BOOK
Clinical Pharmacology - E-Book
Morris J. Brown | Pankaj Sharma | Fraz A. Mir | Peter N. Bennett
(2018)
Additional Information
Book Details
Abstract
‘The very last thing a drug regulator wishes to be able to say is, like Lord Byron (1788-1824), on the publication of his poem Childe Harold’s Pilgrimage, ‘I awoke one morning and found myself famous.’
The twelfth edition of this long-established textbook of clinical pharmacology (first published in 1960) continues its fine tradition of balancing science and practice for improved evidence-based drug therapy and good prescribing in therapeutic settings increasingly complicated by intercurrent disease and polypharmacy.
- Coverage of all major therapeutic topics by body system.
- Introductory sections give brief chapter synopses.
- Case studies where relevant.
- Covers the needs of the developing world with a focus on practical prescribing and health technology assessment.
- Definition, tips, brief explanation boxes throughout.
- Interesting histories, etymologies and provenances of terms throughout.
- Entertaining footnotes throughout.
‘The very last thing a drug regulator wishes to be able to say is, like Lord Byron (1788-1824), on the publication of his poem Childe Harold’s Pilgrimage, ‘I awoke one morning and found myself famous.’
- Fully updated throughout.
- New co-editor: Fraz Mir, Addenbrooke’s Hospital and Department of Medicine, University of Cambridge, Royal College of Physicians Associate International Director for South Asia.
- Now with free e-book on StudentConsult.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | cover | ||
| Inside Front Cover | ifc1 | ||
| Half title page | i | ||
| Dedication | ii | ||
| Clinical Pharmacology | iii | ||
| Copyright Page | iv | ||
| Table Of Contents | v | ||
| Preface | vii | ||
| Contributors | ix | ||
| Acknowledgements | xiii | ||
| 1 General | 1 | ||
| 1 Clinical pharmacology | 2 | ||
| Synopsis | 2 | ||
| Guide to further reading | 4 | ||
| 2 Topics in drug therapy | 5 | ||
| Synopsis | 5 | ||
| The therapeutic situation | 5 | ||
| Some background | 5 | ||
| Treating patients with drugs | 6 | ||
| Drugs can do good | 6 | ||
| Drugs can do harm | 6 | ||
| Uses of drugs/medicines | 7 | ||
| Cure | 7 | ||
| Suppression | 7 | ||
| Prevention | 7 | ||
| Physician-induced (iatrogenic) disease | 7 | ||
| Benefits and risks of medicines | 8 | ||
| Unavoidable risks | 8 | ||
| Reduction of risk | 8 | ||
| Two broad categories of risk | 8 | ||
| Elements of risk | 9 | ||
| Three major grades of risk | 9 | ||
| Whenever a drug is taken a risk is taken | 9 | ||
| Public view of drugs and prescribers | 10 | ||
| Criticisms of modern drugs | 10 | ||
| Drug-induced injury (see also Ch. 9) | 11 | ||
| Negligence and strict and no-fault liability | 11 | ||
| Complementary, alternative and traditional medicine | 12 | ||
| Homoeopathy | 14 | ||
| Conclusion | 15 | ||
| Placebo medicines | 15 | ||
| Guidelines, ‘essential’ drugs and prescribing | 16 | ||
| ‘Essential’ drugs | 17 | ||
| Cost-containment | 17 | ||
| Taking a drug history | 18 | ||
| Repeat prescriptions | 18 | ||
| Warnings and consent | 18 | ||
| Legal hazards for prescribers | 19 | ||
| Compliance | 19 | ||
| Patient compliance | 19 | ||
| Suggestions for doctors to enhance patient compliance/adherence | 21 | ||
| Directly observed therapy | 21 | ||
| Over-compliance. | 21 | ||
| Evaluation of patient compliance. | 21 | ||
| Doctor compliance | 22 | ||
| Underdosing | 22 | ||
| The clinical importance of missed dose(s) | 22 | ||
| Pharmacoeconomics (see also Ch. 5) | 23 | ||
| The economists’ objective | 23 | ||
| Quality of life | 24 | ||
| Guide to further reading | 25 | ||
| Appendix: the prescription | 26 | ||
| Example of a prescription for a patient with an annoying unproductive cough: | 26 | ||
| Medicine containers. | 26 | ||
| Unwanted medicines. | 27 | ||
| Drugs liable to cause dependence | 27 | ||
| Abbreviations | 27 | ||
| Weights and measures | 27 | ||
| Equivalents: | 27 | ||
| Abbreviations: | 27 | ||
| Home/domestic measures. | 27 | ||
| Percentages, proportions, weight in volume | 27 | ||
| 3 Discovery and development of drugs | 28 | ||
| Synopsis | 28 | ||
| Making a new medicine | 28 | ||
| Techniques of discovery | 30 | ||
| Molecular modelling and structural biology | 30 | ||
| High throughput screening | 30 | ||
| Fragments. | 30 | ||
| Proteins as medicines: biotechnology. | 30 | ||
| Antisense approaches. | 31 | ||
| Gene therapy | 32 | ||
| Stem cells. | 32 | ||
| Immunopharmacology. | 32 | ||
| Older approaches | 32 | ||
| Drug quality | 32 | ||
| Studies in animals | 33 | ||
| Pharmacodynamics | 33 | ||
| Pharmacokinetics | 33 | ||
| Toxicology | 33 | ||
| Genotoxicity | 34 | ||
| Carcinogenicity | 34 | ||
| Reproductive and developmental toxicity | 34 | ||
| Local tolerance | 34 | ||
| Biotechnology-derived pharmaceuticals | 34 | ||
| Ethics and legislation | 34 | ||
| Safety prediction | 35 | ||
| Orphan drugs and diseases | 36 | ||
| Guide to further reading | 36 | ||
| 4 Evaluation of drugs in humans | 37 | ||
| Synopsis | 37 | ||
| Experimental therapeutics | 37 | ||
| Research involving human subjects | 38 | ||
| Ethics of research in humans | 38 | ||
| The ethics of the randomised and placebo-controlled trial | 39 | ||
| Injury to research subjects | 40 | ||
| Payment of subjects in clinical trials | 40 | ||
| Rational introduction of a new drug to humans | 40 | ||
| Phases of clinical development | 40 | ||
| Official regulatory guidelines and requirements | 42 | ||
| Therapeutic investigations | 42 | ||
| Therapeutic evaluation | 43 | ||
| Need for statistics | 44 | ||
| Concepts and terms | 44 | ||
| Hypothesis of no difference | 44 | ||
| A statistical significance test | 44 | ||
| Confidence intervals. | 44 | ||
| Types of error | 45 | ||
| Type I error | 45 | ||
| Type II error | 45 | ||
| Types of therapeutic trial | 45 | ||
| Dose–response trials. | 46 | ||
| Superiority, equivalence and non-inferiority in clinical trials. | 46 | ||
| Design of trials | 47 | ||
| Techniques to avoid bias | 47 | ||
| Randomisation | 47 | ||
| Blinding. | 47 | ||
| Some common design configurations | 48 | ||
| Parallel group design | 48 | ||
| Crossover design | 48 | ||
| Factorial designs | 48 | ||
| Multicentre trials | 48 | ||
| N-of-1 trials | 48 | ||
| Historical controls | 49 | ||
| Size of trials | 49 | ||
| Fixed sample size and sequential designs | 49 | ||
| Sensitivity of trials | 50 | ||
| Meta-analysis | 50 | ||
| Results: implementation | 51 | ||
| Relative and absolute risk | 51 | ||
| Pharmacoepidemiology | 52 | ||
| Observational cohort studies | 52 | ||
| Case–control studies | 53 | ||
| Surveillance systems: pharmacovigilance | 53 | ||
| Voluntary reporting. | 53 | ||
| Prescription event monitoring. | 54 | ||
| Medical record linkage | 54 | ||
| Population statistics, | 54 | ||
| Strength of evidence | 54 | ||
| In conclusion | 54 | ||
| Guide to further reading | 55 | ||
| 5 Health technology assessment | 56 | ||
| Synopsis | 56 | ||
| The scope | 56 | ||
| Clinical effectiveness | 57 | ||
| 1. Developing the protocol | 57 | ||
| 2. Defining the methods | 57 | ||
| 3. Analysing the data | 57 | ||
| Qualitative synthesis | 58 | ||
| Quantitative synthesis (meta-analysis) | 58 | ||
| 4. Drawing conclusions | 59 | ||
| Cost-effectiveness | 59 | ||
| 1. Costs | 60 | ||
| 2. Benefits | 60 | ||
| Natural units | 60 | ||
| Health utilities | 60 | ||
| 3. Type of analysis | 60 | ||
| Cost-effectiveness analysis | 60 | ||
| Cost-utility analysis | 61 | ||
| In conclusion | 61 | ||
| Guide to further reading | 62 | ||
| 6 Regulation of medicines | 63 | ||
| Synopsis | 63 | ||
| Basis for regulation | 63 | ||
| Historical background | 64 | ||
| Current medicines regulatory systems | 65 | ||
| Rare diseases | 65 | ||
| Requirements | 65 | ||
| Authorisation for clinical trials in the UK | 65 | ||
| Regulatory review of a new drug marketing application | 66 | ||
| Regulatory review | 66 | ||
| Post-licensing responsibilities | 67 | ||
| Discussion | 67 | ||
| Licensed medicines for unlicensed indications | 68 | ||
| Unlicensed medicines and accelerated licensing | 68 | ||
| Decision-taking | 68 | ||
| Counterfeit drugs | 69 | ||
| Complementary and alternative medicine | 69 | ||
| Medicines regulation: the future | 70 | ||
| Guide to further reading | 70 | ||
| 7 Classification and naming of drugs | 71 | ||
| Synopsis | 71 | ||
| Classification | 71 | ||
| Nomenclature (names) | 71 | ||
| Non-proprietary names | 72 | ||
| Clarity. | 72 | ||
| Economy. | 72 | ||
| Convenience. | 72 | ||
| Proprietary names | 73 | ||
| Confusing names. | 73 | ||
| Guide to further reading | 74 | ||
| 2 From pharmacology to toxicology | 75 | ||
| 8 General pharmacology | 76 | ||
| Synopsis | 76 | ||
| 3 Infection and inflammation | 165 | ||
| 12 Chemotherapy of infections | 166 | ||
| Synopsis | 166 | ||
| History | 166 | ||
| Classification of antimicrobial drugs | 168 | ||
| How antimicrobials act – sites of action | 168 | ||
| The cell wall. | 169 | ||
| The cytoplasmic membrane. | 169 | ||
| Protein synthesis. | 169 | ||
| Nucleic acid metabolism. | 169 | ||
| Principles of antimicrobial chemotherapy | 169 | ||
| Make a diagnosis | 169 | ||
| Remove barriers to cure, | 169 | ||
| Decide whether chemotherapy is really necessary. | 169 | ||
| Select the best drug. | 169 | ||
| Administer the drug | 169 | ||
| Continue therapy | 170 | ||
| Test for cure. | 170 | ||
| Prophylactic chemotherapy | 170 | ||
| Carriers of pathogenic or resistant organisms | 170 | ||
| Use of antimicrobial drugs | 170 | ||
| Choice | 170 | ||
| Knowledge of the likely pathogens | 170 | ||
| Rapid diagnostic tests. | 170 | ||
| Route of administration. | 171 | ||
| Combinations | 171 | ||
| Chemoprophylaxis and pre-emptive suppressive therapy | 171 | ||
| Chemoprophylaxis in surgery | 172 | ||
| Antimicrobials should be selected | 172 | ||
| Antimicrobials should be given | 172 | ||
| Problems with antimicrobial drugs | 173 | ||
| Resistance | 173 | ||
| Mechanisms of resistance | 174 | ||
| Limitation of resistance | 174 | ||
| Superinfection | 175 | ||
| Antibiotic-associated (or Clostridium difficile-associated) colitis | 175 | ||
| Opportunistic infection | 176 | ||
| Masking of infections | 176 | ||
| Drugs of choice | 176 | ||
| Guide to further reading | 177 | ||
| 13 Antibacterial drugs | 178 | ||
| Synopsis | 178 | ||
| Classification | 178 | ||
| Inhibition of cell wall synthesis | 178 | ||
| β-lactams | 178 | ||
| Inhibition of protein synthesis | 178 | ||
| Aminoglycosides. | 178 | ||
| Tetracyclines, | 178 | ||
| Macrolides: | 178 | ||
| Inhibition of nucleic acid synthesis | 178 | ||
| Sulfonamides. | 178 | ||
| Quinolones | 178 | ||
| Azoles | 178 | ||
| Inhibition of cell wall synthesis | 179 | ||
| β-lactams | 179 | ||
| Penicillins | 179 | ||
| Mode of action. | 179 | ||
| Pharmacokinetics. | 179 | ||
| Adverse effects. | 179 | ||
| Narrow-spectrum penicillins | 180 | ||
| Benzylpenicillin | 180 | ||
| Uses. | 180 | ||
| Adverse effects | 180 | ||
| Preparations and dosage for injection. | 180 | ||
| Preparations and dosage for oral use. | 180 | ||
| Antistaphylococcal penicillins | 180 | ||
| Broad-spectrum penicillins | 180 | ||
| Amoxicillin | 181 | ||
| Ampicillin | 181 | ||
| Co-amoxiclav | 181 | ||
| Adverse effects. | 181 | ||
| Mecillinam | 181 | ||
| Temocillin | 181 | ||
| Antipseudomonal penicillins | 181 | ||
| Carboxypenicillins | 181 | ||
| Ticarcillin | 181 | ||
| Ureidopenicillins | 181 | ||
| Piperacillin | 182 | ||
| Cephalosporins | 182 | ||
| Mode of action | 182 | ||
| Pharmacokinetics. | 182 | ||
| Classification and uses. | 183 | ||
| Adverse effects. | 183 | ||
| Ceftobiprole | 184 | ||
| Other β-lactam antibacterials | 184 | ||
| Monobactam | 184 | ||
| Carbapenems | 184 | ||
| Imipenem | 184 | ||
| Adverse effects. | 184 | ||
| Meropenem | 184 | ||
| Ertapenem | 184 | ||
| Penems | 184 | ||
| Other inhibitors of cell wall synthesis and membrane function | 184 | ||
| Vancomycin | 184 | ||
| Uses. | 185 | ||
| Adverse effects. | 185 | ||
| Teicoplanin | 185 | ||
| Daptomycin | 185 | ||
| Oritavancin, dalbavancin and telavancin | 186 | ||
| Inhibition of protein synthesis | 186 | ||
| Aminoglycosides | 186 | ||
| Mode of action. | 186 | ||
| Pharmacokinetics. | 186 | ||
| Antibacterial activity. | 186 | ||
| Uses | 186 | ||
| Adverse effects. | 187 | ||
| Individual aminoglycosides | 187 | ||
| Gentamicin | 187 | ||
| Dose | 187 | ||
| Tetracyclines and glycylcyclines | 188 | ||
| Mode of action. | 188 | ||
| Pharmacokinetics. | 188 | ||
| Uses. | 188 | ||
| Adverse reactions. | 188 | ||
| Interactions. | 188 | ||
| Individual tetracyclines | 188 | ||
| Tetracycline | 188 | ||
| Doxycycline | 188 | ||
| Minocycline | 189 | ||
| Tigecycline | 189 | ||
| Macrolides and lincosamides | 189 | ||
| Erythromycin | 189 | ||
| Uses. | 189 | ||
| Dose | 189 | ||
| Adverse reactions. | 189 | ||
| Interactions. | 189 | ||
| Clarithromycin | 190 | ||
| Azithromycin | 190 | ||
| Telithromycin | 190 | ||
| Clindamycin, | 190 | ||
| Other inhibitors of protein synthesis | 191 | ||
| Chloramphenicol | 191 | ||
| Pharmacokinetics. | 191 | ||
| 4 Nervous system | 287 | ||
| 18 Pain and analgesics | 288 | ||
| Synopsis | 288 | ||
| Pain and analgesics | 288 | ||
| Definition of pain | 288 | ||
| Nociception | 289 | ||
| Classification of clinical pain | 290 | ||
| Acute pain, | 291 | ||
| Chronic pain | 291 | ||
| Neuropathic pain | 291 | ||
| Cancer-related pain | 291 | ||
| Evaluation of pain | 291 | ||
| Pharmacotherapy | 291 | ||
| Non-opioid analgesics | 292 | ||
| NSAIDS (non-steroidal anti-inflammatory drugs) | 292 | ||
| Mechanism of analgesia | 292 | ||
| Clinical use | 292 | ||
| Choice of NSAID and route of administration | 292 | ||
| Adverse effects | 292 | ||
| Acetaminophen (Paracetamol) | 292 | ||
| Nefopam (3,4,5,6-tetrahydro-5-methyl-l-phenyl-1H-2.5-benoxazocine hydrochloride) | 293 | ||
| Opioid analgesics | 293 | ||
| Mechanism of action of opioids | 293 | ||
| Classification of opioid drugs | 293 | ||
| Opioid pharmacodynamics | 293 | ||
| Systemic effects of opioid analgesics | 294 | ||
| Central nervous system | 294 | ||
| Cardiovascular system | 295 | ||
| Gastrointestinal tract | 295 | ||
| Urogenital tract | 295 | ||
| Others | 295 | ||
| Opioid pharmacokinetics | 295 | ||
| Route of administration | 296 | ||
| Pharmacology of individual opioids | 296 | ||
| Opioid agonist drugs | 296 | ||
| Morphine | 296 | ||
| Diamorphine | 296 | ||
| Codeine | 297 | ||
| Dihydrocodeine | 297 | ||
| Oxycodone | 297 | ||
| Hydromorphone | 297 | ||
| Methadone | 297 | ||
| Fentanyl | 297 | ||
| Alfentanil | 298 | ||
| Remifentanil | 298 | ||
| Papaveretum | 298 | ||
| Partial agonist opioid analgesics | 298 | ||
| Buprenorphine | 298 | ||
| Meptazinol | 298 | ||
| Mixed agonist-antagonist opioid analgesics | 298 | ||
| Opioids with action on other systems | 299 | ||
| Meperidine | 299 | ||
| Tramadol | 299 | ||
| Tapentadol | 299 | ||
| Opioid antagonists | 299 | ||
| Naloxone | 299 | ||
| Choice of opioid analgesic | 299 | ||
| Tolerance, dependence and addiction | 300 | ||
| Tolerance | 300 | ||
| Dependence | 301 | ||
| Addiction | 301 | ||
| Pain management in opioid addicts | 301 | ||
| Co-analgesics | 301 | ||
| Multipurpose adjuvant analgesics | 301 | ||
| Corticosteroids | 301 | ||
| Neuroleptics | 301 | ||
| Benzodiazepines | 302 | ||
| Adjuvant analgesics used in neuropathic pain | 302 | ||
| Antidepressants | 302 | ||
| Anticonvulsants | 302 | ||
| Local anaesthetics | 303 | ||
| Capsaicin | 303 | ||
| Clonidine | 303 | ||
| Cannabinoids | 303 | ||
| Ziconotide | 303 | ||
| Ketamine | 304 | ||
| Adjuvants used for bone pain | 304 | ||
| Bisphosphonates | 304 | ||
| Pharmacotherapy of acute migraine headaches | 304 | ||
| Management of migraine | 304 | ||
| Abortive treatment of migraine | 305 | ||
| Selective 5-HT1 agonists (triptans) | 305 | ||
| Sumatriptan | 305 | ||
| Ergotamine | 305 | ||
| Preventive treatment for migraine | 306 | ||
| Beta-adrenergic Blockers | 306 | ||
| Valproic acid | 306 | ||
| Topiramate | 306 | ||
| Other drugs used in migraine prevention | 306 | ||
| Guide to further reading | 307 | ||
| 19 Anaesthesia and neuromuscular block | 308 | ||
| Synopsis | 308 | ||
| General anaesthesia | 308 | ||
| Phases of general anaesthesia | 309 | ||
| Before surgery, | 309 | ||
| During surgery, | 309 | ||
| After surgery, | 309 | ||
| Before surgery (premedication) | 309 | ||
| Anxiolysis and amnesia. | 309 | ||
| Analgesia | 309 | ||
| Timing. | 309 | ||
| Gastric contents. | 309 | ||
| During surgery. | 309 | ||
| Induction | 309 | ||
| Maintenance | 310 | ||
| After surgery | 310 | ||
| Relief of pain | 310 | ||
| Postoperative nausea and vomiting | 310 | ||
| Some special techniques | 310 | ||
| Dissociative anaesthesia | 310 | ||
| Sedation and amnesia | 310 | ||
| Entonox, | 310 | ||
| Methoxyflurane, | 310 | ||
| Pharmacology of anaesthetics | 310 | ||
| Mode of action | 311 | ||
| Inhalation anaesthetics | 311 | ||
| Pharmacokinetics (volatile liquids, gases) | 311 | ||
| Nitrous oxide | 311 | ||
| Advantages. | 311 | ||
| Disadvantages. | 311 | ||
| Uses. | 311 | ||
| Dosage and administration. | 311 | ||
| Contraindications. | 312 | ||
| Precautions. | 312 | ||
| Adverse effects. | 312 | ||
| Halogenated anaesthetics | 312 | ||
| Isoflurane | 312 | ||
| Respiratory effects. | 312 | ||
| Cardiovascular effects. | 312 | ||
| Other effects. | 312 | ||
| Sevoflurane | 312 | ||
| Desflurane | 312 | ||
| Halothane | 312 | ||
| Oxygen in anaesthesia | 313 | ||
| Intravenous anaesthetics | 313 | ||
| Pharmacokinetics | 313 | ||
| Propofol | 313 | ||
| Central nervous system. | 313 | ||
| Cardiovascular system. | 313 | ||
| 5 Cardiorespiratory and renal systems | 391 | ||
| 22 Cholinergic and antimuscarinic (anticholinergic) mechanisms and drugs | 392 | ||
| Synopsis | 392 | ||
| Cholinergic drugs (cholinomimetics) | 392 | ||
| Classification | 392 | ||
| Direct-acting (receptor agonists) | 392 | ||
| Indirect-acting | 393 | ||
| Sites of action (see Fig. 22.1) | 393 | ||
| Pharmacology | 393 | ||
| Autonomic nervous system | 393 | ||
| Parasympathetic division. | 393 | ||
| Sympathetic division. | 394 | ||
| Neuromuscular (voluntary) junction | 394 | ||
| Central nervous system | 394 | ||
| Blood vessels | 394 | ||
| Choline esters | 394 | ||
| Acetylcholine | 394 | ||
| Other choline esters | 394 | ||
| Alkaloids with cholinergic effects | 395 | ||
| Nicotine | 395 | ||
| Pilocarpine, | 395 | ||
| Arecoline | 395 | ||
| Muscarine | 395 | ||
| Anticholinesterases | 395 | ||
| Physostigmine | 395 | ||
| Neostigmine | 396 | ||
| Pyridostigmine | 396 | ||
| Distigmine | 396 | ||
| Edrophonium | 396 | ||
| Carbaryl | 396 | ||
| Anticholinesterase poisoning | 396 | ||
| Typical features | 396 | ||
| Treatment. | 397 | ||
| Poisoning | 397 | ||
| Disorders of neuromuscular transmission | 397 | ||
| Myasthenia gravis | 397 | ||
| Pathogenesis. | 398 | ||
| Diagnosis. | 398 | ||
| Treatment | 398 | ||
| Excessive dosing | 398 | ||
| Lambert–Eaton syndrome | 399 | ||
| Drug-induced disorders of neuromuscular transmission | 399 | ||
| Antimicrobials. | 399 | ||
| Cardiovascular drugs. | 399 | ||
| Other drugs. | 399 | ||
| Drugs that oppose acetylcholine | 399 | ||
| Antimuscarinic drugs | 399 | ||
| Atropine | 399 | ||
| Exocrine glands. | 400 | ||
| Smooth muscle | 400 | ||
| Ocular effects. | 400 | ||
| Cardiovascular system. | 400 | ||
| Central nervous system. | 400 | ||
| Antagonism to cholinergic drugs. | 400 | ||
| Pharmacokinetics. | 400 | ||
| Dose. | 400 | ||
| Poisoning | 400 | ||
| Other antimuscarinic drugs | 400 | ||
| Hyoscine | 401 | ||
| Hyoscine butylbromide | 401 | ||
| Homatropine | 401 | ||
| Tropicamide | 401 | ||
| Ipratropium | 401 | ||
| Tiotropium | 401 | ||
| Flavoxate | 401 | ||
| Oxybutynin | 402 | ||
| Glycopyrronium | 402 | ||
| Propantheline | 402 | ||
| Dicyclomine | 402 | ||
| Benzhexol | 402 | ||
| Solifenacin, darifenacin | 402 | ||
| Promethazine. | 402 | ||
| Propiverine, | 402 | ||
| Guide to further reading | 402 | ||
| 23 Adrenergic mechanisms and drugs | 403 | ||
| Synopsis | 403 | ||
| Adrenergic mechanisms | 403 | ||
| Classification of sympathomimetics | 403 | ||
| By mode of action | 403 | ||
| Tachyphylaxis | 404 | ||
| Interactions of sympathomimetics | 404 | ||
| History. | 405 | ||
| Consequences of adrenoceptor activation | 405 | ||
| Selectivity for adrenoceptors | 405 | ||
| Adrenoceptor agonists (see Table 23.1) | 405 | ||
| α + β effects, non-selective: | 405 | ||
| α1 effects: | 405 | ||
| α2 effects in the central nervous system: | 405 | ||
| β effects, non-selective (i.e. β1 + β2): | 405 | ||
| β1 effects, with some α effects: | 405 | ||
| β1 effects: | 405 | ||
| β2 effects, | 405 | ||
| Adrenoceptor antagonists (blockers) | 405 | ||
| Effects of a sympathomimetic | 405 | ||
| Physiological note. | 407 | ||
| Synthetic non-catecholamines | 407 | ||
| Pharmacokinetics | 407 | ||
| Catecholamines | 407 | ||
| Adverse effects | 407 | ||
| Sympathomimetics and plasma potassium. | 408 | ||
| Overdose of sympathomimetics | 408 | ||
| Individual sympathomimetics | 408 | ||
| Catecholamines | 408 | ||
| Adrenaline/epinephrine | 408 | ||
| Adrenaline/epinephrine is used in anaphylactic shock | 408 | ||
| Accidental overdose | 408 | ||
| Noradrenaline/norepinephrine (chiefly α and β1 effects) | 409 | ||
| Isoprenaline (isoproterenol) | 409 | ||
| Dopamine | 409 | ||
| Dobutamine | 409 | ||
| Dopexamine | 409 | ||
| Non-catecholamines | 409 | ||
| Salbutamol (see also Asthma) | 409 | ||
| Salmeterol | 410 | ||
| Ephedrine | 410 | ||
| Phenylephrine | 410 | ||
| Mucosal decongestants | 410 | ||
| Shock | 410 | ||
| Definition. | 410 | ||
| Treatment | 411 | ||
| Types of shock | 411 | ||
| In poisoning by a cerebral depressant | 411 | ||
| In central circulatory failure | 411 | ||
| Septic shock | 411 | ||
| Choice of drug in shock | 412 | ||
| Monitoring drug use | 412 | ||
| Restoration of intravascular volume | 412 | ||
| Dextran 70 | 412 | ||
| Gelatin products | 412 | ||
| Etherified starch. | 412 | ||
| Chronic orthostatic hypotension | 412 | ||
| Detrusor relaxation for urinary frequency, urgency and urge incontinence | 413 | ||
| Guide to further reading | 414 | ||
| 24 Arterial hypertension, angina pectoris, myocardial infarction and heart failure | 415 | ||
| Synopsis | 415 | ||
| Hypertension: how drugs act | 415 | ||
| Angina pectoris: how drugs act | 416 | ||
| Drugs used in hypertension and angina | 416 | ||
| Diuretics (see also Ch. 27) | 416 | ||
| Vasodilators | 416 | ||
| Organic nitrates | 416 | ||
| Pharmacokinetics. | 417 | ||
| Tolerance | 417 | ||
| Uses. | 417 | ||
| Adverse effects. | 417 | ||
| Interactions. | 417 | ||
| Glyceryl trinitrate (see also above) | 417 | ||
| For prophylaxis, | 418 | ||
| Venepuncture. | 418 | ||
| Isosorbide dinitrate | 418 | ||
| Isosorbide mononitrate | 418 | ||
| Pentaerithrityl tetranitrate | 418 | ||
| Calcium channel blockers | 418 | ||
| Vascular smooth muscle cells. | 418 | ||
| Pharmacokinetics. | 418 | ||
| Indications for use | 418 | ||
| Adverse effects. | 419 | ||
| Interactions | 419 | ||
| Individual calcium channel blockers | 419 | ||
| Nifedipine | 419 | ||
| Amlodipine | 419 | ||
| Verapamil | 419 | ||
| Diltiazem | 420 | ||
| Nimodipine | 420 | ||
| Other members | 420 | ||
| Angiotensin-converting enzyme (ACE) inhibitors, angiotensin (AT) II receptor blockers (ARBs) and renin inhibitors | 420 | ||
| Uses | 420 | ||
| Hypertension. | 420 | ||
| Cardiac failure | 420 | ||
| Diabetic nephropathy. | 421 | ||
| Myocardial infarction (MI). | 421 | ||
| Cautions | 421 | ||
| Adverse effects | 421 | ||
| ACE inhibitors: | 421 | ||
| ARBs | 422 | ||
| 6 Blood and neoplastic disease | 511 | ||
| 29 Drugs and haemostasis | 512 | ||
| Synopsis | 512 | ||
| Introduction | 512 | ||
| The coagulation system | 512 | ||
| Procoagulant drugs | 513 | ||
| Vitamin K | 513 | ||
| Phytomenadione | 514 | ||
| Menadiol | 514 | ||
| Vitamin K is used to treat the following: | 514 | ||
| Coagulation factor concentrates | 514 | ||
| Use of coagulation factor concentrates | 514 | ||
| Desmopressin (DDAVP) | 515 | ||
| Adverse effects. | 515 | ||
| Other agents | 515 | ||
| Adrenaline/epinephrine | 515 | ||
| Fibrin glue | 515 | ||
| Sclerosing agents | 515 | ||
| Anticoagulant drugs | 515 | ||
| Oral vitamin K antagonists (VKA) | 516 | ||
| Pharmacokinetics. | 516 | ||
| Pharmacodynamics. | 516 | ||
| Dose. | 516 | ||
| Adverse effects. | 517 | ||
| Withdrawal of oral anticoagulant therapy. | 517 | ||
| Reversal of anticoagulation | 517 | ||
| Drug interactions. | 517 | ||
| Analgesics. | 517 | ||
| Antimicrobials. | 517 | ||
| Anticonvulsants. | 517 | ||
| Antiarrhythmics. | 517 | ||
| Antidepressants. | 517 | ||
| Gastrointestinal drugs. | 517 | ||
| Lipid-lowering drugs. | 518 | ||
| Sex hormones and hormone antagonists. | 518 | ||
| Sedatives and anxiolytics. | 518 | ||
| Uses of oral VKA | 518 | ||
| Surgery in patients receiving oral VKA | 518 | ||
| Elective surgery. | 518 | ||
| Emergency surgery. | 518 | ||
| Dental extractions. | 518 | ||
| Other vitamin K antagonists | 518 | ||
| Oral direct thrombin and factor Xa inhibitors | 518 | ||
| Dabigatran | 518 | ||
| Rivaroxaban, apixaban and edoxaban | 519 | ||
| Parenteral anticoagulants | 519 | ||
| Heparin | 519 | ||
| Pharmacokinetics. | 520 | ||
| Pharmacodynamics. | 520 | ||
| Monitoring heparin therapy. | 520 | ||
| Adverse effects. | 520 | ||
| Heparin reversal. | 521 | ||
| Use of heparin | 521 | ||
| Treatment of established venous thromboembolism. | 521 | ||
| Prevention of venous thromboembolism. | 521 | ||
| Cardiac disease. | 521 | ||
| Peripheral arterial occlusion. | 521 | ||
| Other anticoagulant drugs | 521 | ||
| Anticoagulant drugs under development | 521 | ||
| Fibrinolytic (thrombolytic) system | 522 | ||
| Plasminogen activators | 522 | ||
| Fibrinolysis inhibitors. | 522 | ||
| Drugs that promote fibrinolysis | 522 | ||
| Uses of thrombolytic drugs | 523 | ||
| Vascular occlusion | 523 | ||
| Adverse effects. | 523 | ||
| Drugs that prevent fibrinolysis | 523 | ||
| Tranexamic acid | 523 | ||
| Aprotinin | 523 | ||
| Platelet function | 523 | ||
| Drugs that inhibit platelet activity (antiplatelet drugs) | 524 | ||
| Aspirin | 524 | ||
| Dipyridamole | 524 | ||
| Clopidogrel | 524 | ||
| Prasugrel | 524 | ||
| Ticagrelor. | 524 | ||
| Epoprostenol | 525 | ||
| Glycoprotein (GP) IIb–IIIa antagonists | 525 | ||
| Abciximab | 525 | ||
| Eptifibatide | 525 | ||
| Adverse effects. | 525 | ||
| Uses of antiplatelet drugs | 525 | ||
| Guide to further reading | 527 | ||
| 30 Red blood cell disorders | 528 | ||
| Synopsis | 528 | ||
| Iron | 528 | ||
| Iron deficiency | 529 | ||
| Management of iron deficiency and prophylactic iron administration | 530 | ||
| Oral iron preparations | 530 | ||
| Liquid iron formulations | 530 | ||
| Sustained or slow-release iron preparations | 530 | ||
| Adverse effects | 530 | ||
| Parenteral iron | 530 | ||
| Adverse effects | 531 | ||
| Drug interactions | 531 | ||
| Anaemia of chronic disease | 531 | ||
| Functional iron deficiency | 532 | ||
| Chronic iron overload | 532 | ||
| Parenteral iron chelator. | 532 | ||
| Oral iron chelators. | 532 | ||
| Deferiprone | 532 | ||
| Deferasirox. | 532 | ||
| Iron poisoning and acute overdose | 532 | ||
| Vitamin B12 | 533 | ||
| Vitamin B12 deficiency | 533 | ||
| Management of vitamin B12 deficiency and prophylactic administration | 534 | ||
| Contraindications to cobalamin | 535 | ||
| Folic acid (pteroylglutamic acid) | 535 | ||
| Folic acid deficiency | 535 | ||
| Management of folic acid deficiency and prophylactic administration | 536 | ||
| Haemolytic anaemia | 536 | ||
| Autoimmune haemolytic anaemia | 536 | ||
| Drug-induced haemolytic anaemia | 536 | ||
| Glucose-6-phosphate dehydrogenase deficiency | 537 | ||
| Haemoglobinopathies | 538 | ||
| Sickle cell anaemia | 538 | ||
| Thalassaemia | 538 | ||
| Aplastic anaemia | 538 | ||
| Polycythaemia vera | 539 | ||
| Management of PV | 539 | ||
| Haemopoietic growth factors | 540 | ||
| Erythropoiesis-stimulating agents | 540 | ||
| Clinical uses of ESAs | 540 | ||
| Anaemia of chronic renal failure. | 540 | ||
| Anaemia due to cancer chemotherapy. | 540 | ||
| Other clinical uses of EPO. | 540 | ||
| Adverse effects | 540 | ||
| Granulocyte colony-stimulating factor | 541 | ||
| Adverse effects | 541 | ||
| Thrombopoietin receptor agonists | 541 | ||
| Guide to further reading | 541 | ||
| 31 Neoplastic disease and immunosuppression | 543 | ||
| Synopsis | 543 | ||
| Neoplastic disease | 543 | ||
| Cancer treatments and outcomes | 543 | ||
| Systemic cancer therapy | 544 | ||
| Rationale for cytotoxic chemotherapy | 545 | ||
| Classes of cytotoxic chemotherapy drugs | 545 | ||
| Adverse effects of cytotoxic chemotherapy | 548 | ||
| Nausea and vomiting | 548 | ||
| Suppression of bone marrow and the lymphoreticular system. | 548 | ||
| Opportunistic infection | 548 | ||
| Diarrhoea and mouth ulcers | 548 | ||
| Alopecia | 548 | ||
| Urate nephropathy | 548 | ||
| Local extravasation | 548 | ||
| Hypersensitivity reactions | 548 | ||
| Specific organ damage | 548 | ||
| Delayed wound healing | 548 | ||
| Germ cells and reproduction | 548 | ||
| Carcinogenicity | 548 | ||
| Classes of cytotoxic agents | 549 | ||
| Alkylating agents | 549 | ||
| Antimetabolites | 549 | ||
| Anthracyclines and related compounds | 549 | ||
| Topoisomerase inhibitors | 549 | ||
| Spindle poisons | 549 | ||
| Platinum drugs | 549 | ||
| Miscellaneous agents | 550 | ||
| Chemotherapy in clinical practice | 550 | ||
| Drug use and tumour cell kinetics | 550 | ||
| Cytotoxic drugs | 550 | ||
| The selection of drugs | 550 | ||
| Drug resistance | 551 | ||
| Resistance | 551 | ||
| Multiple drug resistance | 551 | ||
| Improving efficacy of chemotherapy | 551 | ||
| Hazards to staff handling cytotoxic agents | 551 | ||
| A note of caution. | 552 | ||
| Interactions of anticancer agents with other drugs | 552 | ||
| Endocrine therapy | 552 | ||
| Hormonal influence on cancer | 552 | ||
| Hormonal agents | 552 | ||
| Breast cancer | 552 | ||
| Prostatic cancer | 553 | ||
| Benign prostatic hypertrophy | 553 | ||
| Adrenocortical steroids | 553 | ||
| In general, | 553 | ||
| Immunotherapy | 553 | ||
| ATRA | 554 | ||
| Development of anticancer drug therapy | 554 | ||
| Targeted biological therapies | 555 | ||
| Passive immunotherapy using monoclonal antibodies raised against specific tumour-associated antigens on the cell surface | 555 | ||
| Radioimmunotherapy | 555 | ||
| Chemo-immunotherapy | 556 | ||
| Signal transduction inhibitors | 556 | ||
| Targeting the cell cycle | 557 | ||
| Protease inhibition | 557 | ||
| Chemoprevention of cancer | 557 | ||
| Viral immunisation and cancer prevention | 558 | ||
| Immunosuppression | 558 | ||
| Ciclosporin | 558 | ||
| Pharmacokinetics. | 558 | ||
| Uses. | 558 | ||
| Adverse reactions. | 559 | ||
| Interactions. | 559 | ||
| Tacrolimus | 559 | ||
| Antilymphocyte immunoglobulin | 559 | ||
| Mycophenolate | 559 | ||
| Hazards of immunosuppressive drugs | 559 | ||
| Carcinogenicity | 559 | ||
| Active immunisation during immunosuppressive therapy | 559 | ||
| Guide to further reading | 560 | ||
| 7 Gastrointestinal system | 561 | ||
| 32 Oesophagus, stomach and duodenum | 562 | ||
| Synopsis | 562 | ||
| The oesophagus in health and disease | 562 | ||
| Gastric acid secretion and mucosal protection | 562 | ||
| Gastric acid secretion | 563 | ||
| Gastrin | 563 | ||
| Acetylcholine (ACh) | 563 | ||
| Histamine | 563 | ||
| Prostaglandins | 563 | ||
| Mucosal protective mechanisms | 563 | ||
| Helicobacter pylori (H. pylori): an occasionally silent killer | 563 | ||
| NSAIDs: enemies of the gut | 563 | ||
| Drugs affecting oesophageal motility and the lower oesophageal sphincter | 564 | ||
| Drugs to reduce or neutralise gastric acid | 564 | ||
| Proton pump inhibitors (PPIs) | 564 | ||
| Pharmacology. | 564 | ||
| Pharmacokinetics. | 564 | ||
| Adverse reactions and interactions. | 565 | ||
| H2-receptor antagonists (H2RAs) | 565 | ||
| Pharmacology. | 565 | ||
| Pharmacokinetics and dosage. | 565 | ||
| Adverse effects and interactions. | 565 | ||
| Antacids | 565 | ||
| Individual antacids | 565 | ||
| Other targets for acid suppression | 565 | ||
| Drugs to enhance mucosal protection | 566 | ||
| Sucralfate (SUCRose sulFATE and ALuminium hydroxide complex) | 566 | ||
| Adverse effects and interactions. | 566 | ||
| Bismuth chelate (tripotassium dicitratobismuthate, bismuth sub-citrate) | 566 | ||
| 8 Endocrine system, metabolic conditions | 593 | ||
| 35 Adrenal corticosteroids, antagonists, corticotropin | 594 | ||
| Synopsis | 594 | ||
| Adrenal steroids and their synthetic analogues | 594 | ||
| Mechanism of action | 595 | ||
| On inorganic metabolism. | 595 | ||
| On organic metabolism | 595 | ||
| Individual adrenal steroids | 598 | ||
| Hydrocortisone | 599 | ||
| Prednisolone | 599 | ||
| Methylprednisolone | 599 | ||
| Fluorinated corticosteroids (triamcinolone, fludrocortisone) | 599 | ||
| Triamcinolone | 599 | ||
| Fludrocortisone | 599 | ||
| Dexamethasone and betamethasone | 599 | ||
| Aldosterone | 599 | ||
| Spironolactone | 599 | ||
| Beclometasone, budesonide, fluticasone, mometasone and ciclesonide | 599 | ||
| Pharmacokinetics of corticosteroids | 599 | ||
| Dosage schedules | 600 | ||
| Adverse effects of systemic adrenal steroid pharmacotherapy | 600 | ||
| Endocrine. | 600 | ||
| Musculoskeletal. | 600 | ||
| Immune. | 600 | ||
| Gastrointestinal. | 600 | ||
| Central nervous system. | 600 | ||
| Ophthalmic effects | 600 | ||
| Other effects | 600 | ||
| Adrenal steroids and pregnancy | 600 | ||
| Precautions during chronic adrenal steroid therapy | 601 | ||
| Treatment of intercurrent illness | 601 | ||
| Dosage and routes of administration | 601 | ||
| Systemic commencing doses: | 601 | ||
| Topical applications | 602 | ||
| Contraindications | 602 | ||
| Long-term use of adrenal steroids in children | 602 | ||
| Uses of adrenocortical steroids | 602 | ||
| Replacement therapy | 602 | ||
| Acute adrenocortical insufficiency (Addisonian crisis) | 602 | ||
| Chronic primary adrenocortical insufficiency (Addison’s disease) | 602 | ||
| Chronic secondary adrenocortical insufficiency | 603 | ||
| Iatrogenic adrenocortical insufficiency: abrupt withdrawal | 604 | ||
| Pharmacotherapy | 604 | ||
| Suppression of adrenocortical function | 604 | ||
| Use in inflammation and for immunosuppression | 604 | ||
| Further specific uses | 604 | ||
| Use in diagnosis. | 605 | ||
| Withdrawal of pharmacotherapy | 605 | ||
| Inhibition of synthesis of adrenal and other steroid hormones | 606 | ||
| Competitive antagonism of adrenal steroids | 606 | ||
| Adrenocorticotrophic hormone (ACTH) (corticotropin) | 606 | ||
| Natural corticotropin | 606 | ||
| Synthetic corticotropins | 606 | ||
| Actions | 606 | ||
| The effects | 607 | ||
| Uses. | 607 | ||
| Diagnostic use | 607 | ||
| Therapeutic use | 607 | ||
| Preparations | 607 | ||
| Guide to further reading | 607 | ||
| 36 Diabetes mellitus, insulin, oral antidiabetes agents, obesity | 608 | ||
| Synopsis | 608 | ||
| Diabetes overview | 608 | ||
| History of insulin therapy in diabetes | 608 | ||
| Sources of insulin | 609 | ||
| Insulin receptors | 609 | ||
| Actions of insulin | 610 | ||
| Uses | 610 | ||
| Pharmacokinetics | 610 | ||
| Preparations of insulin (Table 36.1) | 610 | ||
| Notes for prescribing insulin | 613 | ||
| Allergy | 613 | ||
| Antibodies | 613 | ||
| Compatibility. | 613 | ||
| Intravenous insulin. | 613 | ||
| The standard strength | 613 | ||
| Choice of insulin regimen | 613 | ||
| Dose and injection technique | 613 | ||
| Adverse effects of insulin | 614 | ||
| Hypoglycaemia | 614 | ||
| Non-insulin antidiabetes drugs | 615 | ||
| (i) Insulin secretagogues | 615 | ||
| Meglitinides | 615 | ||
| Incretin analogues and mimetics. | 615 | ||
| Dipeptidyl peptidase-4 (DPP-4) inhibitors. | 616 | ||
| (ii) Insulin sensitisers | 616 | ||
| Biguanides | 616 | ||
| Thiazolidinediones. | 617 | ||
| (iii) Agents that increase urinary glucose excretion | 617 | ||
| SGLT-2 inhibitors. | 617 | ||
| (iv) Agents which reduce glucose absorption | 617 | ||
| Acarbose | 617 | ||
| Antidiabetics and cardiovascular outcome studies. | 617 | ||
| Choice of oral antidiabetic drugs in type 2 diabetes | 618 | ||
| Diet and diabetes | 618 | ||
| Interactions with non-diabetes drugs | 618 | ||
| Adrenal steroids, | 619 | ||
| Growth hormone | 619 | ||
| Oral contraceptives | 619 | ||
| Thyroid hormone | 619 | ||
| Drug-induced diabetes | 619 | ||
| Diazoxide | 619 | ||
| Pregnancy and diabetes | 619 | ||
| Surgery in diabetic patients | 619 | ||
| Principles of management | 619 | ||
| Type 1 diabetes | 619 | ||
| Elective major surgery | 620 | ||
| Minor surgery/procedures | 620 | ||
| Emergency surgery | 620 | ||
| Type 2 diabetes | 620 | ||
| Diabetic ketoacidosis | 620 | ||
| Intravenous fluid. | 620 | ||
| Soluble insulin | 620 | ||
| Potassium. | 620 | ||
| Bicarbonate | 621 | ||
| Success in treatment | 621 | ||
| Euglycaemic ketoacidosis | 621 | ||
| Diabetic ketosis without acidosis. | 621 | ||
| Ketosis-prone type 2 diabetes (“Flatbush diabetes”). | 621 | ||
| Hyperosmolar Hyperglycaemic State (HHS) | 621 | ||
| Preventing complications other than by glucose lowering | 621 | ||
| Obesity and appetite control | 622 | ||
| Orlistat | 623 | ||
| Adverse effects | 623 | ||
| Leptin | 623 | ||
| Newer agents | 623 | ||
| GLP-1 agonist | 623 | ||
| Lorcaserin | 623 | ||
| Obesity and diabetes | 623 | ||
| Guide to further reading | 624 | ||
| 37 Thyroid hormones, antithyroid drugs | 625 | ||
| Synopsis | 625 | ||
| Thyroid hormones | 625 | ||
| Calcitonin. | 625 | ||
| Physiology and pharmacokinetics | 625 | ||
| T4 (levothyroxine). | 625 | ||
| T3 (liothyronine) | 626 | ||
| Pharmacodynamics | 626 | ||
| Levothyroxine for hypothyroidism | 626 | ||
| Treatment of hypothyroidism | 626 | ||
| Levothyroxine tablets | 626 | ||
| Liothyronine tabs. | 626 | ||
| Subclinical hypothyroidism. | 626 | ||
| Adverse effects | 627 | ||
| In pregnancy | 627 | ||
| Antithyroid drugs and hyperthyroidism | 627 | ||
| Thionamides (thiourea derivatives) carbimazole, methimazole, propylthiouracil | 627 | ||
| Mode of action (Fig. 37.1) | 627 | ||
| Carbimazole and methimazole | 628 | ||
| Propylthiouracil | 628 | ||
| Immunosuppression | 628 | ||
| Doses | 628 | ||
| Use | 628 | ||
| Adverse reactions | 628 | ||
| Pregnancy. | 628 | ||
| Control of antithyroid drug therapy | 629 | ||
| β-Adrenergic blockade. | 629 | ||
| Iodine (iodide and radioactive iodine) | 629 | ||
| Effects | 629 | ||
| Uses | 629 | ||
| Potassium iodate | 629 | ||
| As an antiseptic | 630 | ||
| Bronchial secretions. | 630 | ||
| Organic compounds | 630 | ||
| Adverse reactions | 630 | ||
| Symptoms of iodism | 630 | ||
| Radioiodine (131I) | 630 | ||
| Risks | 630 | ||
| Radioisotope tests | 631 | ||
| Preparation for surgery | 631 | ||
| Thyroid storm | 631 | ||
| Graves’ ophthalmopathy | 631 | ||
| Treatment of subclinical hyperthyroidism | 632 | ||
| Drugs that cause hypothyroidism | 632 | ||
| Drugs causing either hyper- or hypothyroidism | 632 | ||
| Amiodarone | 632 | ||
| Biological therapies | 633 | ||
| Miscellaneous | 634 | ||
| Treatment of thyroiditis | 634 | ||
| Calcitonin. | 634 | ||
| Guide to further reading | 634 | ||
| 38 Hypothalamic, pituitary and sex hormones | 635 | ||
| Synopsis | 635 | ||
| Hypothalamic and anterior pituitary hormones | 635 | ||
| Corticotropin-releasing hormone (CRH) | 635 | ||
| Adrenocorticotrophic hormone (ACTH) | 635 | ||
| Thyrotrophin-releasing hormone (TRH) | 636 | ||
| Thyroid-stimulating hormone (TSH) thyrotrophin, | 636 | ||
| Sermorelin | 636 | ||
| Octreotide | 636 | ||
| Growth hormone, somatrophin | 636 | ||
| Pegvisomant | 637 | ||
| Gonadotrophin-releasing hormone (GnRH), | 637 | ||
| Follicle-stimulating hormone (FSH) | 637 | ||
| Chorionic gonadotrophin | 637 | ||
| Prolactin | 637 | ||
| Hypopituitarism | 638 | ||
| Posterior pituitary hormones and analogues | 638 | ||
| Vasopressin: antidiuretic hormone (ADH) | 638 | ||
| Desmopressin | 639 | ||
| Diabetes insipidus: vasopressin deficiency | 639 | ||
| Desmopressin replacement therapy | 639 | ||
| Syndrome of inappropriate antidiuretic hormone secretion (SIADH) | 639 | ||
| Emergency treatment of hyponatraemia | 640 | ||
| Oxytocin. | 640 | ||
| Sex (gonadal) hormones and antagonists: steroid hormones | 640 | ||
| Steroid hormone receptors | 640 | ||
| Selectivity. | 640 | ||
| Pharmacokinetics. | 640 | ||
| Androgens | 640 | ||
| Indications for androgen therapy | 641 | ||
| Preparations and choice of androgens | 641 | ||
| Oral preparations | 641 | ||
| Parenteral preparations | 641 | ||
| Transdermal preparations | 641 | ||
| Buccal preparations | 641 | ||
| Testosterone implants | 641 | ||
| Adverse effects | 641 | ||
| Antiandrogens (androgen antagonists) | 642 | ||
| Cyproterone | 642 | ||
| Uses. | 642 | ||
| Anabolic steroids | 642 | ||
| Oestrogens | 642 | ||
| Pharmacokinetics | 642 | ||
| Preparations of oestrogens | 643 | ||
| Choice of oestrogen | 643 | ||
| Oestrogen formulations and routes of administration | 643 | ||
| Oral. | 643 | ||
| Transdermal | 643 | ||
| Subcutaneous implants. | 643 | ||
| Vaginal (ring, cream, tablet or pessary). | 643 | ||
| Others. | 643 | ||
| Indications for oestrogen therapy | 643 | ||
| Replacement therapy in hypo-oestrogenaemia | 643 | ||
| Post-menopausal hormone replacement therapy (HRT) | 643 | ||
| Preparations used for HRT. | 644 | ||
| Contraception. | 644 | ||
| Adverse effects of HRT. | 644 | ||
| Contraindications | 644 | ||
| Anti-oestrogens | 644 | ||
| Clomifene | 644 | ||
| Cyclofenil | 645 | ||
| Tamoxifen | 645 | ||
| Progesterone and progestogens | 645 | ||
| Uses | 645 | ||
| Preparations | 645 | ||
| Adverse effects | 645 | ||
| Antiprogestogens | 645 | ||
| Mifepristone | 646 | ||
| Other progesterone derivatives | 646 | ||
| Gestrinone | 646 | ||
| Fertility regulation | 646 | ||
| Infertility | 646 | ||
| For women, | 646 | ||
| For men, | 646 | ||
| Polycystic ovary syndrome (PCOS) | 646 | ||
| Contraception by drugs and hormones | 647 | ||
| Hormonal contraception in women | 647 | ||
| Combined contraceptives (the ‘pill’) | 647 | ||
| Combined oestrogen–progestogen | 647 | ||
| Important aspects | 647 | ||
| Subsequent fertility. | 647 | ||
| Effect on an existing pregnancy. | 647 | ||
| Carcinomas | 647 | ||
| The effect on menstruation | 647 | ||
| Libido | 648 | ||
| Cardiovascular complications. | 648 | ||
| Major surgery | 648 | ||
| Plasma lipoproteins | 648 | ||
| Plasma proteins. | 648 | ||
| Other adverse effects | 648 | ||
| Absolute contraindications | 648 | ||
| Relative contraindications | 648 | ||
| Duration of use | 649 | ||
| Benefits additional to contraception | 649 | ||
| Formulations of oestrogen–progestogen combination | 649 | ||
| Oestrogen: | 649 | ||
| Progestogen | 649 | ||
| Combined oral contraceptives | 649 | ||
| Choice of oestrogen–progestogen combination | 649 | ||
| Common problems | 649 | ||
| Missed pill. | 649 | ||
| Intercurrent gut upset. | 649 | ||
| Changing of preparation. | 649 | ||
| Breakthrough bleeding | 649 | ||
| Progestogen-only contraception | 649 | ||
| Postcoital (‘morning after pill’) and emergency contraception | 650 | ||
| Progestogen-only treatment | 650 | ||
| Drug interaction with steroid contraceptives | 650 | ||
| Enzyme induction. | 650 | ||
| Hypothalamic/pituitary hormone approach to contraception | 650 | ||
| Other methods of contraception | 650 | ||
| Copper intrauterine devices | 650 | ||
| The intrauterine levonorgestrel system | 651 | ||
| Vaginal preparations, | 651 | ||
| Oil-based lubricants | 651 | ||
| Risks of contraception in relation to benefit | 651 | ||
| Menstrual disorders | 651 | ||
| Amenorrhoea, | 651 | ||
| Menorrhagia | 651 | ||
| The timing of menstruation. | 651 | ||
| Endometriosis. | 651 | ||
| Dysmenorrhoea | 652 | ||
| Premenstrual tension syndrome | 652 | ||
| Cyclical breast pain | 652 | ||
| Myometrium | 652 | ||
| Oxytocics | 652 | ||
| Oxytocin | 652 | ||
| Ergometrine | 653 | ||
| Prostaglandins | 653 | ||
| Dinoprost | 653 | ||
| Gemeprost | 653 | ||
| Carboprost | 653 | ||
| Induction of abortion | 653 | ||
| Induction and augmentation of labour | 653 | ||
| Prevention and treatment of uterine haemorrhage | 653 | ||
| Uterine relaxants | 654 | ||
| Guide to further reading | 654 | ||
| 39 Vitamins, calcium, bone | 655 | ||
| Synopsis | 655 | ||
| Vitamin A: retinol | 655 | ||
| Therapeutic uses | 655 | ||
| Psoriasis | 656 | ||
| Acne | 656 | ||
| Acute promyelocytic leukaemia | 656 | ||
| Vitamin A deficiency | 656 | ||
| Adverse effects | 656 | ||
| Teratogenicity. | 656 | ||
| Vitamin B complex | 656 | ||
| Thiamine (B1). | 656 | ||
| Cobalamins (B12). | 656 | ||
| Folic acid. | 656 | ||
| Pyridoxine (B6) | 656 | ||
| Niacin (nicotinic acid, B3) | 656 | ||
| Vitamin C: ascorbic acid | 657 | ||
| Indications | 657 | ||
| Scurvy | 657 | ||
| Methaemoglobinaemia | 657 | ||
| Adverse effects | 657 | ||
| Vitamin D, calcium, parathyroid hormone, calcitonin, bisphosphonates, bone | 657 | ||
| Vitamin D | 657 | ||
| Pharmacokinetics | 659 | ||
| Actions | 659 | ||
| Indications | 659 | ||
| Vitamin D deficiency | 659 | ||
| Osteoporosis | 660 | ||
| Hypoparathyroidism | 660 | ||
| Psoriasis | 660 | ||
| Renal osteodystrophy | 660 | ||
| Prevention of acute respiratory tract infections | 660 | ||
| Index | 667 | ||
| A | 667 | ||
| B | 672 | ||
| C | 674 | ||
| D | 678 | ||
| E | 681 | ||
| F | 682 | ||
| G | 683 | ||
| H | 684 | ||
| I | 686 | ||
| J | 688 | ||
| K | 688 | ||
| L | 688 | ||
| M | 689 | ||
| N | 691 | ||
| O | 693 | ||
| P | 694 | ||
| Q | 698 | ||
| R | 698 | ||
| S | 699 | ||
| T | 702 | ||
| U | 704 | ||
| V | 704 | ||
| W | 705 | ||
| X | 705 | ||
| Y | 705 | ||
| Z | 705 | ||
| Inside Back Cover | ibc1 |