Clinical Pharmacology and Therapeutics

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ADVERSE DRUG REACTIONS INVOLVING THE SKIN 419 effect of too high a dose of UVB in a subject who has been exposed to a drug. The reaction is like severe sunburn and the threshold returns to normal when the drug is discontinued. Photoallergy (like drug allergy) is a cell-mediated immune reaction that only occurs in certain individuals, is not dose related and may be severe. It is due to a photochemical reaction caused by UVA where the drug combines with a tissue protein to form an antigen. These reactions are usually eczematous, and may persist for months or years after withdrawal of the drug. Some agents that commonly cause photosensitivity are shown in Table 51.6. Key points • Treatment of skin disorders depends on accurate diagnosis; steroids are not useful for all rashes and indeed may cause harm if used inappropriately. • Acne is treated first line with keratolytics; if systemic antibiotics are indicated, use oral oxytetracycline or erythromycin (but do not use tetracyclines in children under 12 years). Vitamin A analogues should only used in refractory cases. • In eczema, it is important to identify the causal agent and minimize/eradicate exposure if possible. • For dry, scaly eczema, use emollients plus a keratolytic; for wet eczema use drying lotions or zinc-medicated bandages. • Topical glucocorticosteroids are often required, but do not use high-potency glucocorticosteroids on the face. Use the lowest potency steroid for the shortest time possible required to produce clinical benefit. • In psoriasis, simple emollients should be used to treat mild cases. Keratolytics may be used in moderate cases. • Additional therapies for more severe cases of psoriasis include topical vitamin D analogues, PUVA, oral acitretin and cytotoxic drugs. Although glucocorticosteroids are effective, tachyphylaxis occurs, and on withdrawal pustular psoriasis may appear. Case history A 45-year-old white woman with a previous history of one culture-positive urinary tract infection (UTI) presents with a three-day history of dysuria and frequency of micturition. Her urinalysis shows moderate blood and protein and is positive for nitrates. She is started on a seven-day course of co-trimoxazole, two tablets twice a day, as she has a history of penicillin allergy with urticaria and wheezing. In the early morning of the last day of therapy, she develops a generalized rash on her body, which is itchy and worsens, despite the fact that she has not taken the last two doses of her antibiotic, her UTI symptoms having resolved. By the following morning she feels much worse, with itchy eyes, has had fevers overnight and is complaining of arthralgia and buccal soreness, and is seen by her community physician. He notes conjunctivitis, with swollen eyelids, soreness and ulceration on her lips and buccal and vaginal mucosa. She has a generalized maculo-papular rash which involves her face and has become confluent in areas on her abdomen and chest, and there is evidence of skin blistering and desquamation on her chest. Question What is the most likely diagnosis here? What is the probable cause, and how should this patient be managed? Answer The most likely diagnosis of a rapidly progressive generalized body rash involving the eyes, mouth and genitalia with systemic fever and early desquamation is erythema multiforme-major (Stevens Johnson syndrome, see Chapter 12, Figures 12.2 and 12.3). The most common causes of this syndrome are viral infections, especially herpes virus, drugs and (less frequently) systemic bacterial infections, such as meningitis, nephritis and streptococcal infection. Many drugs can cause this adverse reaction, but the most commonly incriminated classes of drugs are antibacterial agents such as sulphonamides, β-lactams (especially penicillins), vancomycin and rifampicin, anticonvulsants, salicylates and other NSAIDs, and allopurinol. In this patient the most likely aetiology is that she is taking co-trimoxazole, which contains 400 mg of sulphamethoxazole and 80 mg of trimethoprim per tablet. Stopping the offending agent is the most important part of her initial management. Her further management should include admission to hospital for intravenous fluids to maintain hydration, supportive care for the skin in order to minimize further desquamation and secondary infection with sterile wet dressings and an aseptic environment, analgesia if necessary, and maintenance and monitoring of her hepatic and renal function. If her condition is very severe, the patient may need to be transferred to a burns unit. Short courses of high-dose glucocorticosteroids early in the disease have been recommended, but controlled clinical studies have not demonstrated the benefit of glucocorticosteroids in this condition. The disease may progress for up to four or five days and recovery may take from one to several weeks. The mortality rate for Stevens Johnson syndrome is 5%, but increases to about 30% if the diagnosis is toxic epidermal necrolysis with more extensive desquamation. FURTHER READING Series of articles relating to current treatment of dermatological conditions. Clinical Medicine 2005; 5: 551–75.
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A Textbook of Clinical Pharmacology
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A Textbook of Clinical Pharmacology
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This fifth edition is dedicated to
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CONTENTS FOREWORD PREFACE ACKNOWLED
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PREFACE Clinical pharmacology is th
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PART I GENERAL PRINCIPLES
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CHAPTER 1 INTRODUCTION TO THERAPEUT
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SCIENTIFIC BASIS OF USE OF DRUGS IN
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AGONISTS 7 100 100 Effect (%) Effec
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SLOW PROCESSES 9 100 2 Dose ratio -
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CHAPTER 3 PHARMACOKINETICS ● Intr
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REPEATED (MULTIPLE) DOSING 13 In re
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NON-LINEAR (‘DOSE-DEPENDENT’) P
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CHAPTER 4 DRUG ABSORPTION AND ROUTE
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ROUTES OF ADMINISTRATION 19 ROUTES
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ROUTES OF ADMINISTRATION 21 Transde
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ROUTES OF ADMINISTRATION 23 FURTHER
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PHASE II METABOLISM (TRANSFERASE RE
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ENZYME INDUCTION 27 and lorazepam.
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METABOLISM OF DRUGS BY INTESTINAL O
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CHAPTER 6 RENAL EXCRETION OF DRUGS
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ACTIVE TUBULAR REABSORPTION 33 ACTI
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RENAL DISEASE 35 DISTRIBUTION Drug
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LIVER DISEASE 37 Detailed recommend
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THYROID DISEASE 39 DIGOXIN Myxoedem
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CHAPTER 8 THERAPEUTIC DRUG MONITORI
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DRUGS FOR WHICH THERAPEUTIC DRUG MO
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CHAPTER 9 DRUGS IN PREGNANCY ● In
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PHARMACOKINETICS IN PREGNANCY 47 va
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PRESCRIBING IN PREGNANCY 49 an anti
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PRESCRIBING IN PREGRANCY 51 Case hi
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BREAST-FEEDING 53 METABOLISM At bir
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RESEARCH 55 lifelong effects as a r
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PHARMACODYNAMIC CHANGES 57 DISTRIBU
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EFFECT OF DRUGS ON SOME MAJOR ORGAN
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RESEARCH 61 FURTHER READING Dhesi J
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ADVERSE DRUG REACTION MONITORING/SU
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ADVERSE DRUG REACTION MONITORING/SU
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PREVENTION OF ALLERGIC DRUG REACTIO
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EXAMPLES OF ALLERGIC AND OTHER ADVE
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CHAPTER 13 DRUG INTERACTIONS ● In
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HARMFUL INTERACTIONS 73 Response Re
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HARMFUL INTERACTIONS 75 Table 13.1:
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HARMFUL INTERACTIONS 77 Table 13.5:
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CHAPTER 14 PHARMACOGENETICS ● Int
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GENETIC INFLUENCES ON DRUG METABOLI
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INHERITED DISEASES THAT PREDISPOSE
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INHERITED DISEASES THAT PREDISPOSE
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CLINICAL TRIALS 87 • Discovery
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CLINICAL DRUG DEVELOPMENT 89 Too ma
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GLOBALIZATION 91 ETHICS COMMITTEES
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CELL-BASED AND RECOMBINANT DNA THER
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HUMAN STEM CELL THERAPY 95 duration
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CHAPTER 17 ALTERNATIVE MEDICINES: H
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SOY 99 A case report has suggested
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MISCELLANEOUS HERBS 101 including h
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PART II THE NERVOUS SYSTEM
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CHAPTER 18 HYPNOTICS AND ANXIOLYTIC
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ANXIETY 107 and daytime sleeping sh
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ANXIETY 109 Key points • Insomnia
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SCHIZOPHRENIA 111 Box 19.1: Dopamin
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SCHIZOPHRENIA 113 The Boston Collab
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BEHAVIOURAL EMERGENCIES 115 Oral me
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DEPRESSIVE ILLNESSES AND ANTIDEPRES
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DEPRESSIVE ILLNESSES AND ANTIDEPRES
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LITHIUM, TRYPTOPHAN AND ST JOHN’S
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SPECIAL GROUPS 123 Case history A 4
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PARKINSON’S SYNDROME AND ITS TREA
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PARKINSON’S SYNDROME AND ITS TREA
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MYASTHENIA GRAVIS 129 CHOREA The γ
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ALZHEIMER’S DISEASE 131 Cholinerg
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CHAPTER 22 ANTI-EPILEPTICS ● Intr
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GENERAL PRINCIPLES OF TREATMENT OF
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GENERAL PRINCIPLES OF TREATMENT OF
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WITHDRAWAL OF ANTI-EPILEPTIC DRUGS
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FEBRILE CONVULSIONS 141 Case histor
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DRUGS USED FOR MIGRAINE PROPHYLAXIS
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CHAPTER 24 ANAESTHETICS AND MUSCLE
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INHALATIONAL ANAESTHETICS 147 is th
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SUPPLEMENTARY DRUGS 149 • Respira
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MUSCLE RELAXANTS 151 NON-DEPOLARIZI
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LOCAL ANAESTHETICS 153 have also pr
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CHAPTER 25 ANALGESICS AND THE CONTR
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DRUGS USED TO TREAT MILD OR MODERAT
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OPIOIDS 159 Key points Drugs for mi
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OPIOIDS 161 increases, correlating
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MANAGEMENT OF POST-OPERATIVE PAIN 1
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PART III THE MUSCULOSKELETAL SYSTEM
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CHAPTER 26 ANTI-INFLAMMATORY DRUGS
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DISEASE-MODIFYING ANTIRHEUMATIC DRU
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HYPERURICAEMIA AND GOUT 171 • Sto
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HYPERURICAEMIA AND GOUT 173 Pharmac
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PART IV THE CARDIOVASCULAR SYSTEM
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CHAPTER 27 PREVENTION OF ATHEROMA:
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PREVENTION OF ATHEROMA 179 responsi
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DRUGS USED TO TREAT DYSLIPIDAEMIA 1
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DRUGS USED TO TREAT DYSLIPIDAEMIA 1
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CHAPTER 28 HYPERTENSION ● Introdu
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DRUGS USED TO TREAT HYPERTENSION 18
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OTHER ANTIHYPERTENSIVE DRUGS 193 Ke
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OTHER ANTIHYPERTENSIVE DRUGS 195 Ca
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MANAGEMENT OF STABLE ANGINA 197 Ass
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MANAGEMENT OF UNSTABLE CORONARY DIS
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DRUGS USED IN ISCHAEMIC HEART DISEA
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DRUGS USED IN ISCHAEMIC HEART DISEA
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ANTICOAGULANTS 205 Intrinsic pathwa
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ANTICOAGULANTS 207 that the pharmac
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ANTICOAGULANTS IN PREGNANCY AND PUE
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CHAPTER 31 HEART FAILURE ● Introd
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DRUGS FOR HEART FAILURE 213 The dru
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DRUGS FOR HEART FAILURE 215 therape
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CHAPTER 32 CARDIAC DYSRHYTHMIAS ●
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CARDIOPULMONARY RESUSCITATION AND C
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TREATMENT OF OTHER SPECIFIC DYSRHYT
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SELECTED ANTI-DYSRHYTHMIC DRUGS 223
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PART V THE RESPIRATORY SYSTEM
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CHAPTER 33 THERAPY OF ASTHMA, CHRON
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CHRONIC BRONCHITIS AND EMPHYSEMA 23
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DRUGS USED TO TREAT ASTHMA AND CHRO
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DRUGS USED TO TREAT ASTHMA AND CHRO
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RESPIRATORY FAILURE 241 use in asth
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DRUG-INDUCED PULMONARY DISEASE 243
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PART VI THE ALIMENTARY SYSTEM
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CHAPTER 34 ALIMENTARY SYSTEM AND LI
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PEPTIC ULCERATION 249 • With rega
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PEPTIC ULCERATION 251 Ranitidine ha
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ANTI-EMETICS 253 Vestibular stimula
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INFLAMMATORY BOWEL DISEASE 255 cort
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CONSTIPATION 257 • in hepatocellu
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PANCREATIC INSUFFICIENCY 259 Ciprof
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LIVER DISEASE 261 withdrawal), smal
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DRUGS THAT MODIFY APPETITE 263 Tabl
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CHAPTER 35 VITAMINS AND TRACE ELEME
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VITAMIN C(ASCORBIC ACID) 267 dinucl
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TRACE ELEMENTS 269 Table 35.1: Comm
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PART VII FLUIDS AND ELECTROLYTES
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CHAPTER 36 NEPHROLOGICAL AND RELATE
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DIURETICS 275 Key points Diuretics
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VOLUME DEPLETION 277 is sometimes c
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DRUGS THAT AFFECT THE BLADDER AND G
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DRUGS THAT AFFECT THE BLADDER AND G
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PART VIII THE ENDOCRINE SYSTEM
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CHAPTER 37 DIABETES MELLITUS ● In
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DRUGS USED TO TREAT DIABETES MELLIT
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ANTITHYROID DRUGS 293 deficiency. P
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SPECIAL SITUATIONS 295 fertility. I
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CHAPTER 39 CALCIUM METABOLISM ● I
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BISPHOSPHONATES 299 effective in li
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CINACALCET 301 Further reading Bloc
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ADRENAL CORTEX 303 Table 40.1: Acti
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ADRENAL MEDULLA 305 injection may b
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CHAPTER 41 REPRODUCTIVE ENDOCRINOLO
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FEMALE REPRODUCTIVE ENDOCRINOLOGY 3
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FEMALE REPRODUCTIVE ENDOCRINOLOGY 3
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MALE REPRODUCTIVE ENDOCRINOLOGY 313
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MALE REPRODUCTIVE ENDOCRINOLOGY 315
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ANTERIOR PITUITARY HARMONES AND REL
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POSTERIOR PITUITARY HARMONES 319 FU
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PART IX SELECTIVE TOXICITY
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CHAPTER 43 ANTIBACTERIAL DRUGS ●
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COMMONLY PRESCRIBED ANTIBACTERIAL D
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PRINCIPLES OF MANAGEMENT OF MYCOBAC
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FIRST-LINE DRUGS IN TUBERCULOSIS TH
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MYCOBACTERIUM LEPRAE INFECTION 339
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ANTIFUNGAL DRUG THERAPY 341 POLYENE
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ANTIFUNGAL DRUG THERAPY 343 therapy
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ANTIVIRAL DRUG THERAPY (EXCLUDING A
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ANTIVIRAL DRUG THERAPY (EXCLUDING A
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INTERFERONS AND ANTIVIRAL HEPATITIS
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CHAPTER 46 HIV AND AIDS ● Introdu
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ANTI-HIV DRUGS 353 Table 46.1: Exam
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ANTI-HIV DRUGS 355 NON-NUCLEOSIDE A
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OPPORTUNISTIC INFECTIONS IN HIV-1-S
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ANTI-HERPES VIRUS THERAPY 359 salva
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CHAPTER 47 MALARIA AND OTHER PARASI
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MALARIA 363 Pharmacokinetics Chloro
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HELMINTHIC INFECTION 365 Table 47.2
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CHAPTER 48 CANCER CHEMOTHERAPY ●
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Page 382 and 383: DRUGS USED IN CANCER CHEMOTHERAPY 3
Page 398 and 399: PART X HAEMATOLOGY
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Page 404 and 405: HAEMATOPOIETIC GROWTH FACTORS 393 S
Page 406 and 407: IDIOPATHIC THROMBOCYTOPENIC PURPURA
Page 408 and 409: PART XI IMMUNOPHARMACOLOGY
Page 410 and 411: CHAPTER 50 CLINICAL IMMUNOPHARMACOL
Page 412 and 413: IMMUNOSUPPRESSIVE AGENTS 401 Ag Ant
Page 414 and 415: IMMUNOSUPPRESSIVE AGENTS 403 Table
Page 416 and 417: CHEMICAL MEDIATORS OF THE IMMUNE RE
Page 418 and 419: IMMUNOGLOBULINS AS THERAPY 407 DRUG
Page 420 and 421: PART XII THE SKIN
Page 422 and 423: CHAPTER 51 DRUGS AND THE SKIN ● I
Page 424 and 425: DERMATITIS (ECZEMA) 413 Avoid preci
Page 426 and 427: PSORIASIS 415 Emollients Improving?
Page 428 and 429: ADVERSE DRUG REACTIONS INVOLVING TH
Page 432 and 433: PART XIII THE EYE
Page 434 and 435: CHAPTER 52 DRUGS AND THE EYE ● In
Page 436 and 437: DRUGS USED TO CONSTRICT THE PUPIL A
Page 438 and 439: DRUGS USED TO TREAT INFLAMMATORY DI
Page 440 and 441: CONTACT LENS WEARERS 429 Table 52.6
Page 442 and 443: PART XIV CLINICAL TOXICOLOGY
Page 444 and 445: CHAPTER 53 DRUGS AND ALCOHOL ABUSE
Page 446 and 447: OPIOID/NARCOTIC ANALGESICS 435 Tabl
Page 448 and 449: DRUGS THAT ALTER PERCEPTION 437 whi
Page 450 and 451: CENTRAL DEPRESSANTS 439 Peak plasma
Page 452 and 453: CENTRAL DEPRESSANTS 441 Key points
Page 454 and 455: MISCELLANEOUS 443 FURTHER READING G
Page 456 and 457: INTENTIONAL SELF-POISONING 445 Tabl
Page 458 and 459: INTENTIONAL SELF-POISONING 447 Tabl
Page 460 and 461: CRIMINAL POISONING 449 Commission o
Page 462 and 463: INDEX Note: Page numbers in italics
Page 464 and 465: INDEX 453 atrial fibrillation 217,
Page 466 and 467: INDEX 455 Cushing’s syndrome 302
Page 468 and 469: INDEX 457 5-fluorouracil 375-6 fluo
Page 470 and 471: INDEX 459 children 54 diazepam 108
Page 472 and 473: INDEX 461 non-steroidal anti-inflam
Page 474 and 475: INDEX 463 puberty (male), delay 314
Page 476: INDEX 465 tolerance 9, 433 benzodia
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