 10 ml. vials. Mode of action.-Major tranquilliser.
Pharmacological properties.-Similar to those of chlopromazine but it causes less seda- tion and hypotension.
Uses.1. Psychotic disorders.
2. Severe behavioural disorders in children.
3. Tics and vocal utterances of Gilles de la Tourette’s syndrome in children.
Precautions.- Contraindicated in Parkinsonism, CNS depression and coma. Concomi- tant lithium therapy may result in encephalopathy. May cause mental impairment and slowing of reflexes; may antagonise anti-convulsants. Caution in those with allergic history.
Adverse reactions.-Extrapyramidal symptoms may be marked. Insomnia, headache, vertigo, confusion, anxiety and exacerbation of psychotic syrnptiorns including hallucinations; tachcardia, hypotension, blood dyscrasia, rashes, alopecia, lactation, breast engorgement and mastalgia, menstrual irregularities, gynaecornastia, increased libido, anorexia, nausea, vomit- ing, dry mouth, blurred vision, impaired liver function and laryngospasm.
Drug interactiolls.-Potentiates CNS depressants and causes hypotension with alcohol, adrenaline and antihypertensives. With lithium it causes irreversible brain damage and en- cephalopath y.
Dosage form.-Oral, 0.5-2 mg. two or three times daily. 3-5 mg. or more, two or three times daily for severe cases; then reduce to lowest maintenance dose.
Injection: 2-5 mg. i.m. every 1-8 hours until controlled, then change to oral dosage form. Overdose.-Symptoms and signs-Hypotension, sedation, Extrapyramidal symptoms, coma, respiratory depression.
Treatment.-Gastric lavage, followed by activated charcoal; Symptomatic treatment. Others.-Other anti-psychotic drugs in common use are Clozapine and Lithium carbon-
1.7 Anti-Parkinsonism Drugs \. 7.1 Anticholonergics
BENZHEXOL Dosage forms.-Tablet,2 mg., 5 mg. Elixir, 2 mg./5 ml. Mode of action.-Anticholonergic.
Pharmacological properties.-Anti-parkinsonian by blocking the excitatory effects of the cholinergic system in the nigrostriatal pathway.
Uses.-Parkinsonism-postencephalitic, arteriosclerotic and idiopathic, mainly as ad- j uncti ve treatment.
Drug induced extrapyramidal disturbances.
Precautions=-Care in glaucoma (monitor intraocular pressure); elderly male with pro- static hypertrophy; hypertension, cardiac, hepatic or renal disorders.
Adverse reactions.-Dizziness, nervousness, delusions, hallucinations, confusion, agita- tion, euphoria, drowsiness, headache, nausea, dilation of colon, paralytic ileus, constipation, rashes, tachcardia, blurred vision, mydriasis, increased intraocular pressure, urinary hesitancy or retention, dry mouth.
Drug interactions.-Addictive effect with laevodopa.
Dosage.- Tablet, I mg. daily; increased gradually to 2 mg. daily. Maintenance dose, 5- 15 mg. daily in 3-4 divided doses.
Overdosage.-Symptoms and signs-CNS stimulation (confusion, excitement, agita- tion, hyperpyrexia, disorientation, delirium hallucinations); CNS depression (drowsiness, se- dation, coma).
Treatment.- Treat symptomatically and use supportive measures as needed. Empty stomach. Treat circulatory collapse with vasopressors.
BIPERIDEN Dosageforms.-Tablet 2 mg.; Injection, 5 mg./ml. in I ml. ampoule. Mode of action.-Anticholinergic.
Pharmacological properties.-Anti-parkinsonian. Uses.-Parkinsonism and drug-induced extrapyramidal disorders. Precautions.-As for Benzhexol.
Adverse reactions.-As for Benzhexol.
Drug interactions.-Increased sedative effects with alcohol and CNS depressants. In- creased atropine-like effects and anti-histamines, amantadine, anti-muscarinics, haloperidol MAO inhibitors, tricyclic anti-depressants.
Dosage.-2-10 mg./day in divided doses. Overdosage.-Symptoms, signs and treatment as for Benzhexol. 1.7.2 Dopaminergic Drugs
Dosage forms.-Tablet, 250 mg.; Capsules, 250 mg.
Mode of action.- Replaces brain dopamine because it crosses the blood-brain barrier and is decarboxylaxed in situ.
Pharmacological properties.-Dopamine receptor agonist. Rigidity and bradykinesai re- spond better than does tremor. Speech, gait, handwriting, swallowing and respiration are im- proved. There is improvement in mental function and mood.
Uses.- 1. Idiopathic Parkinson’s disease.
2. Post encephalitic Parkinsonism.
3. Symptomatic Parkinsonism due to carbon monoxide or manganese poisoning.
4. Arteriosclerotic Parkinsonism.
5. Other drug-induced Parkinsonism except those due to phenothiazines or neu- roleptic-induced Parkinsonism.
Precautions.-Contraindicated with, or within 2 weeks of, MAOI therapy, severe psy- choses, raised intraocular pressure. Use with extreme caution in pregnancy, those taking vita- min B6, tranquillisers, anti-depressants, and anti-hypertensives; caution in patients with car- diovascular, renal, hepatic, pulmonary or endocrine disorders, and peptic ulceration.
Adverse reaction.-Nausea, vomiting, cardiac arrhythmias, involuntary movements, ataxia, increased hand tremor, depression, dementia, agitation, confusion, dry mouth, consti- pation, palpitation, orthostatic hypotension, rashes, alopecia, haemolytic anaemia, leukopenia, urinary retention, oedoma, blurred vision, mydriasis, burning sensation of tongue, bitter taste in mouth, sweating and hoarseness of voice.
Drug interactions.-Pyridoxine antagonises levodopa. Methyldopa, haloperidol, pheno- thiazines, papaverine, reserpine and phenytoin reduce its anti-parkinsonism effect. Potentiates anti-hypertensive drugs. Risk of hypertensive crisis with MAO inhibitors. Risk of cardiac arrhythmias with sympathomimetics.
Altered laboratory values.-Increases blood urea, SGOT, SGPT, LDH, bilirubin, alka- line phosphatase, PBI, and causes positive Coornb’s Test.
Dosage.-Oral, initially 125-500 mg. daily in divided doses after meals; increased, gradually, at intervals of 2-3 days, to a maximum of 4g daily in divided doses.
Overdosage.-Symptoms and signs-Anorexia, nausea, vomiting, confusion, headache, insomnia, dystonic and involuntary movements, hypotension and cardiac arrhythmias.
Treatment.-Empty stomach by gastric lavage; normal supportive measures and I.V. fluids. Pyridoxine may reserve the effects.
1.7.3 Dopa Decarboxylase Inhibitor
(Used in combination with Levodopa)
Dosage form.- Tablets:
10 mg. Carbidopa plus 100 mg. Levodopa (10/100); 25 mg. Carbidopa plus 100 mg. Levodopa (25/100); 25 mg. Carbidopa plus 250 mg. Levodopa (251250).
Mode of action.-Peripheral dopa decarboxylase inhibitor, thereby increasing the amount of levodopa reaching the brain.
Pharmacological properties.-Potentiates the effect of levodopa, the dopaminergic re-
ceptor stimulant in the brain substantia nigra.
Uses.-As for Levodopa. It is usually used in conjunction with Levodopa. Precautions and adverse reactions.-As for Levodopa.
Dosage.-The combination of carbidopa with levodopa enables the effective dose of le- vodopa to be greatly reduced, thereby minimising many of the dose-limiting adverse effects of levodopa given alone. In combination with carbidopa, the daily dose of levodopa rarely ex- ceeds 1-1.5 g.
Tablet-One (10/100) or one (25/100) 3 times daily, increasing to two (10/100) or 25/1 00) three times daily or on alternate days; change to 25/250 mg. tablets if more is needed, up to maximum of 6-8 tablets/day in divided doses after meals.
Overdosage.-As for Levodopa. Increased incidence of abnormal involuntary move-
Treatment.-As for Levodopa.
1.7.4 Other Anti-Parkinsonism Drugs.
Other useful drugs are amntadine and Bromcriptine.
2. Anaesthetic Drugs
Anaestheic drugs are discussed under the following headings- 2.1 General Anaesthetics and Oxygen.
2.2 Premedication Drugs.
2.3 Adjuncts to General Anaesthetics. 2.4 Local Anaesthetics.
2.1 General Anaesthetics and Oxygen.-General anaesthetics produce reversible loss of consciousness accompanied by analgesia and muscle relaxation. The ideal general anaesthetic should be easily administered, provide quick induction, be stable, non-flammable, metaboli- cally inert, produce adequate analgesia, muscle relaxation, be rapidly eliminated so that re- covery would occur quickly and be free from adverse effects. No single drug possesses all these ideal properties. Except for short minor procedures, the use of a single anaesthetic agent to produce general anaesthesia has been replaced by balanced anaesthesia.
Balanced anaesthesia employs judicious combination of drugs to achieve optimal anaes- thesia with minimal toxicity so that the recovery of protective reflexes is possible within a few minutes of termination of anaesthesia. It usually involves the use of an intravenous anaesthetic
for induction; inhalation anaesthetics, oxygen and adjuncts to general anaesthetics for mainte- nance of anaesthesia.
2.1.1 Inhalation anaesthetics-These are volatile liquids or gases. To prevent hypoxia they are usually given with oxygen.
Induction is prolonged. It is inflammable and explosive at concentrations necessary for maintaining anaesthesia. It stimulates sympatho-adrenal activity and increase circulating cate- cholamines. Skeletal muscle relaxation is adequate. Recovery is prolonged and it is irritating to the respiratory tract. It produces a high incidence of post-anaesthetic nausea and vomiting.
It is occasionally used in paediatrics as a supplement to nitrous oxide-oxygen mixtures, but because it is inflammable and irritant it is becoming obsolete.
Precaution.-Do not use diathermy.
Drug interactions.-Potentiates curariform neuromuscular blocking drugs. Premedica- tion with anti-muscularinic drugs may minimise excessive bronchial secretions.
Adverse effects.-It produces a high incidence of nausea and vomiting. Transient slight abnormalities in the results of liver function tests have been reported. Other transient effects include reduced urinary output, hyperglycaemia, reduced intestinal tone and motility.
Dosage.-From an open mask or a suitable vaporiser: For induction, 10 to 30% ether vapour in oxygen or in nitrous oxide-oxygen mixture is generally required. For maintenance of surgical anaesthesia, 5% is used.
Halothane is a volatile liquid boiling at 50°C.; it is the most widely used of the volatile agents. It is an extremely convenient anaesthetic, being potent and non-irritant. Induction is smooth and reasonably quick. It is used for maintenance of anaesthesia in major surgery and to supplement the anaesthetic action of nitrous oxide-oxygen mixtures in balanced anaesthe- sia.
Halothane should be used for the induction of anaesthesia in children and in short proce- dures where rapid recovery is needed. Induction is slow (about 5 minutes) and so this is often achieved with thiopentone sodium. Halothane is however used alone for patients with poor veins.
Concentration of up to 5% mixed with at least 25% oxygen are used alone with nitrous oxide-oxygen mixtures. Recovery is less prolonged than intravenous anaesthetic agents. Halothane will produce moderate muscle relaxation, but use of specific muscle relaxants may be necessary where there is need for additional relaxation.
Adverse effects.-Halothane has three important adverse effects namely: hypotension, respiratory depression (rapid, shallow breathing) and cardiac arrhythmia. Halothane, espe- cially when administered repeatedly over short periods, can cause impairment of liver func- tion and rarely hepatocellular jaundice may occur, especially in obese patients. The risk is great when the interval between repeated administration is less than six weeks. The hypoten- sive effect is proportional to the concentration of the anaesthetic administered. Hypotension is an advantage in operations where a controlled relatively bloodless field is required.
Dosage.-Using a suitable vaporiser: For induction: a 1 to 4% concentration, vaporised by a flow of oxygen or a nitrous oxide-oxygen mixture. Children, 1.5-2%. For maintenance, 0.5 to 2%, adults and children.
Nitrous oxide is a sweet-smelling, non-explosive gas with low anaesthetic potency, but a marked analgesic action. It is relatively non-toxic. It is widely used for induction and mainte- nance of anaesthesia. It is also used as a carrier gas for volatile agents in general anaesthesia. More powerful inhalational and intravenous anaesthetic agents and narcotic analgesics are given to increase its weak action when necessary. Due to its good analgesic properties, it is found useful as the sole analgesic in dentistry and in the second stage of labour. However, it should not be used to produce analgesia or slight narcosis for longer than 48 hours (e.g. in patients receiving artificial respiration) because of its tendency to produce leukopenia.
Nitrous oxide does not appear to have any serious effects on the cardiovascular or venti- latory systems or on the liver, kidneys, or metabolic function, provided that an adequate con- centration of oxygen and ventilation are maintained. However, nitrous oxide may have a slight depressant effect on the cardiovascular and ventilatory systems under some circumstances and a sympathetic stimulating effect if given during administration of halothane.
As nitrous oxide diffuses into space, it should not be used in patients with an air- containing closed space, such as tension pneumothorax, pulmonary air cysts or intestinal ob- struction and during pneumo-encephalography. Diffusion hypoxia may develop after discon- tinuing prolonged nitrous oxide anaesthesia, and its advisable to administer oxygen brietly during emergency from anaesthesia.
Dosage.-For analgesia, 25 to 50% nitrous oxide with 75 to 50% oxygen. For induction of anaesthesia, 80% nitrous oxide with 20% oxygen for two or three minutes. For mainte- nance, between 50% nitrous oxide with 34% oxygen depending upon the amount of supple- mented agents used.
Oxygen has no anaesthetic properties as such but it is an invaluable gaseous adjunct to anaesthesia. It is administered in concentration varying from 20 to 50% in conjunction with nitrous oxide and some volatile anaesthetics like other and halothane, alone or in nitrous oxide- oxygen mixtures.
Other uses.-Oxygen is administered by inhalation to correct hypoxaemia in conditions causing under ventilation of the lungs, such as exacerbations of chronic bronchitis, pneumonia or pulmonary oedema; in extensive fibrosing alveolitis or in circulatory failure associated with conditions such as myocardial infarction or after cardiac arrest. It is also used in asphyxia in the new-born, and in infants. Concentrations ranging from 30 to 100% are employed.
2.1.2 Intravenous Anaesthetics.- Intravenous anaesthetics are mainly used for the rapid induction of anaesthesia which is then maintained with an appropriate inhalation agent such as nitrous oxide-oxygen. They may also be used alone to produce a light level of narcosis for short surgical procedures. All the intravenous agents except ketamine depress cerebral func- tion and can cause respiratory depression and hpotension. Facilities for providing resuscitation must be available.
Large doses should be avoided in obstetrics as they rapidly cross the placental barrier.
They are contraindicated in patients where there is no direct access to the air-way or whose unprotected air-ways are likely to become obstructed during the procedure e.g. in mouth or throat surgery.
Where there is concomitant administration of narcotic analgesic or central nervous de- pressant drugs, their dosage should be reduced. Since there is a great individual variation in response, the dosage of these agents should be assessed for each patient. To do this, the esti- mated dose should be injected over 20 seconds while a further 20-30 seconds is needed to assess the effect before giving any supplementary dose. Intravenous anaesthetics should not be given in sufficiently large doses to produce muscle relaxation, except for brief procedures.
For tracheal intubation they should be followed by an inhalational sequence or by a muscle relaxing agent.
Thiopentone is the most widely used anaesthetic but also one of the most toxic. It is po- tent and quick acting and is especially suited to providing a pleasant induction. Induction is generally smooth and takes 10-30 seconds. It lacks analgesic properties.
Anaesthesia may be induced in a healthy adult by injecting 6 to 10 ml. of a 2.5% solution (i.e. 150 to 250 mg.) in 30 seconds (a 5% solution is prone to cause venous thrombosis) and waiting at least one minute before injecting more. In those with a slow circulation time (the old, the diseased) injection should be slower. Laryngospasm is comparatively frequent. The great rapidity with which a patient may pass through the stages of anaesthesia means that the first obvious sign of overdosage may be apnoea due to its potent ventilatory depressant effect. Great care is therefore necessary when using thiopentone. Anaesthesia may be continued by nitrous oxide supplemented if necessary by pethidine or by another inhalation agent e.g. ether.
Thiopentone should not be given to known or suspected perphyriacs and should be avoided in patients with a raised blood urea. It is best avoided in patients with marked conjes- tive heart failure, but with preoxygenation and slow injection, small doses can be given to patients with other cardiac conditions. It should be used with great caution in patients with bronchospasm or upper airway obstruction.
Recovery from thiopentone is slow and it effects persist for 6-8 hours. Return of con- sciousness does not imply return of full mental faculties. Patients are particularly susceptible to alcohol for up to twenty four hours after administration. Given by intermittent dosage or by infusion, thiopentone has a marked cumulative effect which should be allowed for by reducing the dosage. Dosage should be further reduced when narcotic analgesics are administered as supplements.
Dosage.-Intravenous: The dosage required to produce and maintain anaesthesia varies widely and depends on body size, physical status, pre-existing diseases and adequacy of respi- ratory and circulatory systems. In pre-medicated adult, initial 100-150 mg. (4-6 m\. of a 2.5% solution) over 10-15 seconds, repeated if necessary according to patient’s response after 20-30 seconds. Alternatively, a single injection of 3-5mg/kg body weight is given.
By continuous intravenous infusion, as a 0.2-0.4% solution, according to the patient’s response.
2.2 Premedication Drugs.-Premedication agents are given before anaesthesia. They may be divided into those used for their anti-cholinergic effects and those used for the seda- tive effects. Anti-cholinergic premedication agents, usually atropine (or hyoscine) are used to dry bronchial and salivary secretions which are increased by intubation and the inhalation anaesthestica. They are also used to prevent excessive bradycardia and hypotension caused by halothane, thiopentone, suxamethonium and neostigmine.
Hyoscine is a less effective drying agent than atropine but provides a higher degree of amnesia. A disadvantage is its tendency to slow the heart rate.
Dedative premedication agents include the narcotic analgesics (morphine, pethidine), anxiolytics (diazepam) and neuroleptics (e.g. chlorpromazine). These drugs are described in other sections of this formulary.
2.3 Adjuncts to General Anaesthetics.-Drugs as adjuncts to anaesthesia fall into two categories: premedication agents and neuromuscular blocking agents. A number of these drugs are also given practically for other purposes and are discussed in more detail in other sections of the formulary. They also facilitate induction and diminish overall anaesthetic re- quirements by enhancing the effect of the anaesthetic agents. Large doses should be avoided as they also enhance the respiratory depressant and hypotensive effects of anaesthetics.
The narcotic analgesics (morphine, pethidine) provide additional analgesics during sur- gery, and post operatively. They are the most common premedication agents, usually admin- istered an hour before the operation.
There is a trend towards the use of the oral premedicating agents such as diazepam, given the night before and on the morning of the operation. Alternatively, promethazine or chlorpromazine may be given. The phenothiazine derivatives have useful anti emetic action which may prevent post-operative sickness, but they increase respiratory depression and hypo- tension; large doses should therefore be avoided. Barbiturates should be avoided, especially where pain is present, as they cause restlessness and confusion.
Premedication in Children.-Oral or rectal administration is premedication general in- jection where possible, but is not altogether satisfactory. Diazepam may be given. Thiopen- tone is rarely used.
NEOSTIGMINE Dosage forms.-Tablet, I5 mg., Injection, 2.5 mg./ml. in I ml. ampoule. Mode of action.-Reversible anticholinesterase.
Pharmacological properties.–Constricts the pupils and reduces raised intraocular pres- sure; stimulates skeletal muscles paralysed by curariform agents, stimulates intestinal smooth muscles.
Uses.-Termination of effects of competitive neuromuscular blockers; myasthenis gravis; intestinal atony especially post-operative; ileus; atony of urinary bladder.
Adverse reactions.-Alopecia, vomiting, abdominal cramps, diarrhoea, miosis, involun- tary muscle twitchings, general weakness and fatigue, bradycardia, hypotension.
Dosage.-15-30 mg. three times daily. Injection 0.5-2.0 mg. i.m. Overdosage.-Symptoms and signs-Exaggeration and persistence of adverse reactions, extending to bronchospasm, paralysis of respiratory muscles and death.
Treatment.-Atropine injection and supportive measures.
2.3.2 Depolarising Muscle Relaxants.-They act by mimicking the action of acetylcho- line at the neuromuscular junction. Because the receptor membranes are now fully activated, the end plate is refractory to acetylcholine and a depolarisation blockade occurs. Paralysis preceded by muscle fasciculations that are usually visible. This type of blockade is not an- tagonised by anticholinesterase drugs.
They produce rapid, complete and predictable paralysis, and recovery is spontaneous.
Unlike the non-depolarising muscle relaxants, their action cannot be reversed and their clini- cal application is therefore limited.
Suxamethonium is the only commonly used drug among the depolarising blockers. With a 5 minute duration of action, it is the ideal agent for passage of endotracheal tube but may be used in repeated dosage for longer procedures.
Prolonged muscle paralysis may occur in patients with low or a typical plasma pseudo- cholinesterase enzymes. Prolonged paralysis may also occur in dual block which occurs after repeated doses of the drug have been used, and is caused by the development of a non- depolarising block following the primary depolarising block. All patients with prolonged muscle paralysis should be given artificial ventilation. Dual block is diagnosed by giving a short acting anticholinesterase such as edrophonium. If an improvement occurs the block is treated with neostigmine.
lndications.-Depolarising muscle relaxant of short duration.
Caution.-Suxamethonium is contraindicated in severe liver disease and in patients with bums.
Dose.-By intravenous injection, 20-100 mg. (as the chloride), according to the patient’s needs. By i.v. infusion, as a 0.1 % solution in dextrose or sodium chloride infusion, 2-5 mg./minute (2-5 ml./minute).
2.3.3 Non-Depolarising Muscle Relaxants.-Drugs of this group include pancuronium and tubocurarine. They cause blockade by competing with acetylcholine at the receptor site at the neuromuscular junction. They are best suited for the production of paralysis of long dura- tion. They have a slower, less complete action than the depolarising agents, and should be avoided in myasthenia gravis. The action of the non-depolarising agents can be reversed with anticholinesterase such as neostigmine.
Pancuronium is a synthetic bisquartemary ammonium steroid that produces a non- depolarising neuromuscular block. It has replaced tubocurarine as the drug of choice for major surgery.
It is approximately five times more potent than tubocurarine. It also has the advantages of a quicker onset of action and of not causing significant histamine release for significant changes in blood pressure. There is no evidence that it caused ganglionic blockade and hence does not cause hypotension. There is evidence that pancuronium may increase the heart rate, cardiac output, and arterial pressure, probably because of its vagal action and/or stimulation of cardiac adrenergic receptors. Therefore, the drug is indicated where these effects are desired. It may however produce occasional ventricular extrasystoles.
Dosage.-By intraveneous injection, intitially for intubation, 80-100 rnicrograrns/kg; after intubation, 20-80 rnicrograms/kg., and subsequently 30-40 rnicrograms/kg. (every 20-40 minutes, according to patient’s response).
Children.-Initially, 60-80 micrograms/kg., then 15-20 micrograms/kg. Neonates.-Initially 30-40 micrograms/kg. then 15-20 micrograms/kg. Intensive care.-by i.v. 60 micrograms/kg. every 1-11/2 hours;
By i.m. injection, 30-60 micrograms/kg. every 1-2 hours.
Tubocurarine may be regarded as the standard non-depolarising muscle relaxant but its use has declined in recent years. It starts to act between 3-5 minutes and lasts for about 30 minutes after injection. It often causes an erythematous rash on the chest and neck and this is probably caused by histamine release. Onset of blockade is invariably associated with hy- potension, and this, though transient, is dangerous in poor-risk patients.
Dosage.-By i.v. injection, initially, 10-15 mg., then supplements, according to the pa- tient’s response, of 5 mg. to a maximum or 40 mg.
Children.-Initially, 330 micrograms/kg., then 1/3 of the initial dose.
2.4 Local anaesthetics.-Local anaesthetic drugs act by preventing the generation and conduction of impulses along nerve fibres. They do this by preventing the sodium influx through the cell membrane, which is necessary for the generation of the action potential, and by competing with calcium at some site that controls the permeability of the membrane. The blockade caused by local anaesthetics is however completely reversible. The smaller the nerve fibre the more sensitive it is so that a differential block may occur when the smaller fibres carrying pain sensation and automatic impulses are blocked.
The drugs used vary widely in their potency, toxicity, duration of action, stability, solu- bility in water and ability to penetrate mucous membranes. These variations determine their suitability for surface infiltration, regional epidural, and spinal anaesthesia. In estimating the safe dosage of these drugs, it is important to take account of the rate at which they are ab- sorbed and excreted as well as their potency. Other pertinent factors worthy of consideration are the patient’s age, physique, and clinical condition; the degree of vascularity of the area to which the drugs are to be applied, and the duration of administration.
Prolongation of action by vasoconstrictors.-The duration of action of a local anaes- thetic is proportional to the time during which it is in actual contact with nervous tissues. Con- sequently, procedures that maintain the localisation of the drug at the nerve (i.e. use of vaso- constrictors) greatly prolong the period of anaesthesia, and can reduce the systemic toxicity (where large volumes are used). Adrenaline (I in 200,000) is commonly used; while in dental surgery up to I in 80,000 (1,25 mg./J 00 ml.) of adrenaline is used with local anaesthetics.
Higher concentrations are occasionally used but there is no justification for this. The to- tal dose of adrenaline should not exceed 500 micrograms and it is essential not to exceed a concentration of I in 200,000, if more than 500 ml. of the mixture is to be injected. A vaso- constrictor should not be used for nerve block of digits and appendages. For obvious anatomic reasons, the whole blood supply may be cut off by intense vasoconstriction so that the organ may be damaged or even lost.
Local anaesthetics containing adrenaline and noradrenaline should not be used in pa- tients taking tricyclic antidepressants because of an increased risk of cardiac arrhythmia and hypertension. This restriction does not apply to patients on monoamine oxides inhibitors.
Toxicity.- Toxic effects associated with the local anaesthetics are usually a result of ex- cessively high blood concentrations. The main effects are excitaion of the CNS (nervousness and convulsions) followed by respiratory depression. Less commonly, the cardiovascular sys- tem is depressed. Hypersensitivity reactions occur mainly with the ester-type local anaesthet- ics such as amethocaine, benzocaine, cocaine and procaine, toxicity may occur with repeated dosage due to accumulation of the drug; in such cases smaller doses should be given. Toxic effects may also occur if the injection is too rapid. Local anaesthetics should not be injected into intlamed or infected tissues nor should they be applied to the traumatised urethra. Under these conditions the drug may be so rapidly absorbed that a systemic rather than local reaction is produced.
Uses.-Local anaesthetics are generally used for minor operations when loss of con- sciousness is neither necessary nor desirable and also as an adjunct to major surgery to avoid deep general anaesthesia. A local anaesthetic is seldom used alone for major surgery, not be- cause of its impracticability but because patients prefer unconsciousness. Local anaesthetics can also be used topically for short periods to give relief from local pain and itching (but skin allergy is common).
Lignocaine is employed as the hydrochloride salt. It is the most widely used local an- aesthetic drug. It acts more rapidly and is more stable than most other local anaesthetics. It is effectively absorbed from mucous membranes and is a useful surface anaesthetic in concen- trations of 2 to 4%.
Dosage form.-Injection 0.5% (5 mg./ml.) 1% (10 mg./ml.) and 2% (20 mg./ml.) in 20 ml. ampoules and 50 ml. vials. Except for surface anaesthesia, solutions should not exceed 1 % in strength. The duration of the block (with adrenaline) is about I V:z hours.
Uses.-Local anaesthesia by surface infiltration, religions, epidural and caudal routes, dental anaesthesia.
Cautions.-Epilepsy, hepatic impairment, impaired cardiac, conduction, bradycardia.
Reduce dose in elderly or debilitated patients. Resuscitative equipment should be available.
Contra-indications.-Myasthenia gravis, hypovolaemica, complete heart block. Do not use solutions containing adrenaline for anaesthesia in appendages.
Side effects.-Include hypotension, bradycardia, cardiac arrest, agitation, euphorial res- piratory depression and convulsions.
Dosage.-Adjusted according to the site of operation and response of the patient-
(a) By injection.-Maximum dose is 200 mg. or 500 mg. with solutions which also contain adrenaline. Maximum dose of adrenaline is 500 micrograms.
(b) Infiltration anaesthesia.-0.25-0.5% with adrenaline I (one) in 200,000, using 2-50 ml. of a 0.5% solution in minor surgery and up to 60 ml. in more exten- sive surgery.
(c) Nerve block.-With adrenaline I in 200,000, I % to a maximum of 50 ml., 2% to a maximum of 25 ml.
(d) Epidural and caudal block.-With adrenaline I in 200,000, I % to a maximum of 50 ml., 2% to a maximum of 25 ml.
(e) Surface anaesthesia.-Usual strengths, 2-4%. For mouth, throat and upper gastrointestinal track, 1-4%, to a maximum of 200 mg.
Other.-Other commonly used local anaesthetic in Bupivacaine. 3. Cardiovascular system drugs
Drugs acting on the cardiovascular system (CVS) are discussed under the following
3.1 Cardiac Glycosides.
3.2 Antiarrhythmic Drugs. 3.3 Antihypertensive Drugs. 3.4 Anti-angina Drugs.
3.1 Cardiac Glycosides.-Digitalis is the common name given to the cardiotonic drugs which are mostly extracts of the digitalis plant leaves and seeds. The cardiac glycosides are the active principles of these extracts. The two commonly used cardiac glycosides are digoxin and digitoxin. Digoxin is the drug of cbojoe.
Dosage forms.-Tablets 0.25 mg.; Oral Solution; 0.05 mg./ml., 0.25 mg./ml. injection; 0.25 mg./ml. in 2 ml. ampoules.
Model of action.-Inhibits sodium-potassium ATPase thereby allowing entry of sodium and calciumions into the myocardial cell. The calciumions bind to troponin which is an in- hibitor of actomyosin complex. The uninhibited combination of actinmyosin results in myo- cardial contraction.
Pharmacological properties.-lncreases the force of contraction (positive inotropic ef- fect) which reduces total oxygen consumption; it thus increases the efficiency of the heart, slows the heart rate (negative chronotropic effect) the efficiency of the heart, slows the heart rate (negative chronotropic effect) by both direct and indirect vagal action or prolonging the refractory period in atria and Bundle of His, it increases myocardial excitability.
Uses.-Congestive heart failure Atrial fibrillation-reduces ventricular rate but does not convert fibrillation to sinus rhythm. Supraventricular tachycardia Atrial flutter.
Precautions.–Caution in hypokalaemia and in those concurrently using potassium wasting diuretics (thiazides), recent myocardial infarction, hypothyroidism, the elderly and those with renal failure.
Adverse reactions.-Nausea, vomiting, bradycardia, heart block, any kind of arrhythmias but characteristically pulsus paradoxus and ventricular tachycardia and gynaecomastia.
Drug interactions.-Thiazides and related diuretics cause hypokalaemia which predis- poses to digitalis toxicity. Cholestyramine reduces its absorption.
Dosages.-Oral 0.25 mg. 2 or 3 times daily until digitalised (i.e. heart rate 60-80/min) then 0.125-0.5 mg. daily. i.v. 0.5-1 mg. initially, then 0.25 mg. every 4-6 hours; monitor ECG.
Overdosage.-Symptoms and signs-As for Adverse reactions.
Treatment.-Stop digoxin; Symptomatic treatment; i.v. KCL 40 m. in 500 ml. 5% Dex-
trose in water over 1-2 hours. Monitor ECG and check serum potassium.
For bradycardia: atropine 0.6 mg. i.m.
For ventricular arrhythmias, i. v. lignocaine, phenytoin, or propranolol.
3.2 Anti-Arrhythmic Drugs.-Management of any arrhythmia requires precise diagnosis of the type of arrhythmia. Drugs used in supraventricular arrhythmias include digoxin, beta- adrenoceptor blockers and quinidine. Those used in ventricular arrhythmias include ligno-
caine, procainamide, phenytoin, and beta adrenoceptor blockers. They may be broadly classi- fied as membrane stabilisers, beta adrenoceptor blockers and calcium entry antagonists.
3.2.1 Membrane Stabilisers.-These include quinidine, procainamide, lignocaine and phenytoin.
Dosage form.-Injection 20 mg./ml. (Hydrochloride) in 5 ml. ampoules. Mode of action.-Membrane stabiliser.
Pharmacological properties.-Prolongs effective refractory period of myocardium. Uses.-Ventricular arrhythmias occurring during acute myocardial infraction. Precautions.-Contraindicated in supraventricular tachycardias, heart block, Stokes Ad-
ams syndrome, hypersensitivity to amid-type local anaesthetics. Use with caution in patients with hypovolaemia, shock, heart block, hepatic or renal impairment.
Adverse reactions.-Vomiting, hypotension, bradycardia, cardiac arrest, light headed- ness, drowsiness, dizziness, tinnitus, blurred vision, convulsions, coma, respiratory depres- sion, allergic reactions and soreness at side of i.m. injection.
Drug interactions.-Propranolol potentiates, while phenobarbitone and phenytoin inhibit its effect.
Dosage.-i. v., 50-100 mg. at 20-50 mg./min repeated in 5 minutes if necessary. No more than 200-300 mg. in I hour.
Overdosage.-Symptoms and signs.-Drowsiness, confusion, dyspnoea, prolonged P-R interval, widened QRS complex, increase in arrhythmias, convulsions, respiratory depression and cardiac arrest.
Treatment.-Stop injection. Symptomatic and supportive treatment. Give i.v. diazepam for convulsions.
3.2.2 Beta-Adrenoceptor Blockers
Dosage forms.-Tablets, 10 and 40 mg. (Hydrochloride); Injection, I mg. (Hydrochlo- ride) in 1 ml. ampoule.
Mode of action.-Non-selective beta-adrenoceptor blocker with membrane stabilising action but without intrinsic sympathomimetic activity.
Pharmacological properties.-Decreases heart rate, cardiac output and blood pressure; myocardial oxygen consumption is reduced; anti arrhythmic which decreases spontaneous rate of depolarisation of ectopic pacemaker and slows conduction in atrial and A-V node; in- creases airways resistance and broncho-constriction.
Uses.-Hypertension, cardiac arrhythmias including both supraventricular and ventricu- lar arrhythmias, digitalis-induced arrhythmias and unaesthetic agents-induced arrhythmias; angina pectoris; prophylasis of migraine. Hypertrophic obstructive cardiomyopathy; adjunct to alpha adrenoceptor blockers in the management of phaeochromocytoma.
Precautions.-Contraindicated in bronchial ash ma, congestive heart failure, sinus brady- cardia. A void abrupt discontinuation of therapy in coronary or thyrotoxic patients. Care in diabetes, as premonitory signs and symptoms of hypoglycaemia may be masked.
Adverse Reactions.-Bradycardia, A-V block, congestive heart failure, Raynauds phe- nomenon, paraesthesia of hands, light headed ness, insomnia, depression, hallucination, loss of memory, nausea, vomiting, abdominal cramps, diarrhoea, constipation, mesenteric artery thrombosis, ischaemic colitis, bronchospasm, rash, agranulocytosis, reversible alopecia.
Drug Interactions.-Reduced A-V conduction with digitalis; antagonises bronchodila- tors. Produces increased risk of hypotension, syncope, vertigo when used with reserpin.
Altered laboratory values.-Increased values of blood urea, SOOT, SOPT, LDH and al- kaline phosphatase.
Dosage.-Oral-Hypertension: 40 mg. twice daily increasing to 160-480 mg./day in 3 to
4 doses, combined with diuretic;
Arrhythmias: 10-30 mg. 3 or 4 times daily; Angina pectoris: 10-40 mg. 3 or 4 times daily; Migraine: 80-240 mg./day in 2-4 doses;
Hypertrophic obstructive cardiomyopathy: 20-40 mg. 3 or 4 times daily, Injection, 1-3 mg. i.v., may be repeated after 10-15 minutes.
Overdosage.-Symptoms and signs: Severe bradycardia, hypotension.
Treatment.-For bradycardia, use i.v. atropine, 0.25-1.0 mg.; for bronchospasm, use aminophylline and adrenaline; for hypotension, use adrenaline or noradrenaline; for cardiac failure, use digoxin and diuretics.
Others.-Other antiarrhythmic drugs in use are phenytoin, Procainamide and Quinidine. 3.3 Anti-Hypertensive Drugs
3.3.3 Thiazide Diuretics
BENDROFLUAZIDE Dosage form.- Tablets, 2.5 and 5 mg.
Mode of action.-Inhibits sodium reabsorption mainly at the proximal part of the distal tubule.
Pharmacological properties.-Induces diuresis and lowers blood pressure.
Uses.-Oedema associated with congestive heart failure, nephritic syndrome, cirrhosis of liver. Mild hypertension (useful alone). Moderate to severe hypertension (in combination with other drugs);
Precautions.–contraindicated in renal failure; may precipitate or aggravate diabetes mellitus and gout; may predispose to digitalis toxicity. Caution in renal or hepatic impairment.
Adverse reactions.-Hypokalaemia, hyperglycaemia, hyperuricaemia, rashes, thrombo-
Drug Interactions.-Predisposes to digitalis toxicity. Dosage.-Hypertension, 2.5-5 mg. in the morning. 3.3.2 Direct vasodilators
HYDRALAZINE Dosageform.-Injection, 20 mg. in 1 ml. ampoule. Mode of action.-Direct vasodilator. Pharmacological properties.-Antihypertensive.
Uses.-Moderate to severe hypertension. Hypertensive emergencies. Congestive heart failure.
Precautions.–Contraindicated in coronary artery disease, rheumatic valvular disease and early pregnancy. Obtain full blood count, LE cell preparation and antinuclear antibody (ANA) titre before and periodically during the prolonged treatment.
Stop treatment if patient develops malaise, fever, chest pain or other unexplained symp- toms or if ANA titre rises or LE cell reaction becomes positive.
Adverse reactions.-Headache, anorexia, tachycardia, palpitations, hypotension, angina pectoris, paradoxical hypertension, diarrhoea, rash, lupus erythematosus-like syndrome, ar- thralgia, peripheral neuropathy responsive to pyridixine, anaemia, leukopenia, agranulocyto- sis, thrombo-cytopenia, lymphadenopathy, splenomegaly and fluid retention.
Drug Interactions.-Potentiated by antihypertensive drugs. Altered laboratory values, positive ANA titre, LE-cell phenomenon and direct Coombs’ test. Increased plasma renin activity.
Dosage.-Injection, 20-40 mg. i.v. slowly as infusion or i.m., repeated as necessary 4-8 hourly.
Overdosage.-Symptoms and signs-Hypotension, tachycardia, headache, myocardial ischaemia, cardiac arrhythmia and shock. Treat shock with plasma expander. Digitalisation may be necessary.
PRAZOSIN Dosage form.- Tablet, I, 2 and 5 mg.
Mode of action.-Direct vasodilator; also with pot-synaptic alpha I adrenergic blockade. Pharmacological properties.-First dose syncope especially with large initial doses or
rapid dose increase. Caution in renal function impairment.
Adverse reactions.-Postural hypotension, tachycardia, palpitation, weakness, dizziness, headache, drowsiness, nausea, syncope, impotence, urinary incontinence, nasal congestion, tinnitus, rashes, blurred vision, reddened sclera, pigmentary mottling cataract retinopathy.
Drug interactions.-Potentiates other anti-hypertensives; increases risk of hypotension with beta adrenoceptor blockers.
(a) Hypertension: 0.5-1 mg., 2-3 times daily, increased every 2 days to a maximum of 20 mg. daily;
(b) Heart Failure: 0.5 mg., initially, then I mg., 3-4 times daily; maintenance dose 4-20 mg. daily.
3.3.3 Beta-Adrenoceptor Biockers
See 3.2.2, under Anti-arrhythmic Drugs. Propranolol is used here to represent the thera- peutic group of Beta-adrenocepto blocking drugs.
3.3.4 Centrally-Acting Drugs
METHYLDOPA Dosageform.-Tablets, 250, 500 mg.
Mode of action.- Acts centrally and peripherally both directly and indirectly by forming alpha methyl noradrenaline, a false transmitter. Thus, it reduces brain and peripheral stores of noradrenaline.
Pharmacological properties.- Lowers the blood pressure. Uses.-Hypertension.
Precautions.–Contraindicated active hepatic disease e.g. hepatitis and cirrhosis. Para- doxically, hypertension may occur on i.v. injection. Caution in renal impairment. Dialysis patients may be difficult to control since it is removed by dialysis.
Adverse reactions.-Sedation, postural dizziness, nausea, vomiting, fever, parkinsonism, nightmares, depression, bradycardia, oedema and weight gain, impairment of liver function, positive direct coombs’ test, haemolytic anaemia, loss of libido, impotence, breast enlargment, gynaecomastia, nasal stuffiness, rashes, arthralgia, myalgia, lupus erythemaessus.
Drugs interactions.-Potentiates other antihypertensive drugs.
Dosage.-Oral, 250 mg. 2 or 3 times daily initially, may be gradually increased to 2-3 g. daily in divided doses.
Children – 10 mg’/kg./day in divided doses, may be increased to 55 mg./kg./day.
3.3.5 Other Antihypertensive Drugs.-Direct Vasodilators-Diazoxide, Minoxidil, So- dium nitroprusside Alpha-Adrenoceptor Blocker-Phenoxybenzamine. Centrally-acting Drugs.–Clonidine, Reserpine.
3.4. Anti-angina Drugs
3.4.1 Nitrates and Nitrites
CLYCERYL TRINITRATE Dosage form.-Tablet (Sublingual) 0.5 mg.
Mode of action.-Dilates peripheral vessels, thereby reducing the cardiac work and re- lieving angina.
Uses.-Prevention of angina pectoris. Treatment of angina pectoris. Congestive heart failure.
Precautions.-Contraindicated in early myocardial infection, severe anaemia, increased intraocular pressure, increased intracranial pressure, postural hypotension, and hypersensitiv- ity to nitrites or nitroglycerin. Tolerance may develop.
Adverse reaction.- Throbbing headache, dizziness vertigo, palpitation, tachycardia, syn- cope, nausea and vomiting, rashes.
Drug Interaction.-Alcohol increase cerebral ischaemic symptoms (dizziness, weakness, palpitations, syncope).
Dosage.-Sublingual Tablet: 1 tablet (0.5 mg.) under the tongue immediately upon indi- cation of attack; repeated as needed.
Overdosage.-Symptoms and signs-severe headache, blurred vision and dry mouth. Treatment.-Discontinue drug and treat symptomatically.
Diuretics are described in this section under the following heading- 4. I Thiazide Diuretics;
4.2 Loop Diuretics;
4.3 Other Diuretics;
Diuretics are drugs used to increase the volume of urine excreted by the kidneys with a net loss of sodium and/or chloride ions (block of renal re-absorption of these ions). They are employed principally for the relief of oedema and ascites. Diuretics are most effective in the treatment of cardiac oedema particularly that associated with congestive heart failure. They are also used in ascites of cirrhosis, nephritic syndrome, diabetes, insipidus, hypertension, oedema of pregnancy, and to reduce cerebrospinal and intraocular t1uid pressure. Some diu- retics have highly specialised use in glaucoma.
4.1 Thiazide Diuretics
BENDROFLUAZIDE Dosage form.- Tablets, 2.5 and 5 mg.
Mode of action.-Inhibits sodium reabsorption at the proximal part of the distal tubule, has weak carbonic anhydrase inhibitory effect and promotes urinary loss of potassium.
Pharmacological properties.-Diuretic, antihypertensive.
Uses.-oedema due to congestive heart failure, nephritic syndrome, liver disease; mild hypertension; as an adjunct to other antihypertensives in moderate to severe hypertension; Diabetes insipidus; Indiopathic hypercalciuria.
Precautions.-Contraindicated in renal failure, liver failure, pregnant women allergy to thiazides. May aggravate diabetes mellitus and precipitate gout.
Adverse reactions.-Hypokalaemia, hyperglycaemia, hyperuricaemia and gout, rashes, hypovolaemia, thrombocytopenia, anorexia, nausea, vomiting, acute pancreatitus, cholestatic jaundice.
Drug interactions.-Predisposes to digitalis toxicity. Dosage.- 2.51O mg. daily.
Others.-Other commonly used thiazide diuretics are Hydrochlorothiazide, Hydroflu- methiazide, Poly thiazide and Clopamide.
4.2. Loop Diuretics.-These are also called high ceiling diuretics because they reached a peak diuresis much greater than other diuretics. They include frusemide, ethacrynic acid and bumetanide.
Dosage forms.-Tablets, 40 mg.Injection: 10 mg.lm!. in 2, 5 and 25 m!. ampoules. Mode of action.-Inhibits sodium and chloride reabsorption in the ascending limb of the loop of Honle.
Pharmacological properties.-Potent diuretic.
Uses.-Oedema of cardiac, renal or hopatic origin: Refractory oedema; early phase of acute renal failure; symptomatic hypercalcaemia, to lower plasma calcium by increasing its urinary loss.
Precautions.-Contraindicated in cirrhosis of the liver with hepatic failure.
Adverse reactions.-Hypovolaemia, postural hypotension, hypokalaemia, hyperuricae- mia, tinnitus rashes.
Drug interactions.-Increased potassium loss when used with corticosteroids and aceta- zolamide.
Dosage.-Oral: 20-80 mg., once or twice daily. In oliguric renal failure, initially 250 mg. repeated if necessary, 4-6 hourly to a maximum of 2 g. By i.m. or slow i.v. injection, 20- 50 mg. By i.v. infusion, in oliguria, 0.25 g. at a rate not exceeding 4 mg.lminute.
Overdosage.-Symptoms and signs-See Adverse reactions. Treatment.-Gastric lavage and life supportive measures. Others.-Bumetanide; Ethacrynic acid.
4.3 Other Diuretics.-Osmotic diuretics, e.g. Mannitol Potassiumsparing diuretics, e.g.
Amiloride, Triamterence, Aldosterone antagonists, e.g. Spironolactone. Combination diuret- ics-See Formulary Section.
5. Blood and Nutrition
Drugs treated in this section include- 5.1 Haematinics.
5.3 Plasma substitutes.
5.4 Plasma fraction for specific use. 5.5 Vitamins.
5.7 Oral rehydration salts. 5.8 Parenteral fluids.
5.9 Peritoneal dialysis solution and haemodialysis solution.
5.1 Drugs used in anaemias. Anaemia may be due to blood loss (i.e. haemorrhoids, hookworms, menorrhagia, duodenal ulcer), poor intake or malabsorption of essential nutrients (e.g. irons folate, vitamin B 12), reduced red cell life span (haemolysis e.g. sickle cell disease) or failure of adequate production of red cells by the bone marrow. A refractory type of anae- mia may also be secondary to severe system disease such as uraemia, infection, malignant disease or connective tissue disease. In these cases, the pathogenesis or mechanism of the anaemia may vary (e.g. reduced red cell life span, non-utilisation of available iron, hypoplasia of marrow) and the anaemia responds only to effective control of the primary disease. Protein malnutrition apart from being accompanied often by malnutrition of haemopoietic nutrients, can also cause a secondary red cell hypoplasia. Treatment of anaemia lies in the treatment of its root cause. Harm can be done by treatment with the wrong agent. For example, patients
with sickle cell anaemia suffer from haemolysis and not from iron deficiency and often have excess iron in their stores. Further administration of iron preparations leads to dangerous hae- rnosiderosis. Blood transfusion does not cure anaemia and should not be used with that inten- tion. It may in fact delay the diagnosis of anaemia apart from introducing side effects which are sometimes fatal. Its main use is to replace massive blood loss or to buy time in severe sec- ondary anaemia while the primary disease is being tackled.
The blood stores of iron are usually depleted before the anemia develops. Therefore the aims of therapy are-
(a) to correct anaemia;
(b) to replenish the stores.
The latter is accomplished by the continuation of oral iron therapy for a further 3 months after the haemoglobin level is restored to normal or by giving an additional I to 1.5g of iron parenterally.
5.1.1 Iron Preparations
Dosage forms.-The drug of choice is ferrous sulphate tablets B.P. 200 mg. (60 mg.
elemental iron). Suitable but more expensive alternatives are-
(i) Ferrous gluconate tablets B.P. 300 mg. (35 mg. elemental iron); (ii) Ferrous fumarate tablets. B.P. 200 mg. (65 mg. elemental iron); (iii) Slow-release ferrous sulphate tablets.
Liquid preparations recommended are ferrous sulphate mixture for infants B.P.C. con- taining 12 mg. of elemental iron per 5 ml. proprietary preparations of ferrous fumarate and colloidal ferric hydroxide containing respectively, 45 mg., 40 mg. elemental iron in 5 ml..
Pharmacological properties.- The oral iron preparations are best absorbed from an empty stomach but when rare gastrointestinal side effects occur, they should be taken after meals at the cost of reduced absorption. The ferrous salts are better absorbed than the ferric salts. High doses of ascorbic and succinic acids aid absorption but are rarely necessary. Ab- sorption is enhanced by iron deficiency.
Uses.-To cure or prevent iron deficiency-
1. Chronic blood loss.
2. Pregnancy. Foetus required up to 600 mg. of iron from mother.
3. Malabsorption syndromes where proportion of dietary iron absorbed may be reduced, e.g. gastrojejunostomy, gastrectomy, sprue.
4. Babies who are born prematurely or weaned late.
5. Lack of the iron-containing items (e.g. meat, liver, plantain, green vegetables) in the diet.
6. Frequent urinary iron loss during haemoglobinuria e.g. due to C-S-P-D defi- ciency and haematuria crises.
I. Sickle cell anaemia or chronic haemolytic states. 2. Aplastic anaemia.
Dosage.-Ferrous sulphate (200 mg.), gluconate (300 mg.) or fumarate (200 mg.) one tablet three times daily, on empty stomach. Slow release ferrous sulphate preparations 1-2 tablets daily. Ferrous sulphate mixture 5-20 ml. daily in divided doses depending on age of child.
Side Effects.-Gastrointestinal symptoms namely nausea, diarrhoea, abdominal pain and constipation occur rarely. If they do, different preparations may be tried. The faeces are black- ened by iron therapy.
Overdosage.–Clinical manifestations of iron poisoning are- I. Gastrointestinal irritation and vomiting.
2.Haematemesis and melaena.
4.Brain and liver damage.
5.Late gastrointestinal obstruction from scarring.
5.1.2 Folic Acid
Dosage forms.-Folic acid is converted to tetrahydrofolic acid (Folinic acid) which is used for biosynthesis of amino and nucleic acids essential for DNA and cell division.
Pharmacological properties.-The liver storage is limited (5-10 mg.) and lasts for a few weeks only and therefore deficiency occurs quite readily due to increased demand (haemoly- sis, pregnancy, neoplasis) poor intake (anorexia, over-cooking, malnutrition) malabsorption (sprue, gut resections) and drugs (anticonvulsants, pyrimethamine, methotrexate). Deficiency causes magaloblastic anaemia.
Uses.-Treatment and prevention of folic acid deficiency especially in pregnancy, mal- nutrition, malabsorption, chronic haemolytic state e.g. sickle cell disease and therapeutic trial in megaloblastic anaemia.
Dosage.-1 mg. daily for therapeutic trial for foliate deficiency. More folic acid will give false response in those with vitamin B 12 deficiency. For prevention and treatment: 0.5-5 mg. daily.
Contra-indication= Vitamin B 12 deficiency. Side Effects.-Rare hypersensitivity may occur. Toxic Effects-
I. Precipitates neurological lesions in Vitamin B 12 deficiency.
2. High doses may cause deposits of crystalline folic acid in the kidney.
5.2.1 Parenteral Anticoagulants
Dosage form.-Injection, 1000 units/ml. and 25,000 units/m\. in 5 rnl. ampoules.
Mode of action.-Heparin is antithrombin and antithromboplastin in action. It is inactive orally and is best given intravenously. Intramuscualr or subcutaneous administration can lead to painful haematomas and erratic effect. Half life of injected heparin is only about \-2 hours and it is partly destroyed in the liver and partly excreted in the urine.
I. For induction of anticoagulant therapy for 48 hours before the effect of simul-
taneously administered oral anticoagulant drugs becomes established.
2. Acute peripheral artery occlusion.
3. For pulmonary embolism.
5. Extracorporeal circulation in cardiac surgery.
6. Dissembinated intravascular coagulation.
7. Prophylaxis of deep vein thrombosis during and after surgery in high-risk pa- tients.
(a) For continuous intravenous administration, 30,000 units are added to I litre of per cent dextrose or normal saline, and infused at the rate of 20-25 drops per minute, over 24 hours. If speed of action is desired an initial primary dose of 5,000 units should be given into the infusion tubing initially. Whole blood clotting time is checked every 2 to 3 hours, to maintain coagulation times be- tween 2-3 normal values;
(b) For intermittent intravenous injection 4 hourly doses are more effective than 8 hourly ones in which cases 5,000-7,500 units given preferably into an indwell- ing intravenous needle is recommended for children, the dose is 50 units/kg. body weight followed by 100 units/kg. body weight 4 hourly;
(c) Low-Dose Heparin.
This is useful for-
(1) prophylaxis of deep vein thrombosis (DVT) during and after surgery in high-risk patients;
(2) treatment of disseminated intravascular coagulation. The advantage of the low dose is that it is sub-anticoagulant and does not require laboratory control. It is supposed to prevent thrombosis by suppression factor IT acti- vation. Usual dosage is 5,000 units subcutaneously 2 hours before surgery and postoperatively every 12 hours for one week.
Side effects. toxicity and complications (1 ) Haemorrhage.
(2) Rare hypersensitivity reactions including rhinitis, urticaria, asthma and death.
Test dose of 1,000 units is desirable in patients with history of allergic disease.
(3) Rare transient alopecia 3-4 months later.
(4) Rare cases of osteoporosis and spontaneous fracture and priapism following prolonged use.
I. Haemorhagic disease or presence of a source of bleeding e.g. active peptic ulcer 2. Visceral carcinoma.
3. Regional or lumbar block anaesthesia. 4. Severe hypertension. 5. Previous cerebro-vascular accident-unless embolic.
6. Recent surgery or traumat to CNS.
7.Sub-acute bacterial endocarditis.
Antidote.-i.v. protamine sulphate 1 mg. for every 100 units of heparin in the last dose, may be given in an emergency.
5.2.2 Oral Anticoagulants.-The drugs of choice are coumarins e.g. warfarin, because serious and sometimes fatal sensitivity reactions can occur to the indanediones (e.g. phenindi- one) any time from a few days to 6 weeks from the start of therapy. They produce anticoagu- lant effect after 36-48 hours by inhibiting the synthesis of vitamin K dependent coagulation factors in the liver.
Dosage form.- Tablets as warfarin sodium. Uses-
I. Prevention of venous thrombosis in high-risk patients.
2. Prevention of recurrent DVT or pulmonary embolism.
3. Prevention of thrombosis and embolism in patients with prosthetic heart valves and rheumatic heart disease with arterial fibrillation or a history of cerebral embolism.
4. Use for prevention of arterial thrombosis is controversial.
Side Effects, toxicity and complications
1. As for heparin.
2. Severe hepatic or renal disease.
4. Concomitant use of certain other drugs.
Drug Action Anticoagulant effect of Warfarin
Phenobarbitone …………………..Induce liver microsomal enzyme activity …….Decreased
Alcohol Chloramphenicol …….Reduce liver microsomal enzyme activity ……Increased
Aspirin Sulphonamides ………..Displace warfarin from protein binding ……….Increased
Broad spectrum antibiotics …..Decreased Vitamin K synthesis in gut …………Increased
Griseofylvin ……………………….Unknown …………………………………………………Increased
Thyroxine …………………………..Unknown …………………………………………………Increased
Quinidine …………………………..Unknown ………………………………………………… Increased
Vitamin K ………………………….Stimulation of synthesis of clothing factors …. Decreased
Nitrazepam is a safe hypnotic during warfarin therapy.
Antidote.-Vitamin K’ (phytomenadione) can be given orally, i.v. or i.m. depending on clinical situation. Other vitamin K preparations have a variable effect.
Dosage Vitamin K’
For frank haemorrhage and no plan for further anti-coagulation ……..10-20 mg. i. v.
For frank haemorrhage but continuation of anti-coagulant desired …. 5 mg. or omit warfarin
When the desire is to reduce excessive effect before haemorrhage … omit warfarin
I. 48 hours after start of therapy.
2. Daily or alternate days until control is established, then increased interval.
3. When fully controlled on long-term therapy, check laboratory result every 4-6 weeks.
4.Prothrombin time to be between 2-3 times normal value. 5.3 Plasma Substitutes
Dosage form.-Solution 500 ml. bottle containing 6% dextran (m.wt 70,000) in 0.9% NaCI or 5% dextrose.
Mode of action.-Plasma expander.
Pharmacological properties.-Restores and maintains blood volume, reduces the ten- dency for sludging of blood that may accompany many forms of shock.
Uses.-Hypovolaemic shock due to loss of whole blood and plasma, prevention of thrombosis in postoperative thromboembolic disease.
Precaution.-Interferes with typing, cross matching or Rhesus determination of blood.
Therefore blood must be taken before its emergency administration; contraindicated in anae- mia, thrombocytopenia and hypofibrin ogenaemia.
Adverse reactions.-Antigenic and may precipitate allergic reactions such as itching, ur-
ticaria, joint pains.
Dosage.-500 ml.-I 000 ml, i. v. while waiting for blood to be matched. Overdosage.-Rare and most unlikely.
5.4 Plasma Fraction for Specific Use
Dosage form.-5% or 25% solution; 5% solution in 250 and 500 ml, bottles; 25% solu-
tion in 20 rnl., 50 rnl. and 100 ml. bottles.
Mode of action.-Plasma expander.
Pharmacological properties.-Restores and maintains blood volume. Uses.-Hypovolaemia due to loss of whole blood or plasma (burns). Hypoalbuminaemia
in nephritic syndrome or severe hepatic insufficiency.
Precautions.-Salt content may aggravate oedema. Adverse reactions.-Risk of hepatitis B virus infection. Dosage.-Whole blood or plasma loss: 250-1,000 ml. 5%; Nephrotic syndrome or Cirrhosis: 50-100 ml. of 25%.
Overdosage.-Symptoms and signs: oedema and heart failure due to sodium overload. Treatment.-Diuretics.
5.5 Vitamins and Minerals.-Vitamins should be used for the prevention and treatment of specific deficiency states and not for conditions in which there is no evidence of vitamin deficiency.
RETINOL (VITAMIN A)
Dosage forms.-Capsules or tablets: 1.5 mg. (5,000 units), 7.5 mg. (25,000 units).
Mode of action.-Cofactor in various biochemical reactions e.g. mucopolysaccharide synthesis, sulphate activitation, hydroxysteroid dehydrogenation, cholesterol synthesis, he- patic microsomal demethylation and hydroxylation of drugs.
Pharmacological properties.-Maintains healthy skin, interferes with carcinogenesis, essential for vision in dim light, growth and differentiation of epithelial tissues, bone, tissues, reproduction and embryonic development, regulates membrane permeability.
Uses.-deficiency of Vitamin A.
Prophylaxis during periods of increased requirement such as infancy, pregnancy and lactation, skin diseases like acne, psoriasis, Darier’s disease and ichthyosis.
Precautions.-Avoid excessively large doses as symptoms of hypervitaminosis may oc-
Adverse reactions.-Erythema, skin desquamation, sensitises skin to sunlight allergic dermatitis, decreased skin pigmentation, dizziness, thirst, potechiae, liver damage.
Drug interactions.-Vitamin E increases its efficacy and protects against its toxicity by increasing its storage in the liver.
Dosage.-Pregnancy and lactation; 1,000-1,200 units retinol equivalents or retinol per
Overdosage.-Symptoms and signs-irritability, vomiting, anorexia, headache, dry and itchy skin, skin desquamation, dermatitis, fatigue, pain in ankles and feet, myalgia, loss of body hair, papilloedema, nystagmus gingivitis, mouth fissures, lymphadenopathy, Hepatos- plenomegaly, cirrhosis with portal hypertension, ascites. Increased intracranial pressure and neurological symptoms may mimic brain tumour. Hyperstosis, increased osteoblastic activity and hypercalcaemia.
Treatment.-Withdrawal of Vitamin A. Supportive treatment.
VITAMIN B I (THIAMINE) Dosage forms.-Tablets: 25, 50 mg.; Injection: 25 mg./m!. in I ml. ampoule.
Mode of action.-Coenzyme in carbohydrate metabolism in the decarboxylation of alpha ketoacids such as pyruvate and alpha ketoglutarate; its requirement is greatest when carbohy- drate is the source of energy.
Pharmacological properties.- Thiamine, given in usual therapeutic doses, is practically devoid of pharmacodynamic actions.
Uses.- Treatment or prophylaxis of thiamine deficiency diseases, e.g. beriberi (dry and
Wernicke’s encephalopathy; Korsakoffs syndrome; Alcoholic polyneuropathy; Precautions.-Nil
Adverse reaction.-Parenteral administration may rarely be associated with hypersensi-
tivity reaction in the form of shock.
Alcoholic neuritis – 50-100 mg. daily orally;
Infantile beriberi – 25 mg. intravenously for collapse; Alcoholic cardiomyopathy – 10-30 mg. three times daily; Neuritis of pregnancy – 5-10 mg. daily, i.m.
VITAMIN B6 (PYRIDOXINE) Dosage form.- Tablet: 10 mg.
Mode of actiol/.-Coenzyme for a wide variety of metabolic transformation of amino acids including decarboxylation, transamination, and racemisation; cofactor in the conversion of trytophan to 5-hydroxytryptamine.
Uses.-Treatment and prophylaxis of deficiency diseases, e.g. therapy with isoniazid- Oestrogen therapy;
Oral contraceptive therapy;
Pyridoxine-responsi ve anaemia. Precautiol1s.-Dependence may occur to large doses. Adverse reaction.-Very rare.
Drug interactiol1s.-Isoniazid increases its urinary excretion, prolonged use of penicil- lamine may cause its deficiency, cycloserine and hydralazine antogonise its effect. It enhances peripheral decarboxylation of levodopa and reduces its therapeutic effect.
Dosage- 5-20 mg./day;
50-200 mg./day in Pyridoxine deficiency anaemia.
VITAMIN C (ASCORBIC ACID) Dosage forms.-Tablets: 100,500 mg.
Mode of action.-Reducing agent which converts proline to hydroxyproline in collagen synthesis, also used in synthesis of steroids by adrenal cortex, conversion of folic acid to fo- linic acid, microsomal drug metabolism, tyrosine metabolism, also needed for synthesis of intercellular substances including collagen, matrix of bone and tooth, capillary endothelium.
Pharmacological properties.-Very large doses are reputed to prevent or cure viral res- piratory infections and beneficial in cancer.
Uses.- Treatment and prophylaxis of deficiency states, e.g, scurvy idiopathic
methaemoglobinaemia; vital respiratory infections.
Precautiol1.-High doses may result in oxalate kidney stones.
Drug Interactions= Iron absorption enhanced; Interferes with anticoagulant therapy. Dosage.-Tablets 50-250 mg. three times daily.
VITAMIN D (ERGOCALCIFEROL) Dosage forms.-Capsules 0.25 mg. (10,000 units) and 1.25 mg. (50,000 units).
Mode of action.-Active form increases plasma calcium concentration by facilitating the intestinal absorption and enhancing mobilisation from bone; it also increases proximal tubular reabsorption of calcium and phosphorus.
Pharmacological properties.-Deficiency results in rickets in children and osteomalacia in adults. Excessive doses result in deranged calcium metabolism.
Uses.-Prophylaxis and treatment of rickets, treatment of metabolic rickets and asteo- malacia as treatment of hypoparathyroidism.
Precautions.-Excessive doses result in hypervitaminosis.
Adverse reactions.-Phenytoin and phenobarbitone reduce its intestinal absorption, in- crease target organ resistance to vitamin D and reduce its effect on bone re-absorption. Hence hypocalcaemia occurs leading to rickets or osteomalacia.
Vitamin D deficiency: up to 0.25 mg. (10,000 units) daily. Rickets: up to 1.25 (50,000 units) daily.
Overdosage.-Symptoms and signs-Weakness, fatigue, headache, nausea, vorruting, diarrhoea, polyuria, nocturia, polydipsia, proteinuria, nephrolithiasis, diffuse nephrecalcinosis, metastatic calcification in blood vessels, heart, lungs, skin and hypertension. There is hypercalcaemia, raised blood urea but the phosphate concentrations are variable. Maternal hypocal- caemia may result in non-familial congenital supravalvular aortic stenosis, suppression of parathyroid, tetany and seizures.
Treatment.-Withdrawal of vitamin D treatment, low calcium diet, liberal fluid intake and administration of corticosteroids.
Others.-Other vitamins include Vitamins E and K. Vitamin K has been discussed under Antidotes (section 16). Minerals occasionally used in general practice include Calcium gluco- nate, Calcium lactate and Sodium fluoride. The indications for them are sufficiently few not to include them in the Essential Drugs List.
5.7 Oral Rehydration Salts – see section 7.6.1 5.8 Parenteral i. v. Fluids
Dosage forms and routes.-5% (50 mg./m!.) in 500 rnl. and I litre bottles. Also 20, 25% and 50% in 20 m!., 25 ml., and 50 ml. ampoules.
I. Fluid replacement after mainly pure water loss.
2. Provision of energy as well as fluid.
Adverse reactions.-thrombophlebitis. Dosage.-2-6 litres per day when necessary.
SODIUM CHLORIDE AND DEXTROSE I.V. INFUSION Dosage form.-Sodium chloride 0.18% and 4.3% anhydrous dextrose. Uses.-When need for water replacement is far greater than that for sodium.
I. Dehydration from vomiting.
2. Hyperosmotic: diabetic coma.
Dosage.-2-6 per day as required.
SODIUM CHLORIDE l.V. INFUSION Dosage form.-0.9% in 500, 1000 ml. bottles (normal strength). 0.45% in 500, 1000 ml. bottles (Half-normal strength).
I. Diabetic ketosis.
2. Severe diarrhoea.
3. Pancreatic fistulae.
4. Small bowel fistulae.
Dosage.-2-6 litres per day as required.
POTASSIUM CHLORIDE Dosage form.-lnjection, 10% in IO ml. ampoules. Uses. -H ypokalaemia.
Precautions.-Monitor ECG; ensure adequate urine is being passed. Jnfuse at not more than 20mmol/hour.
Dosage.-Up to 6 g. (80 mmol) daily. Adverse reactions.-Cardiac asystole.
SODIUM BICARBONATE l.V. INFUSION Dosage form.-1.4% (167mmol) in 500 ml. 1.4.% (167mmol) in 500 ml. Uses.-Metabolic acidoses e.g. after cardiac arrest.
Dosage.-Continuous i. v. infusion of a meek solution e.g. 1.4% to correct base deficit or restore pH to 7.2.
SODIUM LACTATE COMPOUND SOLUTION
Dosage form.-Solution for i. v. infusion. Containing the following irons in mmol/litre:
Na + + 131, K + 5, Ca + + 2, HC03.-(as lactate) 29, and Cl-Ill. Uses.-Diabetic coma; diminished alkali reserve.
Dosage.-IOO ml. or according to patient’s need.
5.9 Peritoneal Dialysis Fluid
Dosage forms.-(Injection for peritoneal) I L or 2 L containing per litre of infusion- Sodium: 130.5mmol;
Dextrose: either 1.5% (isotonic) or 4.25% (hypertonic);
Mode of action.-Withdraws urea and other toxic products from blood, the peritoneum acting as semi-permeable membrane.
Acute renal failure; Chronic renal failure;
Chronic ambulatory peritoneal dialysis (CAPD).
Precautions.-Sterile procedure must be kept.
Adverse Reactions.-Peritonitis; dehydration if too much of hypertonic solution is used. Others.-Include the Haemodialysis Fluid which is used only in specialised centres and
is not included in the Essential Drugs List.
6. Respiratory System Drugs
Drugs acting on the respiratory tract are described under the following headings- 6.1 Anti-asthmatics.
6.1. Anti-Asthmatics.-Drugs are used in asthma to treat acute attacks or for mainte- nance therapy in the chronic asthmatics.
Treatment of acute attack.-A mild attack of asthma may respond to oral bronchodila- tors. The bronchodilator of choice is any of the selective bera–adrenocepror stimulants. These drugs dilate the bronchus without producing cardiac stimulation and are therefore preferred to the non-selective beta-adrenoceptor agonists like isoprenaline. At least three types of beta– agonists are presently available in Nigeria: salbutamol, terbutaline and fenoterol. There is little to choose between these three as far as efficacy and safety are concerned. However, fenoterol has a significantly longer duration of action than salbutamol and can therefore be given at longer intervals. A small number of patients previously controlled with non-selective bron- chodilators continue to express preference for this class of drugs over the newer betar stimulants. The non-selective adrenocepto stimulants such as adrenaline, isoprenaline and orciprenaline are now less suitable and less safe for prolonged use because they produce seri- ous cardiac irregularities. However, adrenaline continues to be useful in the relief of bronchial spasm of acute attacks of asthma.
For moderate attacks and mild ones that fail to respond to oral beta–agonists, response is usually obtained with aerosols of the selective betayagonists.
Severe asthmatic attacks and status asthmatics should be treated in hospital using oxy- gen, intravenous eminophylline or salbutamol and, if necessary, intravenous hydrocortisone.
Prophylaxi.-For frequently occurring mild to moderate attacks of asthma, prophylaxis is given with sodium cromoglycate, ketotifen or corticosteriod inhalation. Regular administra- tion of betaj-simulant tablets or aerosols can also be used for prophylaxis either as adjunct to the above or as substitutes for them if they are not available. Repeated severe attacks that fail to stabilise with the above will require oral corticosteroid prophylaxis.
AMINOPHYLLINE Dosage form.-Injection 25 mg./ml. in 5 ml. ampoules.
Pharmacological properties.-Aminophylline is a I: 1 complex of theopylline and ethyl- enediamine. The latter merely serves to increase the solubility of theophylline. The main ef- fects of aminophylline are-
(i) relaxation of bronchial and vascular smooth muscle;
(ii) increased cardiac excitability and tachycardia;
(iii) stimulation of the central nervous system
I. Relief of severe airways obstruction due to asthma and other causes of bron- chospasm.
2. Emergency relief of severe acute left ventricular failure. However, the potent vasodilators like sodium nitroprusside, high ceiling diuretics like frusemide and specific cardiac inotropic agents are now generally preferred.
Precaulion.-The injection should be given very slowly preferably over 15 minutes. Adverse effects.-Vomiting even after intravenous injection. Headaches, palpitations, utahycardia, dizziness, hypotension, anginal pain, restlessness and agitation. Collapse and sudden death if injected rapidly.
Dosage.-By slow intravenous injection over a period of minutes- Adults: 250-500 mg. (5 mg’/kg.);
Children: 5 mg./kg.
Dosage form.-Oral inhalation (aerosol) 0.5 mg. (dipropionate) per metered dose. Pharmacological effects.-A potent synthetic anti-intlammatory glucocorticoid which, delivered by metered aerosol, exerts a topical effect on the bronchi at dosages that do not pro- duce significant systemic effects.
Uses.-Prophylaxis of asthma.
Adverse effects.-Oral candidiasis can occur with prolonged use.
Dosage.-2 inhalations, 3-4 times daily. This can be increased according to response to a maximum of 20 inhalations per day.
Children’s dose.-approximately half of adult dose.
HYDROCORTISONE [See section 8.1.]
6.1.3 Adrenoceptor Stimulants
184.108.40.206 Selective betas-Adrenoceptor Stimulants
Tablets, 2 mg., 4 mg. (sulphate); Syrup, 2 mg./5 rnl. (sulphate);
Oral inhalation (metered aerosol), 0.1 mg. per dose; Injection, 0.5 mg. (sulphate) in Irnl. ampoule.
Pharmacological properties.-A selective beta–adrenoceptor stimulant with potent bronchodilator activity and relatively weak cardiovascular effects.
Uses.-Relief of bronchospasm due to asthma and other causes. Uterine relaxant in pre- mature labour.
Precaution.-Aerosol inhalation may be ineffective in the presence of severe broncho-
spasm, hypertension, pregnancy.
Adverse effects.-Overdosage may cause significant cardiovascular stimulation. Dosage.-Oral tablets:
Adults, 2-4 mg., 3 or 4 times daily;
Children (2-5 years), 1-2 mg., 3 or 4 times daily;
Aerosol inhalation.-Adults 1-2 inhalations, 3-4 times daily; Children (2-5 years) 1 inhalation, 3-4 times daily.
Subcutaneous or intramuscular injection: 0.5 mg., 4 hour, Intravenous injection: 0.25 mg., 4 hourly.
220.127.116.11 Non-selective Adrenoceptor Stimulants
ADRENALINE Dosageform.-Injection, Img. (bitartrate)/ml. in Iml. ampoules.
Pharmacological properties.-Relaxes bronchial smooth musculature by stimulation of bera=adrenoceptors.
Uses.-In severe acute attacks of bronchial asthma; injected subscutaneously to relieve
Caution.-Tolerance or refractoriness may develop with prolonged usage. Adverse effects.-See 1.5.2.
Dosage.-By subcutaneous injection of a Iin 1000 solution 9 or Img./ml. solution)- Adults – 0.2-0.5 m\. (200-500 mg.);
Children – 0.01 ml, or lOug per kg. body weight, up to max. of 0.5 mJ. (500 mg.) as a
Relief is obtained within 5 minutes, or it may be repeated after 15-30 minutes. Others.-Isoprenaline. Orciprenaline.
6.1.4 Prophylactic Drugs
KETOTIFEN Dosage forms.-Tablets or Capsule Img.; Syrup Img./5ml.
Pharmacological properties.-A prophylactic drug used to reduce the frequency of asthmatic attacks. Mode of action is not certain but appears to act like sodium cromoglycate to prevent release of histamine and other mediators of allergy. Has advantage over cromoglycate in being given by mouth, thus removing the problems many patients have in the correct use of cromoglycate inhalation. Ketotifen also has some classical antihistamine properties.
Use.-Prophylaxis of asthma; prohylaxis of allergic reactions. Symptomatic relief of allergy such as urticaria.
Dosage.-1-2 mg. twice daily.
Children (over 2 years), 1 mg. twice daily.
6.1.5 Compound Bronchodilator Preparations
EPHEDRINE PLUS HYDROXYZINE PLUS THEOPHYLLINE Dosage form.-Tablet or syrup containing:
Ephedrine 25 rng.; Hydroxyzine 10 rng.;
Theophylline 30 mg. per tablet or per 5 m\. syrup.
Pharmacological properties.-Combines two bronchodilators and an antihistaminic sedative, hydroxyzine.
Uses.-Relief of mild to moderate asthma. There is little place for this kind of prepara- tion in the modern treatment of asthma.
Dosage.- Tablets: Adult, 1-2 tablets, 4 times daily;
Syrup: Children (over 5 years), 5-10 m\., 2 to 4 times daily; (2-5 years), 2.5-5 m\., 2-4 times daily.
6.2 Anti-Tussives.-Drugs are used in the symptomatic treatment of coughs either to suppress coughs or to aid the expectoration of mucus. A dry, irritant, non-productive cough, needs to be suppressed especially if it disturbs sleep at night. Codeine has a weak cough sup- pressant action. Methadone has a stronger suppressant action but its repeated use may lead to habituation or even addiction.
E CODEIN Dosage fjorm.- Tablets, 10 mg. (Phosphate). Syrup, 5 mg. (Phosphate)/5ml
Pharmacological properties.-Codeine is an opiate analgesic which also suppresses the
cough reflex. It also increases smooth muscle tone and reduces its mobility.
Uses.-Suppression of dry or painful cough. Symptomatic treatment of diarrhoea.
Adverse effects.-Constipation when used as a cough suppressant. Dosage.-Adult, Tablet: 2 tablets, 3-4 times daily.
6.3 Expectorants.-Although expectorants are used extensively in general medical practice, there is no evidence that they have more than a placebo effect. The best treatment for cough is to diagnose its cause and give appropriate treatment.
See formulary section for different expectorant formulations.
7. Gastrointestinal System Drugs
Drugs acting on the gastrointestinal system are described under the following headings- 7.1 Antacids.
7.3 Antihaemorrhoidals. 7.4 Antispasmodics.
7.7 Ulcer healing drugs.
7.1 Antacids.-Gastric acid is generally believed to be responsible for most of the symptoms in peptic ulcers, gastritis, coesophageal reflux with heartburn and a variety of dys- pepsias. High gastric acidity is also considered a hindrance to the healing of peptic ulcers.
The PH of the gastric acid is normally between I and 2. The aim in antacid medication is to raise it to about 4 without producing systemic alkalosis. Complete neutralisation is not helpful. It inhibits pepsin and may cause rebound hypersecretion of gastric acid.
Antacids are usually classified as systemic and non-systemic. The only systemic antacid that has been used to any great extent is sodium bicarbonate. It is now no longer used because of the systemic alkalosis that it causes. The non-systemic antacids are not absorbed and in- clude calcium, magnesium and aluminium compounds. Calcium compounds cause acid re- bound, are constipating and, with prolonged use, may cause hypercalcaemia. They are there- fore no longer recommended. At present, the choice of antacid should be between magnesium and aluminium compounds. Aluminium compounds constipate whilst magnesium compounds cause diarrhoea.
There are many antacid preparations in the market but aluminium hydroxide, magnesium hydroxide and magnesium trisilicate are as effective as any.
ALUMINIUM HYDROXIDE Dosage forms.-Tablets, 500 mg.;
Mixture, 320 mg./5 ml.;
See formulary for composition.
Pharmacological properties.-A non-systemic gastric antacid. Uses.-Peptic ulcer;
Dyspepsia from various causes; Hyperphosphataemia.
Adverse effects.-Constipation; loss of phosphate in faeces.
Precaution.-Best taken at least I hour after food. May interfere with the absorption of many drugs.
Dosage.-1-2 tablets or 5-10 ml. of mixture at hourly, 2-hourly or 3-hourly intervals de- pending on severity of symptoms.
MAGNESIUM HYDROXIDE Dosage forms.-Tablet, 500 mg.;
Mixture, 250 mg./5 ml.;
See formulary section for composition.
Pharmacological properties.-A non-systemic gastric antacid. Uses.-Peptic ulcer;
Dyspepsia from various causes; constipation. Adverse effect.-Diarrhoea.
Precaution.-Not to be taken with food or with other drugs.
Dosage.-For peptic ulcers and dyspepsia; 1-2 tablets or 5-10 ml. when required. For constipation: 25-50 ml. as required.
MAGNESIUM TRISILICATE Dosage forms.- Tablets, 500 mg.;
Mixture, 250 mg./5ml.
See formulary section for composition.
Pharmacological properties.-A non-systemic gastric antacid. Uses.-Peptic ulcer;
Dyspepsia from various causes. Adverse effects.-Diarrhoea.
Precaution.-Not to be taken with food or other drugs. Drug interaction.-Reduces absorption of iron.
Dosage.-1-2 tablets chewed when required or 10-20 ml. mixture taken when required. 7.2 Anti-Emetics.-Nausea and vomiting can be classified into two main groups-
(i) those resulting from vestibular disorders; and (ii) those due to other causes.
Vomiting of labyrinthine or vestibular origin occurs in motion sickness, Meniere’s dis- ease, positional vertigo and labyrinthitis. This kind of vomiting usually requires anti-emetic treatment. Antihistamines (e.g. promethazine), anticholinergics (e.g. hyoscine) or phenothnazines (e.g. chlorpromazine) are the drugs of choice. Anti-histamines are probably better tolerated than anti-cholinergics.
Non-labyrinthine vomiting arises from stimulation of the vomiting centre either via af- ferent nerves from the viscera or cerebral cortex or from the nearby chemoreceptortrigger zone (ClZ). The CTZ is stimulated by circulating substances such as appornorphine and other narcotic analgesics, digitalis and urquemia, and the ClZ in turn stimulates the vomiting centre.
Antihistamines and anticholinergics act directly on the vomiting centre and so suppress vomiting from any cause. Although they are often prescribed for non-labyrinthine vomiting they are much less effective than in motion sickness. The phenothiazines are the drugs of choice for non-labyrinthine vomiting.
CHLORPROMAZINE [See section 1.1.6.]
PROMETHAZINE [See section 15.1.]
7.3 Anti-Haemorrhoidals.-Patients suffering from haemorrhoids may experience anal and perianal pruritus, soreness and exdoriation. Considerable relief can be obtained in haem- orrhoids by careful local toilet and adjustment of the diet to avoid hard stools. When necessary local preparations containing local anaesthetics and corticosteroids can be used to relieve the pain and inflammation associated with haemorrhoids.
LIGNOCAI NE PLUS BETAMETHASONE RECTAL PREPARATIONSDosage forms.-Cream, ointment or suppository.
See formulary section for composition.
Pharmacological properties.-Lignocaine is a local anaesthetic which relieves pain whilst the cast corticosteroid, betamethasone, relieves inflammation.
Uses.-To relieve pain and inflammation in haemorrhoids as well as in anal fissure, proctitis and related conditions.
Precaution.-The presence of infection should be excluded. Prolonged use of lignocaine may cause sensitisation of the anal skin. Prolonged use of betamethasone may lead to perianal thrush.
Adverse effects.-Skin sensitisation; thrush.
Dosage.-Suppository: Insert into the rectum night and morning and after defecation. Ointment and cream: apply night and morning and after defecation, externally or by
rectumusing a rectal nozzle.
7.4 Anti-spasmodics.-Anti-spasmodics reduce spasm of hollow visceral. The most commonly used antispasmodics are anticholinergic drugs which inhibit parasympathetic in- nervation and therefore reduce motility and contraction. For most anticholinergic drugs the dose that reduces spasm also produces other unwanted anticholinergic effects like paralysis of accommodation, dryness of the mouth, constipation and especially in the elderly, urinary re- tention and glaucoma. Hyoscine butyl bromide is described here as an example of antispas- modic drugs. It has only little unwanted peripheral anticholinergic effects at the dose that re- duces spasm of hollow viscera. Mixture of belladonna is also commonly used. Propantheline is useful in peptic ulcer both as an antispasmodic and as an inhibitor of gastric acid secretion. However, reduction of gastric acid secretion is now better achieved by H2-antagonists.
HYOSCINE BUTYLBROMIDE Dosage forms.- Tablet, IOmg.
Injection, 20 mg.lml. in 1 ml. ampoule. Pharmacological properties.-Anticholinergic drug.
Uses.-Relief of gastrointestinal and colonic spasm. Relief of spasm in renal or biliary colic. Relief of spasmodic dysmenorrhoea.
Adverse effects.-Peripheral anticholinergic effects including dry mouth, blurring of vision, constipation.
Dosage.-Tablet: 20 mg. 4 times daily; children, tomg. 3 times daily. Injection: 20 mg. intramuscularly or intravenously when necessary. Others.-Belladonna mixture-See formulary section.
7.5 Purgatives.-The common indications for the use of purgatives are- (i) Treatment of helminthic infections of the bowel;
(ii) Before surgery on the colon and rectum;
(iii) Before radiology of the bowel and other abdominal organs;
(iv) In local disease of the anus or rectum such as haemorrhoids or anal fissure; (v) Following ingestion of poisons.
Purgatives can be classified into three groups depending on their mode of action-
(i) bulk purgatives;
(ii) lubricant purgatives; and (iii) irritant purgatives.
The bulk purgatives act by increasing the bulk of the intestinal contents, thus promoting normal peristalis and defaecation. There are many types of which the most widely used are the osmotic purgatives. There are salts having a non-absorbable ion such as magnesium in magne- sium hydroxide. The salt absorbs water by osmosis, providing liquid bulk.
Liquid paraffin is the best known of the lubricant purgatives. It lubricates faecal material in the colon and rectum. However, with chronic use, it can reduce absorption of the fat soluble vitamins A and D and can produce paraffinomas in the mesenteric lymph nodes. It can also leak from the anus and soil clothing. It is therefore not recommended except for the special indication when straining is undesirable or when defecation is painful such as after haemor- rhoidectomy or in anal fissure. Even here, it can delay healing after anal surgery.
The term “irritant purgatives” covers a wide variety of drugs which produce purgation by direct or indirect stimulation of the wall of the small or large intestine.
Most irritant purgatives have a slow onset of action, and are usually given at night for an effect in the morning. Where rapid purgation is required, as after ingestion of a poison, an osmotic purgative is best.
As a rule purgatives should be avoided unless specifically indicated. Chronic purgation can lead to hypokalaemia, dehydration, weight loss and muscle weakness. Purgatives should never be given to a patient with undiagnosed acute abdominal pain.
MAGNESIUM HYDROXIDE BISACODYL [See section 7.1.]
Dosage forms.-Tablets,5 mg. Suppository, IOmg.
Pharmacological properties.-Irritant purgative. Probably acts by stimulating sensory nerve endings in the mucosa of the large intestine. Tablets act within 10-12 hours, supposito- ries within 1 hour.
Bowel evacuation before surgery, endoscopy or radiological investigations.
Adverse effect.-General adverse effects of purgatives (see above). In addition, tablets
may cause gastrointestinal disturbances; suppositories may cause local irritation.
Precaution.-Not to be taken with milk or antacids. Dosage.- Tablet: Adult, 5-10 mg. at night (for constipation).
Suppository: Adult 10 mg.; child 5 mg., usually in the morning (for constipation).
Before radiological procedures and colonic surgery: 10 mg. by mouth at bedtime for the two preceding days. If necessary, a 10 mg. suppository may be given in addition, I hour be- fore a radiological examination.
Others.-Magnesium sulphate, senna, liquid paraffin.
7.6 Anti-Diarrhoeals.-The treatment of diarrhoea can be considered under the following headings-
7.6.1 Drugs for symptomatic treatment. 7.6.2 Replacement fluids.
7.6.3 Specific anti-infective agents.
7.6.1 Drugs for Symptomatic Treatment of Diarrhoea.-Most diarrhoeas are viral in origin and are self-limiting. Such diarrhoeas would only require treatment for the symptomatic relief of the diarhoea and to prevent or correct salt and water loss.
Kaolin can be given to absorb irritants. Opiates, particularly morphine and codeine, in- crease smooth muscle tone in the bowel and reduce its motility. The compound kaolin and morphine mixture remains a very popular anti-diarrhoeal preparation. Diphenoxylate, a de- rivative of codeine, is combined with atropine in a popular antidiarrhoeal preparation. The dose of morphine in antidiarrhoeal preparations is small and there is no danger of systemic effects or dependence.
Dosage form.-Mixture; See formulary for composition. Pharmacological property.-Absorbent. Uses.-Diarrhoea.
Drug interaction.–Can reduce the intestinal absorption of some antibiotics, e.g. Linco- mycin.
Dosage.-1O-20 ml every 4 hours.
KAOLIN AND MORPHINE MIXTURE Dosage form.-Mixture. See formulary for compositon. Pharmacological properties.-Absorbent and anticolic. Uses.-Diarrhoea.
Dosage – 10 rnl. every 4 hours. Others.-Diphenoxylate plus Atropine.
7.6.2 Replacement fluids.-Diarrhoea is associated with varying degrees of water and electrolyte loss form the body. In some cases, particularly in children, this may be so severe that, if not promptly corrected, death may result from the salt and water loss. The traditional method for fluid replacement is by intravenous therapy. Recently, oral rehydration salts have been prepared which are readily absorbed in diarrhoea, regardless of the causative agent or the age of the patient. Oral rehydration therapy does not stop the diarrhoea, which is usually self- limiting. Oral rehydration salts are suitable and adequate for the treatment of mild and moder- ate degrees of dehydration in all age groups. Severe dehydration is treated initially with an appropriate intravenous solution and then continued with oral rehydration salts.
ORAL REHYDRATION SALTS (ORS)
Dosage form.- Solids contained in sachets for 1 litre of solution:
Glucose (anhydrous) ……………………………………………………….. 20 g.
Potassium chloride …………………………………………………………..1.5 g.
Sodium bicarbonate ………………………………………………………… 2.5 g.
Sodium chloride ……………………………………………………………… 3.5 g.
Properties.-ORS solution provides adequate quantities of electrolytes to correct the deficits associated with acute diarrhoea. The bicarbonate corrects the acidosis; the potassium and sodium replace the body losses. The absorption of sodium and water in the small intestine is greatly enhanced by glucose. This fact forms the physiological basis of oral rehydration therapy using ORS solution.
Uses.-Prevention and treatment of dehydration in diarrhoea.
Dosage.-Approximate guide. Mild dehydration: 50 m\./kg. within 4 hours. Moderate dehydration; 10 ml./kg. within 4 hours, followed by 10 ml./kg. after each loose stool for in- fants and children below 5 years of age, or as much as required for older children and adults.
Caution.-The above regimen is only a guide and liquid administration should depend on clinical evaluation of loss and requirements.
7.6.3 Specific anti-infective agents.-Several pathogenic bacteria, viruses and intestinal parasites have been identified as causes of diarrhoea. Anti-infective drugs are not indicated for the routine treatment of acute diarrhoea. Specific indications for their use include-
Severe shigella dysentery; Amoebic dysentery; Acute giardiasis;
The drugs of choice for the treatment of these conditions are described in section 9.
7.7 Ulcer healing Drugs.-In recent years, drugs have been introduced which promote healing of peptic ulcers. The earliest of these was carbenoxolone, a synthetic derivative of glycyrrhizic acid (a constituent of liquorice). It probably acts by increasing mucus production and protecting the mucosa from acid-pepsin attack. It has anti-inflammatory and aldosterone- like effects, the latter of which include salt and water retention and hypokalaemia. It is there- fore not suitable for old persons and those with cardiac or renal disease. Cimet cidine and ranitidine are H2-receptor blockers which heal peptic ulcers by reducing gastric acid output. Pirenzepine is a selective muscarinic anticholinergic drug which promotes ulcer healing. It specifically inhibits gastric acid and pepsin secretion and thus has fewer peripheral side ef- fects than the non-selective anticholinergic drugs. There is, however, little experience of this drug in the country.
Dosage forms.-Tablet, 200 mg.; Injection, i.m., slow i.v. injection or i.v. infusion, 100
mg./ml. in 2 ml. ampoule.
Mode of action.-Histamine H2-receptor antagonist.
Pharmacological properties.-Reduces gastric acid secretion, promotes ulcer healing. Uses.-Gastric and duodenal ucler.
Adverse effects.-Rare but include reversible impotence and gynaecomastia.
Drug interaction.-Potentiates action of drugs like oral anticoagulants, phenytoin and tolbutamide by inhibiting oxidative metabolism.
Dosage.-For gastric or duodenal ulcer, 200-400 mg. 2 or 3 times daily in courses of 4-8 weeks. By i.m. or i. v. injection, lOO-ISO mg./hour for 2 hours, repeated after an interval of 4-6 hours.
Precaution.-Reduce dosage in impaired renal and liver function.
RANTIDINE Generally similar to cimetidine except
Dosage forms.- Tablet, 150 mg. (hydrochloride); Injection, i.m., slow i. v. and infusion,
25 mg. (hydrochloride)/ml. in 2 ml. amps.
Adverse effect.-Has no anti-androgenic effect.
Drug interaction.-Does not inhibit hepatic drug metabolising Aldative enzymes. Dosage.-150 mg. 2 or 3 times daily for 4-8 weeks, repeated if relapses occur. By slow
intravenous injection, 50 mg. every 6-8 hours.
Others.–Carbenoxolone, Pirenzepine, and Propantheline.
8. Endocrine System Drugs
Drugs in this section are discussed under the following headings- 8.1 Corticosteroids and synthetic substitutes.
8.5 Oral contraceptives. 8.6 Ovulation inducers. 8.7 Oxytocics.
8.8 Drugs used in diabetes millitus. 8.9 Thyroid and anti-thyroid drugs.
8.1 Corticosteroids and synthetic substitutes.-The adrenal corticosteroids are of two main types: glucocorticoids and mineralocorticoids. The most important naturally occurring glucocorticoid is hydrocortisone. Glucocorticoid activity covers a wide variety of actions on fat, protein and carbohydrates metabolism, on the haemolymphatic system as well as a marked anti-inflammatory action. In addition, hydrocortisone has some mineralocorticoid activity. Prednisolone, dexamethasone and betamethasone are synthetic glucocorticoids. Prednisolone has about five times the glucocorticoid activity of hydrocortisone but about the same miner- alocorticoid activity. Dexamethasone and betamethasone have about thirty-five times the glu- cocorticoid activity of hydrocortisone with much less mineralococorticoid activity.
The most important naturally secreted mineralocorticoid is aldosterone while fludrocorti- sone is a well known synthetic analogue. Fludrocortisone is given with hydrocortisone in the replacement therapy of Addison’s disease.
Pharmacological dose of the glucocorticoids are used-
(i) in the treatment of lymphomas and leukaemias;
(ii) as immunosuppresives to prevent rejection in tissue and organ transplanta- tion;
(iii) to suppress or modify allergic reactions and therefore provide relief in asthma allergic skin diseases, nephrotic syndrome, auto-immune haemo- lytic anemia, thomboacy-topenic purpura, etc;
(iv) as anti-inflammatory therapy in a variety of conditions including rheuma- toid arthritis;
(v) rheumatic fever, active chronic hepatitis, severe inflammatory conditions of the eye and skin, etc.;
(vi) to save life in septicaemic shock before specific measures can take effect.
For maintenance oral treatment of conditions requiring pharmacological doses of gluco- corticoids, prednisolone is the drug of choice. Dexamethasone and betamethasone are satis- factory alternatives but being more potent than prednisolone they are particularly useful where very high doses of prednisolone would have been required. They are also used in local condi- tions of the eye and skin.
Adverse effects.–Corticosteroids are toxic drugs and great caution should be exercised when using them because of the wide variety and potential seriousness of the adverse effects. The following adverse effects can occur when varying degrees of severity on prolonged use-
1. Superinfection and reactivation of latent infections.
2. Muscle weakness and myopathy.
3. Diabetes mellitus.
5. Salt and water retention.
6. Psychotic reaction.
7. Hirsutism and menstrual disturbances.
9. Cushingoid appearance.
10. Retardation of growth in children.
11. Reactivation of a latent peptic ulcer.
Corticosteroid withdrawal.-Prolonged use of high doses of corticosteroids leads to suppression of the adrenal cortex due to negative feedback inhibition of corticotrophin (ACTH) secretion by the anterior pituitary. Abrupt withdrawal of a corticosteroid after long term use in high doses would therefore lead to signs and symptoms of adrenocortical insufficiency. To avoid this, corticosteroids should be withdrawn gradually with progressive reduc- tion of doses over severel weeks to allow the reactivation of the pituitary-adrenal axis.
DEXAMETHASONE Dosage forms.-Tablets, 0.5 mg. and 4 mg. Injection, 2 mg’/in 2 ml. ampoules.
Pharmacological properties.-Very potent glucocorticoid with minimal mineralocorti-
Uses.-Suppression of inflammatory and allergic disorders. Adverse effects.-See above.
Dosage.-Oral: 0.5-2 mg. daily in divided doses; up to 15 mg. daily in severe diseases; By injection: i.m., or slow i.v. injection or infusion: initially 0.5-20 mg. Children,
0.2-0.5 mg./kg. daily.
Dosage forms.-Injection, powder in 100 mg. vial (as sodium hemisucinate): Tablets, 10,20 mg.
Pharmacological properties.-Naturally occurring glucocorticoid with some mineralo-
Uses.-Adrenocortical insufficiency, (with tludrocortisone)- Shock;
Suppression of inflammation and allergy; Adverse effects.-See above. Precaution.-See above.
Dosage.-Oral: for replacement therapy only, 20-30 mg. daily in divided doses;
i.m. injection or slow i.v. injection or infusion: 100-500 mg. 3-4 times in 24 hours or as required.
PREDNISOLONE Dosage form.-Tablets, Img., 5mg.
Pharmacological properties.-Synthetic corticosteroid with high glucocorticoid but low mineralocorticoid activity.
Uses.-Suppression of inflammatory and allergic disorders. Treatment of lymphomas
Adverse effects.-See above. Precaution.-See above.
Dosage.-Oral: up to 45 mg. daily in divided doses.
8.2 Androgens.-Androgens are the male sex hormones. They are produced mainly in the testes and, to a less extent, in the adrenal cortex, under the influence of interstitial cell stimulating hormone (same as follicle stimulating hormone) of the anterior pituitary. Testos- terone is the main naturally secreted androgen. The unmodified compound is rapidly metabo- lised and is therefore unsuitable for clinical use. Esterification prolongs the duration of action.
Androgens have two main classes of action-
(i) development and maintenance of the male secondary sexual characteris- tics, the male sex organs and related structures; and
(ii) anabolic effects.
Androgens are used as replacement therapy in hypogonadism. They would thus induce sexual development in boys when puberty is delayed, and would restore potency and libido in adults who have developed androgen deficiency. Androgens are of no value in the treatment of impotence unless the impotence is a manifestation of hypogonadism.
Although androgens improve sexual function in hypogonadism, fertility is not restored.
Restoration of fertility is possible only if the seminiferous tubules of the testes are functional and would then need to be stimulated with gonadotrophins.
The discovery of the anabolic effects of testosterone led to the synthesis of a group of drugs known as the anabolics steroids in which the anabolic effect is predominant. Norethan- drolone is a well known example of this group of drugs. They have many adverse effects in- cluding sodium retention and cholestatic jaundice. They are also subject to abuse especially by athletes. Their clinical usefulness is limited.
Dosage form.-Injection, 200 mg. (enanthate) in 1 ml. ampoule; 25 mg. (Propionate) in
1 rnl. ampoule.
Pharmacological properties.-Masculinising hormone with some anabolic effects. Uses.-Hypogonadism.
Adverse effects.-Oedema, increase in weight, premature closure of epiphyses in early puberty, masculinisation in women.
Dosage.-Enanthate: Initially 200 mg. every 2-3 weeks, maintenance 200 mg. every 3-6 weeks, by intramuscular injection. Propionate: 10-50 mg., 2-3 times weekly, by i.m.
8.3 Oestrogens.-Oestrogens are the female sex hormones. They are produced mainly in the ovary and placenta. Oestrogens are responsible for the development of the female sec- ondary sexual characteristics and have important effects on the cyclic endometrial changes that are a feature of the menstrual cycle. There are two main groups of oestrogens-
(i) the naturally occurring steroid hormones and their semisynthetic deriva- tives; and
(ii) the synthetic, non-steriod compounds with oestrogenic effects. The main naturally occurring oestrogens are oestrone, oestradiol and oestriol. They are rapidly metabolised, the resulting short duration of action making them unsuitable for use clinically. Ethinyloestradiol and mestranol are two orally active derivatives of the natural oestrogen, oestradiol. They are longer act- ing than the parent compound and are widely used clinically. For example, most combined oestrogen-progesterone contraceptive pills are based on the two oestrogens.
The non-steroidal synthetic oestrogens can produce all the effects of naturally occurring oestrogens in the body. They are highly effective by mouth. The best known example is stil- boestrol.
Oestrogens are widely used for menopausal and menstrual disturbances, atrophic vagini- tis, carcinoma of the prostate and breast and to suppress lactation.
ETHINYLOESTRADIOL Dosageform.-Tablets, 0.01 mg. and 0.02 mg.
Pharmacological properties.-A semisynthetic derivative of the naturally occurring oestrogen, oestradiol.
Uses.-Menopausal symptoms. Primary amenorrhoea. Contraception (combined with a progestogen). Carcinoma of the breast and prostate.
Adverse effects.-Nausea and vomiting, weight gain, salt and water retention, jaundice, breast enlargement and tenderness, withdrawal bleeding, depression, headache.
Contra-indication.-Oestrogen-dependent carcinoma, history of thromboembolism, he- patic impairment.
Dosage.–0.10-0.05 mg. 1-3 times daily depending on diagnosis.
8.4 Progestogens.-Progesterone is the main naturally occurring progestogen. It is pro- duced by the corpus luteum and the placenta. It apparently has two main physiological roles-
(i) it induces secretory changes in the endometrium in the luteal phase of the menstrual cycle; and
(ii) it maintains pregnancy after implantation of the ovum.
Progesterone itself is insoluble and has a short duration of action. Synthetic derivatives like norethisterone and laevonorgesteral are therefore used in practice. These compounds have some androgenic effect in addition to their progestogenic effects. They are also partly metab- olised to oestrogenic substances, but this notwithstanding, they are usually administered with oestrogens to suppress ovulation for contraceptive purposes and to treat a variety of menstrual disorders.
Dosage form.- Tablet,S mg.
Pharmacological properties.-Synthetic progestogen. Uses.-Combined with oestrogens in-
(i) oral contraceptives;
(ii) the treatment of a variety of menstrual disorders, including menorrhagia, metrorrhagia, dysmenorrhoea and endometriosis.
Used alone in the treatment of- (i) threatened abortion;
(ii) carcinoma of the uterine body.
Adverse effect.-Masculinisation, liver dysfunction and jaundice, headache, depression. Contra-indication.-Pregnancy.
Caution.-Should not be used for undiagnosed vaginal bleeding. Dosage.-5-10 mg., 1-3 times daily depending on the diagnosis. 8.5 Oral Contraceptives.-Contraceptive pills are of three types-
(i) progestogen-oestrogen combinations;
(ii) sequential oestrogen-progestogen contraceptives, and (iii) low dosage progestogens.
The progestogen-oestrogen combinations are the most widely used and are the ones in- cluded in the Essential Drugs List. A number of effects contribute to the contraceptive action of these drugs. They include-
(i) inhibition of ovulation;
(ii) reduction in the volume and alteration in the quality of cervical mucus; (iii) pseudo-decidual reaction in the endometrium;
(iv) alteration of the function of the corpus luteum, if ovulation occurs.
A number of adverse effects can occur with oral contraceptives. They include; nausea and vomiting, breast tenderness, weight gain, mid-cycle “spotting”, post-pill amenorrhoea and infertility, thrombo-embolaic phenomena, ischaemic cerebro vascular disorders, hypertension and jaundice. Adverse effects appear to be less with the low-oestrogen pills.
ETHINYLOESTRADIOL PLUS LAEVONORGESTREL
Dosage form.- Tablet, 0.03 mg. ethinyloestradiol plus 0.15 mg. laevonorgestrel. Pharmacological properties.-Low-oestrogen dose combined oral contraceptive. Uses.-Contraception.
Adverse effects.-See above.
Contra-indication.-History of thromboembolic disease, acute and chronic liver disease, mammary carcinoma.
Caution.-Should be used with great care in the presence of hypertension, cardiac or re- nal disease, migraine, depression, asthma, and also in obese patients, cigarette smokers, those over 35 years, breast-feeding subjects, and those with varicose veins.
Dosage.-1 tablet at the same time each day for 21 days starting on 5th day of cycle, and repeated after a 7-day interval.
ETHINYLOESTRADIOL PLUS NORETHISTERONE Similar to ethinyloestradiol plus laevonorgestrel except-
Dosage form.- Tablet, 0.05 mg. ethinyloestradiol plus 1 mg. norethisterone.
8.6 Ovulation Inducers.-Ovulation inducers are drugs which can be used to induce ovulation and corpus luteum formation in certain cases of anovulatory infertility. The best known examples of this class of drugs are Clomiphene and human menopausal gonadotro- phin.
Clomiphene is an antioestrogen. It stimulates pituitary gonadotrophin output in women by blocking the negative feedback inhibition of gonadotrophin release by circulating oestro- gens.
In subjects with proven hypopituitarism, ovulation and orpus luteum formation can be induced with human menopausal gonadotrophin which contains both follicle stimulating hor- mone and luteinising hormone and acts directly on the ovary. Such treatment can only be given in specialised centres.
CLOMIPHENE Dosageform.-Tablet, 50 mg. (citrate).
Pharmacological properties.-Antioestrogen; stimulates the release of pituitary gona- dotrophin.
Uses.-Anovulatory infertility with normal anterior pituitary.
Adverse effects.-Ovarian hyperstimulation, multiple pregnancies, menopausal symp- toms.
Conira-indications – Ovarian cyst, abnormal uterine bleeding.
Dosage.-50 mg. daily for 5 days starting on 5th day of menstrual cycle or at any time if cycles have stopped. Maximum 6 courses.
In the absence of ovulation, dose may be increased by 50 mg. amounts each month to a maximum of 200 mg. daily for 5 days.
8.7 Oxytocics.-Oxytocics are used to stimulate uterine contraction. The best known examples are oxytocin, ergometrine and prostaglandins. Oxytocin is a posterior pituntary hormone. It causes rhythmic contraction of the uterus and is used to induce labour at term or to augment uterine contraction. In larger doses it can be used at the third stage of labour to control postpartum bleeding.
Ergometrine causes sustained contraction of the uterus. Prostaglandins also cause sus- tained contraction of the uterus. They are useful-
(i) in the induction of abortion, including missed abortion and hydatidiform mole;
(ii) in induction of preterm labour in which they are more effective than oxyto- cin; and
(iii) to a less extent in the induction of labour at term.
Dosage forms.-Tablet, 0.5 mg. Injection 0.5 mg/ml. in 1 rnl. ampoule. Pharmacological properties.-Ergot alkaloid, causes sustained contraction of the uterus. Uses.-
(i) Prophylaxis of postpartum haemorrhage; (ii) Treatment of postpartum haemorrhage;
(iii) Control of bleeding due to incomplete abortion.
Adverse effects.-Vasoconstriction, transient hypertension.
Contra-indications -Pus: and second stages of labour; vascular disease; impaired hepatic and renal function.
Precaution.-Extra care must be taken in patients with hypertension, toxaemia, sopsis, cardiac disease and multiple pregnancy.
Dosage-Oral: 0.5-1 mg.;
Intramuscular injection; 0.2-0.5 mg.; Intravenous injection: 0.1-0.5mg.
OXYTOCIN Dosage form.-Injection, 5 and 10 units/ml
Pharmacological properties.-Posterior pituitary hormone. Polypeptide, therefore inef- fective by mouth. Rapidly metabolised.
(i) Induction and augmentation of labour;
(ii) Management of missed or incomplete abortion;
(iii) Prophylaxis of postpartum haemorrhage (withergometrine);
(iv) Control of atonic postpartum haemorrhage.
Adverse effects.-High doses may cause violent uterine contraction which may lead to rupture; subarachnoid haemorrhage.
Contra-indications.-Hypertonic uterine inertia, obstructed labour, failed rial of labour, severe toxaemia, foetal distress, placenta praevia.
Precaution.-Extra care should be taken in patients with hypertension and therefore on hypotensive drugs; multiple pregnancy; high parity and previous caesarian section.
Dosage.-By slow intravenous infusion-
(i) induction and augmentation of labour; solution containing I unit per litre, 1-3 milliunits per minute, adjusted according to response;
(ii) missed abortion: solution containing 20-40 units/litre every hour to a maximum of 200 units/litre;
(iii) control of postpartum haemorrhage: 10-20 units/litre given at a rate of 15 drops/minute, adjusted according to response.
By intramuscular injection: 5 units (plus 0.5 mg. ergometrine) at or after delivery of the
anterior shoulder for prophylaxis of postpartum haemorrhage.
Othe rs. -Prostaglandins.
8.8 Drugs used in Diabetes Mellitus.-Antidiabetic drugs fall into two groups- 8.8.1 Insulins.
8.8.2 Oral hypoglycaemic agents.
8.8.1 Insulins.-Insulin is the hormone mostly responsible for carbohydrate metabolism in the body. It is a polypeptide and is produced in the beta cells of the pancreatic islets of Langerhans. Diabetes mellitus occurs when there is absolute or relative insulin deficiency.
A good percentage of diabetics would require treatment with insulin. These incIude-
(i) those presenting in coma or precoma;
(ii) those who are underweight and ketotic;
(iii) diabetic children and others falling under the group of juvenile-onset dia- betics;
(iv) maturity-onset diabetics who have failed to respond to diet and oral hypo- glycaemic agents;
(v) patients formerly controlled with diet or oral hypoglycaemic agents devel- oping intercurrent illness or about to undergo surgery.
Insulin preparation can be sub-divided into two main groups according to their duration of action-
(i) soluble insulin; and
(ii) medium or long-acting insulins.
Soluble insulin is short-acting. It can be given intravenously in an emergency. Given subcutaneously, its action starts within 30 minutes and lasts 4-8 hours.
The medium and long-acting insulins are depot preparations from which insulin is gradually released. There are many varieties. They are longer acting than soluble insulin and so it is more convenient to stabilise patients on one or other of these preparations. They can be combined with soluble insulin but not mixed in the same syringe.
Insulins can also be classified on the basis of their source and immunogenicity into- (i) standard insulins;
(ii) purified insulins; and (iii) human insulins.
Standard insulins are derived from beef pancreas and purified by crystallisation. They are antigenic but immunological resistance to them is quite uncommon. The antigenic proper- ties are caused mainly by small amounts of protein impurities, particularly pro-insulin, derived from the pancreas.
There are two types of purified insulins- (i) pro-insulin free; and
(ii) highly purified.
They have been submitted to more rigorous purification procedures to eliminate pro- insulin and other insulin precursors which are relatively more immunogenic than insulin. Highly purified insulins are obtained from pork insulin which is less immunogenic than beef insulin. Consequently, standard insulins are usually more immunogenic and slightly longer acting than their highly purified equivalents.
The dose requirement for highly purified insulins are lower than for standard insulins.
Allowance should be made for this when transferring a patient from the latter to the former. Highly purified insulins provoke fewer allergic reactions; do not cause fat necrosis at injection sites, and do not form IgG insulin antibodies which can cross the placenta and reach the foetus during pregnancy.
Recently, insulin with human amino-acid sequence has been produced by modification of the porcine insulin and by biosynthesis. Human insulins do not appear to have any advan- tage over highly purified insulins.
(Soluble Insulin) Dosage form.-Injection, 40, 80 units per millilitre. Pharmacological properties.-Short-acting insulin. Uses.-Diabetes mellitus; diabetic coma.
Adverse effects.-Hypoglycaemia, local reaction at injection site.
Dosage.-By subcutaneous, intramuscular or intravenous injection: variable, depending on patient’s state.
INSULIN ZINC SUSPENSION (LENTE) Dosage form.-Injection, 40, 80 units/m!.
Pharmacological properties.-Long-acting insulin made up of three parts of Insulin zinc
suspension (Semilents) and seven parts of Insulin zinc suspension (sultralente).
Adverse effects.-As for soluble insulin.
Dosage.-By subcutaneous injection: according to patient’s need.
8.8.2 Oral Hypoglycaemic Drugs.- There are two classes of oral hypoglycaemic drugs: 18.104.22.168 Sulphonylureas.
Sulphonylureas stimulate the release of insulin from the pancreas. Some residual func- tional islet tissue is therefore essential for their action. Chlorpropamide is a widely used ex- ample of this group. Other sulphonylureas are satisfactory alternatives. Glibenclamide is one of the most recent of these.
The biguanides can act in the absence of residual functioning islet tissue. They promote peripheral utilisation of glucose. These compounds can lead to lactic acidosis. Of the two best known members of the group, phenformin and metformin, the former is far more likely to cause lactic acidosis and its use is no longer recommended.
Oral hypoglycaemic agents are indicated in maturity onset diabetics who have failed to respond to dietary measures alone.
CHLORPROPAMIDE Dosageform.-Tablet, 250 mg.
Pharmacological properties.-Long-acting sulphonylurea. Uses.-Maturity-onset diabetes mellitus.
Adverse effects.-Hypersensitivity reactions; alcohol induced facila flushing; hypogly- caemia.
Drug interaction.–Can be displaced from protein binding sites by other drugs that are extensively protein-bound leading to potentiation of its effect.
Dosage form.- Tablet, 500 mg. Pharmacological properties.-Biguanide. Uses.-Maturity-onset diabetes mellitus. Adverse effects.-Lactic acidosis.
Dosage.-500 mg. every 8 hours up to a maximum of 3 g. per day. Others.-Glibenclamide, Gliclazide.
8.9 Thyroid and Anti-Thyroid Drugs.-These include- 8.9.1 Thyroid hormones.
8.9.2 Antithyroid drugs.
The thyroid gland secretes two hormones: thyroxine (T4) and triiodothyronine (T2). T3 is about four times more potent than T4, but it is more usual to use T4 in replacement therapy of hypothyroidism.
In hypothyroidism there is excessive production of the thyroid hormones. Treatment is aimed at reducing the synthesis and release of these hormones. This can be achieved by using a variety of drugs like potassium perchlorate which blocks the uptake of iodine by the thyroid gland or carbimazole and propylthiouracil which block the iodination of tyrosine in the gland. Iodine and iodides cause inhibition of the release of T3 and T4 from the gland.
This effect is transient. These drugs are therefore used in the preparation of patients pre- viously made euthyroid with other drugs, for surgery. Radioactive iodine is also useful in the treatment of thyrotoxicosis, but it can only be used in specialised centres and is contra- indicated in children and women in the child-bearing age. Carbimazole and the iodine plus potassium iodine preparation are the antithyroid drugs described here.
Beta-adrenoceptor blocking drugs like propronolol can reduce the heart rate, anxiety and other authonomic manifestations of hyperthyroidism. They are therefore useful adjuncts to treatment with antithyroid drugs.
8.9.1 Thyroid Hormones
ENIXORYHT LDosage form.- Tablets, 0.05 mg., 0.1 mg. (sodium salt).
Pharmacological properties.-Iodine–containing amino acid component of the thyro- globulin protein, responsible for the maintenance of the body’s normal basal metabolic reac- tion rates.
Adverse effects.-Arrhythmias, angina, restlessness. Contra-indications.-Breast feeding, cardiovascular disorders. Dosage.-Oral, maintenance: 50-300 micrograms daily. Children, 2.5-5 micrograms/kg initially.
8.9.2 Antithyroid Drugs
Dosage form.- Tablets, 5 mg.
Pharmacological properties.-Inhibits the enzyme responsible for the iodination of tyro-
sine in the thyroid gland.
Adverse effects.-Rashes, blood dyscrasias.
Dosage.-Starting dose: 30-60 mg. daily depending on severity. Continue until patient is euthyroid, then maintenance dose: 5-15 mg. daily.
AQUEOUS IODINE SOLUTION
Dosage forms.-Solution containing: iodine 5%, potassium iodine 10% in purified wa- ter, freshly boiled and cooled, total iodine 130 mg./ml.
Pharmacological properties.-Inhibits release of T3 and T4 from thyroid gland, and re- duces vascularity of the gland thus making surgical removal easier. Effects continue for only 3-4 weeks.
Uses.-Pre-operative treatment of thyrotoxicosis.
Adverse effects.-Hypersensitivity reactions with coryza-like symptoms. Goitre in in- fants of mothers taking iodides.
Caution.-Iodine should not be used for long-term treatment.
Contra-indication.-Breast feeding. Dosage.-O..I-O.3 ml. 3 times daily.
Others.-Propranolol, Propylthiouracil, Radioactive Sodium Iodide.
9. Anti-infective drugs
Anti-infective drugs are described under the following headings- 9.1 Amoebicides.
9.3 Antifilarial drugs.
9.4 Antischistosomal drugs. 9.5 Antitrypanosomal drugs. 9.6 Antimalarial drugs.
9.7 Antiflagellate drugs.
9.8 Antibacterial drugs.
9.9 Antileprosy drugs.
9.10 Antituberculosis drugs. 9.11 Systemic antifungal drugs.
9.1 Amoebicides.-Amoebiasis is caused by Entamoeba hystolytica. Three clinical cate- gories are recognised-
1. Acute amoebic dysentery due to invasion of the wall of the large bowel causing severe ulcerati ve lesions.
2. Extra-intestinal amoebiasis in which the amoebae find their way to the tissues causing abscesses. The most common extra-intestinal site is the liver; less common sites are the lungs, brain and other tissues.
3. Chronic amoebiasis in which the amoebae live in the intestine without causing any symptoms. The patients are diagnosed by the passing of amoebic cysts in the stool.
Metronidazole is effective in all forms of amoebiasis. Other drugs which are currently found useful in amoebiasis are.
Chloroquine, which is particularly useful in hepatic amoebiasis and diloxanide which is used in chronic intestinal amoebiasis:
Dosage forms.-Tablet, 200 mg.; injection, 500 mg./lOO ml. for i.v. infusion. Pharmacological properties.-A nitromidazole with a direct action on protozoa and naerobic bacteria.
Uses.-Amoebiasis: acute invasive amoebic dysentery and extra-intestinal amoebiasis.
Relatively ineffective in cyst passers. Trichomoniasis: urogenital infection in both males and females.
Infections due to anaerobic bacteria: Treatment and prophylaxis of surgical and gynae- cological sepsis due to colonic anaerobes, particularly Bacteriodes fragilis. Other conditions successfully treated include brain abscess, osteomyellitis, necrotising pneumonia.
Adverse effects.-Metallic taste is common, otherwise metronidazole is well tolerated.
Precaution.-Alcohol should be avoided during treatment.
Drug interaction.-Disulfirman-Iike reaction with alcohol; effect of oral anticoagulants potentiated.
Dosage.-For amoebiasis, 400-800 mg. three times daily for 5-10 days. For trichomo- niasis, 200 mg. three times daily for 7 days. For giardiasis, 2 g. as a single dose for 3 succes- sive days. For anaerobic infections, 0.5 g. by i.v. infusion 8 hourly until oral administration is possible, then 400 mg. three times daily for up to 7 days.
For children: 5-10 years, Y2 adult dose; 6 months-I year, 1,4 the adult dose.
9.2 Anthelmintics.-The term helminth refers to nematodes (round worms) as well as trematodes and cestodes. In this discussion, however, anthelmintics will deal with drugs used in predominantly intestinal helminthiasis. Drugs used in the predominantly tissue helminthia- sis (i.e. filariasis and schistosomiasis) will be treated under separate headings.
The helminthic infections for which these drugs are usually indicated include- Round worm: caused by Ascaris lumbricoides;
Pin worm: caused by Enterobiu vermicularis;
Hook worm: caused by Ancylostoma-avodenale or Necator ;americanus- Tape worm: caused by Taenia saginata or Taenia solium;
Thread worm: caused by Strongyloides stercoralis;
Whip worm: caused by Trichuris trichuria;
Guinea worm: caused by Dracunculus medinensis.
Some of the anthelmintic drugs are specific for particular infections (e.g. niclosamine for tapeworm) while others are broad spectrum drugs effective for most of the infections (e.g. mebendazole and thiabendazole).
MEBENDAZOLE Dosage forms.-Chewable tablet, 100 mg.; suspension, 100 mg./5ml. Mode of action.-Broad-spectrum anthemintic.
Uses.-Trichuriasis, ascariasis, enterobiasis, and hookworm in single or mixed infec- tions.
Contra-indication.-Should be avoided in early pregnancy since embryotoxicity and teratogenicity have been demonstrated in animal studies.
Caution.-In heavily parasitised young children, ascaris worms are occasionally ex- pelled through the nose and mouth during treatment.
Adverse effects.-Remarkably well tolerated at therapeutic doses.
Dosage.- The same dose is used for all patients over’ 2 years of age. For ascariasis, a single dose of 100 mg.; for hookworm and trichuriasis, 100 mg. twice daily on 3 consecutive days; for enterobiasis, 100 mg. repeated after an interval of 2 weeks.
NICLOSAMIDE Dosage form.-Chewable, tablet 500 mg.
Pharmacological properties.-An anthelmintic specific for tapeworms. Parasites af- fected by the drug are more susceptible to the gut proteolytic enzymes, hence portions of the worm are avoided in partially digested form and the scolex is rarely identifiable. The eggs are not so affected thus exposing the patient with T. solium infection to the risk of cysticercosis.
Uses.- Treatment of tapeworm infections.
Dosage – A single dose of 2 g. in adults, 1 g. in children 2-6 years, 500 mg. in children under 2 years.
Precaution.-In T. solium infection, a purgative should be given 2 hours after dosage.
Dosage form – Tablet, 500 mg. (adipate or citrate). Elixir or syrup 500 mg./5 ml. Pharmacological properties.-Anthelmintic effective in ascariasis. Paralyses the worms
by competitive antagonism of actylcholine at the neuromuscular junction.
Adverse effect.-Transient skeletal muscle weakness may occur.
Dosage.-As a single dose, Adults 4 g. (hydrate); Children, 120 mg./kg. up to a maxi- mum of 2-3 g. (hydrate).
Dosage forms.-Chewable tablet, 125 mg. (pamoate). Syrup, 125 mg./mt. (pamoate). Pharmacological properties.-A depolarising neuromuscular blocker, it produces spas- tic paralysis in susceptible helminths.
Uses.-For single or mixed helminthic infections involving; ascaris, enterobius and hookworm.
Precaution.-Causes transient elevation of SOOT and should therefore be used with care in patients with liver disease.
Adverse effects.-Well tolerated.
Drug interaction.-May be mutually antagonistic to piperazine because of their oppos- ing modes of action.
Dosage.-For ascariasis, a single dose of 10 mg./kg. up to 1 g. for hookworm, this dose is repeated after 24-28 hours.
Dosage form.-Chewable tablet, 500 mg. Syrup, 500 mg./5 rnl.
Pharmacological properties.-Well absorbed, broad-spectrum anthelmintic; active against adult and larval forms of some tissue nematodes.
Uses.-Stronglyloidiasis, cutaneous larva migrans, dranontiasis, trichiniasis. Pyrantel and mebendazole are preferred for the other nematode worm infections because of the high incidence of adverse drug reactions to thiabendazole.
Adverse effects.-Occurs in about 50% of patients. Commonly, dizziness and gastroin- testinal upset. Less commonly, drowsiness, headache, pruritus and hypersensitivity reactions. Occasionally, tinnitus, collapse, disturbance of vision, hepatic dysfunction.
Contra-indication.-Previous hypersensitivity reaction to thiabendazole. Caution.-Liver and renal function should be monitored and patients should refrain from driving or operating machinery during treatment.
Dosage.-For dracontiasis, 50-lOO mg./kg. in 2 divided doses; may be repeated after 7 days. For strongyloidiasis and trichiniasis, 25 mg./kg. daily in 3 divided doses for 5 days.
Others.-Other anthelmintic drugs in use are; Bephenium hydroxynaphthoate, Levarni- sole and Niridazole.
9.3 Anti-Filaria! Drug.-The filarial diseases commonly encountered in Nigeria are:
I. Onchocerciasis – caused by Onchocerca volvulus, is transmitted by Simulium spp and causes severe dermatitis and blindness.
2. Loaiasis–caused by Loa loa and is transmitted by Chrysops spp. The microfilariae are present in the circulating blood. The adult worms migrate in subcutaneous tissues caus- ing Calabar swellings.
DIETHYLCARBAMAZINE Dosage form.-Tablet, 50 mg. (citrate). Uses.-Loaiasis-radical cure. Onchocerciasis-microf1laricidal effect only.
Dosage regime.-Loaiasis: 9 mg./kg. daily for 10 days.
Onchocerciasis: 25 mg. initially, doubled on successive days to 100 mg. twice daily on day 4. Then 200 mg. daily until microfilatialload in the skin approaches zero.
Adverse effects.- Mazzotti reactions in onchocerciasis patients.
Precautions.- Care should be taken in bases with eye involvement. The intensity of Mazzotti reactions can be reduced by small initial dose and steroid cover.
NIMARUS Dosage form.-Powder for injection, I g vial.
Pharmacological properties.-Does not penetrate into the CSF. It is excreted unchanged in the urine.
Uses.-Onchocerciasis-Kills the adult worms African trypanosomiasis-early haemo- lymphatic stage only.
Adverse effects.- Toxic drug, poorly tolerated. Albuminuria, stomal ulceration, severe diarrhoea, postration occur quite commonly.
Dosage regimen.-IO% aquenous solution given by slow i.v. injection. Onchocerciasis: successive weekly doses of 0.2,0.4,0.6,0.8, 1.0 and 1.0g (i.e. total of 4.0 g.).
Trypanosomiasis.-I g. on days 1,3,7,14and 21 followed by Ig. weekly for 5 weeks.
If there is CNS involvement:- 250-500 mg. 2-4 times on alternate days before starting melarsoprol.
Precaution.-Because collapse has occasionally occurred during the first injection of the
drug, a test dose of 0.2 g. in 2 ml. should be given as follows-
(i) inject a few microlitres and wait 1 minute; (ii) inject 0.5 ml. and wait Iminute;
(iii) inject the remainder over Iminute.
9.4 Anti-Schistosomal Drugs.-In Nigeria, schistosomiasis is caused by one of two dif- ferent species of Schistosoma. They are-
I. Schistosoma haeatobium.-This is the cause of urinary schistosomiasis. The adult worms lodge in the venous plexuses of the bladder wall. Some of the eggs are passed in urine, others are retained in the tissues causing irritation, ulceration, fibrosis granuloma and papilloma formation.
2. Schistosoma mansoni.-This is the cause of intestinal schistosomiasis. The adult worms lodge in the branches of the inferior mesenteric veins in the wall of the large bowel, and deposit many eggs there. Some of these eggs reach the bowel, lumen and are passed in
the faeces. Others remain in the wall of the bowel causing inflammation, ulceration, granuloma and sometimes papilloma. Eggs that migrate to the liver induce similar irrita- tion, provoke periportal fibrosis resulting in portal hypertension.
Dosage form.-Tablet. 100 mg.
Pharmacological properties.-Organophorus anticholinesterase; effective only against
schistosoma haematobium infections.
Uses.-S. haematobium infections.
Adverse effects.-Rare; transient reduction in true and false cholinesterase occurs. Caution.-Use with care in patients Likely to be exposed to organophosphorus insecticides.
Drug interation.-Depolarising neuromuscular blockers may be potentiated. Dose.-7.5 mg./kg. on three occasions at intervals of 2 weeks.
Dosage form.-Capsule, 250 mg.
Pharmacological properties.-A tetrahydroquinoline derivative with selective activity against Schistosema mansoni. Male schistosomes are more susceptible than females but resid- ual female worms cease to lay eggs and lose pathological significance.
Uses.-S. mansoni infections.
Adverse effects.-Mild and transient dizziness and drowsiness occurs in one third of pa- tients. Hallucinations, psychic excitement and epileptiform convulsions have been reported very occasionally. Minor elevation of serum transaminases occur in a small proportion of cases.
Dose.-15 mg./kg. daily for 1-3 days.
Dosage form.-Tablet, 600 mg.
Pharmacological properties.-Highly active against all species of schistosomes patho- genic to man. Induces a sustained contraction of the worms followed by a rapid liver shift and subsequent vacuolisation and disintegration of the tegument.
Uses.-Double infection with S. haematobium and S. mansoni. Adverse effects.-Well tolerated.
Dose.–40 mg./kg. as a single oral dose.
Others.-Niridazole is still in use, but it is no longer a drug of choice for any form of schistosomiasis. It is also effective against guinea worm infections (dracontiasis).
9.5 Anti-Trypanosomal Drugs.-African trypanosomiasis (sleeping sickness) is caused by either of two Trypanosoma species T. brucei rhodesiese and T. brucei gambiense. Sleeping sickness is characterised by two distinct clinical stages. The first stage is caused by invasion of the blood stream and the reticuloendothelial system by the parasites. The clinical manifes- tation of this state is marked by irregular fever, lymphadenitis, tachycardia, rashes and spleno- megaly. The second stage is due to invasion of the central nervous system and is characterised by personality changes, headache, apathy, somnolence, tremors, speech and gait disturbances, anorexia, malnutrition and finally coma and death. Pentamidine and suramin are used for the early stage of the disease while melarsoprol is used when CNS involvement has occurred.
Dosage form.-Power for injection 200 mg. (isethionate or mesylate) for i.m. or i.v. use. Pharmacological properties.-Diamidine compound; poorly absorbed from the gut, therefore given parenterally. Does not enter the cerebrospinal fluid.
Uses.-African (T. gambiense and T. rhodesiense) trypanosomiasis –cases without CNS involvement, and prophylaxis in endemic areas. Visceral leishmaniasis (L donavani) or ka- laazar and cutaneous leishmaniasis in patients who are unresponsive to or intolerant of anti- mony compounds.
Adverse effects.-Occasionally, changes in blood sugar concentration and renal impair- ment.
Precaution.-i.v. route should be used only in exceptional situations because of the risk of sudden severe hypotension.
Contra-indication- Should not be used when there is also CNS involvement. Dose.-For African trypanosomiasis: Treatment, 7-15 injections of 300 mg. i.m. or 4 mg./kg. i.m., daily or on alternate days. Prophylaxis, 300 mg. i.m. every 3-6 months.
MELARSOPROL Dosage form.-Injection, 3.6% solution in propylene glycol.
Pharmacological properties.-Organic arsenical compound, insoluble in water, given intravenously. Attains trypanocidal concentrations in the CSF. Largely metabolised into non- toxic pentavalent compounds.
Uses.-African trypanosomiasis: meningoencephalitic stage.
Adverse effects.-Reactive encephalopathy; hypersensitivity reactions.
Dosage regimen.-3.6 mg./kg. by slow intravenous injection, daily for 4 days. Course may be repeated once or twice at intervals of 7-1 0 days.
Precaution.-Parasites should first be eliminated from the haemolymphatic system with suramin before treatment with melarsoprol.
SURAMIN [See section 9.3.]
9.6 Anti-malarial drugs.-Malaria, in Nigeria, is caused by three species of Plasmiodium- P, .fulciparumP. malariae and P. ovale. Of these, P.fulciparum is responsible for over 95% of infections. P. vivax malaria does not occur in Nigeria.
Anti-malarial drugs are used to achieve a variety of clinical objectives-
I. Clinical cure.- This refers to the cure of a clinical attack. The drugs used for this pur- pose are those which attack the erythrocytic stage of the parasite, the so-called blood schizonticidal drugs. The main drugs under this category are the 4-aminoquinolines (ex- emplified by chloroquine and amodiaquine), quinine and pyrimethamine sulphadoxine- combination.
2. Radical cure.-Refers to the elimination of the exo-erythrocytic forms. This is only ap- plicable in P. vivax in which true relapses from hepatic hypnozoites occur. Since P. vivax infections are not seen in Nigeria, the need for radical cure does not arise. The drug used for radical cure is primaquine.
3. Prophylaxis.-Suppresive prophylaxis is the suppression of the disease in the erythyro- cytic stage. The drugs used are pyrimethamine, proguanil and those used for clinical cure.
Dosage forms.- Tablet, 150 mg. (base phosphate or sulphate). Syrup, 50 mg. Base/5 ml. (phosphate or sulphate). Injection, 200 mg. in 5 ml. ampoule (as the sulphate).
Pharmacological properties.-A 4-aminoquinoline anti-malarial. It is active against the sexual erythrocytic stage of all Plasmodia species. It is also amoebicidal and is useful (in combination with other anti-amoebic drugs) in the treatment of hepatic amoebiasis. It has anti- inflammatory properties and is useful in the treatment of rheumatoid arthritis and discoid lupus erythematous, the treatment of which employs large doses for long periods, hence asso- ciated with more adverse reactions.
Uses.–Clinical cure of malaria. Prophylaxis of malaria. Hepatic amoebiasis. Rheuma- toid arthritis and discoid lupus erythematrosus.
Adverse effects.-Itching; retinopathy in prolonged use.
Dosage.- For treatment of acute malaria: Adults: 600 mg. first and second days, 300 mg. third day. It is often not necessary to continue beyond the first day. Children: 10 mg./kg. first and second days; 5 mg./kg. third day.
PYRIMETHAMINE Dosageform.-Tablets, 12.5 and 25 mg.
Pharmacological properties.-An antifolate. Has weak action against primary pre- erythrocytic and erythrocytic forms of plasmodia. Kills the primary exo-erythrocytic parasites.
Uses.-Prophylaxis of malaria for special groups, e.g. pregnant women, children under 5 years, sicklers.
Dosage.-Adult: 25-50 mg. weekly. Children: 5- IO years, 12.5 mg. weekly. Under 5 years, 6.25 g. weekly.
Dosage form.- Tablets, 25 mg. pyrimethamine plus 500 mg. sulphadoxine; Syrup, 25 mg. pyrimethamine plus 500 mg. sulphadoxine in 5 ml.; Injection, 20 mg. pyrimethamine plus 200 mg. sulphadoxine in 2.5 m\. ampoule.
Pharmacological properties.-Sulphadoxine is a long-acting sulphonamide. It potenti- ates the anti-malarial activity of pyrimethamine, the combination being highly active against the erythrocytic forms of Plasmodia.
Uses.-Clinical cure of acute malaria.
Adverse effects.- Rashes, prolonged use may lead to folic acid deficiency.
Dosage.-A single dose of: Adults: 3 tablets. Children: 9-14 years, 2 tablets. 4-9 years 1 tablet, under 4 years, tablet.
Others.-Other widely used drugs, amodiaquine, proguanil, quinine, and the newly in- troduced drug, mefloquine, can be used as alternatives to chloroquine in the treatment of choloroquine-resistant faIciparum malaria.
9.7 Anti-flagellate Drugs.- The two flagellate protozoa of clinical importance in Nigeria are Trichomonas vaginalis and Giardia Lamblia. Metronidazole is the drug of choice for both infections. Patients who fail to respond satisfactorily to metronidazole can be given tinidazole.
METRONIDAZOLE [See section 9.1.]
Dosage forms.-Tablet, 500 rng.; Intravenous infusion, 2 mg./ml. in 400 ml. bottle. Pharmacological properties.-Similar to metronidazole but has a longer duration of ac- tion, and can therefore be given less frequently.
Uses.-Protozoal and anaerobic infections as for metronidazole.
Precautions.-It should not be given to nursing mothers or in the first trimester of preg- nancy.
Dosage.-By mouth: 2 g. initially followed by Ig. daily, or 500 mg. twice daily, for 5-6 days.
By intravenous infusion: 800 mg. daily until treatment by mouth can be given.
9.8 Antibacterial Drugs.-Antibacterial drugs are agents which interfere with bacterial growth and reproduction (bacteriostiatic agents) or survival (bactericidal agents) at concentra- tions or at doses which do not notably affect the functions of the human body. Antibacterial activity may be due to interference with processes occurring only in the bacteria, or processes occurring both in human cells and in bacteria.
Spectrum.-Every antibacterial agent is effective only against a limited number of species of micro-organisms. Ideally, therefore, antibacterial drugs should be given only after identification of the micro-organism responsible for an infection and determination of its sen- sitivity against antibacterial agents. In practice, however, antibacterial drugs are often given on the basis of the clinical features of an infection and the known local sensitivities of micro- organisms to antibacterial drugs. When necessary, culture and sensitivity tests should be per- formed to aid the choice of antibacterial drugs.
Resistance.-Resistance to antibacterial drugs may develop in species and strains origi- nally sensitive. Resistance may be due to-
I. the selection of resistant mutants in the presence of the antibacterial agent;
2. the transmission of DNA from resistant to originally sensitive bacteria by bacteriophages (transduction);
3. the incorporation into originally sensitive bacteria of resistance-conferring DNA from the environment into which this DNA may have been excreted by other bacteria (trans- formation), or
4. the transfer of DNA coding for resistance factors from resistant to primarily non-resistant bacteria by a sex pilus or bridge (conjugation).
The last mechanism is responsible for the transfer of resistance to intestinal, mainly gram-negative bacteria.
Bacteria may also become resistant by learning to synthesise enzymes inactivating the antibacterial drug, or by developing metabolic mechanisms insensitive to a drug. Resistance may develop rapidly, usually in a step-wise fashion or slowly and continuously. The devel- opment of resistance may sometimes be delayed by combining several antibacterial drugs which act on the same bacteria by different mechanisms.
Elimination.-Most antibacterial drugs are eliminated either by the kidneys or by the liver. Some are metabolised by the liver before excretion. Drugs excreted by the kidneys will accumulate in the body in renal failure and their dosage must therefore be reduced; these drugs also may become less effective against infections of the urinary tract in the presence of renal failure because their concentration in the urine falls to low levels. Similarly, drug mainly
metabolised or excreted by the liver will accumulate in severe liver disease unless the dosage is reduced but they will also become effective against infections of the liver itself or of the biliary tract.
Combination therapy.-Different antibacterial agents are often combined in the treat- ment of infections. Such combinations are warranted if a patient is infected with several species of pathogenic micro-organisms. In some circumstances the combination of several antibacterial drugs may delay the appearance of resistant strains. There are, however, only very few examples in which synergistic action of different antibacterial drugs against one spe- cies of micro-organisms has been demonstrated to be clinically significant. Thus, combina- tions of benzylpenicillin with streptomycin are more effective than penicillin alone in entero- coccal endocarditis and also in endocarditis caused by Streptococcus viridans. Pseddomonas infections in patients with neutrophenia may effectively be treated with the combination of carbenicillin and an aminoglycoside antibiotic. A combination of sulphamethoxazole and tri- methorprim is effective in many infections, some of which are not sensitive to either the sulpho- mamide or trimethorprim. Finally, the most effective treatment of brucellosis is the combina- tion of tetracycline and streptomycin. A combination of two antibacterial agents may, how- ever, be less effective than a single agent. For example, a combination of penicillin and chlor- amphenicol is less effective against pneumococcal meningitis than penicillin alone. A combination of penicillin and tetracycline is less effective than penicillin alone in severe pneumo- cocccal pneumonia.
Elimination of one infection by antibacterial drugs may sometimes induce superinfection with either other bacteria or fungi or other micro-organisms not sensitive to the drug used.
Administration.-For practical reasons, antibacterial agents should be given orally whenever effective plasma concentrations can be obtained by this route. When antibacterial drugs are given by mouth, they should preferably be given on an empty stomach, i.e. some- time before meals, in order to ensure maximal absorption from the gut. Drugs which tend to irritate the stomach should be given with or after meals, even if this entails some loss of activ- ity. Antibacterial drugs should not be given with bicarbonate or with milk in order to diminish gastric discomfort because this procedure could decrease their effectiveness due to decreased absorption.
Non-absorbed antibacterial agents should be given parenterally, and parenteral routes may be preferable for absorbed agents in severely ill patients. Whatever the route of admini- stration, doses and dosage intervals are usually selected in a manner to obtain persistent, con- stant, bacteriostatic or bactericidal plasma concentration of the drug.
Duration of treatment.-Treatment with antibacterial agents should be continued after the disappearance of the symptoms and signs of disease until such a time when it may be rea- sonably expected that the pathogenic micro-organisms are eliminated. Therefore, treatment with antibacterial agents should be continued for at least some days after the disappearance of symptoms. During this time, full doses of the antibacterial agent must be given. There is no rational justification for the widespread attitude of decreasing the doses of antibacterial agents after the disappearance of symptoms of a bacterial infection.
Age.- The doses and the use, in general, of an antibacterial agent, often depend on the age of the patient. In the newborn and in infants, the mechanisms of the renal and the hepatic elimination of antibacterial drugs may be poorly developed and lower doses of the drugs may be required. Similarly, elimination of antibacterial drugs may be slowed in the elderly. Ad- verse effects may be due to the characteristics of a given age; thus, tetracyclines bind to de- veloping teeth and bone and may damage the teeth and retard bone growth. In newborn in- fants, sulphonamides may displace bilirubin from protein binding and induce kernicterus.
Pregnancy.-Most antibacterial agents cross the placenta. Some of them may damage the foetus. For example, streptomysin given to pregnant mothers may induce hearing loss in the child; tetracyclines given to the mother may cause injury to their developing teeth
(tetracyclines are, furthermore, particularly toxic to the pregnant female and may induce se- vere disease of the liver or renal damage). There are few examples in which transmission of an antibacterial agent through breast feeding has damaged the child: this may, however, occur more frequently than actually known. Sulphonamides given to a breast feeding mother have induced haemolysis in children with glucose-S-phosphate-dehydrogenase deficiency, and may have induced kernicterus in infants.
9.8.1 The Penicillins.-Generally, the penicillins are bactericidal, broad-spectrum anti- biotics. They are well absorbed into body tissues and fluids, but penetrate poorly into the cerebro-spinal fluid except when the meninges are inflamed. Penicillins readily cross the pla- centa and also appear in breast milk.
Penicillins are susceptible to degradation in the body by two main processes (achemical (acid or alkaline) hydrolysis; and
(b) enzymatic degradation by the bacterial penicillinase (beta-lactamase) enzymes produced by resistant bacteria.
The choice of a penicillin drug is therefore usually influenced by two general considera- tion-
1. desired spectrum of microbial activity;
2. stability of the penicillin.
Penicillins are thus further classified into-
(a) acid (gastric)-stable, penicillinase-sensitive drugs, e.g. phenoxymethyl penicillin, ampicillin and amoxycillin, and
(b) penicillinase-resistant, also acid-stable penicillins, i.e. cloxacillin, flucloxacillin, and methicillin.
Adverse effects.-The most important adverse effect of the penicillins is hypersensitivity, which causes rashes and mild to fatal anaphylaxis. They are therefore contraindicated in patients with a history of allergic reactions to penicillin. Other serious adverse effects include encephalopathy due to cerebral irritation and gastrointestinal disorders. Crossthypersensitivity exists between all penicillins and to a lesser extent, with the cephalosporins.
As with other broad-spectrum antibiotics, prolonged treatment with oral penicillins may lead to super infections with non-susceptible bacteria or fungi, e.g. pseudomonas, proteus, candida.
Dosage form.- Capsules, 250 and 500 mg.
Powder for oral suspension, 125 mg./5 ml. Powder for injection, 250 and 500 mg. (Sedium salt) in vials.
Pharmacological properties.-Semi-synthetic, bactericidal, broad spectrum, acid-stable, penicillinase-sensitive penicilline.
Uses.-It is active against a wide range of gram-positive and gram-negative bacteria, in- cluding Salmonella typhr. It is extensively used in chest and urinary tract infections.
Adverse effects.-As for the penicillins. Additionally, maculopapular rashes, apparently not attributable to hypersensitivity or penicillin allergy, have been reported in patients with glandular fever and chronic lymphatic leukaemia.
Dosage.-Adults: Oral, 0.25-1 g. every 6 hours.
Injection, LM. or LV., 500 mg. every 4-6 hours. Children: Any route, ½ the adult dose.
BENZYL PENICILLIN Dosage form.-Injection powder in 0.6 g. (I million units) vial.
Pharmacological properties.- The first of the penicillins. It is highly active against many gram-positive and gram-negative cocci. It is acid labile and penicillinase sensitive.
Uses.-Infections by streptococci, pneumococci, gonococci, meningococci, clostridium, treponema.
Adverse effects.-Hypersensitivity reactions; encephalopthy in high doses. Contraindication.-Known hypersensitivity to penicillins.
Dosage.-f:JOO mg., 3-4 times daily, by intramuscular injection; children up to 12 years; 10-20 mg./kg. daily. Neonates, 30 mg./kg. daily.
Dosage form.–Capsule, 250 mg.; syrup 125 mg./5 ml.; injection, powder in 250 mg. and 500 mg. vials.
Pharmacological properties.-Semi-synthetic penicillin, acid-stable, and penicillinase- resistant.
Uses.–Cloxacillin should be reserved for serious infections due to penicillinase- producing staphylococci.
Dosage.-Oral 250 mg./500 mg., 6 hourly; i.m. 500 mg., every 4-6 hours; i. v. 0.5-1 g. every 4-6 hours. Children: – 1,4 Y2 adult dose.
Precaution.-Solution for injection should be used within thirty minutes and should not be mixed with blood or other protein containing fluids,
FORTIFIED PROCAINE PENICILLIN
Dosage form.-Injection, powder in 400,000 units vial, containing: procaine penicillin 300,000 units (300 mg.) and benzylpenicillin 100,000 units (60 mg.).
Pharmacological properties.-Procaine penicillin is a repository preparation of benzyl- penicillin. Fortified procaine pencillin combines the rapid onset of action of benzylpenicillin with the prolonged action of procaine penicillin.
Uses.-Treatment of benzylpenicillin sensitive infections when prolonged action is re- quired.
Dosage.-Variable, depending on the nature and severity of the infection. For acute streptococcal and pneumococcal infections, 300-600 mg., i.m., 1-2 times daily for a minimum of seven days. Higher doses are required for gonorrhoea and syphilis.
Others.-Amoxycillin and Carbenicillin.
9.8.2 The Tretacyclines.- The tetracyclines are bacteriostatic, broad spectrum antibiot- ics whose usefulness has gradually decreased as a result of increasing bacterial resistance. Absorption of tetracyclines from the gut is decreased by milk, milk products, sodium bicar- bonate, antacids, aluminium, calcium, magnesium and iron salts. These act by the formation of unabsorbable complexes with tetracycline. Concomitant administration with the above should be avoided. Tetracyclines cross the placenta and are also excreted into breast milk.
The tetracyclines are deposited in growing bone and teeth, causing permanent discolora- tion of teeth and dental hypoplasia. They should not be given to pregnant women and to chil- dren under 12 years of age.
Dosage form.- Tablet or capsule, 250 mg. (hydrochloride). Pharmacological properties.-Bacteriostatic, broad spectrum antibiotic.
Uses.-Active against a wide variety of infections caused by gram-positive and gram- negative micro-organisms. However, because of the high incidence of resistant organisms, the use of tetrarcycline should be limited to-
(i) Chlamydial infecuons=-causing trachoma (in which ophthalmological tetracycline is drug of choice), psittacosis, urethritis and lymphogranuloma venereum;
(ii) Rickettsial infections;
(iii) Mycoplasma infections of the lungs and urogenital tract;
(iv) Brucella, in which tetracyclines are generally more effective than chloram- phenicol.
Contra-indications.-Pregnancy; children under 12 years of age; pre-existing hepatic or renal damage; known hypersensitivity to the tetracyclines.
Precaution.-Should not be given in renal impairment. Absorption from the gut is re- duced by milk, milk products, antacids, aluminium, magnesium, calcium and iron salts.
Adverse effecls.-Superinfection; hepatotoxicity especially following high doses in pregnancy; aggravation of pre-existing renal insufficiency; depression of bone growth and discoloration of teeth in children.
Drug interaction.-Combination with penicillin results in reduced antibacterial activity in pneumoccal and possibly other infections.
Dosage.-500 mg., six hourly.
Others.-Other tetracyclines commonly used are; oxytetracycline, chlor-tetracycline, Doxycycline and Demeclodycline.
9.8.3 The Aminoglycosides.-The aminoglycosides are narrow spectrum, usually bacte- ricidal antibiotics. They are selectively active against aerobic gram-negative bacilli, including pseudomonas, proteus and most enterococci. Activity is greatly reduced in acidic and anaero- bic environments.
Aminoglycosides are poorly absorbed from the gut, but better absorbed from the paren- teral route and from denuded skin or wound surfaces if applied locally. They penetrate poorly into the cerebro-spinal fluid but can cross the placenta. Accumulation in body tissues may account for the ototoxicity and nephrotoxicity associated with them.
Precaution.-Ototoxicity and nephrotoxicity are the most serious adverse effects of aminoglycosides therapy. These effects are most likely to occur in the elderly, dehydrated patients, patients with renal impairment, and patients receiving one of the drugs in high doses or for prolonged periods. Patients receiving an aminoglycoside (by any route of administra- tion) should be monitored for toxicity symptoms and be under close medical supervision. The aminoglycosides are physically or chemically incompatible with many drugs including peni- cillins, the cephalosporins and erythromycin.
Dosage form.-Injection, 10 and 80 mg. in 2 m\. vials. Pharmacological properties.-As above for Aminoglycosides. Uses.-
(i) Empirical treatment of severe infections in combination with: carbenicilin (infections by Ps. aeruginosa and proteus spp.), metronidazole (if anaer- obes are also likely to be present as in post-bowel surgery peritonitis);
(ii) Enterococcal endocarditis (combined with penicillin);
(iii) Gram-negative bacillary meningitis;
(iv) Urinary tract infections due to Ps. aeroginosa unresponsive to other antibi- otics;
(v) Chest infections due to penicillin-resistant staphylococci.
Contra-indication.-Pregnancy, since it crosses the placenta.
Precaution.-Should be used with ex.tra care when renal insufficiency is present. Pa- tients should remain well hydrated during treatment, and a urinary alkalising agent should be used in urinary infections.
Adverse effects.-Ototoxicity and nephrotoxicity.
Dosage.-Intramuscular injection: 2-5 mg./kg. daily in divided doses every eight hours.
Dosing interval lengthened in renal impairment. Intrathecal injection:1 mg. daily, with 2-4 mg’/kg. daily by intramuscular injection, in divided doses every eight hours. For children: intramuscular injection up to 2 weeks-3 mg./kg. every twelve hours: 2 weeks to 12 years-2 mg./kg. every eight hours.
Others.-Other commonly used aminoglycoside antibiotics are: kanamycin neomycin and streptomycin.
9.8.4 Other Broad Spectrum Antibiotics
Dosage.-Capsule, 250 mg.; Syrup, 125 mg./5 rnl.; Injection. Powder in I g. vial.
Pharmacological properties.-Broad spectrum, bacteriostatic antibiotic. Penetrates the
CSF and crosses the placental barrier.
Meningococcal and haemophilus meningitis; Whooping cough.
Caution.-Bacause of bone marrow tox.icity, chloramphenicol should not be used as a general purpose broad spectrum antibiotic when the condition can be effectively treated by other antibiotics. Even when indicated (see uses above) prolonged or repeated courses should be avoided.
Adverse effects.-Bone marrow depression leading to a-plastic anaemia; grey baby syn- drome.
Dosage.-0.5-1 g., six. hourly, orally or by i.m. or i.v. injection.
Others.-Other broad spectrum antibiotics in use are: Cephalosporins, Erythromycin, Lincomycin and Spectinomycin.
PHTHALYSULPHATHIAZOLE Dosage form.- Tablet 500 mg.
Pharmacological properties.-Poorly absorbed sulphonamide. Use.-Acute diarrhoeas of bacterial origin.
Dosage.- 0..5-2 g. six hourly.
Caution.-Most acute diarrhoeas are not of bacterial origin and are usually self-limiting.
Essential treatment is to prevent or correct salt and water depletion by appropriate oral or intra- venous fluid replacement therapy.
Dosage form.- Tablet, 500 mg. Syrup, 500 mg./5ml.
Pharmacological properties.-Well absorbed, rapidly excreted sulphonamide. Bacterio-
Uses.-Limited use. Bacillary dysentery and urinary tract infections. Dosage.-Initially 2 g., then I g. six hourly, for adults.
Children: 6 months to Iyear, 1- 6 adult dose;
1-5 years 1/3adult dose;
6-12 years 1/2 adult dose;
13-15 years 2/3adult dose.
Dosage form.- Tablets. 400 mg. sulpharnethoxazole plus 80 mg. trimethoprim; 100 mg. sulphamethoxazole plus 20 mg. trimethoprim. Syrup, 200 mg. sulphamethoxazole plus 40 mg. trimethoprirn in 5 ml.
Pharmacological properties.-Combination of a long acting sulphonamide with a dihydro- folate reductase inhibitor, trimethoprirn. Combination is far more active against susceptible micro-organisms than the individual drugs.
Uses.-Useful against infections caused by Streptococci, Staphylococci, Pheumococci Neisseria, E Coli, Klebsiella, Proteus, Haemophilus, Salmonella, Shigella. It is particularly effective in urinary tract, respiratory tract and gastro-intestinal tract infections.
Dosage.-Usual adult dosage is 2 tablets of the stronger formulation, twice daily. Children 6 weeks-6 months 1/8,6months-6 years 1/4,6-12 years 1/2, adult dose.
Others.-Sulphaguanidine and Sulphathiazole. 9.8.6 Other Antimicrobial Drugs
ELOZADINORTEM [See section 9.1.]
NITROFURANTOIN Dosage form.-Tablets, 50 mg., 100 mg.
Pharmacological properties.- A broad spectrum synthetic urinary antiseptic. It is con- centrated in the renal tubules and excreted unchanged in the urine. It does not attain therapeu- tic concentration in the plasma or renal parenchyma.
Uses.-Urinary tract infection resistant to other drugs.
Precautions.-Not useful in acute pyelonephritis in which renal parenchymal inflamma- tion is also present. The urine should be acidified during therapy. Excessive fluid intake is not helpful since this reduces the concentration of nitrofurantoin in the urine.
Adverse effects.-Gastrointestinal irritation; intravascular haemolysis especially in sub- jects deficient in glucose-6-phosphate dehydrogenase.
Dosage.-Adults 100 mg., six hourly for a maximum period of 14 days. Children 0.5-1 mg./kg., six hourly. For prophylaxis following recurrent urinary infection: 50-100 mg. nightly.
9.9 Anti-Leprosy Drugs.-Leprosy is a communicable disease caused by Mycobacte-
rium Leprae. Four clinical forms are described-
(iii) tuberculoid; and
Three anti leprosy drugs have been described here, dapsone, clofazirnine and rifampicin.
It is now clear that treatment with dapsone alone leads to rapid emergence of dapsone resistance. Treatment should therefore be initiated with all three drugs to prevent development of resistance. Rifampicin should be continued for at least 4 weeks, clofazirnine for Iyear and dapsone for life.
In the course of treatment of leprosy especially with dapsone, reactions occur which take the form of exacerbations of the lepromatous form or of erythema nodosum leprosum in bor- derline or lepromatous forms. In both conditions the patient develops high fever, neuritis, malaise, arthralgia and high white blood cell count. This is referred to as Lepra Reaction, and is treated with corticosteroids or c1ofazimine.
DAPSONE Dosage form.-Tablets, 50 mg., l00 mg.
Pharmacological properties.-Dapsone is a sulphone, chemically related to the sul- phonamides. It is bacteriostatic or weakly bactericidal against M. leprae. Also has anti malaria activity.
I. Leprosy, in combination with rifampicin and c1ofazimibe.
2. Malaria, as a prophylactic in a fixed dosage combination with pyrimethamine.
3. Dermatitis herpetiformis.
Adverse effects.-Intravascular haemolysis especially in patients deficient in glucose-6- phosphate dehydrogenase; methaloglobinaemia; headache, nervousness, insomnia, blurred vision paraesthesia, peripheral neurophathy, psychosis; lepra reacti s-fever, erythema nodo- sum iritis, painful polyneuritis; hepatitis, anorexia, nausea, vomiting; allergic dermatitis.
Caution.-Monotherapy with dapsone leads to rapid development of resistant M. leprae. Dosage.-For leprosy; Dapsone 25-50 mg. twice weekly, gradually increased to 100 mg. daily plus Rifampicin 600 mg. once monthly plus clofazimine 50 mg. daily (self- administered) or 300 mg. once monthly (supervised). This regime would be continued for at least two years and preferably until smears are negative. For patients weighting less than 35 kg., the daily dose of dapsone is adjusted to 1-2 mg./kg. and the dose of rifampicin to 450 mg.
Dosage form.—Capsule, 100 mg.,
Pharmacological properties.-A phenazine congener. Weakly bactericidal to M. laprae.
It accumulates in tissues thus making discontinuous therapy possible.
Uses.-Leprosy, in combined therapy with dapsone and rifampicin. Prevents the devel- opment of erythema nodosum leprosum (Lepra reactions).
Adverse effects.—Causes red-purple discoloration of the skin lesions and darkening of skin areas exposed to sunlight.
Dosage.-For leprosy: 50 mg. daily. See also under dapsone. For lepra reactions: 300 mg. daily for 3 months.
RIFAMPICIN [See section 9.10.]
9.10 Anti-Tuberculosis Drugs.-Tuberculosis is a communicable disease caused by Myco- bacterium tuberculosis-Availability of modern anti-tuberculosis drugs has made the isolation of the patient from his normal environment unnecessary. Treatment should not be regarded as sufficient when clinical symptoms or bacteriological tests have become negative. Continua- tion of treatment for an extended period of one year or longer is often necessary. As far as possible the uninfected population, particularly children, should be vaccinated against tuber- culosis. The drugs described here for use against tuberculosis are isoniazid, rifampicin, strep- tomycin and thiacetazone plus isoniazid combination.
Combinations of the above drugs, administered regularly in adequate doses, for an ade- quate period of time, should constitute effective treatment for all forms of tuberculosis.
STREPTOMYCIN Dosage form.-Injection, 1g. and 5g. (sulphate) vials.
Pharmacological properties.-A member of the aminoglycoside group of antibiotics.
Bactericidal; acts by inhibiting protein synthesis. Active against a wide variety of gram- negative and a smaller variety of gram-positive bacteria. Most widely used now for its activity against Mycobacterium tuberculosis. Resistance develops to it very readily as a result of muta- tion and acquisition of plasmids. It is not absorbed from the gut, little enters the CSF. It is excreted unchanged in the urine by glomerular filtration.
Tuberculosis-as one of a three five drug combination therapy; Bacterial endocardits-in combination with benzylpenicillin; Brucellosis-in combination with tetracycline.
Precaution.-In renal insufficiency, dose is reduced and treatment carefully monitored. Adverse effects.-Hypersensitivity reaction-skin rashes and fever. Ototoxicity and nephro-
Dose.-For tuberculosis; 1 g. twice a week combined with other anti-tuberculosis drugs.
Dosage form.-Tablet 100 mg.
Pharmacological properties.-Rapidly bactericidal against rapidly growing tubercle bacilli. Dormant bacilli survive exposure to the drug and may subsequently multiply. The
dormant organisms are however destroyed when rifampicin is combined with isoniazid. Resis- tant tubercle bacilli emerge rapidly if isoniazid is used alone.
Uses.-First line anti-tuberculosis drug.
Precaution.-Pyridoxine, 15-50 mg. daily should be given concurrently to reduce the risk of peripheral neuropathy especially in poorly nourished patients.
Adverse effects.-Hypersensitivity reactions, peripheral neuropathy and psychotic be- haviour may occur.
Dosage.-Standard dosage 300 mg. daily, or for non-compliant patients 15 mg./kg. twice weekly under supervision. Tuberculous meningitis: 10 mg./kg. daily.
Children: Standard dosage 1O-20mg./kg. daily up to a maximum of 300 mg.
THIACETAZONE PLUS ISONIAZID
Dosage form.-Tablets, thiacetazone 50 mg. plus isoniazid lOO mg.; and thiacetazone 150 mg. plus isoniazid 300 mg.
Pharmacological properties.-Fixed dosage combination of isoniazid and thiacetazone helps compliance.
Uses.-Combined with a third drug in the initial treatment of tuberculosis. Adequate maintenance treatment of infection with sensitive organisms.
Dosage.-Standard adult dosage: 3 tablets of the lower strength or 1 tablet of the higher strength daily.
RIFAMPICIN Dosage form.-Capsule or tablet, 150 mg., 300 mg.
Pharmacological properties.-A broad spectrum antibiotic with a potent bactericidal action against mycobacteria. Acts by inhibiting DNA synthesis. Must be used with other drugs in the treatment of tuberculosis and leprosy to prevent development of resistance. Crosses the blood-brain barrier readily.
Uses.-Tuberculosis; leprosy, in combination with other drugs. Contra-indications.-Jaundice; first trimester of pregnancy since it has been shown to be teratogenic in animal studies.
Precautions.-Liver and renal functions should be monitored during treatment. The drug should be withdrawn if renal impairment, haemolysis or thrombocytopenic purpura occur during treatment. Breast feeding is inadvisable during treatment since rifampicin is excreted into breast milk. Non-hormonal methods of birth control should be used by patients during treatment, as the reliability of steroid contraceptives is reduced. Paraamino salicylic acid im- pairs the absorption of rifampicin, hence the two drugs when used concurrently should be given at least eight hours apart.
Adverse effects.-Gastrointestinal irritation, hypersensitivity reactions and transient rise in serum bilirubin and transaminases. Reddish discoloration of urine, sputum and tears may be produced.
Dosage.-For tuberculosis: adults, 450-600 mg. (10 mg’/kg.) daily or 600 mg. twice weekly; children, 20 mg./kg. daily up to a maximum of 600 mg., preferably before breakfast. For leprosy: 600 mg. monthly.
Drug interactions.-Para-amino salicylic acid delays the absorption of rifampicin. Being a potent inducer of hepatic microsomal enzymes, rifampicin enhances the metabolism of drugs like steroid contraceptives, other corticosteroids, oral hypoglycaemic agents, dapsone, and digitalis glycosides.
Others.-Pyrazinamide, rifampicin plus isoniazid.
9.11 Systemic anti-Fungal Drugs.-Systemic anti-fungal drugs as used in this section refer to anti-fungal drugs which are taken and absorbed into the blood as against those which are applied locally on the affected part of the body.
Fungal infections can be divided into three groups from the therapeutic standpoint.
(i) Systemic fungal infections.-In which internal organs and tissues are af- fected. Systemic mycoses, e.g. histoplasmosis, are serious diseases, diffi- cult to diagnose and difficult to treat. Amphotericin Band f1ucytosine are the drugs commonly used in treatment but these have not been included in the Essential Drugs list because of the specialised facilities needed for monitoring and controlling their use;
(ii) Superficial fungal infections.-Involving the skin and its appendages.
Dermatophytes cause local infections of the skin (tinea, corporis, ungium or pedis), trichophytons produce different infections of the scalp or nails while epidermophytons may produce infections in the skin or its append- ages. Superficial fungal infections respond well to the topical anti-fungal drugs, but occasionally systemic anti-fungals may be needed for serious or widespread skin involvement. The only systemic anti-fungal drug de- scribed here is griseofulvin;
(iii) Candidiasis, caused by Candida albicans may be superficial (involving the skin or mucous membranes), gastrointestinal or systemic. Treatment of su- perficial and gastrointestinal candidiasis is with nystatin (see section lOon dermatological drugs) while systemic candidiasis is treated with ampho- tericin Band f1ucytosine as with other systemic fungal infections.
Dosage form.- Tablet, 125 mg.
Pharmacological properties.-A fungistatic antibiotic with selective activity against various dermatophytes. It has no effect on other fungi or bacteria.
Uses.-Superficial fungal infections of the skin, hair and nails due to trichophyton, epi- dermophyton or microsporum. It is particularly valuable for infections of the hair and finger nails.
Contra-indications.-Pregnancy, prophyria. Adverse effects.-Hypersensitivity reactions.
Dosage.-Adults: 500 mg.-l g. daily, in divided doses or as a single dose. Children 10 mg./kg. daily, in divided doses. Treatment should be continued for several weeks after appar- ent clinical microscopic cure.
Others.-Amphotericin, tlucytosine, miconazole and ketoconazole.
10. Dermatological drugs
The dermatological drugs in this section have been described under the following headings-
10.1 Anti-infective preparations (topical).
10.2 Anti-inflammatory preparations (topical). 10.3 Astringents.
10.4 Dusting powder.
10.5 Fungicides (topical).
10.6 Keratolytic preparations. 10.7 Scabicides and pediculicides. 10.8 Antiseptics.
Topical drug administration is the best method for treating many simple skin diseases but often systemic administration of drugs is necessary.
Systemic drug administration is required when-
(i) the skin disease has extended to deeper layers of the skin or to adjacent tissues;
(ii) the skin disease has a common cause and pathology with disease of inter- nal organs (e.g. collagen vascular disease);
(iii) the skin disease is too widespread to permit topical drug application;
(iv) the drug effective against a given skin disease accumulates in cutaneous keratin (e.g. griseofulvin);
(v) there is evidence of blood spread (e.g. multiple pyogenic infection of skin).
Skin diseases which are manifestations of an internal disease (e.g. purpura in thrombo- cytopenia) do not require tropical treatment. Treatment of the underlying cause would remove the skin manifestation.
The base or vehicle in which the drug is applied to the skin is of great importance. As a rule, lotions and pastes are best for weeping and wet lesions, while greasy ointments are for dry lesions. Creams may be suitable for either.
10.1 Anti-Infective Preparations
NEOMYCIN PLUS BACITRACIN
Dosage forms.-Ointment and cream, 5 mg. neomycin sulphate plus 500 units bacitracin zinc per gram of ointment in 5 g. and 30 g. tubes. Dusting powder, 0.5% neomycin sulphate plus 250 units bacitracin zinc per g.
Pharmacological properties.-Preparation containing two poorly absorbed, wide spec- trum antibiotics.
(a)Open superficial infections;
(b)Infected eczema, dermal ulcers and wounds.
Contra-indications.-Known history of hypersensitivity to neomycin or bacitracin. Caution.-Ototoxic when applied to extensive bums. Deep infective lesions (e.g. furun- cuinis pyoderma, carbuncle, superficial and deep abcesses) require not topical but systemic administration of antibiotics.
Adverse effects.-Skin sensitisation; ototoxicity if absorbed. Dosage regimen.-It is applied to the affected surface twice daily. 10.2 Anti-Inflammatory Preparations
BETAMETHASONE Dosage form.-Ointment and cream, 0.1 % (valerate).
Pharmacological properties.-A potent, topical corticosteriod preparation.
Uses.-To suppress inflammatory or proliferative responses in various non-infective skin conditions, including: eczematous conditions, allergic dematoses, seborrhoeic dermatitis
intertrigo, intractable pruritus unresponsive to other treatment, discoid lupus erythematosus, lichen planus and psoriasis unresponsive to keratolytic treatment.
Contra-indications.-Acne, rosacea, perioral dermatitis.
Caution.-Potentially dangerous skin conditions such as pemphigus and generalised ex- foliative dermatitis should be treated with systemic corticosteroids from the onset.
Dosage.-A thin film is applied to the affected areas 2-3 times daily. 10.3 Astringents
CALAMINE PLUS ZINC OXIDE
Dosage form.-Calamine lotion containing calamine 15%, zinc oxide 5%, glycerol 5%, bentonite 3%, sodium citrate 0.5%, liquefied phenol 0.5%, in freshly boiled and purified wa- ter.
Pharmacological properties.-An anti-pruritic preparation.
Uses.-Pruritus; acute intlammations of skin with vascular eruptions, exudation, oozing and crusting.
Dosage regime -Frequent application to the affected parts. 10.4 Dusting Powder
ZINC STARCH AND TALC
Dosage form.-Zinc, Starch and Talc dusting powder, containing zinc oxide 25%, starch 25%, purified (sterilised) talc 50%.
Pharmacological properties.-Zinc oxide acts as an astringent forming a relatively im- permeable film of coagulated protein on the surface treated. Talc acts as a lubricant powder but does not absorb moisture. Starch is less lubricant but absorbs moisture.
Uses.-In folds where friction may occur between opposing skin surfaces. Contra-indication.-They should not be applied to areas that are very moist as they tend to cake and abrade the skin.
Dosage.-2-3 applications to affected parts daily. 10.5 Fungicides
BENZOIC ACID PLUS SALICYCLIC ACID Dosage form.-Ointment and cream, 6% plus 3% respectively.
Pharmacological properties.-Salicylic acid acts as a keratolytic agent. Benzoic acid is a fungi static antiseptic.
Uses.-Mild superficial fungal infections. Dosage.-2-3 applications daily.
Dosage form.-Ointment and cream, I %; Spray, I % in aerosol; Pessary, 100 mg. Uses.-Superficial fungal infections.
Dosage.-2-3 applications daily.
NYSTATIN Dosageform.-Oral suspension, 100,000 units/rnl.; Pessary, 100,000 units/pessary;
Tablet, 500,000 units;
Ointment or cream 100,000 u/g.
(b)Candidiasis of skin, vagina, mucous membranes.
Dosage.-Oral administration: 500,000 units four times daily for 7-14 days. Topical.- Three applications daily.
Vaginal pessary.-Insertion twice daily for 14 days. 10.6 Keratolytic Preparations
Dosage form.-Solution, topical, 12% in flexible collodion.
Pharmacological properties.-A keratolytic agent that promotes desquamation of the stratum corneum.
Uses.-Hyperkeratotic conditions including: psoriasis, ichthyosis, seborrhoeic dermati- tis, chronic eczema, hyperkeratosis of the palms and soles, warts, acne.
Dosage.-l or 2 applications daily. 10.7 Scabicides and Pediculicides
BENZYL BENZOATE Dosage form.-Emulsion and lotion, 25%.
Pharmacological properties.-An efficient scabicide and pediculicide. Slightly irritant
Uses.-Scabies; pediculosis of the scalp, body and pubis.
Adverse effects.-Transient burning of the skin; occasionally skin eruptions. Precautions.-Should not be allowed to come in contact with the eyes. Dilutel: I(adults)
or 1:3 (children) with water before use.
Dosage and administration.-For scabies, the lotion is applied over the whole body be- low the neck after thorough washing. A second application is made without washing twenty- four hours later. The lotion can be washed away twenty-four hours after the second applica- tion.
10.8 Antiseptic and Disinfectants.-These are cleansing agents used to sterilise broken and unbroken skin surfaces. They are commonly used for cleansing of wounds and ulcers, as adjuncts in the treatment of infected skin conditions and in preparing the skin for surgery.
Dosage form.-Compound tincture. See formulary composition. Uses.-Skin disinfection.
Dosage form.-solution 5% (gluconate) to be used after appropriate dilution. Uses.-Pre-operative skin preparation: obstetrics and wound cleansing; bladder irriga-
Caution.-Avoid contact with mucous membranes and meninges. Bladder inigations containing more than 0.01 percent may cause haematuria.
Dosage form.-Solution, 5%.
Uses.-Hand disinfection: vaginal lubricant during labour; skin disinfection. Adverse effect.-Can cause skin irritation and sensitisation.
Dosage form.-Solution. See formulary for composition. Uses.-Skin disinfection; antiseptic on cuts and wounds. Adverse effects.-Pain on wounds, stains skin and clothes. Others.-Other preparations in common uses are-
Tar (keratolytic agent); Lindane and monosulphiram (scabicide and pediculicide); Methylated spirit-(alcohol 19 parts: methanol Ipart, tinted with gentian violet); Hydrogen peroxide 6% w/v; Potassium permanganate I%; Gentian violent 0.5%, and silver nitrate stick (silver nitrate 95%; potassium nitrate 5%) (antiseptics).
11. Drugs acting on the eye
The ophthalmological drugs in this section have been described under the following
11.1 Anti-infective drugs.
11.2 Anti-inflammatory drugs. 11.3 Local anaesthetics.
11.4 Miotics and anti-glaucoma drugs. 11.5 Mydriatics.
11.6 Others, e.g. sodium chloride eye lotion.
Eye preparations are applied locally in the form of eye-drops, eye ointment, eye lotions, packs, lamellae, corneal baths and by iontophoresis and sub-conjunctival injection. All prepa- rations must be sterile. One of the best preparations is sodium chloride (0.9% w/v), eye lotion which is a useful irrigation for removing conjunctival discharges. Any lotion remaining un- used after twenty-four hours should be discarded because of bacterial contamination. Most external bacterial infections can be controlled by proper selection of a suitable anti-bacterial agent that does not readily produce sensitisation and/or that is rarely or never administered systemically (e.g. sulfacetarnide, chloramphenicol). The choice of these drugs should avoid possible sensitisation to commonly used systemic drugs and should discourage the develop- ment of strains of organisms resistant to commonly used agents. Intraocular infections and severe external ocular infections require intensive systemic therapy in addition to local ad- ministration.
Adrenal corticosteroids are used in the symptomatic treatment of ocular inflammatory disorders, to control intlammation and thereby reduce the amount of permanent scarring and prevent visual loss. Corticosteroids generally should be avoided in most ocular infections be- cause the course of the disease may be worsened by the weakening of bodily defence mecha- nisms and also lead to ulceration of the cornea.
Eye preparations containing anti-cholinergics are used to achieve mydriasis, as for ex- ample in diagnostic retinoscopy; those containing parasympathomimetics are used as miotics in the treatment of glaucoma, and those containing local anaesthetics for the removal of for- eign bodies and for routine intraocular tonometry.
Acetazolamide is administered systemically for the treatment of glaucoma. It reduces the secretion of aqueous humour by inhibiting the enzyme carbonic anhydrase, and thus lowers raised intraocular pressure.
11.1 Anti-infective Drugs
CHLORAMPHENICOL Dosage forms.-Eye-drops, 0.5%.
Eye ointment, 1%.
Uses.-Local treatment of a wide variety of bacterial infections of the eye. Dosage.-Apply every three hours.
SULPHACETAMIDE Dosag eforms.-Eye-drops, 10% 30%;
Eye ointment, 10%.
Pharmacological properties.-Highly soluble, non-irritant sulphonamide. Uses.-Acute and chronic bacterial conjunctivitis.
Precaution.-Known hypersensitivity to sulphonamides. Dosage.-Apply every 2-6 hours.
CHLORTETRACYCLINE Dosage form.-Eye ointment, 1 %. Uses.-Trachoma.
Caution.-For the general treatment of bacterial infection of the eye, chemotherapeutic agents like chloramphenicol and sulphacetamide which are seldom or never used for systemic infections are preferred to the tetracyclines.
Dosage.-Apply three times daily for six weeks.
Others.-Other anti-infective preparations in common use include Gentamicin eye-drops, Framycetin eye-drops and ointment and idoxuridine eye-drops.
11.2 Anti-inflammatory Drugs
Dosage forms.-Eye-drops and ointment, 0.1%. Uses.-Iridocyclitsis; sclerities, other local inflammations.
Caution.-A “red eye” may be due to Herpes simplex virus infection which produces a dendritic ulcer. This condition is aggravated by corticosteroids.
Adverse effects.-Prolonged application of steroid eye-drops may lead to steroid glaucoma.
Dosage.-Eye-drops: apply every 1-2 hours. Eye ointment: apply 2-4 times daily.
OXYPHENBUTAZONE Dosage form.-Eye ointment, 10%.
Pharmacological properties.-An effective anti-inflammatory drug. Does not aggravate dendritic corneal ulceration and does not cause glaucoma.
Uses.-Local treatment of eye inflammation including iridocylcitis and episcleritis. Dosage.-Apply 1-2 drops, 2-5 times daily.
TETRAPHYDROZOLINE Dosage form.-Eye-drops, 0.05%.
Pharmacological properties.- Tetrahydrozoline is an alpha-adrenoceptor agonist. Uses.-Allergic conjunctivitis.
Dosage.-Apply I or 2 drops, 4-6 times daily.
Others.-Other anti-intlammatory drugs in common use are Hydrocortisone eye-drops and ointment, and Prednisolone eye-drops and ointment.
11.3 Local Anaesthetics
Dosage form.-Eye-drops, 0.5. 1 % (hydrochloride).
Uses.-Ocular local anaesthetic.
Dosage.-Instil 1 or 2 drops onto the conjunctiva.
Others.-Lignocaine with or without adrenaline. 11.4 Miotics and Anti-glaucoma Drugs
11.4.1. Topical Preparations
Dosage form.-Eye-drops, 1,2,3 and 4% (hydrochloride).
Pharmacological properties.-A parasympathomimetic drug. Contracts the circular
muscle of the iris and promotes drainage of the aqueous humour.
Uses.-Primary (narrow angle and wide angle) glaucoma. Adverse effect.-Spasm of accommodation. Dosage.-1-2 drops, 3-6 times daily.
PHYSOSTIGMINE Dosage form.-Eye-drops, 0.25, 0.5% (sulphate).
Pharmacological properties.-A reversible anticholinesterase. Causes narrowing of the
pupil and enhances drainage of the aqueous humour.
Uses.-Primary glaucoma. Dosage.-1-2 drops, 2-6 times daily. 11.4.2 Systemic Preparations
ACETAZOLAMIDE Dosage form.-Tablets, 250 mg.
Pharmacological properties.–Carbonic anhydrase inhibitor; reduces the secretion of acqueous humour, leading to fall in intraocular pressure.
Use.-Primary glaucoma. Dosage.-250 rng., 6-hourly.
HOMATROPINE Dosage form.-Eye-drops, 1, 2%.
Pharmacological properties.-Anticholinergic drug, relaxes the circular muscles of the
iris and reduces drainage of the aqueous humour.
Uses.-For producing mydriasis and cycloplegia for refraction. Contra-indication.-Glaucoma.
Adverse reaction.-Loss of accommodation: raised intraocular pressure. Dosage.-1-2 drops.
TROPICAMIDE Dosage form.-Eye-drops, 0.5, 1%.
Pharmacological properties.-Same as homatropine but shorter acting (duration of effect: tropicamide 3 hours, homatropine 24 hours).
Uses-Contra-indications, adverse reactions and dosage.-Same as Homatropine. Others.-Other mydriatics in relatively common use are Atropine eye-drops, 1 %and Cyclopentolate eye-drops, 1%.
12. Drugs acting on the ear, nose and throat
The drugs acting on the ear, nose and throat have been described in this section under the
12.1 The Ear.
12.1.1 Anti-infective drugs.
12.1.2 Combined anti-infective and anti-inflammatory drugs. 12.1.3 Preparations for removal of earwax.
12.2 The Nose.
12.2.1 Combined anti-allergic and nasal decongestants. 12.3 The Throat.-Other Drugs.
12.1 The Ear.-Infections of the external ear should not be treated with eardrops containing antibiotics which may later be used systemically because of the danger of sensitisation.
Acute infections of the middle ear should be treated not topically, but with appropriate systemic antibiotics.
Earwax is best removed firstly by softening with sodium bicarbonate eardrops, glycerol or warm olive oil on three successive nights and then syringing out with water.
Eardrops containing aminoglycoside antibiotics like neomycin should be avoided when the tympanic membrane is perforated because this may lead to permanet deafness.
12.1.1 Anti-infective Drugs
CHLORAMPHENICOL EARDROPS Dosage form.-Eardrops, 5%.
Uses.-Bacterial infections of the external ear. Caution.-Avoid prolonged use. Contra-indication.-Perforated ear drum.
Adverse effects.-Hypersensitivity reaction.
Dosage.-Apply 2-3 drops, 2-3 times daily. Others.-Framycetine and Gentamicin eardrops.
12.1.2 Combined Anti-infective and Anti-inflammatory Drugs
PORDRAE ENICYMOEN SULP ENOSITROCORDYH Dosage form.-Eardrops, Hydrocortisone 1.5% (acetate) plus neomycin 0.5% (sulphate). Uses.-When bacteria infection of the external ear is associated with inflammation. Dosage.-2-3 drops every 2-3 hours.
Contra-indication.-Perforated ear drum.
Caution.-Avoid prolonged use as this can lead to fungal infection.
HYDROCORTISONE PLUS OXYTETRACYCLINE PLUS POLYMYXIN EAR DROPS
Dosage form.-Eardrops, Hydrocortisone 1.5.% (acetate), oxytertacycline 0.5% (hydro-
chloride) polymycin B O. I 19% (sulphate).
Uses.-Bacterial infection with inflammation. Dosage.-2-3 drops, 2-3 times daily.
Others.-Dexamethasone plus Framycetin plus Gramicidin eardrops. 12.1.3 Preparations for removing Earwax
GLYCEROL PLUS SODIUM BICARBONATE
Dosage form.-Eardrops, 5 mg. sodium bicarbonate plus 30 mI. glycerol in 100 ml. so- lution.
Uses.-To soften ear wax prior to removal.
Dosage.-Introduce a generous amount of the solution into the affected ear for three successive nights.Syringe out with warm water.
Other Drugs.-Aluminium acetate eardrops, a local astringent used to reduce inflamma- tion in otitis externa.
12.2 The Nose.-Nasal drops decongesting the mucosa often contain a vasoconstrictor – This aids drainage, gives temporary relief, but the repeated or prolonged use of sympatho- mimetics may cause a rebound secondary vasodilation with recurrence of nasal congestion.
Mild cases of nasal allergy can be controlled with oral antihistamines and topical decon- gestants.
12.2.1 Combined Antiallergic and Nasal Decongestant
ANTAZOLINE PLUS NAPHAZOLINE
Dosage form.-Nasal and drops spray, 0.5% Antazoline plus 0.025% Naphazoline. Pharmacological properties.-Naphazoline is an alpha-adrenoceptor agonist whose clinical usage has been restricted to nasal decongestion. It has the advantage that its use is not associated with the rebound secondary vasodilation which occurs with adrenaline and some other sympathomimetic agents. Antazoline is an antihistamine.
Uses.-Nasal congestion of allergic origin.
Dosage.-2-3 drops or I spray into each nostril, 3-4 times daily.
12.3 The Throat.-Infections of the oropharynex such as ulcers and sore throat are best treated by the use of systemic anti-infective drugs. The use of antiseptic lozenges, etc., is of doubtful benefit in therapy. For the useful systemic anti-infective drugs-see appropriate sec- tions of this formulary.
Other drugs used for the throat include the cleansing (oral hygiene) gargles such as Phe- nol and Glycerol plus Thymol gargles.
13. Dental drugs
The dental drugs in this section are described under the following headings- 13.1 Local anaesthetics.
Drugs are used in dentistry to control infection and inflammation in lesions of the mouth, to provide oral toilet and relieve pain.
Infection is best treated by the use of systemic anti-infective agents. The use of topical antibiotics in the oral cavity in the form of pastes and lozenges is not advised. It predisposes to the development of sensitisation in susceptible individuals and leads to the rapid appearance of resistant strains of oral micro-organisms. Oral antisepsis can be achieved by the use of anti- septic mouthwashes and gargles. These also have a mechanical cleansing action and they freshen the mouth. Oral candidiasis (thrush) can be treated with mystatin mouthwash.
Symptomatic relief of pain can be achieved by the use of the antipyretic analgesics, aspi- rin and paracetamol. Occasionally pain from superficial lesions in the mouth can be alleviated with local anaesthetic lozenges. Local anaesthetic injections are required for dental extraction.
The systemic analgesic and anti-infective drugs, and the local antifungal drugs used in oral disease have been described in appropriate sections of this formulary.
13.1 Local Anaesthetics
Dosage form.-Lozenges 10 mg.
Uses.-For relieving pain in oral lesions; to facilitate impression and for the removal of
sutures in sensitive patients.
Adverse effects.-Sensitisation with sore, inflamed lips and tongue. Caution.-Avoid prolonged use.
Dosage.-One three times daily or as directed.
LIGNOCAINE DENTAL CARTRIDGES Dosage form.-Dental cartridges, 2% with 1:80,000 adrenaline. Uses.-Local anaesthesia for dental use.
Direction for use.-Administer by infiltration.
GLYCEROL MOUTHWASH Dosage form.-Solution. See formulary for composition. Uses.-Oral hygiene.
Direction for use.-To be used undiluted or diluted with three volumes of warm water.
PHENOL MOUTHWASH Dosage form.-Solution. See formulary for composition. Uses.-Oral hygiene.
Direction for use.-Use diluted with equal volume of warm water.
Dosage form.-Solution-tablet. See formulary for composition. Uses.-Oral hygiene.
Direction for use.-Dissolve one solution-tablet in half a tumblerful of warm water. Others.-Isotomic saline mouthwash. For systemic analgesics and anti-infective drugs, and local antifungal drugs used in oral disease-See appropriate section of this formulary.
14. Drugs for musculoskeletal and joint diseases
Drugs for musculoskeletal and joint diseases are described under the following headings- 14.1 Non-Steroidal Anti-inflammatory Drugs (NSAIDs).
14.2 Drugs used for the treatment of Gout.
The term musculoskeletal and joint diseases is used in this section to describe a variety of diseases including rheumatoid arthritis, rheumatic joint diseases, osteoarthritis, fibrositis and other types of soft-tissue rheumatism and gout.
The non-steroidal anti-inflammatory drugs relieve pain as well as reduce inflammation and they are the drugs of choice for the conditions listed above, with the exception of gout. Aspirin is the oldest and best known of these agents. Taken at the dose of 2-3 tablets 3-4 hourly, it provides relief in most cases of acute and chronic inflammatory joint disease. The other NSAIDs differ from aspirin in duration of action and tolerability and can therefore be used in patients who have failed to respond to aspirin or cannot tolerate it. This group of NSAIDs is represented in the Essential Drugs List by lbuprofen. Other examples for which there is substantial experience in this country include diflunisal, indomethacin, piroxicam and sulindac. The choice of which NSAID to use will be determined by the prescriber’s experi- ence with the drug’s acceptability by the patient, relative cost and availability and considera- tions of duration of action and frequency of dosage.
In some instances reheurnatoid arthritis fails to respond to NSAIDs and other classes of drugs become necessary. These include corticosteroids and the anti-malarial, chloroquine. For the treatment of rheumatoid arthritis, chloroquine is given in doses of 300 mg. daily and above for many months or years. Such prolonged use of the chloroquine carries the risk of increased toxicity, particularly to the eye.
Drugs are used to treat acute attacks of gout and for long-term control of the disease during remission. Acute attacks of gout: Colchicine can be used as the first-line drug. Failing this, the NSAIDs, indomethacin and piroxicam have been found very useful.
Long-term control: This can be achieved with the xanthine oxidase inhibitor, allopurinol or the uricosuric agent, probenecid.
14.2 Non-Steroidal Anti-Inflammatory Drugs (NSAlDs)
[See section 1.1.3.]
Dosage form.- Tablet, 200 mg.
Pharmacological properties.-Non-steroidal anti-inflammatory analgesic. Anti- inflammatory properties weak compared with aspirin.
Uses.-In rheumatic disease and other musculoskeletal disorders where the pain and inflammation are mild to moderate. Unsuitable for conditions where inflamrnations are severe like in acute gout.
Dosage.-200-400 mg., 3-4 times daily, maximum 2.4 g. daily.
14.2 Drugs Used for Gout
Dosage form.- Tablet, 0.5 mg.
Pharmacological properties.-Selectively relieves the pain and inflammation of acute gout by a mechanism that is still uncertain.
Uses.- Treatment of acute gout.
Adverse effects.-Gastrointestinal disturbances such as anorexia, nausea, vomiting, diar- rhoea and abdominal pain.
Dosage.-1 mg. initially followed by 0.5 mg. every 2-3 hours until relief of pain occurs or until there is nausea or vomiting. The course should not be repeated within three days.
Dosage form.- Tablet, lOO mg.
Pharmacological properties.-A xanthine oxidase inhibitor. It inhibits conversion of xanthine and hypoxanthine to uric acid. Serum uric acid level falls. Urate deposition and ex- cretion are reduced.
Uses.-Gout prophylaxis; prevention of hyperuricaemia during treatment of leukaemias and polycythaemia.
Adverse effects.-Rashes; gastrointestinal disorders; drowsiness.
Dosage.-Initially 100 mg. daily gradually increasing over a period of 1-3 weeks to a maintenance dose of 200-600 mg. daily.
15. Drugs used in allergic disorders
Drugs used in allergic disorders in this section are described under the following headings-
15.1 Antihistamines. 15.2 Anti-anaphyactics. 15.3 Prophylactic Drugs.
The word allergy means “altered response”. It signifies that the subject has responded in an unusual way to a substance with which he has come in contact.
All types of allergies respond to treatment. Drugs used in the treatment of allergic reac- tions such as acute anaphylaxis, serum sickness, hay fever, angioneurotic oedema, urticaria and asthma, fall into three pharmacologic groupings-the sympathomimetics, the antihista- mines and the corticosteroids. In additon, drugs like ketotifen and sodium cromoglycate can be used in the prophylaxis of allergic reactions.
Several sympathomimetic drugs are primarily used as vasoconstrictors for local applica- tion to the nasal mucous membrane or the eye. With their alpha-receptor actions, they cause marked vasoconstriction and blanching when applied to nasal and pharyngeal mucosal sur- faces. They are therefore useful in the treatment of mucosal congestion accompanying hay fever, allergic rhinitis, acute coryza and sinusitis.
Adrenaline is the drug of choice to relieve the symptoms of acute hypersensitivity reac- tions to drugs, (e.g. penicillin, aspirin and sulphonamides), and of other acute reactions to sera and other allergens. It readily comes to use in acute anaphylactic shock and for angioneurotic
oedema, which may be temporarily very disabling around the face, or fatal if it affects the larynx. A subcutaneous injection of adrenaline, I ml. or I in 1000 solution, rapidly relieves itching, urticaria, and swelling of lips, eyelids, and tongue, and the drug may be life-saving when oedema of the glottis threatens respiration. Large doses cause palpitation but may be necessary in an emergency.
Antihistamines are used systematically for the control of hay fever, drug rashes urticaria and angioneurotic oedema, all of which are mediated through release of histamine. However, the limitation of antihistamines is due to the fact that other potent autocoids (e.g. 5- Hydroxytryptamine) are released in addition to histamine. It follows that the efficacy of anti- histamines in countering allergic disorders will vary, depending on the degree to which symptoms are due to histamine release. Thus, since arthralgia and fever of serum sickness are not due to histamine release, they are not relieved by the drugs.
The onset of action of antihistamines occurs within thirty minutes following an oral ad- ministration. The effects last for several hours. Their action is rapid when administered by injection. Topical use, whether on the skin or in the eyes or nose, is liable to cause sensitisa- tion.
They all cause some central sedation which may be a desirable side-effect in the treat- ment of hospitalised patients or patients about to retire for the night. This effect is however undesirable for ambulant patients as the slowing of retlex activity may cause accidents.
Ketotifen and sodium cromoglycate appear to act by preventing the release of pharma- cological mediators of allergy and can therefore be useful in the prevention of allergic reac- tions.
CHLORPHENIRAMINE Dosage forms.-Injection, 10 mg. (Maleate) in I ml. ampoule. Tablet, 4 mg. (maleate). Syrup, 2 mg. per 5 ml.
Pharmacological properties.-A histamine H I-receptor antagonist. Shorter acting and less sedative than promethazine. Has no antiemetic effect.
Uses.-Symptomatic relief of allergy. With adrenaline in the emergency treatment of anaphylaxis and angioneurotic oedema.
Adverse effecls.-Sedation; dryness of mouth and other anticholinergic effects; gastro- intestinal irritation.
Drug interaction.-Potentiates effects of central nervous system depressants including alcohol.
Dosage.-Adults: oral, 4 mg., 3-4 times daily.
Parenteral, 10-20 mg. intramuscularly or in emergency by slow intravenous injection after dilution in the syringe with 10 ml. of blood.
Children: oral, up to I year, I mg. twice daily 1-5 years, 1-2 mg. 3 times daily; 6-12 years, 2-4 mg. 3-4 times daily.
Intravenous injection: 0.2 mg./kg. diluted and given slowly.
Dosage form.-Injection, 25 mg. and 50 mg. (Hydrochloride); In Iand 2 ml. ampoules respectively;
Tablets, 10 mg. and 25 mg. (Hydrochloride);
Syrup,S mg. per 5 ml. (Hydrochloride).
Pharmacological properties.-This is a phenothiazine derivative that blocks histamine H l-receptors. It also has pronounced anti-cholinergic activity, it is markedly sedative and has a long duration of action-about 12 hours. Has a marked antiemetic effect.
(1) As an antihistamine, it is used in the relief of allergic reactions and as an adjunct to adrenaline in the treatment of anaphylaxis and severe angioneurotic oedema.
(2) As an anticholinergic and particularly as an artiemetic and anti-sialagogue in-
(i) motion sickness and Meniere’s disease;
(ii) disorders characterised by vomiting including uraemia, malaria, drug- induced vomiting; and
(iii) premedication prior to anaesthesia and obstetrics procedures. (3) As a sedative or hypnotic especially in children.
Caution.-Although there is at present no evidence that promethazine is embryopathic or teratogenic, it should be used during pregnancy only when it is considered unavoidable. Suffi- cient is excreted in the maternal breast milk to cause sedation in the breast-fed infant.
Adverse effects.-Sedation, dry mouth; gastrointestinal irritation; allergic effects is used topically.
Drug interaction.-Potentiates the effect of other central nervous system depressants in- cluding alcohol.
Dosage.-Adult: Oral, 20-50 mg. daily in divided dose, or as a single dose at night. Parenteral, 25-50 mg. intramuscularly or in emergency by slow intravenous injection af- ter l0-fold dilution with water for injection.
Children: Daily Oral dose, as single or divided doses-
6 months-I year, 5-10 mg.;
1-5 years, 5-15 mg.;
6-10 years, 10-25 mg.
Half the oral dose may be administered parenterally, when necessary, in children aged 6- 10 years.
Other.–Other commonly used antihistamines are mepyramine and diphenhydramine. 15.2 Anti-Anaphylactics
ADRENALINE Dosage form.-Injection,l mg. (Bitartrate) in 1 ml. ampoule.
Pharmacological properties.-A naturally occurring catecholamine secreted by the ad- renal medulla. It is inactive by mouth. Has a short duration of action when given parenterally. Its effects are similar to those of sympathetic stimulation.
Uses.-Emergency treatment of-
(i) anaphylactic shock induced by drugs and other allergens;
(ii) airways obstruction due to asthma and other causes. Selective beta 2- adrenoceptor stimulants are now preferred for this purpose;
(iii) cardiac arrest, following failure of physical measures and in the absence of a defibrillator;
(iv) prolongation of the action of infiltrated local anaesthetics.
Contra-indication – It should not be used for ring block in local anaesthesia because of the intense vasoconstriction it produces.
Adverse effects.-Anxiety, tremor, anginal pain, tachycardia, palpitations and cardiac ar- rhythmias.
1 mg. i.m. immediately or, in extreme urgency, 0.5 mg. diluted 10-fold with normal sa- line by slow i.v. injection.
The intramuscular dose may be repeated after three minutes according to the clinical condition.
Adrenaline, by raising blood pressure and reversing bronchospasm, acts as a physiologi- cal antagonist to histamine. Provided the peripheral circulation is adequate the therapeutic effect should become evident within one minute of injection.
Chlorpheniramine 10 mg. i. v. or other H I-receptor blocking agent, will reduce the re- sponse to further histamine release.
Hydrocortisone l00 mg. i.m. or i.v. may suppress the immune reaction and reduce vas- cular permeability.
These three drugs should be assembled as kit for immediate use wherever drugs or sera are routinely administered.
Bronchospasm.-Initially 0.1-0.5 mg. subcutaneously or intramuscularly. Subsequent injections may be given subcutaneously at 15 to 20 minute intervals as required.
Cardiac arrest and heart block with syncopal seizures (Stokss-Adams attacks).-Intra- cardiac injection of adrenaline may be justified in extremis in the absence of an electrical pacemaker or defibrillator.
Full restoration of circulation may necessitate slow intravenous infusion of adrenaline as in anaphylactic shock. However, repeated subcutaneous injection is generally preferable be- cause of the high risk of ventricular fibrillation.
Drug treatment serves only as a temporary expedient pending availability of an electrical pacemaker.
Prolongation of infiltration anaesthesia.- The addition of adrenaline 1: 100,000 to local anaesthetic solutions slows systemic absorption and prolongs the anaesthetic effect.
15.3 Prophylactic Drug
[See section 6.4.1.]
Antidotes in this section are described under the following headings- 16.1 Non-specific (General) Antidotes.
16.2 Specific Antidotes.
The problems of poisoning by drugs and chemicals have been described in detail In Chapter 2, the Emergency Treatment of Poisoning
This section deals with a selected number of antidotes useful in specific cases of poi- soning. Antidotes fall under two categories-general and specific. A general antidote is appli- cable for a wide variety of poisons. The action is of a general nature like preventing absorp- tion of the poison from the gut, e.g. activated charcoal or promoting its elimination, e.g. so- dium bicarbonate for acidic poisons and ammonium chloride for basic poisons.
The specific antidotes either antagonise the poisoning agent at the receptor, for example naloxone against morphine, or are chemical antagonists, like protamine sulphate against hepa- rin
16.1 Non-Specific (General) Antidote
ACTIVATED CHARCOAL Dosage form.-Powder 50 g.
Pharmacological properties.-Prevents or reduces the absorption of poisons from the
gut by absorbing them.
Use.-Treatment of ingested poisons.
Dosage.-By mouth, 5-50 g. as a thick suspension in water. 16.2 Specific antidotes
ATROPINE Dosage form.-Injection, 1mg. (Sulphate) in 1 ml. ampoule.
Pharmacological properties.-Anti-cholinergic drug. Competitively antagonises acetyl- choline at muscarinic receptor sites.
(1) In anaesthetic premedication, to inhibit bronchi la secretion and prevent the excessive bradycardia and hypotension caused by some of the drugs used during anaesthesia.
(2) To antagonise the muscarinic effects of overdosage with chlolinergic drugs and anti- cholinesterases.
(3) For control of muscarinic side effects of neostigmine used in reversing competitive neuromuscular block.
Adverse effects.-Any unwanted antimuscarinic effect. Dosage.-
(1) For premedication: intravenously, 0.3-0. 6 mg. just before induction: intramuscularly 0.3-0.6 mg. 30-60 minutes before induction.
(2) For cholinergic drug over-dosage: 2 mg. i.m. or i.v. every 20-30 minutes until signs of atropine excess appear. Pralidoxime, a specific cholinesterase regenerator in organophosphorus anti-cholinesterase poisoning is only useful if given within twenty-four hours of the poisoning.
(3) For preventing muscarinic effects of neostigmine used to reverse competitive neu- romuscular block in anaesthesia: 0.6-1.2 mg. intravenously.
DESFERRIOXAMINE Dosage form.-Injection. 500 mg. (mesylate) powder in vial.
Pharmacological properties.-A water soluble specific iron chelating agent. It is not ab- sorbed from the intestine and blocks the absorption of iron. In the blood, it removes iron from ferritin and transferrin but not from haemoglobin.
Dosage.-Orally, 5-10 mg. in 50-100 ml. of liquid after gastric lavage, i.m. injection, 2 g. in 8-12 ml. of water for injection every 3-12 hours.
I.V. infusion, up to 15 mg./kg./hour up to a maximum of 80 mg./kg. in twenty-four hours. Adverse effects.-Pain at site of i.m. injection: anaphylactic reactions and hypertension when infused too rapidly.
Precaution.-Give i.v. infusion very slowly.
DIMERCAPROL Dosage form.-Injection, 50 mg./ml. in 2 ml. ampoule.
Pharmacological properties.-It is a dithiol compound which combines with metals to form complexes which are not toxic to the body.
Uses.-Poisoning by antimony, arsenic, bismuth, gold and mercury.
Adverse effects.-In high doses, it can combine with metal-containing enzymes and in- hibit them. Other adverse effects include pain at site of injection, weakness, nausea, salivation, hypertension.
Dosage.-By i.m. injection, 2-3 mg./kg., every 4 hours for two days, then 1-4 times daily until recovery.
NALOXONE Dosage form.-Injection, 0.4 mg. (Hydrochloride) in 1 ml. ampoule.
Pharmacological properties.-Narcotic antagonist. Competitively antagonises morphine and other opiates and narcotic analgesics. Respiratory depressant effects of these drugs are antagonised before the analgestic effect. It has a short duration of action.
Uses.-Over-dosage with morphine-like compounds.
Adverse effects.-Will precipitate withdrawal syndrome in morphine addicts. Dosage.-0.4-2 mg. repeated every 2-3 minutes to a maximum of 10 mg. subcutane-
ously, intramuscularly or intravenously.
PROTAMINE SULPHATE Dosage form.-Injection, 10 mg./ml. in 5 ml. ampoule.
Pharmacological properties.-Combines chemically with heparin milligram for milli-
gram to block its anticoagulant effect.
Uses.-Overdosage with heparin.
Adverse effe.cts.-Can itself cause anticoagulant effect if given in excess.
Dosage.-By slow intravenous injection. 1 mg. protamine sulphate for every 100 units of heparin. Less protamine is required if a longer time has elapsed after heparin overdosage. Maximum dose 50 mg.
VITAMIN K1 (PHYTOMENADIONE) Dosage form.-Injection, 10 mg./ml. in 1 ml. ampoule.
Pharmacological properties.-Vitamin K is necessary for the production of prothrombin by the liver. Its deficiency leads to haemorrhage. Liver disease causes impaired synthesis of prothrombin and oral anticoagulants also cause hypoprothrombinaemia by interfering with vitamin K metabolism. Vitamin K1 s a fat-soluble preparation of vitamin K.
Uses.-Hypoprothrombinaemia with or without haemorrhage caused by overdosage with oral anti-coagulants or by liver disease.
Dosage.-Slow intravenous injection, 2.5-20 mg. Oral, 10-20 mg. Others.-Other commonly used antidotes are-
Disodium calcium edetate for poisoning by heavy metals, particularly lead; Penicilla- mine for copper poisoning and Pralidoxime for organophosphorus poisoning.
17. Drug used for cancer chemotherapy
Drugs used for cancer chemotherapy, also called the anti-neoplastic and immuno- suppressive drugs are described in this section under the following headings.
17.1 Alkylating Agents. 17.2 Anti-rnetabolites,
17.3 Cytotoxic Antibiotics. 17.4 Vinca Alkaloids.
17.5 Hormones and synthetic substitutes.
Treatment of cancer requires the judicious use of surgery, radiotheraphy, cytotoxic and endocrine drugs, analgesics, antibiotics and blood products. A few tumour types can be man- aged in secondary institutions but most can be satisfactorily managed only in specialised in- stitutions where the above modalities of treatment are available as well as laboratory facilities to monitor the biological effects of the treatment.
Only in exceptional cases is chemotherapy alone curative for cancer. More often drugs are used in combination with surgery or radiation therapy.
Anti-cancer drugs are mostly toxic drugs. Many cause unpleasant side effects such as nausea, vomiting, diarrhoea, alopecia and myelosuppression which may cause fatal infections or haemorrhage. Many of the drugs are also expensive.
The principles of cancer chemotherapy can be summarised as follows-
(i) for most drug-sensitive tumours, a combination of drugs, each used at an optimal dose, is likely to be more effective than sequential single drug therapy;
(ii) the first therapy employed is often the most important in determining pa- tient survival;
(iii) treatment should not be delayed nor should a suboptimal treatment pro- gramme be given as a trial, if the tumour is potentially curable;
(iv) the use of toxic multi-drug combinations for an incurable cancer in the doubtful hope of palliation is probably inappropriate.
From the point of view of chemotherapy, cancers can be divided into the following groups-
Group I.-Tumours for which there is evidence that the use of one drug or a combina- tion of drugs, alone or in conjunction with other therapeutic modalities, will result in a cure or a significant prolongation in the survival of some patients with this tumour.
Acute lymphoblastic leukaemia.
Acute non-lymphoblastic or myelongenous leukaemia. Hodgkin’s disease.
Germ cell cancers of the testis and ovary. Wilm’s tumour.
Paediatric soft tissue sarcomas. Lung cancer-small cell type. Kaposi’s sarcoma.
Group 2.- Tumours for which there is controversial evidence that treatment may pro- long life:
Breast cancer, early stages with only histological node involvement in premenopausal women.
Group 3.-Tumours in which drugs will cause tumour shrinkage and improvement in quality of life. Whether prolongation of life occurs is uncertain.
Chronic lymphocytic leukaemia. Chronic myelogeneous leukaemia. Multiple myeloma.
Group 4.-Tumours for which there is evidence that tumour shrinkage may occur but it
is not clear whether clinical benefit outweighs drug toxicity.
Head and neck cancers.
Primary cancers of the central nervous system. Osteosarcoma; adrenal cell cancer; hepatoma.
Group 5.-Tumours for which there are no effective drugs- Lung epidermoid, adenocarcinoma, and large cell type- Oesophageal carcinoma.
Pancreatic carcinoma (non-endocrine). Cervical carcinoma.
The drugs described here are not inclusive of all those agents which might be effective in every case. However, practically all curable tumours and all those in which the cost/benefit ratio clearly favours drug treatment can be managed appropriately using them. It should also be noted that information given here is not meant to substitute for formal training and experience in cancer management.
In the classified information on the individual drugs that follows, tumours for which a drug is useful are divided into two categories-
Category I.-Tumour for which there is evidence that the drug, alone or in combination with other drugs-
(i) effects a cure; or
(ii) prolongs survival of the patient.
Category 2.-Tumours for which there is evidence that the drug, alone or in combination with other drugs-
(i) causes shrinkage and improves quality of life; (ii) may marginally prolong survival of patient. 17.1 Alkylating Agents
Dosage form.- Tablets, 2 mg.
Pharmacological properties.-An alkylating agent with selective depressant action on bone marrow. Readily absorbed from the gut.
Uses.-Category 1: None.
Category 2: Induction and maintenance of remission in chronic myelogeneous leukaemia and other myeloproliferative conditions like polycythaemia vera and myelofibrosis with myeoid hyperplasia.
Adverse effects.-See above. Also, hyperuiricaemia, hyperpigmentation, diffuse pulmo- nary fibrosis cataracts.
Dosage.-For induction of remission, 2-4 mg. daily. May be raised cautiously to 6 mg. daily.
Maintenance dose of 0.5-2 mg. daily may be given to maintain a white cell count of 10- 15,000 mm.
Precautions.-During induction of remission-
(i) full blood counts should be done weekly;
(ii) treatment should be suspended if white cell count falls below 20-25,000 -mmor platelets below 100,00 mrn .-
At least 4 weeks should elapse between a previous course of cytotoxic threrapy or irra- diation and the use of busulphan.
CHLORAMBUCIL Dosage form.-Tablets, 2 mg. 5 mg.
Pharmacological properties.-Alkylating agent. Action similar to, but slower than cy- clophosphamide. Frequently used for its immunosuppressive effects in non-malignant conditions.
Uses.-Category 1: Breast cancer, testicular cancer, Hodgkin’s disease, non-Hodgkin’s
lymphomas, Burkitt’s lymphoma.
Category 2: Ovarian carcinoma, chronic lymphocytic leukaemia. Adverse effects.-See general remarks above.
Dosage.-5 – 10 mg. daily for 3-6 weeks, for induction of remission.
Dosage form.-Injection, powder in 100 mg. and 500 mg. vials. Tablets. 25 mg. and 50 mg. Pharmacological properties.-Alkylating agent requires metabolic conversion of active substance in the body; action is similar to, but more intense than, that of chlorambucil. Readily absorbed from the gut.
Uses – Category I: To induce and maintain remission in: Hodgkin’s disease, non- Hodgkin’s lymphomas, Burkitt’s lymphoma, lung cancer-small cell type, breast cancer. Ewing’s sarcoma, paediatric soft tissue sarcomas.
Category 2: Ovarian carcinoma, neuroblastoma, chronic lymphocytic leukaemia, chronic
myelogeneous leukaemia, multiple myeloma, acute lymphoblastic leukaemia.
Adverse effects.-Haemorrhagic cystitis-See general notes above. Precautions.-Adequate fluid intake is important: 3-4 litres/day.
Dosage.-Can be given orally, intramuscularly, intravenously, intrapleurally, intraperi- tioneally. Intravenous doses are usually administered over a period of 2-3 minutes into the tubing of a tree-flowing infusion of sodium chloride or dextrose. Dose is determined by the nature of the tumour being treated.
ENIRUPOTPACREM 6- Dosage form.- Tablet, 50 mg.
Pharmacological properties.-Analogue of the naturally occurring purine bases, hy-
poxanthine and guanine. Acts as an anti-metabolite. It is both cytotoxic and immunosuppressive.
Uses – Category 1: Acute Iymphobliastic leukaemia.
Category 2: Acute non-lymphoblastic leukaemia. Acute myelogeneous leukaemia. Also: As an immuno-suppressant-
(i) to prevent transplant rejection;
(ii) to treat a variety of autoirnrnune and collagen disease inadequately respon- sive to corticosteroids alone or when steroids are contraindicated.
Adverse effects.-See general notes above; hyperuricaemia.
Drugs interaction.-Allopurinol inhibits conversion of 6-mercaptopurine to 6-thiouric acid, thus enhances its toxicity.
Dosage.-Oral, initially 2.5 mg./kg. daily.
METHOTREXATE Dosageform.-Injection, power in 50 mg. vial. Tablet, 2.5 mg.
Pharmacological properties.-Folic acid analogue: competitively inhibits dihydrofolate reductase.
Uses.-Category 1: Acute Lymphoblastic leukaemia, Burkitt’s lymphoma, breast cancer, gestational/trophoblastic cancers.
Category 2: Head and neck cancers.
Adverse effects.-See general notes above. Precautions.-Reduce dose if renal insufficiency is present.
Dosage.-Can be given orally, intramuscularly, intravenously and intrathecally: 10-25 mg. weekly.-See manufacturer’s literature.
17.3 Cytotoxic Antibiotics
BLEOMYCIN Dosage form.-Injection, powder in 15 mg. vial (as Sulphate).
Pharmacological properties.-Antibiotic, selectively toxic to the lungs and skin. Uses.-Category 1: Hodgkin’s disease, non-Hodgkin’s lymphoma germ-cell cancers of the testis and ovary.
Category 2: Kaposi’s sarcoma.
Adverse effects.-See general notes above: also, pulmonary toxicity, acute anaphylaxis, rash, fever.
Precautions.-Test dose is advisable to prevent anaphylaxis. Contra-indications.-Acute chest infection; grossly impaired lung functions. Dosage.–Can be given subcutaneously, intramuscularly or intravenously.
Standard dose when used alone is 0.25-0.5 mg./kg. (10-20 mg./m.) weekly or twice weekly up to a maximum of 300 mg.
DACTIONOMYCIN (ACTINOMYCIN D) Dosage form.-Injection, powder in 0.5 mg. vial. Pharmacological properties.–Cytotoxic antibiotic.
Uses.-Category 1: Gestation trophblastic cancers, germ-cell cancers of the testis, Kaposis sarcoma, Wilm’s tumour, Ewing’s sarcoma, paediatric soft tissue sarcomas.
Category 2: Neuroblastoma.
Adverse effects.-Local extravasation necrosis.
Dosage.-Given intravenously; dose determined by diagnosis and response 0.5 mg. daily for maximum of 5 days.
Dosage interval, 2-4 weeks.-See manufacturer’s literature.
DOXORUBICIN (ADRIAMYCIN) Dosage form.-Injection, powder in 10 mg. and 50 mg. vials (as hydrochloride). Pharmacological properties.–Cytotoxic antibiotic.
Uses.-Category 1: Acute non-lymphoblastic leukaemia, acute myelogeneous leukae- mia, Hodgkin’s disease, non-Hodgkin’s lymphomas, lung cancer, small cell type; breast can- cer, Ewing’s sarcoma, paediatric soft tissue sarcomas.
Category 2: Gastric cancer, ovarian cancer, multiple myeloma, germ cell cancer of the testis, osteosarcoma, neuroblastoma, hapatoma.
Adverse effects.-Local extravasation necrosis, cardiomyopathy, hyperpigmentation, red discoloration of urine.
Precautions.-Cumulative dose of 500 mg. should not be exceeded. Dose should be reduced in patients with moderate liver or cardiac disease.
Dosage.-Given intravenously. Best administered through the tubing of a free-flowing intravenous infusion of sodium chloride or dextrose. Initial dosage, when used alone: 1.2-2.4 mg./kg. (37.5-75 mg.zm”) three times weekly. It should not be added to an alkaline infusion fluid. It should not be mixed with other drugs.
Drug interaction.-Will precipitate in intravenous lines if administered with heparin.
17.4 Vinca Alkaloids
VINCRISTINE Dosage form.-Injection, powder in Img. and 5 mg. vial (as Sulphate). Pharmacological properties.-Cytotoxic alkaloid of Vinca rosea.
Uses.-Category 1 :Vincristine given with prednisolone is the treatment of choice for the induction of remission in acute lymphoblastic leukaemia of childhood. Other Category 1 tumours are: Hodgkin’s disease, non-Hodgkin’s lymphomas, Bukitt’s lymphoma, lung cancer; small cell type, germ cell tumours of the testis and ovary, Kaposi’s sarcoma, paediatric soft tissue sarcomas.
Adverse effects.-Neuropathy, extravasation necrosis, severe constipation, depression. Dosage.-Given intravenously. Best given through the tubing of a freely running intra- venous infusion of sodium chloride or dextrose. Dosage determined individually by response and toxicity: At weekly intervals 0.05 mg./kg. (or 2 mg./m2) weekly.
17.5 Hormones and Synthetic Substitutes
Dosage form.- Tablet, 5 mg.
Pharmacological properties.-Corticosteroid. Can be replaced by other members of the group such as, prednisone, dexamethasone, betarnethasone and hydrocortisone.
Uses.-Category 1 : Acute lymphoblastic leukaemia, Hodgkins disease, non-Hodgkins
Category 2: Chronic lymphocytic leukaemia, breast cancer, multiple myloma. Adverse effects.-Metabolic. See also section 8.1.
Precautions.-Should be used with caution when infection is present or suspected see also section 8.
Contra-indications.-Peptic ulcer, diabetes mellitus.
Dosage.-Prednisolone is given orally. Intramuscular or intravenous dosage forms are available for hydrocortisone if the routes are desired. Initial dosage, usually 40-60 mg. prednisolone orally. This is gradually reduced to the lowest dose compatible with control of the tumour.
STILBOESTROL Dosage form.- Tablets, Img. and 5 mg.
Pharmacological properties.-Non-steroidal, synthetic compound with oestrogenic ac-
tions, can be substituted with other oestrogenic compounds, particularly ethinyloestradiol,
Well absorbed from the gut.
Uses – Category 1: None.
Category 2 :Postmenopausal breast cancer; prostate cancer.
Adverse effects.-Nausea, fluid retention, venous and arterial thrombosis; gynaecomastia and impotence in the male; withdrawal bleeding in the female; hypercalcaemia and a transient increase in bone pain may be seen in some breast cancer patients with bone metastases.
Precaution.-Not effective in premenopausal women. Contra-indications.-Severe vascular disease. Dosage.-For breast cancer; 10-20 mg. daily.
For prostate cancer: 1-3 mg. daily.
TAMOXIPHEN Dosage form.-Tablets, 10 mg. and 20 mg. (as citrate).
Pharmacological properties.-Synthetic oestrogen receptor antagonist. Now preferred to
oestrogens as the drug of choice for postmenopausal metastatic breast cancer.
Uses.-Category 1: None. Category 2: Breast cancer.
Adverse effects.-Postmenopausal bleeding, hypercalcaemia, transient increase in bone pain in patients with bone metastases.
Dosage.-Initially, 10 mg. twice daily.
18. Immunological Products
18.1 Sera and Immunoglobulins. 18.2 Vaccines.
There are three types of immunological products-
1. Immunoglobulins which are antibodies of human origin.
2. Sera (or antisera) are antibodies prepared in animals.
3. Vaccines are antigens given to induce specific antibodies against a particular disease.
Vaccines may be-
(1) live attenuated forms of an infective agent e.g. poliomyelitis and measles vaccines and BCG;
(2) inactivated preparations of the infective agents as in pertussis and cholera vaccines or;
(3) extracts of, or endotoxins produced by a micro-organism as in tetanus vaccine.
The immunity induced by attenuated vaccines appears more quickly and is more long lasting than immunity induced by inactivated vaccines. With the exception of live attenuated poliomyelitis vaccine which is given by mouth, vaccines are given by injection.
Adverse reactions to vaccines are variable and depend on the type of vaccine. Tolerabil- ity can be improved if certain precautions are taken when using vaccines.
Vaccination should be avoided in febrile subjects or if an active infection is known or suspected to be present. Live attenuated virus vaccines should not be given to pregnant women or to subjects with impaired immune responsiveness.
Immunoglobulins and sera, being antibodies, provide immediate passive immunity against an infection. Because of the risk of serum, sickness after administration of sera, im- munoglobulins are now used, as much as possible, for passive immunity.
The condition of storage is very important for immunological products. These are usu- ally specified for each product by the manufacturer. As a general rule these products need to be refrigerated but not frozen storage. Temperatures being usually in the range of 2-80 cc.
18.1 Sera and Immunoglobulins
Anti-D immunoglobulin (human).
Anti-rabies hyperimmune serum.
Snake venom antiserum.
Tetanus antitoxin (anti-tetanus serum).
ANTI-D IMMUNOGLOBULIN (HUMAN) Dosage form.-Injection.
Effects.-Combines with the D (Rhesus) antigen on Rhesus-positive red blood cells. Uses.-Given to a Rhesus-negative mother to prevent formation of anti-bodies to foetal rhesus-positive red cells which may pass into the maternal circulation during childbirth or abortion. Any further child is thus protected against the risk of intravascular haemolysis.
Precaution.- To be effective, it must be given within 72 hours of the birth or abortion. Dosage.-250-500 units by intramuscular injection.
ANTI-RABIES HYPERIMMUNE SERUM
Dosage form.-Injection, 1,000 units in 5 ml. ampoules. It is a purified concentrate prepared from the serum of actively immunised animals, usually horses.
Uses.-Post-exposure prophylaxis of rabies. Adverse reaction.-Serum sickness.
Dosage.-Not less than 40 units per kg. all at once partly by local infiltration into the ar- eas of the bite and the remainder by intramuscular injection.
TETANUS ANTITOXIN Dosage form.-Injection, 1000u and 3,000u/ml. Uses.-Post-exposure prophylaxis and treatment of tetanus. Adverse reaction.-Hypersensitivity reactions.
Dosage.-Prophylaxis-I ,500 units after test dose. Treatment: 20,000 units intravenously or intramuscularly after test dose.
SNAKE VENOM ANTISERUM (POLYVALENT)
Dosage form.-Freeze-dried venom-neutralising globulins obtained from the serum of
healthy horses immunised against venoms of different species of pit vipers.
Uses.- Treatment of snakebite.
Adverse effects.-Hypersensitivity reactions.
Dosage.-100 ml. of reconstituted anti-venom intravenously after test dose. 18.2 Vaccines
18.2.1 Vaccines for Universal Immunisation BCG vaccine (dried).
Diphtheria-Pertussis- Tetanus vaccine. Measles vaccine.
Poliomyelitis (live attenuated) vaccine. Tetanus vaccine.
BCG VACCINE (DRIED)
Dosage form.-Dried vaccine, reconstituted just before use into a solution for intrader- mal or percutaneous injection.
Pharmacological properties.-Freeze-dried preparation of live attenuated bacilli of the Calmette-Guerin strain.
Uses.-Active immunisation against tuberculosis.
Dosage- 1 ml. (adults), 0.05 ml. (neonates). The first dose to be given at six weeks of life.
DIPHTHERIA, PERTUSSIS AND TETANUS VACCINE
Dosage form.-Injection, 0.5 ml. ampoule,5 ml. vial. Prepared from diphtheria formol toxoid. Tetanus formol toxoid and pertussis vaccine.
Uses.-For primary immunisation of children against whooping cough, diphtheria and tetanus.
Dosage.–0.5 ml. by intramuscular or deep subcutaneous injection. Three doses are re- quired at intervals of not less than 4 weeks. The first dose to be given at six weeks of life.
MEASLES VACCINE Dosage form.-Injection, 0.5 ml. vial.
Pharmacological properties.-Freeze-dried, stabilised aqueous suspension of live-
attenuated measles virus strain.
Uses.-Active immunisation against measles.
Adverse effects.-Mild measles-like syndrome and neurological complication can occur. Dosage.-0.5 ml. by subcutaneous or intramuscular injection. The first dose to be given at nine months of life.
POLIOMYELITIS VACCINE (LIVE ATTENUATED)
Dosage form.-Oral, suspension of suitable li ve attenuated strains of poliomyelitis virus, types1, 2 and 3. Single dose and ten-dose containers.
Uses.-Active immunisation against poliomyelitis.
Dosage.- Three drops. For primary immunisation, three doses are required at intervals of not less than four weeks. The first dose to be given at six weeks of life.
Dosage form.-Injection, tetanus formol toxoid, 0.5 ml. ampoule or 5 ml. vial. Also available combined with diphtheria vaccine or with diphtheria and pertussis vaccines.
Uses.-Active immunisation against tetanus.
Dosage.—0.5 ml. by intramuscular or deep subcutaneous injection. The initial injection should be followed by a booster dose at 6-12 weeks and a second booster dose at 4-12 months.
18.2.2 VaccinesforSpecific Indications
Yellow fever vaccine.
Dosage form.-Injection, contains two or more killed serotypes of Vibrio cholera, 1.0,
1.5 ml. ampoules; 10, 50 ml. vials.
Uses.-Protection against cholera.
Dosage.–.5 ml. by intramuscular or deep subcutaneo us injection. Repeated every six months for those living in or travelling to endemic areas.
Dosage form.-Injection inactivates suspension of suitable strains of rabies virus grown
in cell cultures, 1.0 ml. vial.
Uses.-Pre-and post-exposure prophylaxis of rabies
Adverse effects.-Common; particularly allergic manifestations.
Dosage.-1.0 ml. subcutaneously daily for about fourteen days.
YELLOW FEVER VACCINE
Dosage form.-Injection, consists of live attenuated yellow fever virus (17D strain) grown in developing chick embryos. The vaccine is made up from the dried state with saline and must be used within thirty minutes.
Uses.-Active immunisation against yellow fever.
Adverse effects.-In children, encephalitis may occur.
Contra-indications.-Children under nine months, pregnant women, patients sensitive to eggs, patients with impaired immune responsiveness.
Dosage.–0.5 ml. by subcutaneous injection. Immunity appears ten days after primary vaccination and lasts for at least ten years. Revaccination at ten-yearly intervals.
19. Diagnostic Agents
These are described under the following headings-
19.1 Diabetes mellitus
Glucose oxidase reagent ………………………………………………………….Clinistix (R)
19.2 Gastric function …………………………………………………………………… Dextrostix (R)
19.3 Myasthenia Gravis Edrophonium
19.5 Radiocontrast Agents
19.5.1 Alimentary tract Barium sulphate
19.5.2 Oral Cholecystography
lopanic acid ………………………………………………… Telepaque (R)
19.5.3 Intravenous Cholecystograph and cholangioraph
Meglumine lodipamide……………………………………. Biligratin (R)
Meglumine diatrizoate …………………………………………… Urografin (R)
Sodium diatrizoate ………………………………………………… Hypaque (R)
Meglumine iothalamate……………………………………………………Conray (R)
Sodium iothalamate ……………………………………………Angio-Conray ) (R
Iophendylate…………………………………………………………… . Myodil (R)
19.1 Diabetes Mellitus
GLUCOSE OXIDASE REAGENT
Dosage form.-Impregnated, coloured, cellulose strip, (Clinistix ,(R)Dextrostix ) .((RPharmacological properties.- The strips contain glucose oxidase, orthotolidine and a peroxidase.
Uses.-To detect sugar (glucose) in urine. In the presence of glucose, the red colour of the strip changes to a light, medium or dark purple colour, with increasing concentrations of glucose from less than 0.25% over 0.5%.
Precaution.-The test is essentially qualitative not quantitative. It does not reliably detect urine sugar concentrations in excess of 0.5%.
(R) = Brand Name
False negative may occur-
(i) when large amounts of ascorbic acid are present in the urine;
(ii) following parentesal administration of antibiotics which use ascorbic acid as a preservative (e.g. oxytetracycline, tetracycline).
Method of us e.-Dip strip briefly into urine sample. 19.2 Gastric function
Dosage form.-Injection, solution containing 2.75 mg. (phosphate) per milliliter in 1m ampoule.
Pharmacological properties.-Histamine possesses a wide variety of effects on tissues all over the body. It has two types of receptors H1 and H2. Its stimulant action on gastric acid secretion is medicated via H2-receptors.
Uses.-Diagnostic test for gastric acid secretion-
1. In pernicious anaemia, atrophic gastritis, gastric cancer.
2. In Duodenal ulcer, post-operative stomal ulcer, Zollinger-Ellison syndrome.
3. After vagotomy or gastric resection.
Adverse effects.-Headache, tachycardia, nervousness, flushing, bronchospasm and a va- riety of other pharmacological effects of histamine.
Precaution.–Care should be taken in patients with a history of asthma or allergy, and in elderly patients.
Dosage.-0..3-0.5 mg. base subcutaneously (I mg. base is equivalent to 2.75 mg. phos- phate) following the administration of a large dose of an antihistamine.
Dosage form.-Injection, 0.25 mg. per ml. in 2 ml. ampoules.
Pharmacological properties.-Synthetic analogue of the natural polypeptide hormone, gastrin. Produces the same effects as the natural hormone. In particular, it stimulates the se- cretion of gastric acid.
Uses.-To evaluate gastric secretion (see histamine above).
Adverse effects.-Fewer and milder than those produced by histamine. They include ab- dominal cramps, nausea, vomiting, palpitation.
Precaution.-Should be used with care in patients with pancreatic, hepatic or biliary tract disease. High doses can inhibit gastric acid secretion.
Contra-indication.-Known hypersensitivity to the drug. Patients with acute, penetrating or bleeding peptic ulcers.
Dosage.–0.006 mg./kg. subcutaneously. 19.3 Mysthenia Gravis
EDROPHONIUM TENSILON Dosage Form.-Injection, 10 mg. (chloride) in l. ampoule.
Pharmacological properties.-Synthetic, short-acting, reversible anticholinesterase. Af-
ter intravenous injection action starts within 30-60 seconds and lasts about five minutes.
Uses.-Diagnosis of myasthenia gravis.
To distinguish between myasthenic crisis and cholinergic crises. Adverse effects.-Some patients may experience cholinergic reactions. Dosage.-I0 mg. by intravenous injection over one minute. Overdosage.-Treat with atropine.
FLUORESCEN Dosage form.-Eye-drops, 2% (sodium salt). Paper strips impregnated with the dye.
Pharmacological properties.-Auorescein is a dye applied to the eye. Paper strips im- pregnated with the dye are safer than the 2% solution because of the transfer of infection re- lated to the use of the latter. Ulcers of the cornea stain green, whereas the normal cornea does not retain the dye. The dye is washed out after the examination of the eye.
Uses.-Diagnosis of corneal lesions.
Detection of foreign bodies embedded in the cornea. Dosage.-Apply to the eye.
19.5 Radiocontrast Agents
The radiocontrast agents are used as aids in the diagnosis of diseases involving the gastro- intestinal, bilary, urogenital, cardiovascular, neurological and respiratory systems. In this sec- tion the radiocontrast agents are discussed in groups. Because this is an area in which it is customary not to use the generic names, proprietary names have been given side by side with the generic names. Not to do this could make the list of little practical value to expected users.
19.5.1 Alimentary Tract
BARIUM SULPHATE Dosage form.-Powder, in 125, 250, 500 g. jars.
Pharmacological properties.-Insoluble, white powder, not absorbed, not toxic. Uses.-Radiography of the alimentary tract.
Dosage.-200-750 g. suspended in 1-3 parts of water.
19.5.2 Oral Cholecystography
Radiocontrast media administered orally for radiological examination of the biliary tract include Iopanoic acid (Telepaque (R», Iocetamic acid (Cholebrine (R», Calcium ipodate (Biloptin (R» and Sodium ipodate (Solubiloptin (R», Iopanoic acid is included in the Essen- tial Drugs List as a representative of the group without prejudice to institutional preferences for other members of the group.
IOPANOIC ACID (TELEPAQUE (R)) Dosage form.- Tablets, 500 mg.
Pharmacological properties.-Absorbed from the gut, conjugated in the liver, excreted
in the bile and concentrated in the gall bladder.
Adverse effects.-Mild gastrointestinal disturbances. Contra-indication.-Uraemia.
Dosage.-3 g. orally with plenty of water, ten hours before the scheduled X-ray exami- nation.
19.5.3 Intravenous Cholecystography
Radiocontrast media can also be injected intravenously to produce X-ray definition of the gall bladder and biliary tract. Megulumine iodipamide and sodium iodipamide are the commonest agents used for this purpose. They are similar in most respects but the meglumine salt, being more soluble, can be given in a more concentrated solution.
MEGLUMINE IODIPAMIDE (BILIGRAFlN (R)) Dosage form.-Injection, 52% in 20 ml. ampoules and vials.
Pharmacological properties.-Radio-opaque organic iodine compound containing
49.4% iodine. Freely soluble in water and rapidly excreted by the liver.
Uses.-Cholecystography and cholangiography.
Adverse effects.-Anaphylactic reaction in hypersensitive subjects.
Precaution.-A test dose of 1 ml of the solution should be given slowly, intravenously, before the full dose is given.
Contra-indication.-Patients hypersensitive to iodides; patients with hyperthyroidism;
severe impairment of renal function.
Dosage.-Normal adult dose is 20 m\. of a 52% solution. 19.5.4 Urography
Radiocontrast media used in urography include meglumine diatrizoate, sodium diatrizo- ate and meglumine iothalamate. They can be administered intravenously for intravenous urog- raphy. They can also be used for retrograde pyelography and injected into a ureteral catheter.
MEGLUMINE DIATROZOATE (UROGRAFIN ) ((R
Injection, 60% in 25 ml. ampoules and 30 ml. vial. Injection, 76% in 20 ml. ampoule and vial. Injection, 85% in 50 ml. vial.
Injection, 34.3% with sodium diatrizoate 35% in 25 ml. and 50 ml. vials. Injection, 50% with sodium diatrizoate 25% in 20 ml. and 50 ml. vials. Injection, 60% with sodium diatrizoate 30% in 20 ml. and 50 ml. vials.
Pharmacological properties.-Rapidly circulates through the vascular system and ex-
creted unchanged by the kidney.
Excretory urography. Retrograde pyelography. Peripheral arteriography. Venography.
Cerebral angiography. Aortography. Angiocardiography. Hysterosalpingography.
Adverse effects.-Anaphylaxis, gastrointestinal disturbances; dyspnoea, headache, dizzi- ness, flushing.
Precaution.-Care should be taken in administering to patients with severe cardiovascular disease, hypertension, asthma. A Iml. test dose should be given before the full dose.
Contra-indication.-Severe renal or hepatic disease, hyperthyroidism, known hypersen- sitivity to iodides.
Dosage.-Preparation and dose varies with the procedure.
SODIUM DIATRlZOATE (HYPAQUE ) ((RSimilar to Meglumine diatrizoate.
Radiocontrast media which are used for angiography include the following which are also used for urography: meglumine diatrizoate, sodium diatrizoate and meglumine iothalam- ate. In additon, sodium iothalamate is used only for angiography but this compound should not be used for cerebral angioraph.
MEGLUMINE IOTHALAMATE (CONRAY ) ((R
Dosage form.-Injection, 60% in 20 ml. and 30 ml. vials and 30 ml. ampoules. Pharmacological properties.-Radio-opaque iodine-containing compound. It is an iso- mer of meglumine diatrizoate. Rapidly transported throughout the vascular system and ex- creted unchanged in the urine.
Peripheral arteriography and venography. Excretory urography.
Adverse effects.-Similar to meglumine diatrizoate. Precaution.-Similar to meglumine diatrizoate. Contra-indications.-Similar to meglumine diatrizoate. Dosage.-Dose depends on procedure.
SODIUM IOTHALAMATE (ANGIO-CONRAY (R)) Similar to meglumine iothalamate, except-
Dosage form.-Injection, 80% in 20 m\. and 50 ml, vials. Uses.-Angiocardiography, aortography, excretory urography. Contra-indications.-Should not be used for cerebral angiography. 19.5.6 Myelography
Only one radiocontrast substance is included in the Essential Drugs List for the radio- logical examination of the spinal canal: Iophendylate.
IOPHENDYLATE (MYODlL ) ((R Dosage form.-Injection, 1 ml, 3 m\. and 6 ml. ampoules.
Pharmacological properties.-Absorbable iodised fatty acid compound designed
specially for myelography and particularly for the study of the lumber region.
Adverse effects.-Headache; transient elevation of temperature.
Precaution.–Care should be taken to ensure that the needle point is in the subarachnoid space.
Contra-indications.-Should not be used:
(i) when lumber puncture is contra-indicated;
(ii) within ten days of a previous lumber puncture.
Dosage.-2-5 ml., injected slowly intrathecally by lumber puncture technique, usually between the 3rd and 4th lumber segments.
TUBERCULIN (PURIFIED PROTEIN DERIVATIVE, PPD)
Dosage form.-Injection, 1 TU, 5 TU or 250 TU per 0.1 m\.; see formulary for details of composition.
Pharmacological properties.-Sterile solution derived from the concentrated, soluble growth products of the tubercle bacillus. In sensitised individuals, it produces a delayed hy- persensitivity reaction manifested as erythema and an area of induration at the site of injec- tion.
Uses.-As an aid in the diagnosis of tuberculosis. A positive reaction to tuberculin may be indicative of hypersensitivity to the antigenic protein mixture as a result of past or present infection with tubercle bacilli.
Dosage.-Mantoux Test: 0.1 ml. of appropriate concentration is injected intradermally.
Multiple Puncture Test: as in the manufacturer’s information sheet.
2. Acetylsalicylic acid.
3. Actinomycin D.
6. Aluminium Hydroxide.
1l. Antazoline +Naphazoline.
12. Ascorbic acid (Vitamin C).
1. Barium Sulphate.
2. B.C.G. Vaccine.
3. B-Complex Vitamin.
8. Benzoic acid +Salicylic Acid.
10. Benzyl Benzoate. 11. Benzyl Penicillin.
l. Calamine +Zinc Oxide.
3. Charcoal, Activated.
13. Cholera Vaccine
1. Oral Rehydration Salts (Glucose, Potassium Chloride, Sodium Bicarbonate and Sodium Chloride).
No Subsidiary Legislation