A Guide to Drugs in Current Use PDF
Preview A Guide to Drugs in Current Use
A Guide to Drugs in Current Use EDITED BY J. PROFESSOR R. TROUNCE Professor of Clinical Pharmacology Guy's Hospital Medical School London MTP MEDICAL AND TECHNICAL PUBLISHING CO LTD· AYLESBURY 1970 Published in Great Britain by MTP (Medical and Technical Publishing Co Ltd) Chiltem House, Aylesbury Copyright © MTP 1970 (Medical and Technical Publishing Co. Ltd.) Softcover reprint of the hardcover 1s t edition 1970 All rights reserved. This book, or parts thereof, must not be reproduced without permission SBN 852 000 200 ISBN-l3: 978-94-011-5898-5 e-ISBN-13: 978-94-011-5896-1 DOl: 10.10071978-94-011-5896-1 Contents Introduction page I Category I Drugs Used in Neurological Disease 2 Category 2 Hypnotics 13 Category 3 The Analgesics 19 Category 4 Psychotropic Drugs 40 Category 5 Drugs Affecting the Autonomic Nervous System and Motor End-Plate 57 Category 6 Drugs used in Cardiac Disease 76 Category 7 Drugs used in the Treatment of Hypertensive Disease 91 Category 8 Diuretics and Cation Exchange Resins 102 Category 9 Drugs Used in Haematology III Category 10 Antimicrobials 121 Category II Drugs used in Tropical Medicine 139 Category 12 Cytotoxic Drugs 152 Category 13 Drugs used in the Treatment of Hormonal Disorders 163 Category 14 Miscellaneous Drugs 182 Category 15 Vitamins 190 Category 16 Vaccines and Sera 193 Supplement 198 Index 203 A* A Guide to Drugs in Current Use Introduction One of the major problems which face those who are engaged in treating patients is the large number of drugs available. These drugs are often powerful agents with potential to do harm as well as good. This book is not a treatise on therapy and the particular drug or drugs which should be used in a given clinical situation can be found elsewhere. Once however the line of treatment has been decided it is the duty of the doctor to know as much as possible about the drugs which he intends to use. It has been our aim to provide a short account of most of the drugs in current use with particular emphasis on side effects and contraindications. There is also a short review of drug interaction at the end. In some 70,000 words it has obviously not been possible to cover every aspect of every drug and a certain amount of selection of what is considered important has had to be made. However, it is hoped that nothing of real importance has been omitted. A few references have been included where they were considered useful. These will prove useful if the reader requires a more complete knowledge of a drug. In the case of drugs not covered by a reference, one of the many large textbooks of pharmacology should be adequate. The main difficulty is with very new drugs which are not yet in standard texts and further information about them can usually only be obtained from the litera ture. It will be noted that only approved names of drugs have been used. It is arguable that trade names are widely known and easier to re member. However, many drugs have more than one trade name and if these were used or even given as an alternative in the text it would lead to considerable confusion and difficulty. Category I Drugs Used in Neurological Disease THE TREATMENT OF EPILEPSY Phenobarbitone Pharmacological action. The drug is an effective anticonvulsant for generalised convulsive seizures and focal seizures. The neural synapse is probably its major site of action. It is thought that the drug slows or blocks cation transport of sodium and potassium across the cellular membrane and that this action damps down both excitatory and inhi bitory post-synaptic potential generation. Barbiturates exert a markedly depressant effect upon repetitive activity in eNS pathways. Therapeutic use [I]. The drug is used in the treatment of grand mal epilepsy and focal epilepsy. Temporal lobe epilepsy responds less satis factorily. The usual starting daily intake for adults is about 100 mg per day, taken in three divided doses or in a single dose at bedtime. Daily doses are increased if seizures persist, but should rarely exceed 300 mg per day. Initial daily doses for children are smaller, usually 45 to 60 mg per day. If phenobarbitone must be discontinued after prolonged use, withdrawal should proceed slowly over a period of a week to avoid the possibility of withdrawal convulsions. However, this complication is uncommon with phenobarbitone because ofi ts slow rate of metabol ism and elimination. Side effects and contra indications. 1. The sedative effect of the drug is a drawback. This can be circumvented by giving the total daily dose in the early evening and perhaps by medicating with central nervous system stimulants (amphetamines) during the waking hours. 2. Occasionally, for reasons as yet not clearly explained, pheno barbitone has a paradoxical exciting effect on children, the mentally retarded, and the elderly. 3. One or two per cent of patients receiving the drug develop derma titis, which necessitates withdrawal of the drug. Rare instances of ex foliative dermatitis have been reported. The drug is contraindicated in hepatic failure, as it is normally metabolised by hepatic enzymes; in acute intermittent porphyria it may produce a precipitous and danger- 2 Drugs Used in Neurological Disease ous rise in the level of porphyrins which is associated with the develop ment of symptoms ofa cute porphyria. Primidone Pharmacological action [I]. This drug is structurally closely related to phenobarbitone and its mechanism and site of action are probably the same. It is effective in the treatment of convulsive seizures refractory to other medications. However, its effectiveness against temporal lobe epilepsy and sometimes against petit mal suggests mechanisms ofa ction additional to those ofp henobarbitone. Therapeutic use. It is used for grand mal epilepsy and temporal lobe seizures. The drug is approximately one-fifth to one-tenth as potent as phenobarbitone. The average daily dose for adults is 750 mg, and for children 150 to 250 mg. Side effects. The effectiveness of the drug as an anticonvulsant is limited by its sedative properties. Skin rashes and leucopenia have been re ported, but are rare. Phenytoin sodium (Diphenylhydantoin, USA) Pharmacological action. The drug suppresses local spread of epileptiform activity but it does not depress spontaneous epileptiform discharge from the epileptic focus itself. The primary action of the drug is in stabilising excitable membranes. Therapeutic use. The drug is the most effective and widely used anti convulsant in the treatment of generalised convulsive seizures and focal epilepsy. Therapy is usually started in the adult with 100 mg three times per day. Doses can be increased to the point of intoxication or of cessa tion ofs eizures. Lack ofe ffect on seizures ofp rescribed daily doses above 500 to 600 mg suggests that the patient is not taking that amount of drug, or, in rare instances, that intestinal absorption is inadequate or that metabolism of the drug is over active. Doses above 500 mg per day arc rarely necessary or tolerated. Side effects. I. Very few patients arc hypersensitive to the drug or be come intoxicated with the usual daily doses. In the few patients this may be due to a defect in the metabolism of the drug by the liver or to interference with metabolism of the drug by other drugs. In such a case reduction of dosage to 100-200 mg per day may provide adequate pro tection from seizures and prevent intoxication. 3 A Guide to Drugs in Current Use 2. The features of overdosage are mainly neurological; the most striking effccts are ataxia, nystagmus, dysarthria, incoordination and unstcadiness. Lethargy and drowsiness commonly occur. 3. Chronic intoxication and severe acute intoxication have resulted in Purkinje cell degencration in the cerebellum. 4. Gum hypertrophy is common with chronic use and may be partially prevcntcd by good dental hygiene. 5. A morbilliform rash occurs in 2-5 per ccnt of patients. It clc~lfS aftcr discontinuing the drug, and docs not recur when the drug is restarted. 6. Lupus crythematosus is a rare complication. When it does occur there is a positive family history of lupus erythematosus in 20 per cent of the patients. 7. Hirsutism occurs to some degree in 75 per cent of the patients who take the drug. 8. Megaloblastic anaemia occurs rarely. It is due to interference with folic acid mctabolism and can be prevented by daily folic acid ad ministration. Othcr blood dyscrasias are rare. 9. Hcpatitis is rare. The drug should be withdrawn ifit occurs. Methoin (Mephenytoin, USA) Pharmacological action. Thc drug is related chemically and pharmaco logically to diphcnylhydantoin. It simulates the activity of the anti convulsant barbituratcs, and it also acts as a hydantoin in preventing the tonic phase of major motor convulsions. Therapeutic lise. The drug is of value in the treatment of generalised and major motor convulsions. It is also effective to some extent in prevent ing tcmporallobe automatisms. It has little effect on petit mal seizures, and may makc thcm worse. The dose is 100 mg daily, increased to 600 mg in accordancc with thc nccds of thc patient. Side ~lJects ami coHtrailldicatioHs. The drug possesses the disagrecable charactcristics of thc barbiturates (sedation and lethargy) often at lcss than optimum therapeutic lcvels. As a hydantoin it is considerably more toxic than diphenylhydantoin. The most dangerous toxic effccts are leukopcnia, pancytopenia, agranulocytosis, and aplastic anaemia. Lymphadcnopathy may occur. Troxidone (Trimethadione, USA) Pharmacological action. Troxidonc is an anti-cpileptic drug with speci ficity for thc trcatmcnt of pctit mal scizurcs. It is probable that troxidone 4 Drugs Used in Neurological Disease blocks the propagation of an epileptic discharge from a cortical epi leptic focus to the thalamus, while the local cortical spread of the epi leptiform activity is only slightly reduced, if at all. Therapelltic lise. The drug is used for the treatment of petit mal epi lepsy. For an adult the dose is 900 mg daily, in divided doses, increasing to I'S g. daily, according to the needs of the patient. For children the dose is 300 mg. daily, in divided doses, increasing to 900 mg. Side effects and contrail1dicatiol1s. A frequently observed side effect is hemeralopia or night blindness. This probably represents a drug action at the ganglion layer of the retina. Skin rashes occur with troxidone; they indicate a sensitivity reaction and their occurrence is an indication for drug withdrawal. Bone marrow depression may occur, usually during the first year of treatment. Nephrosis, hepatitis and lupus erythematosus have been reported. Ethosuximide Pharmacological action. This is the drug of choice in the treatment of petit mal and myoclonic seizures. It is extremely effective. TherapclItic usc. The adult dose is 500 mg daily, in divided doses, in creasing to 2 g., according to the needs of the patient. Side ~Bccts alld colltrailldicatiol1s. The drug is relatively non-toxic. Side effects occur infrequently, viz. gastro-intestinal upset, headache, dizzi ness, and skin rash. Blood changes are rare. Sulthiame Pharmacological actiol/. This drug is a sulfonamide congener with weak carbonic anhydrase activity. It has reported success in the treatment of temporal lobe epilepsy, although its mode of action is not known and trials have not shown the drug to be convincingly superior to other available medications. Therapeutic lise. The drug is given for psychomotor epilepsy in doses of 200-S00 mg daily. . Side ~Bccts. As the drug is a carbonic anhydrase inhibitor it may pro duce features of metabolic acidosis such as over-breathing. It potenti ates phenobarbitone and the hydantoins, and this may aCCOlll1t for some of its therapeutic effect. Headache, nausea, vomiting, dizziness, drowsi- 5 A Guide to Drugs in Current Use ness, visual blurring, gastric disturbances and rarely psychoses may complicate its use. Diazepam Pharmacological action. This drug is thought to exert an action upon the limbic system or its connections to reduce the intensity of emotional feeling. In addition, it has an anti-epileptic effect and in particular it appears to be extremely effective in arresting status epilepticus without producing overwhelming narcosis. Therapeutic use [2]. The chief value of the drug in epilepsy is in the control of status epilepticus. The drug is given parenter,illly, either in a single dose of 10 mg by slow intravenous injection, or by intravenous infusion of 100 mg over a I2-hour period. Side eJfects. Weakness, drowsiness and ataxia may be produced. Long term usage may result in habituation and very rarely in dependence. The drug may 'normalise' an abnormal E.E.G. tracing and therefore should not be given in the 10 days preceding an E.E.G. examination. THE TREATMENT OF MIGRAINE Ergotamine tartrate Pharmacological action. This drug causes vasoconstriction of the cerebral vessels. It is the only drug which is sufficiently constant in effect and duration in the management ofa ttacks of migraine. Therapeutic use (3). Patients vary enormously in their response to the drug; to obtain optimum results experiment is necessary in dosage and route of administration. It can be given orally, rectally, by inhalation, or by injection, and must be taken in adequate dosage as early as possi ble in the attack. Ideally the patient should rest in a dark room for an hour or two afterwards. The addition of caffeine is deftnitely ad vantageous; a sedative anti-emetic is added to some preparations. Taken orally ergotamine is often ineffective, and vomiting prevents its absorption. Chewing or sucking one or two tablets before the head ache is well established frequently aborts the attack. The best ways of giving ergotamine are usually by suppository or inhalation, although with inhalation there is the hazard of overdosage. Some patients require injection of the drug at the very onset of an attack. Patients must be in- 6 Drugs Used in Neurological Disease structed not to exceed the permitted dose. Details of preparations and doses are given in the following table: Tablets: Ergotamine I mg; (Ergotamine I mg {Ergotamine I mg or Medozine 10 mg Caffeine 100 mg Caffeine 100 mg I or 2 at first sign of attack, repeated as required, i-I hour later. Solution Dihydroergotamine 2 rug/ml 20 drops, repeated as required !-I hour later. Suppository Ergotamine 2 rug } Caffeine 100 mg Belladonna 0·25 mg Isobutalyl barbituric acid 100 mg Medihaler Vials: 9 rug Ergotamine/ml. A measured dose of 0'36 mg is delivered at each operation of the aerosol. MAXIMUM DOSES: 4 mg ERGOTAMINE DAILY; 8 mg WEEKLY Injection: Ampoules: 0·5 mg Ergotamine/rnl 0·25 mg I.M. or S.C. at onset of symptoms Not more than o· 5 mg in the day. Side effects and cOlltrailldicatiotls. The common side effects of ergotamine are numbness, tingling and chilling of the extremities, a rise in blood pressure, painful uterine contractions, and, particularly when it is in jected, nausea and vomiting. Variability in tolerance to the drug is marked; some patients can tolerate frequent large doses, and in others extreme sensitivity may be encountered. The contraindications to its use include peripheral vascular disease (particularly Raynaud's and Buerger's disease), hypertension, coronary, renal and hepatic insufficiency, pregnancy, and sepsis and infections which seem to sensitise to the drug. In migrainous hemiparesis the drug may prolong arterial spasm and induce a true cerebral thrombosis. Methysergide Pharmacological actiol1. The exact pharmacological action of methy sergi de in migraine is not known. This drug is the most powerful known antagonist to serotonin; it is structurally similar to serotonin and this antagonism is possibly due to competition for similar receptors. It is therefore possible that methysergide acts by competitively inhibiting 7
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