A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition

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CINACALCET 301 Further reading Block GA, Martin KJ, de Francisco ALM et al. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. New England Journal of Medicine 2004; 350: 1516–25. Delmas P. Treatment of postmenopausal osteoporosis. Lancet 2002; 359; 2018–26. Jackson RD, LaCroix AZ, Gass M et al. Calcium plus vitamin D supplementation and the risk of fractures. New England Journal of Medicine 2006; 354: 669–83. Kleerekoper M, Schein JR. Comparative safety of bone remodeling agents with a focus on osteoporosis therapies. Journal of Clinical Pharmacology 2001; 41: 239–50. Lopez FJ. New approaches to the treatment of osteoporosis. Current Opinion in Chemical Biology 2000; 4: 383–93. Marx SJ. Medical progress – Hyperparathyroid and hypoparathyroid disorders. New England Journal of Medicine 2000; 343: 1863–75. Meunier PJ, Roux C, Seeman E et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. New England Journal of Medicine 2004; 350: 459–68. Reeve J. Recombinant human parathyroid hormone: osteoporosis is proving amenable to treatment. British Medical Journal 2002; 324: 435–6. Reichel H, Koeftler HP, Norman AW. The role of the vitamin D endocrine system in health and disease. New England Journal of Medicine 1989; 320: 980–91. Rosen CJ, Bilezekian JP. Anabolic therapy for osteoporosis. Journal of Clinical Endocrinology and Metabolism 2001; 86: 957–64.
CHAPTER 40 ADRENAL HORMONES ● Adrenal cortex 302 ● Adrenal medulla 305 ADRENAL CORTEX The adrenal cortex secretes: 1. glucocorticosteroids, principally cortisol (hydrocortisone); 2. mineralocorticoids – principally aldosterone; 3. androgens (relatively small amounts). GLUCOCORTICOSTEROIDS The actions of glucocorticosteroids and the effects of their oversecretion (Cushing’s syndrome) and under-secretion (Addison’s disease) are summarized in Table 40.1. Glucocorticosteroids influence carbohydrate and protein metabolism, and play a vital role in the response to stress. Glucocorticosteroids stimulate the mobilization of amino acids from skeletal muscle, bone and skin, promoting their transport to the liver where they are converted into glucose (gluconeogenesis) and stored as glycogen. Fat mobilization by catecholamines is potentiated by glucocorticosteroids. The major therapeutic uses of the glucocorticosteroids exploit their powerful anti-inflammatory and immunosuppressive properties. They reduce circulating eosinophils, basophils and T-lymphocytes, while increasing neutrophils. Applied topically to skin or mucous membranes, potent steroids can cause local vasoconstriction and massive doses administered systemically can cause hypertension due to generalized vasoconstriction. Mechanism of action Glucocorticosteroids combine with a cytoplasmic glucocorticosteroid receptor causing its dissociation from a phosphorylated heat shock protein complex. The receptor–glucocorticosteroid complex translocates to the nucleus, where it binds to glucocorticosteroid response elements (GREs) in DNA and acts as a transcription factor. This increases the transcription of various signal transduction proteins. In addition, the glucocorticosteroid receptor interacts with both NFκB and AP-1 and inhibits them from enhancing transcription of many pro-inflammatory proteins. Thus glucocorticosteroids produce a delayed but profound anti-inflammatory effect. Adverse effects Adverse effects of glucocorticosteroids are common to all members of the group, and will be discussed before considering the uses of individual drugs. Chronic administration causes iatrogenic Cushing’s syndrome (see Table 40.1). Features include: • Cushingoid physical appearance; • impaired resistance to infection; • salt and water retention; hypokalaemia; • hypertension; • hyperglycaemia; • osteoporosis; • glucocorticosteroid therapy is weakly linked with peptic ulceration, and can mask the symptoms and signs of gastrointestinal perforation; • mental changes: anxiety, elation, insomnia, depression and psychosis; • posterior cataracts; • proximal myopathy; • growth retardation in children; • aseptic necrosis of bone. Acute adrenal insufficiency can result from rapid withdrawal after prolonged glucocorticosteroid administration. Gradual tapered withdrawal is less hazardous. However, even in patients who have been successfully weaned from chronic treatment with glucocorticosteroids, for one to two years afterwards a stressful situation (such as trauma, surgery or infection) may precipitate an acute adrenal crisis and necessitate the administration of large amounts of sodium chloride, glucocorticosteroids, glucose and water. Suppression of the adrenal cortex is unusual if the daily glucocorticosteroid dose is lower than the amount usually secreted physiologically. The rate at which patients can be weaned off glucocorticosteroids depends on their underlying condition and also on the dose and duration of therapy. After long-term glucocorticosteroid therapy has been discontinued the patient should continue to carry a steroid card for at least one year.
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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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Page 268 and 269: CONSTIPATION 257 • in hepatocellu
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Page 282 and 283: PART VII FLUIDS AND ELECTROLYTES
Page 284 and 285: CHAPTER 36 NEPHROLOGICAL AND RELATE
Page 286 and 287: DIURETICS 275 Key points Diuretics
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Page 290 and 291: DRUGS THAT AFFECT THE BLADDER AND G
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Page 296 and 297: CHAPTER 37 DIABETES MELLITUS ● In
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Page 308 and 309: CHAPTER 39 CALCIUM METABOLISM ● I
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Page 316 and 317: ADRENAL MEDULLA 305 injection may b
Page 318 and 319: CHAPTER 41 REPRODUCTIVE ENDOCRINOLO
Page 320 and 321: FEMALE REPRODUCTIVE ENDOCRINOLOGY 3
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Page 324 and 325: MALE REPRODUCTIVE ENDOCRINOLOGY 313
Page 326 and 327: MALE REPRODUCTIVE ENDOCRINOLOGY 315
Page 328 and 329: ANTERIOR PITUITARY HARMONES AND REL
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Page 332 and 333: PART IX SELECTIVE TOXICITY
Page 334 and 335: CHAPTER 43 ANTIBACTERIAL DRUGS ●
Page 336 and 337: COMMONLY PRESCRIBED ANTIBACTERIAL D
Page 346 and 347: PRINCIPLES OF MANAGEMENT OF MYCOBAC
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Page 350 and 351: MYCOBACTERIUM LEPRAE INFECTION 339
Page 352 and 353: ANTIFUNGAL DRUG THERAPY 341 POLYENE
Page 354 and 355: ANTIFUNGAL DRUG THERAPY 343 therapy
Page 356 and 357: ANTIVIRAL DRUG THERAPY (EXCLUDING A
Page 358 and 359: ANTIVIRAL DRUG THERAPY (EXCLUDING A
Page 360 and 361: 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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COMMON COMPLICATIONS OF CANCER CHEM
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DRUGS USED IN CANCER CHEMOTHERAPY 3
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PART X HAEMATOLOGY
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CHAPTER 49 ANAEMIA AND OTHER HAEMAT
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HAEMATINICS - IRON, VITAMIN B 12 AN
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HAEMATOPOIETIC GROWTH FACTORS 393 S
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IDIOPATHIC THROMBOCYTOPENIC PURPURA
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PART XI IMMUNOPHARMACOLOGY
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CHAPTER 50 CLINICAL IMMUNOPHARMACOL
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IMMUNOSUPPRESSIVE AGENTS 401 Ag Ant
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IMMUNOSUPPRESSIVE AGENTS 403 Table
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CHEMICAL MEDIATORS OF THE IMMUNE RE
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IMMUNOGLOBULINS AS THERAPY 407 DRUG
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PART XII THE SKIN
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CHAPTER 51 DRUGS AND THE SKIN ● I
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DERMATITIS (ECZEMA) 413 Avoid preci
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PSORIASIS 415 Emollients Improving
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ADVERSE DRUG REACTIONS INVOLVING TH
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ADVERSE DRUG REACTIONS INVOLVING TH
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PART XIII THE EYE
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CHAPTER 52 DRUGS AND THE EYE ● In
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DRUGS USED TO CONSTRICT THE PUPIL A
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DRUGS USED TO TREAT INFLAMMATORY DI
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CONTACT LENS WEARERS 429 Table 52.6
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PART XIV CLINICAL TOXICOLOGY
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CHAPTER 53 DRUGS AND ALCOHOL ABUSE
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OPIOID/NARCOTIC ANALGESICS 435 Tabl
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DRUGS THAT ALTER PERCEPTION 437 whi
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CENTRAL DEPRESSANTS 439 Peak plasma
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CENTRAL DEPRESSANTS 441 Key points
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MISCELLANEOUS 443 FURTHER READING G
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INTENTIONAL SELF-POISONING 445 Tabl
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INTENTIONAL SELF-POISONING 447 Tabl
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CRIMINAL POISONING 449 Commission o
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INDEX Note: Page numbers in italics
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INDEX 453 atrial fibrillation 217,
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INDEX 455 Cushing’s syndrome 302
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INDEX 457 5-fluorouracil 375-6 fluo
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INDEX 459 children 54 diazepam 108
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INDEX 461 non-steroidal anti-inflam
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INDEX 463 puberty (male), delay 314
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INDEX 465 tolerance 9, 433 benzodia
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