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Book Details
Abstract
A thorough knowledge of pharmacological and therapeutic principles is vital if drugs are to be used safely and effectively for increasingly informed patients. Those who clearly understand how drugs get into the body, how they produce their effects, what happens to them in the body, and how evidence of their therapeutic effect is assessed, will choose drugs more skilfully, and use them more safely and successfully than those who do not. Now in a fully revised 11th edition, Clinical Pharmacology is essential reading for undergraduate medical students, junior doctors and anyone concerned with evidence-based drug therapy.
Indian Advisory Board will ensure content reflects the needs of the devloping world.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Clinical pharmacology | iii | ||
| Copyright | iv | ||
| Contents | v | ||
| Contributors | vii | ||
| Preface | ix | ||
| Acknowledgements | xi | ||
| Section 1: General | 1 | ||
| Chapter 1: Clinical pharmacology | 2 | ||
| Synopsis | 2 | ||
| Guide to further reading | 4 | ||
| Chapter 2: Topics in drug therapy | 5 | ||
| Synopsis | 5 | ||
| Prescribing | 6 | ||
| Getting it right | 6 | ||
| Examples of when things went wrong | 6 | ||
| Focusing on the presenting complaint and forgetting other medical conditions | 6 | ||
| Forgetting that women get pregnant | 6 | ||
| Not knowing what you are prescribing | 6 | ||
| Forgetting that a newly prescribed drug can interact with long-term drug treatment | 7 | ||
| Top ten prescribing errors in a UK hospital setting1 | 7 | ||
| Why do mistakes happen? | 7 | ||
| The therapeutic situation | 8 | ||
| Some background | 8 | ||
| Treating patients with drugs | 8 | ||
| Drugs can do good | 9 | ||
| Drugs can do harm | 9 | ||
| Uses of drugs/medicines | 9 | ||
| Cure | 9 | ||
| Suppression | 9 | ||
| Prevention | 9 | ||
| Physician-induced (iatrogenic) disease | 9 | ||
| Benefits and risks of medicines | 10 | ||
| Unavoidable risks | 10 | ||
| Reduction of risk | 11 | ||
| Two broad categories of risk | 11 | ||
| Elements of risk | 11 | ||
| Three major grades of risk | 11 | ||
| Whenever a drug is taken a risk is taken | 12 | ||
| Public view of drugs and prescribers | 12 | ||
| Criticisms of modern drugs | 13 | ||
| Drug-induced injury17 (see also Ch.9) | 13 | ||
| Negligence and strict and no-fault liability | 13 | ||
| Complementary, alternative and traditional medicine | 14 | ||
| Homoeopathy | 16 | ||
| Conclusion | 17 | ||
| Placebo medicines | 17 | ||
| Guidelines, `essentialĀ“ drugs and prescribing | 18 | ||
| `EssentialĀ“ drugs | 19 | ||
| Cost-containment | 19 | ||
| Taking a drug history | 19 | ||
| Repeat prescriptions | 20 | ||
| Warnings and consent | 20 | ||
| Legal hazards for prescribers | 21 | ||
| Compliance | 21 | ||
| Patient compliance | 21 | ||
| Suggestions for doctors to enhance patient compliance/adherence | 22 | ||
| Directly observed therapy | 22 | ||
| Over-compliance | 23 | ||
| Evaluation of patient compliance | 23 | ||
| Doctor compliance | 23 | ||
| Underdosing | 24 | ||
| The clinical importance of missed dose(s) | 24 | ||
| Pharmacoeconomics (see also Ch. 5) | 24 | ||
| The economists' objective | 25 | ||
| Quality of life | 25 | ||
| Guide to further reading | 26 | ||
| Appendix: the prescription | 27 | ||
| Example of a prescription | 27 | ||
| Medicine containers | 27 | ||
| Unwanted medicines | 27 | ||
| Drugs liable to cause dependence | 27 | ||
| Abbreviations | 28 | ||
| Weights and measures | 28 | ||
| Equivalents: | 28 | ||
| Abbreviations: | 28 | ||
| Home/domestic measures | 28 | ||
| Percentages, proportions, weight in volume | 28 | ||
| Chapter 3: Discovery and development of drugs | 29 | ||
| Synopsis | 29 | ||
| Making a new medicine | 29 | ||
| Techniques of discovery | 31 | ||
| Molecular modelling and structural biology | 31 | ||
| High throughput screening | 31 | ||
| Fragments | 31 | ||
| Proteins as medicines: biotechnology | 31 | ||
| Antisense approaches | 31 | ||
| Gene therapy | 32 | ||
| Stem cells | 32 | ||
| Immunopharmacology | 32 | ||
| Older approaches | 32 | ||
| Drug quality | 33 | ||
| Studies in animals | 33 | ||
| Pharmacodynamics | 33 | ||
| Pharmacokinetics | 33 | ||
| Toxicology | 33 | ||
| Genotoxicity | 33 | ||
| 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 | ||
| Chapter 4: Evaluation of drugs in humans | 37 | ||
| Synopsis | 37 | ||
| Experimental therapeutics | 37 | ||
| Research involving human subjects | 38 | ||
| Ethics of research in humans44For extensive practical detail, see Council for International Organisations of Medical Sciences ( | 38 | ||
| The ethics of the randomised and placebo-controlled trial | 39 | ||
| Injury to research subjects9 | 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 requirements12 | 41 | ||
| Therapeutic investigations | 42 | ||
| Therapeutic evaluation | 42 | ||
| Need for statistics | 43 | ||
| Concepts and terms | 43 | ||
| Hypothesis of no difference | 43 | ||
| A. statistical significance test17 | 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 | 46 | ||
| Techniques to avoid bias | 46 | ||
| Randomisation | 46 | ||
| Blinding | 46 | ||
| Some common design configurations | 47 | ||
| Parallel group design | 47 | ||
| Crossover design | 47 | ||
| Factorial designs | 47 | ||
| Multicentre trials | 47 | ||
| N-of-1 trials | 47 | ||
| Historical controls | 48 | ||
| Size of trials | 48 | ||
| Fixed sample size and sequential designs | 48 | ||
| Sensitivity of trials | 49 | ||
| Meta-analysis | 49 | ||
| Results: implementation | 50 | ||
| Relative and absolute risk | 50 | ||
| Pharmacoepidemiology | 51 | ||
| Observational cohort35 studies | 51 | ||
| Case-control studies | 52 | ||
| Surveillance systems: pharmacovigilance | 52 | ||
| Voluntary reporting | 52 | ||
| Prescription event monitoring | 52 | ||
| Medical record linkage | 53 | ||
| Population statistics | 53 | ||
| Strength of evidence | 53 | ||
| In conclusion43 | 53 | ||
| Guide to further reading | 53 | ||
| Chapter 5: Health technology assessment | 55 | ||
| Synopsis | 55 | ||
| The scope | 55 | ||
| Clinical effectiveness | 56 | ||
| 1. Developing the protocol | 56 | ||
| 2. Defining the methods | 56 | ||
| 3. Analysing the data | 56 | ||
| Qualitative synthesis | 57 | ||
| Quantitative synthesis (meta-analysis) | 57 | ||
| 4. Drawing conclusions | 58 | ||
| Cost-effectiveness | 58 | ||
| 1. The costs | 59 | ||
| 2. Benefits | 59 | ||
| Natural units | 59 | ||
| Health utilities | 59 | ||
| 3. Type of analysis | 59 | ||
| Cost-effectiveness analysis | 59 | ||
| Cost-utility analysis | 60 | ||
| In conclusion | 60 | ||
| Guide to further reading | 61 | ||
| Chapter 6: Official regulation of medicines | 62 | ||
| Synopsis | 62 | ||
| Basis for regulation | 62 | ||
| Historical background | 63 | ||
| Current medicines regulatory systems | 63 | ||
| Requirements | 64 | ||
| Authorisation for clinical trials in the UK | 64 | ||
| Regulatory review of a new drug application | 64 | ||
| Regulatory review | 64 | ||
| Post-licensing responsibilities | 65 | ||
| Discussion | 66 | ||
| Licensed medicines for unlicensed indications | 66 | ||
| Unlicensed medicines and accelerated licensing | 66 | ||
| Decision-taking | 67 | ||
| Counterfeit drugs | 67 | ||
| Complementary and alternative medicine | 67 | ||
| Medicines regulation: the future | 68 | ||
| Guide to further reading | 68 | ||
| Chapter 7: Classification and naming of drugs | 69 | ||
| Synopsis | 69 | ||
| Classification | 69 | ||
| Nomenclature (names) | 69 | ||
| Non-proprietary names | 70 | ||
| Clarity | 70 | ||
| Economy | 70 | ||
| Convenience | 70 | ||
| Proprietary names | 71 | ||
| Confusing names | 71 | ||
| Guide to further reading | 71 | ||
| Section 2: From pharmacology to toxicology | 73 | ||
| Chapter 8: General pharmacology | 74 | ||
| Synopsis | 74 | ||
| Pharmacodynamics | 74 | ||
| Qualitative aspects | 74 | ||
| Mechanisms | 75 | ||
| Receptors | 75 | ||
| Agonists | 75 | ||
| Antagonists | 75 | ||
| Partial agonists | 75 | ||
| Inverse agonists | 76 | ||
| Receptor binding | 76 | ||
| Physiological (functional) antagonism | 76 | ||
| Enzymes | 76 | ||
| Selectivity | 77 | ||
| Modification of drug structure | 77 | ||
| Selective delivery (drug targeting) | 77 | ||
| Stereoselectivity | 77 | ||
| Quantitative aspects | 77 | ||
| Dose-response relationships | 77 | ||
| Potency and efficacy | 78 | ||
| Potency | 78 | ||
| Pharmacological efficacy | 78 | ||
| Therapeutic efficacy | 78 | ||
| Therapeutic index | 78 | ||
| Tolerance | 78 | ||
| Bioassay and standardisation | 78 | ||
| Pharmacokinetics | 79 | ||
| Drug passage across cell membranes | 79 | ||
| Passive diffusion | 79 | ||
| Drugs that ionise according to environmental pH | 80 | ||
| pH variation and drug kinetics | 80 | ||
| Drugs that are incapable of becoming ionised | 80 | ||
| Permanently ionised drugs | 80 | ||
| Brain and cerebrospinal fluid (CSF) | 81 | ||
| Placenta | 81 | ||
| Filtration | 81 | ||
| Carrier-mediated transport | 81 | ||
| The order of reaction or process | 81 | ||
| First-order (exponential) processes | 81 | ||
| Zero-order processes (saturation kinetics) | 82 | ||
| Alcohol | 82 | ||
| Time course of drug concentration and effect | 83 | ||
| Plasma half-life and steady-state concentration | 83 | ||
| Decrease in plasma concentration after an intravenous bolus injection | 83 | ||
| Increase in plasma concentration with constant dosing | 83 | ||
| Time to reach steady state | 83 | ||
| Change in plasma concentration with change or cessation of dosing | 84 | ||
| Biological effect tĀ½ | 84 | ||
| Therapeutic drug monitoring | 84 | ||
| Plasma concentration may not be worth measuring | 84 | ||
| Plasma concentration has no correlation with effect | 85 | ||
| Plasma concentration may correlate poorly with effect | 85 | ||
| Plasma concentration may correlate well with effect | 85 | ||
| Interpreting plasma concentration measurements | 85 | ||
| Individual pharmacokinetic processes | 85 | ||
| Absorption | 85 | ||
| Absorption from the gastrointestinal tract | 85 | ||
| Enterohepatic circulation | 86 | ||
| Systemic availability and bioavailability | 86 | ||
| Pharmaceutical factors7 | 86 | ||
| Biological factors | 87 | ||
| Presystemic (first-pass) elimination | 87 | ||
| Advantages and disadvantages of enteral administration | 87 | ||
| By swallowing | 87 | ||
| For systemic effect | 87 | ||
| For effect in the gut | 87 | ||
| Sublingual or buccal for systemic effect | 88 | ||
| Rectal administration | 88 | ||
| For systemic effect (suppositories or solutions) | 88 | ||
| For local effect, | 88 | ||
| Advantages and disadvantages of parenteral administration | 88 | ||
| Intravenous (bolus or infusion) | 88 | ||
| Intramuscular injection | 88 | ||
| Subcutaneous injection | 88 | ||
| By inhalation | 88 | ||
| As a gas | 88 | ||
| As an aerosol | 88 | ||
| As a powder | 88 | ||
| Topical application | 89 | ||
| For local effect | 89 | ||
| For systemic effect | 89 | ||
| Distribution | 89 | ||
| Distribution volume | 89 | ||
| Selective distribution | 90 | ||
| Plasma protein and tissue binding | 90 | ||
| Albumin | 90 | ||
| Disease | 91 | ||
| Tissue binding | 91 | ||
| Metabolism | 91 | ||
| Reducing lipid solubility | 91 | ||
| Altering biological activity | 91 | ||
| The metabolic processes | 92 | ||
| Phase I | 92 | ||
| Phase II | 93 | ||
| Transporters17 | 93 | ||
| Enzyme induction | 93 | ||
| Inducing substances | 93 | ||
| Enzyme inhibition | 94 | ||
| Elimination | 94 | ||
| Renal elimination | 94 | ||
| Glomerular filtration | 94 | ||
| Renal tubular transport | 95 | ||
| Renal tubular diffusion | 95 | ||
| Faecal elimination | 95 | ||
| Biliary excretion | 95 | ||
| Pulmonary elimination | 95 | ||
| Clearance | 95 | ||
| Breast milk | 95 | ||
| Drugs and breast feeding20 | 95 | ||
| Drug dosage | 96 | ||
| Dosing schedules | 96 | ||
| To specify an initial dose | 96 | ||
| To specify a maintenance dose: | 96 | ||
| Dose calculation by body-weight and surface area | 97 | ||
| Prolongation of drug action | 97 | ||
| Sustained-release (oral) preparations | 97 | ||
| Depot (injectable) preparations | 97 | ||
| Reduction of absorption time | 97 | ||
| Fixed-dose drug combinations | 98 | ||
| Chronic pharmacology | 98 | ||
| Interference with self-regulating systems | 98 | ||
| Feedback systems | 98 | ||
| Regulation of receptors | 98 | ||
| The rebound phenomenon | 99 | ||
| Abrupt withdrawal | 99 | ||
| Resurgence | 99 | ||
| Drug discontinuation syndromes, | 99 | ||
| Other aspects of chronic drug use | 99 | ||
| Metabolic changes | 99 | ||
| Specific cell injury | 99 | ||
| Drug holidays | 99 | ||
| Dangers of intercurrent illness | 99 | ||
| Dangers of interactions with other drugs, herbs or food | 99 | ||
| Conclusions | 99 | ||
| Individual or biological variation | 100 | ||
| Prescribing for special risk groups | 100 | ||
| Pharmacogenomics | 101 | ||
| Introduction | 101 | ||
| Sources of variability | 101 | ||
| Identifying genetic variation | 101 | ||
| Examples of pharmacogenomic variation | 102 | ||
| Drug efficacy | 102 | ||
| Cancer therapy | 102 | ||
| Warfarin | 102 | ||
| Drug toxicity | 102 | ||
| Immune-mediated adverse drug reactions | 102 | ||
| Statin myopathy | 103 | ||
| Summary | 103 | ||
| Environmental and host influences | 103 | ||
| Age | 103 | ||
| The neonate, infant and child24 | 103 | ||
| Distribution | 103 | ||
| Metabolism | 103 | ||
| Elimination | 103 | ||
| Pharmacodynamic responses | 103 | ||
| Dosage in the young | 103 | ||
| The elderly | 105 | ||
| Absorption | 105 | ||
| Distribution | 105 | ||
| Metabolism | 105 | ||
| Elimination | 105 | ||
| Pharmacodynamic | 105 | ||
| Rules of prescribing for the elderly29 | 105 | ||
| Pregnancy | 106 | ||
| Section 3: Infection and inflammation | 161 | ||
| Chapter 12: Chemotherapy of infections | 162 | ||
| Synopsis | 162 | ||
| History | 162 | ||
| Classification of antimicrobial drugs | 163 | ||
| How antimicrobials act - sites of action | 164 | ||
| The cell wall | 164 | ||
| The cytoplasmic membrane | 164 | ||
| Protein synthesis | 164 | ||
| Nucleic acid metabolism | 164 | ||
| Principles of antimicrobial chemotherapy | 164 | ||
| Make a diagnosis | 164 | ||
| Remove barriers to cure, | 165 | ||
| Decide whether chemotherapy is really necessary | 165 | ||
| Select the best drug | 165 | ||
| Administer the drug | 165 | ||
| Continue therapy | 165 | ||
| Test for cure | 165 | ||
| Prophylactic chemotherapy | 165 | ||
| Carriers of pathogenic or resistant organisms | 165 | ||
| Use of antimicrobial drugs | 165 | ||
| Choice | 165 | ||
| Knowledge of the likely pathogens | 165 | ||
| Rapid diagnostic tests | 166 | ||
| Route of administration | 166 | ||
| Combinations | 166 | ||
| Chemoprophylaxis and pre-emptive suppressive therapy | 167 | ||
| Chemoprophylaxis in surgery | 167 | ||
| Antimicrobials should be selected | 167 | ||
| Antimicrobials should be given | 167 | ||
| Problems with antimicrobial drugs | 168 | ||
| Resistance | 168 | ||
| Mechanisms of resistance | 169 | ||
| Limitation of resistance | 169 | ||
| Superinfection | 170 | ||
| Antibiotic-associated (or Clostridium difficile-associated) colitis | 170 | ||
| Opportunistic infection | 171 | ||
| Masking of infections | 171 | ||
| Drugs of choice | 171 | ||
| Guide to further reading | 171 | ||
| Chapter 13: Antibacterial drugs | 173 | ||
| Synopsis | 173 | ||
| Classification | 173 | ||
| Inhibition of cell wall synthesis | 173 | ||
| Ī²-lactams | 173 | ||
| Inhibition of protein synthesis | 173 | ||
| Aminoglycosides | 173 | ||
| Tetracyclines, | 173 | ||
| Macrolides: | 173 | ||
| Inhibition of nucleic acid synthesis | 173 | ||
| Sulfonamides | 173 | ||
| Quinolones | 173 | ||
| Azoles | 173 | ||
| Inhibition of cell wall synthesis | 174 | ||
| Ī²-lactams | 174 | ||
| Penicillins | 174 | ||
| Mode of action | 174 | ||
| Pharmacokinetics | 174 | ||
| Adverse effects | 174 | ||
| Narrow-spectrum penicillins | 175 | ||
| Benzylpenicillin | 175 | ||
| Uses | 175 | ||
| Adverse effects | 175 | ||
| Preparations and dosage for injection | 175 | ||
| Preparations and dosage for oral use | 175 | ||
| Antistaphylococcal penicillins | 175 | ||
| Broad-spectrum penicillins | 175 | ||
| Amoxicillin | 176 | ||
| Co-amoxiclav | 176 | ||
| Ampicillin | 176 | ||
| Adverse effects | 176 | ||
| Mecillinam | 176 | ||
| Monobactam | 176 | ||
| Antipseudomonal penicillins | 176 | ||
| Carboxypenicillins | 176 | ||
| Ticarcillin | 176 | ||
| Ureidopenicillins | 176 | ||
| Piperacillin | 176 | ||
| Cephalosporins | 176 | ||
| Mode of action | 177 | ||
| Pharmacokinetics | 177 | ||
| Classification and uses | 177 | ||
| Section 4: Nervous system | 277 | ||
| Chapter 18: Pain and analgesics | 278 | ||
| Synopsis | 278 | ||
| Pain and analgesics | 278 | ||
| Definition of pain | 278 | ||
| Nociception | 279 | ||
| Classification of clinical pain | 280 | ||
| Acute pain, | 280 | ||
| Chronic pain | 281 | ||
| Neuropathic pain | 281 | ||
| Cancer-related pain | 281 | ||
| Evaluation of pain | 281 | ||
| Pharmacotherapy | 281 | ||
| Non-opioid analgesics | 281 | ||
| NSAIDs (non-steroidal anti-inflammatory drugs) | 281 | ||
| Mechanism of analgesia | 281 | ||
| Clinical use | 282 | ||
| Choice of NSAID and route of administration | 282 | ||
| Side-effects | 282 | ||
| Paracetamol (acetaminophen) | 282 | ||
| Nefopam | 282 | ||
| Opioid analgesics | 283 | ||
| Mechanism of action of opioids | 283 | ||
| Classification of opioid drugs | 283 | ||
| Opioid pharmacodynamics | 283 | ||
| Systemic effects of opioid analgesics | 284 | ||
| Central nervous system | 284 | ||
| Cardiovascular system | 284 | ||
| Gastrointestinal tract | 284 | ||
| Urogenital tract | 284 | ||
| Others | 284 | ||
| Pharmacokinetics | 284 | ||
| Route of administration | 285 | ||
| Pharmacology of individual opioids | 285 | ||
| Opioid agonist drugs | 285 | ||
| Morphine | 285 | ||
| Diamorphine | 285 | ||
| Codeine | 286 | ||
| Dihydrocodeine | 286 | ||
| Oxycodone | 286 | ||
| Hydromorphone | 286 | ||
| Methadone | 286 | ||
| Fentanyl | 286 | ||
| Alfentanil | 287 | ||
| Remifentanil | 287 | ||
| Papaveretum | 287 | ||
| Partial agonist opioid analgesics | 287 | ||
| Buprenorphine | 287 | ||
| Meptazinol | 287 | ||
| Mixed agonist-antagonist opioid analgesics | 287 | ||
| Opioids with action on other systems | 287 | ||
| Pethidine (meperidine) | 287 | ||
| Tramadol | 288 | ||
| Opioid antagonists | 288 | ||
| Naloxone | 288 | ||
| Choice of opioid analgesic | 288 | ||
| Tolerance, dependence and addiction | 289 | ||
| Tolerance | 289 | ||
| Dependence | 289 | ||
| Addiction | 289 | ||
| Pain relief in opioid addicts | 289 | ||
| Co-analgesics | 290 | ||
| Multipurpose adjuvant analgesics | 290 | ||
| Corticosteroids | 290 | ||
| Neuroleptics | 290 | ||
| Benzodiazepines | 290 | ||
| Adjuvant analgesics used in neuropathic pain | 290 | ||
| Antidepressants | 290 | ||
| Anticonvulsants | 290 | ||
| Local anaesthetics | 291 | ||
| Capsaicin | 291 | ||
| Clonidine | 291 | ||
| Cannabinoids | 291 | ||
| Ziconotide | 292 | ||
| Ketamine | 292 | ||
| Adjuvants used for bone pain | 292 | ||
| Bisphosphonates | 292 | ||
| Pharmacotherapy of acute migraine headaches | 292 | ||
| Management of migraine | 293 | ||
| Abortive treatment of migraine | 293 | ||
| Selective 5-HT1 agonists (triptans) | 293 | ||
| Sumatriptan | 293 | ||
| Ergotamine | 294 | ||
| Preventive treatment for migraine | 294 | ||
| Pizotifen | 294 | ||
| Topiramate | 294 | ||
| Guide to further reading | 294 | ||
| Chapter 19: Anaesthesia and neuromuscular block | 295 | ||
| Synopsis | 295 | ||
| General anaesthesia | 295 | ||
| Phases of general anaesthesia | 296 | ||
| Before surgery, | 296 | ||
| During surgery, | 296 | ||
| After surgery, | 296 | ||
| Before surgery (premedication) | 296 | ||
| Anxiolysis and amnesia | 296 | ||
| Analgesia | 296 | ||
| Timing | 296 | ||
| Gastric contents | 296 | ||
| During surgery | 296 | ||
| Induction | 296 | ||
| Maintenance | 297 | ||
| After surgery | 297 | ||
| Relief of pain | 297 | ||
| Postoperative nausea and vomiting | 297 | ||
| Some special techniques | 297 | ||
| Dissociative anaesthesia | 297 | ||
| Sedation and amnesia | 297 | ||
| Entonox, | 297 | ||
| Pharmacology of anaesthetics | 297 | ||
| Mode of action | 297 | ||
| Inhalation anaesthetics | 298 | ||
| Pharmacokinetics (volatile liquids, gases) | 298 | ||
| Nitrous oxide | 298 | ||
| Advantages | 298 | ||
| Disadvantages | 298 | ||
| Uses | 298 | ||
| Dosage and administration | 298 | ||
| Contraindications | 298 | ||
| Precautions | 298 | ||
| Adverse effects | 298 | ||
| Halogenated anaesthetics | 299 | ||
| Isoflurane | 299 | ||
| Respiratory effects | 299 | ||
| Cardiovascular effects | 299 | ||
| Other effects | 299 | ||
| Sevoflurane | 299 | ||
| Desflurane | 299 | ||
| Halothane | 299 | ||
| Oxygen in anaesthesia | 300 | ||
| Intravenous anaesthetics | 300 | ||
| Pharmacokinetics | 300 | ||
| Propofol | 300 | ||
| Central nervous system | 300 | ||
| Cardiovascular system | 300 | ||
| Respiratory system | 300 | ||
| Thiopental | 300 | ||
| Central nervous system | 301 | ||
| Cardiovascular system | 301 | ||
| Respiratory system | 301 | ||
| Methohexitone | 301 | ||
| Etomidate | 301 | ||
| Ketamine | 301 | ||
| Advantages | 301 | ||
| Disadvantages | 301 | ||
| Uses | 301 | ||
| Dosage and administration | 301 | ||
| Contraindications | 301 | ||
| Use in pregnancy | 301 | ||
| Muscle relaxants | 302 | ||
| Neuromuscular blocking drugs | 302 | ||
| Mechanisms | 302 | ||
| Competitive antagonists | 303 | ||
| Atracurium | 303 | ||
| Cisatracurium | 303 | ||
| Vecuronium | 303 | ||
| Rocuronium | 303 | ||
| Mivacurium | 303 | ||
| Pancuronium | 303 | ||
| Tubocurarine | 303 | ||
| Antagonism of competitive neuromuscular block | 303 | ||
| Neostigmine | 303 | ||
| Sugammadex | 303 | ||
| Depolarising neuromuscular blocker | 303 | ||
| Suxamethonium (succinylcholine) | 303 | ||
| Uses of neuromuscular blocking drugs | 304 | ||
| Other muscle relaxants | 304 | ||
| Baclofen | 304 | ||
| Dantrolene | 304 | ||
| Anaphylaxis | 304 | ||
| Local anaesthetics | 304 | ||
| Desired properties | 304 | ||
| Mode of action | 304 | ||
| Pharmacokinetics | 305 | ||
| Ester compounds | 305 | ||
| Amide compounds | 305 | ||
| Prolongation of action by vasoconstrictors | 305 | ||
| Other effects | 305 | ||
| Uses | 305 | ||
| Regional anaesthesia | 306 | ||
| Nerve block | 306 | ||
| Intravenous | 306 | ||
| Extradural | 306 | ||
| Subarachnoid (intrathecal) block (spinal anaesthesia) | 306 | ||
| Opioid analgesics | 306 | ||
| Adverse reactions | 306 | ||
| Individual local anaesthetics | 306 | ||
| Amides | 306 | ||
| Lidocaine | 306 | ||
| Prilocaine | 306 | ||
| Bupivacaine | 306 | ||
| Levobupivacaine | 306 | ||
| Ropivacaine | 306 | ||
| Esters | 307 | ||
| Cocaine | 307 | ||
| Obstetric analgesia and anaesthesia | 307 | ||
| Pethidine | 308 | ||
| Nitrous oxide and oxygen | 308 | ||
| Epidural | 308 | ||
| Spinal anaesthesia | 308 | ||
| General anaesthesia | 308 | ||
| Anaesthesia in patients already taking medication | 308 | ||
| Drugs that affect anaesthesia | 308 | ||
| Adrenal steroids | 308 | ||
| Antibiotics | 308 | ||
| Anticholinesterases | 308 | ||
| Antiepilepsy drugs | 308 | ||
| Antihypertensives | 308 | ||
| Ī²-Adrenoceptor blocking drugs | 308 | ||
| Diuretics | 308 | ||
| Oral contraceptives | 308 | ||
| Psychotropic drugs | 308 | ||
| Antidepressants | 308 | ||
| Anaesthesia in the diseased, and in particular patient groups | 309 | ||
| Respiratory disease and smoking | 309 | ||
| Cardiac disease | 309 | ||
| Hepatic or renal disease | 309 | ||
| Malignant hyperthermia | 309 | ||
| Muscle diseases | 309 | ||
| Sickle cell disease | 309 | ||
| Atypical (deficient) pseudocholinesterase | 309 | ||
| Raised intracranial pressure | 309 | ||
| The elderly | 309 | ||
| Children | 309 | ||
| Sedation in critical care units | 309 | ||
| Diabetes mellitus | 310 | ||
| Thyroid disease | 310 | ||
| Porphyria | 310 | ||
| Guide to further reading | 310 | ||
| Chapter 20: Psychotropic drugs | 311 | ||
| Synopsis | 311 | ||
| Diagnostic issues | 311 | ||
| Drug therapy in relation to psychological treatment | 311 | ||
| Antidepressant drugs | 312 | ||
| Mechanism of action | 313 | ||
| Pharmacokinetics | 314 | ||
| Therapeutic efficacy | 316 | ||
| Selection | 316 | ||
| Mode of use | 316 | ||
| Changing and stopping antidepressants | 316 | ||
| Augmentation | 317 | ||
| Other indications for antidepressants | 318 | ||
| Adverse effects | 318 | ||
| Selective serotonin reuptake inhibitors | 318 | ||
| The serotonin syndrome | 318 | ||
| Novel compounds | 318 | ||
| Venlafaxine | 318 | ||
| Duloxetine | 318 | ||
| Mirtazapine | 318 | ||
| Trazodone | 318 | ||
| Agomelatine | 318 | ||
| Tricyclic antidepressants | 318 | ||
| Overdose | 319 | ||
| Reboxetine | 319 | ||
| Monoamine oxidase inhibitors | 319 | ||
| Interactions | 319 | ||
| Pharmacodynamic interactions | 319 | ||
| Pharmacokinetic interactions | 320 | ||
| Enzyme inhibition | 320 | ||
| Enzyme-inducing drugs, | 320 | ||
| Monoamine oxidase inhibitors | 320 | ||
| Hypertensive reactions | 320 | ||
| Symptoms | 320 | ||
| The rational and effective treatment | 320 | ||
| Patient education | 320 | ||
| Many simple remedies | 320 | ||
| Foods | 320 | ||
| MAOI interactions with other drugs | 321 | ||
| Overdose | 321 | ||
| St John's wort | 321 | ||
| Adverse effects | 321 | ||
| Electroconvulsive therapy | 322 | ||
| Antipsychotics | 322 | ||
| Classification | 322 | ||
| Indications | 322 | ||
| Mechanism of action | 323 | ||
| Pharmacokinetics | 323 | ||
| Efficacy | 323 | ||
| Mode of use | 323 | ||
| Alternative administration strategies in acute antipsychotic use | 324 | ||
| Long-acting depot injections | 324 | ||
| Rapid tranquillisation | 325 | ||
| Adverse effects (Table 20.5) | 325 | ||
| Classical antipsychotics | 325 | ||
| Extrapyramidal symptoms | 325 | ||
| Akathisia | 325 | ||
| Tardive dyskinesia | 325 | ||
| Cardiovascular effects | 327 | ||
| Prolactin increase | 327 | ||
| Sedation | 327 | ||
| Atypical antipsychotics | 327 | ||
| Neuroleptic malignant syndrome | 328 | ||
| Comparison of conventional and atypical antipsychotics | 328 | ||
| Mood stabilisers | 328 | ||
| Lithium | 328 | ||
| The mode of action | 329 | ||
| Pharmacokinetics | 329 | ||
| Indications and use | 329 | ||
| Pharmaceutics | 329 | ||
| Monitoring | 329 | ||
| Adverse effects | 329 | ||
| Overdose | 330 | ||
| Interactions | 330 | ||
| Carbamazepine | 330 | ||
| Valproate | 330 | ||
| Other drugs | 330 | ||
| Drugs used in anxiety and sleep disorders | 331 | ||
| Classification of anxiety disorders | 331 | ||
| Panic disorder (PD) | 331 | ||
| Treatment | 331 | ||
| Social anxiety disorder | 331 | ||
| Section 5: Cardiorespiratory and renal systems | 371 | ||
| Chapter 22: Cholinergic and antimuscarinic (anticholinergic) mechanisms and drugs | 372 | ||
| Synopsis | 372 | ||
| Cholinergic drugs (cholinomimetics) | 372 | ||
| Classification | 372 | ||
| Direct-acting (receptor agonists) | 372 | ||
| Indirect-acting | 372 | ||
| Sites of action (Fig.22.1) | 373 | ||
| Pharmacology | 373 | ||
| Autonomic nervous system | 373 | ||
| Parasympathetic division | 373 | ||
| Sympathetic division | 373 | ||
| Neuromuscular (voluntary) junction | 374 | ||
| Central nervous system | 374 | ||
| Blood vessels | 374 | ||
| Choline esters | 374 | ||
| Acetylcholine | 374 | ||
| Other choline esters | 374 | ||
| Alkaloids with cholinergic effects | 374 | ||
| Nicotine | 374 | ||
| Pilocarpine, | 375 | ||
| Arecoline | 375 | ||
| Muscarine | 375 | ||
| Anticholinesterases | 375 | ||
| Physostigmine | 375 | ||
| Neostigmine | 375 | ||
| Pyridostigmine | 375 | ||
| Distigmine | 375 | ||
| Edrophonium | 375 | ||
| Carbaryl | 376 | ||
| Anticholinesterase poisoning | 376 | ||
| Typical features | 376 | ||
| Treatment | 376 | ||
| Poisoning | 377 | ||
| Disorders of neuromuscular transmission | 377 | ||
| Myasthenia gravis | 377 | ||
| Pathogenesis | 377 | ||
| Diagnosis | 377 | ||
| Treatment | 378 | ||
| Excessive dosing | 378 | ||
| Lambert-Eaton syndrome | 378 | ||
| Drug-induced disorders of neuromuscular transmission | 378 | ||
| Antimicrobials | 378 | ||
| Cardiovascular drugs | 378 | ||
| Other drugs | 379 | ||
| Drugs that oppose acetylcholine | 379 | ||
| Antimuscarinic drugs | 379 | ||
| Atropine | 379 | ||
| Exocrine glands | 379 | ||
| Smooth muscle | 379 | ||
| Ocular effects | 379 | ||
| Cardiovascular system | 379 | ||
| Central nervous system | 380 | ||
| Antagonism to cholinergic drugs | 380 | ||
| Pharmacokinetics | 380 | ||
| Dose | 380 | ||
| Poisoning | 380 | ||
| Other antimuscarinic drugs | 380 | ||
| Hyoscine | 380 | ||
| Hyoscine butylbromide | 381 | ||
| Homatropine | 381 | ||
| Tropicamide | 381 | ||
| Ipratropium | 381 | ||
| Tiotropium | 381 | ||
| Flavoxate | 381 | ||
| Oxybutynin | 381 | ||
| Glycopyrronium | 381 | ||
| Propantheline | 381 | ||
| Dicyclomine | 381 | ||
| Benzhexol | 381 | ||
| Promethazine | 381 | ||
| Propiverine, | 381 | ||
| Guide to further reading | 381 | ||
| Chapter 23: Adrenergic mechanisms and drugs | 382 | ||
| Synopsis | 382 | ||
| Adrenergic mechanisms | 382 | ||
| Classification of sympathomimetics | 382 | ||
| By mode of action | 382 | ||
| Tachyphylaxis | 383 | ||
| Interactions of sympathomimetics | 383 | ||
| History | 383 | ||
| Consequences of adrenoceptor activation | 384 | ||
| Selectivity for adrenoceptors | 384 | ||
| Adrenoceptor agonists (see Table23.1) | 385 | ||
| Ī± Ī² effects, non-selective: | 385 | ||
| Ī±1 effects: | 385 | ||
| Ī±2 effects in the central nervous system: | 385 | ||
| Ī² effects, non-selective (i.e. Ī²1 Ī²2): | 385 | ||
| Ī²1 effects, with some Ī± effects: | 385 | ||
| Ī²1 effects: | 385 | ||
| Ī²2 effects, | 385 | ||
| Adrenoceptor antagonists (blockers) | 385 | ||
| Effects of a sympathomimetic | 385 | ||
| Physiological note | 386 | ||
| Synthetic non-catecholamines | 386 | ||
| Pharmacokinetics | 386 | ||
| Catecholamines | 386 | ||
| Adverse effects | 386 | ||
| Sympathomimetics and plasma potassium | 387 | ||
| Overdose of sympathomimetics | 387 | ||
| Individual sympathomimetics | 387 | ||
| Catecholamines | 387 | ||
| Adrenaline/epinephrine | 387 | ||
| Adrenaline/epinephrine is used in anaphylactic shock | 387 | ||
| Accidental overdose | 387 | ||
| Noradrenaline/norepinephrine (chiefly Ī± and Ī²1 effects) | 387 | ||
| Isoprenaline (isoproterenol) | 388 | ||
| Dopamine | 388 | ||
| Dobutamine | 388 | ||
| Dopexamine | 388 | ||
| Non-catecholamines | 388 | ||
| Salbutamol (see also Asthma) | 388 | ||
| Salmeterol | 388 | ||
| Ephedrine | 388 | ||
| Phenylephrine | 389 | ||
| Mucosal decongestants | 389 | ||
| Shock | 389 | ||
| Definition | 389 | ||
| Treatment | 389 | ||
| Types of shock | 390 | ||
| In poisoning by a cerebral depressant | 390 | ||
| In central circulatory failure | 390 | ||
| Septic shock | 390 | ||
| Choice of drug in shock | 390 | ||
| Monitoring drug use | 391 | ||
| Restoration of intravascular volume9 | 391 | ||
| Dextran 70 | 391 | ||
| Gelatin products | 391 | ||
| Etherified starch | 391 | ||
| Chronic orthostatic hypotension | 391 | ||
| Guide to further reading | 392 | ||
| Chapter 24: Arterial hypertension, angina pectoris, myocardial infarction and heart failure | 393 | ||
| Synopsis | 393 | ||
| Hypertension: how drugs act | 393 | ||
| Angina pectoris: how drugs act | 393 | ||
| Drugs used in hypertension and angina | 394 | ||
| Diuretics (see also Ch. 27) | 394 | ||
| Vasodilators | 394 | ||
| Organic nitrates | 394 | ||
| Pharmacokinetics | 394 | ||
| Tolerance | 395 | ||
| Uses | 395 | ||
| Adverse effects | 395 | ||
| Interactions | 395 | ||
| Glyceryl trinitrate (see also above) | 395 | ||
| For prophylaxis, | 395 | ||
| Venepuncture | 396 | ||
| Isosorbide dinitrate | 396 | ||
| Isosorbide mononitrate | 396 | ||
| Calcium channel blockers | 396 | ||
| Vascular smooth muscle cells | 396 | ||
| Pharmacokinetics | 396 | ||
| Indications for use | 396 | ||
| Adverse effects | 396 | ||
| Interactions | 397 | ||
| Individual calcium blockers | 397 | ||
| Nifedipine | 397 | ||
| Amlodipine | 397 | ||
| Verapamil | 397 | ||
| Diltiazem | 397 | ||
| Nimodipine | 397 | ||
| Other members | 397 | ||
| Angiotensin-converting enzyme (ACE) inhibitors, angiotensin (AT) II receptor blockers (ARBs) and renin inhibitors | 397 | ||
| Uses | 398 | ||
| Hypertension | 398 | ||
| Cardiac failure | 398 | ||
| Diabetic nephropathy | 398 | ||
| Myocardial infarction (MI) | 399 | ||
| Cautions | 399 | ||
| Adverse effects | 399 | ||
| ACE inhibitors: | 399 | ||
| ARBs | 399 | ||
| Interactions | 399 | ||
| Individual drugs | 399 | ||
| Captopril | 399 | ||
| Enalapril | 400 | ||
| Other members | 400 | ||
| Losartan | 400 | ||
| Other ARBs | 400 | ||
| Renin inhibitors | 400 | ||
| Interactions | 400 | ||
| Individual drugs | 400 | ||
| Aliskiren | 400 | ||
| Other vasodilators | 400 | ||
| Minoxidil | 400 | ||
| Sodium nitroprusside | 400 | ||
| Diazoxide | 401 | ||
| Hydralazine | 401 | ||
| Nicorandil | 401 | ||
| Papaverine | 401 | ||
| Alprostadil | 401 | ||
| Vasodilators in heart failure | 401 | ||
| Vasodilators in peripheral vascular disease | 402 | ||
| Intermittent claudication | 402 | ||
| Raynaud's phenomenon | 402 | ||
| Adrenoceptor-blocking drugs | 402 | ||
| Ī±-Adrenoceptor-blocking drugs | 402 | ||
| Adverse effects | 403 | ||
| Notes on individual drugs | 403 | ||
| Prazosin | 403 | ||
| Doxazosin | 403 | ||
| Indoramin | 403 | ||
| Phentolamine | 403 | ||
| Phenoxybenzamine | 403 | ||
| Moxisylyte | 403 | ||
| Labetalol | 403 | ||
| Chlorpromazine and amitriptyline, | 403 | ||
| Ī²-Adrenoceptor-blocking drugs | 403 | ||
| Actions | 403 | ||
| Intrinsic heart rate | 403 | ||
| Effects | 404 | ||
| Ī²-Adrenoceptor selectivity | 404 | ||
| Pharmacokinetics | 405 | ||
| Lipid-soluble | 406 | ||
| Water-soluble | 406 | ||
| Classification of Ī²-adrenoceptor-blocking drugs | 406 | ||
| Uses of Ī²-adrenoceptor-blocking drugs | 406 | ||
| Cardiovascular uses: | 406 | ||
| Endocrine uses | 406 | ||
| Other uses: | 407 | ||
| Adverse reactions due to Ī²-adrenoceptor blockade | 407 | ||
| Adverse reactions not certainly due to Ī²-adrenoceptor blockade | 407 | ||
| Overdose | 408 | ||
| Interactions | 408 | ||
| Pharmacokinetic | 408 | ||
| Pharmacodynamic | 408 | ||
| Pregnancy | 408 | ||
| Notes on some individual Ī²-adrenoceptor blockers | 408 | ||
| Propranolol | 408 | ||
| Atenolol | 409 | ||
| Bisoprolol | 409 | ||
| Nebivolol | 409 | ||
| Combined Ī²1- and Ī±-adrenoceptor-blocking drug | 409 | ||
| Labetalol | 409 | ||
| Peripheral sympathetic nerve terminal | 409 | ||
| Adrenergic neurone-blocking drugs | 409 | ||
| Depletion of stored transmitter (noradrenaline/norepinephrine) | 409 | ||
| Inhibition of synthesis of transmitter | 410 | ||
| Autonomic ganglion-blocking drugs | 410 | ||
| Hexamethonium | 410 | ||
| Trimetaphan, | 410 | ||
| Central nervous system | 410 | ||
| Ī±2-Adrenoceptor agonists | 410 | ||
| Clonidine | 410 | ||
| False transmitter | 410 | ||
| Methyldopa | 410 | ||
| Drug treatment of angina, myocardial infarction and hypertension | 410 | ||
| Angina pectoris25 | 410 | ||
| Antiangina drugs | 411 | ||
| Summary of treatment | 411 | ||
| For long-term prophylaxis: | 411 | ||
| Newer therapies | 411 | ||
| Ivabradine | 411 | ||
| Myocardial infarction (MI) | 411 | ||
| An overview | 411 | ||
| Other antiplatelet agents | 412 | ||
| Unstable angina | 412 | ||
| Secondary prevention | 413 | ||
| Drugs for secondary prevention | 413 | ||
| Arterial hypertension | 413 | ||
| Aims of treatment | 413 | ||
| Threshold and targets for treatment | 413 | ||
| Principles of antihypertensive therapy | 414 | ||
| Drug therapy | 414 | ||
| Treating hypertension | 415 | ||
| Treatment and severity | 415 | ||
| Monitoring | 416 | ||
| Diuretics and potassium | 416 | ||
| Compliance | 416 | ||
| Treatment of hypertensive emergencies | 416 | ||
| Accelerated phase hypertension | 417 | ||
| Treatment | 417 | ||
| Pregnancy hypertension | 417 | ||
| Unwanted interactions with antihypertensive drugs | 417 | ||
| Alcohol intake | 417 | ||
| Prostaglandin synthesis | 417 | ||
| Enzyme inhibition | 417 | ||
| Pharmacological antagonism | 418 | ||
| Surgical anaesthesia | 418 | ||
| Sexual function and cardiovascular drugs | 418 | ||
| Sexual intercourse and the cardiovascular system | 418 | ||
| Pulmonary hypertension | 418 | ||
| Idiopathic (primary) pulmonary arterial hypertension (PAH) | 419 | ||
| Treatment of secondary hypertension | 419 | ||
| Phaeochromocytoma | 419 | ||
| Diagnosis | 419 | ||
| Control of blood pressure | 419 | ||
| Conn's syndrome | 420 | ||
| Heart failure and its treatment | 420 | ||
| Some physiology and pathophysiology | 420 | ||
| Definition of chronic heart failure | 421 | ||
| The Starling curve and heart failure | 421 | ||
| Natural history of chronic heart failure | 422 | ||
| Objectives of treatment | 422 | ||
| Haemodynamic aims of drug therapy | 422 | ||
| Classification of drugs | 423 | ||
| Reduction of preload | 423 | ||
| Diuretics | 423 | ||
| Nitrates | 423 | ||
| Reduction of afterload | 423 | ||
| Reduction of preload and afterload | 423 | ||
| ACE inhibitors and angiotensin receptor II blockers (ARBs) | 423 | ||
| Ī²-Adrenoceptor blockers | 423 | ||
| Spironolactone | 423 | ||
| Stimulation of the myocardium | 424 | ||
| Digoxin | 424 | ||
| Drug management of heart failure | 424 | ||
| Chronic heart failure | 424 | ||
| Acute left ventricular failure | 425 | ||
| Surgery for heart failure | 426 | ||
| Guide to further reading | 426 | ||
| Chapter 25: Cardiac arrhythmia | 428 | ||
| Synopsis | 428 | ||
| Objectives of treatment | 428 | ||
| Some physiology and pathophysiology | 429 | ||
| Ionic movements into and out of cardiac cells | 429 | ||
| Classification of antiarrhythmic drugs | 429 | ||
| Classification of drugs | 430 | ||
| Class I: sodium channel blockade | 430 | ||
| Class II: catecholamine blockade | 430 | ||
| Class III: lengthening of refractoriness | 430 | ||
| Class IV: calcium channel blockade | 430 | ||
| Principal drugs by class | 430 | ||
| Class 1A (sodium channel blockade with lengthened refractoriness) | 430 | ||
| Quinidine | 430 | ||
| Pharmacokinetics | 431 | ||
| Adverse reactions | 431 | ||
| Disopyramide | 432 | ||
| Section 6: Blood and neoplastic disease | 481 | ||
| Chapter 29: Drugs and haemostasis | 482 | ||
| Synopsis | 482 | ||
| Introduction | 482 | ||
| The coagulation system | 482 | ||
| Procoagulant drugs | 483 | ||
| Vitamin K | 483 | ||
| Phytomenadione | 484 | ||
| Menadiol | 484 | ||
| Vitamin K is used to treat the following: | 484 | ||
| Coagulation factor concentrates | 484 | ||
| Use of coagulation factor concentrates | 484 | ||
| Desmopressin (DDAVP) | 485 | ||
| Adverse effects | 485 | ||
| Other agents | 485 | ||
| Adrenaline/epinephrine | 485 | ||
| Fibrin glue | 485 | ||
| Sclerosing agents | 485 | ||
| Anticoagulant drugs | 485 | ||
| Oral vitamin K antagonists (VKA) | 485 | ||
| Pharmacokinetics | 485 | ||
| Pharmacodynamics | 486 | ||
| Dose | 486 | ||
| Adverse effects | 486 | ||
| Withdrawal of oral anticoagulant therapy | 487 | ||
| Reversal of anticoagulation | 487 | ||
| Drug interactions | 487 | ||
| Uses of oral VKA | 487 | ||
| Surgery in patients receiving oral VKA | 487 | ||
| Elective surgery | 487 | ||
| Emergency surgery | 487 | ||
| Dental extractions | 488 | ||
| Other vitamin K antagonists | 488 | ||
| Oral direct thrombin and factor Xa inhibitors | 488 | ||
| Dabigatran | 488 | ||
| Rivaroxaban | 488 | ||
| Parenteral anticoagulants | 488 | ||
| Heparin | 488 | ||
| Pharmacokinetics | 488 | ||
| Pharmacodynamics | 489 | ||
| Monitoring heparin therapy | 489 | ||
| Adverse effects | 489 | ||
| Heparin reversal | 489 | ||
| Use of heparin | 489 | ||
| Treatment of established venous thromboembolism | 489 | ||
| Prevention of venous thromboembolism | 490 | ||
| Cardiac disease | 490 | ||
| Peripheral arterial occlusion | 490 | ||
| Other anticoagulant drugs | 490 | ||
| Anticoagulant drugs under development | 490 | ||
| Fibrinolytic (thrombolytic) system | 490 | ||
| Plasminogen activators | 490 | ||
| Plasminogen activator inhibitors | 491 | ||
| Drugs that promote fibrinolysis | 491 | ||
| Uses of thrombolytic drugs | 491 | ||
| Coronary artery thrombolysis | 491 | ||
| Adverse effects | 491 | ||
| Non-coronary thrombolysis | 491 | ||
| Pulmonary embolism | 491 | ||
| Deep vein thrombosis | 492 | ||
| Arterial occlusion | 492 | ||
| Ischaemic stroke | 492 | ||
| Drugs that prevent fibrinolysis | 492 | ||
| Tranexamic acid | 492 | ||
| Aprotinin | 492 | ||
| Platelet function | 492 | ||
| Drugs that inhibit platelet activity (antiplatelet drugs) | 493 | ||
| Aspirin | 493 | ||
| Dipyridamole | 493 | ||
| Clopidogrel | 493 | ||
| Prasugrel | 493 | ||
| Epoprostenol | 493 | ||
| Glycoprotein (GP) IIb-IIIa antagonists | 493 | ||
| Abciximab | 493 | ||
| Eptifibatide | 494 | ||
| Adverse effects | 494 | ||
| Other drugs | 494 | ||
| Uses of antiplatelet drugs | 494 | ||
| Guide to further reading | 495 | ||
| Chapter 30: Red blood cell disorders | 496 | ||
| Synopsis | 496 | ||
| Iron | 496 | ||
| Iron deficiency | 496 | ||
| Management of iron deficiency and prophylactic iron administration | 498 | ||
| Drug interactions | 499 | ||
| Anaemia of chronic disease | 499 | ||
| Functional iron deficiency | 499 | ||
| Chronic iron overload | 499 | ||
| Parenteral iron chelator | 500 | ||
| Oral iron chelators | 500 | ||
| Iron poisoning and acute overdose | 500 | ||
| Vitamin B12 | 500 | ||
| Vitamin B12 deficiency | 501 | ||
| Management of vitamin B12 deficiency and prophylactic administration | 502 | ||
| Contraindications to cobalamin | 502 | ||
| Folic acid (pteroylglutamic acid) | 502 | ||
| Folic acid deficiency | 502 | ||
| Management of folic acid deficiency and prophylactic administration | 503 | ||
| Haemolytic anaemia | 503 | ||
| Autoimmune haemolytic anaemia | 503 | ||
| Drug-induced haemolytic anaemia | 504 | ||
| Glucose-6-phosphate dehydrogenase deficiency | 504 | ||
| Haemoglobinopathies | 505 | ||
| Sickle cell anaemia | 505 | ||
| Thalassaemia | 505 | ||
| Aplastic anaemia | 505 | ||
| Polycythaemia vera | 506 | ||
| Management of PV | 506 | ||
| Hydroxycarbamide | 506 | ||
| Interferon-Ī± | 506 | ||
| Anagrelide, | 506 | ||
| Busulfan | 506 | ||
| Therapy of other clinical features of PV | 506 | ||
| Haemopoietic growth factors | 507 | ||
| Erythropoiesis-stimulating agents | 507 | ||
| Clinical uses of ESA | 507 | ||
| Anaemia of chronic renal failure | 507 | ||
| Anaemia due to cancer chemotherapy | 507 | ||
| Other clinical uses of EPO | 507 | ||
| Granulocyte colony-stimulating factor | 507 | ||
| Guide to further reading | 508 | ||
| Chapter 31: Neoplastic disease and immunosuppression | 509 | ||
| Synopsis | 509 | ||
| Neoplastic disease | 509 | ||
| Cancer treatments and outcomes | 509 | ||
| Systemic cancer therapy | 509 | ||
| Rationale for cytotoxic chemotherapy | 511 | ||
| Classes of cytotoxic chemotherapy drugs | 511 | ||
| Adverse effects of cytotoxic chemotherapy | 511 | ||
| Nausea and vomiting | 511 | ||
| Suppression of bone marrow and the lymphoreticular system | 514 | ||
| Opportunistic infection | 514 | ||
| Diarrhoea and mouth ulcers | 514 | ||
| Alopecia | 514 | ||
| Urate nephropathy | 514 | ||
| Local extravasation | 514 | ||
| Hypersensitivity reactions | 514 | ||
| Specific organ damage | 514 | ||
| Delayed wound healing | 514 | ||
| Germ cells and reproduction | 514 | ||
| Carcinogenicity | 514 | ||
| Classes of cytotoxic agents | 514 | ||
| Alkylating agents | 514 | ||
| Antimetabolites | 514 | ||
| Anthracyclines and related compounds | 515 | ||
| Topoisomerase inhibitors | 515 | ||
| Spindle poisons | 515 | ||
| Platinum drugs | 515 | ||
| Miscellaneous agents | 515 | ||
| Chemotherapy in clinical practice | 515 | ||
| Drug use and tumour cell kinetics | 515 | ||
| Cytotoxic drugs | 516 | ||
| The selection of drugs | 516 | ||
| Drug resistance | 516 | ||
| Resistance | 516 | ||
| Multiple drug resistance | 516 | ||
| Improving efficacy of chemotherapy | 517 | ||
| Hazards to staff handling cytotoxic agents | 517 | ||
| A. note of caution | 517 | ||
| Interactions of anticancer agents with other drugs | 517 | ||
| Endocrine therapy | 517 | ||
| Hormonal influence on cancer | 517 | ||
| Hormonal agents | 518 | ||
| Breast cancer | 518 | ||
| Prostatic cancer | 518 | ||
| Benign prostatic hypertrophy | 518 | ||
| Adrenocortical steroids | 518 | ||
| In general, | 518 | ||
| Immunotherapy | 518 | ||
| ATRA | 519 | ||
| Development of anticancer drug therapy | 519 | ||
| Targeted biological therapies | 519 | ||
| Passive immunotherapy using monoclonal antibodies raised against specific tumour-associated antigens on the cell surface | 519 | ||
| Radioimmunotherapy | 521 | ||
| Chemo-immunotherapy | 521 | ||
| Signal transduction inhibitors | 521 | ||
| Targeting the cell cycle | 521 | ||
| Protease inhibition | 521 | ||
| Chemoprevention of cancer | 521 | ||
| Viral immunisation and cancer prevention | 523 | ||
| Immunosuppression | 523 | ||
| Ciclosporin | 523 | ||
| Pharmacokinetics | 523 | ||
| Uses | 523 | ||
| Adverse reactions | 523 | ||
| Interactions | 524 | ||
| Tacrolimus | 524 | ||
| Antilymphocyte immunoglobin | 524 | ||
| Mycophenolate | 524 | ||
| Hazards of immunosuppressive drugs | 524 | ||
| Carcinogenicity | 524 | ||
| Active immunisation during immunosuppressive therapy | 524 | ||
| Guide to further reading | 524 | ||
| Section 7: Gastrointestinal system | 527 | ||
| Chapter 32: Oesophagus, stomach and duodenum | 528 | ||
| Synopsis | 528 | ||
| The oesophagus in health and disease | 528 | ||
| Gastric acid secretion and mucosal protection | 528 | ||
| Gastric acid secretion | 529 | ||
| Gastrin | 529 | ||
| Acetylcholine (ACh) | 529 | ||
| Histamine | 529 | ||
| Prostaglandins | 529 | ||
| Mucosal protective mechanisms | 529 | ||
| Helicobacter pylori (H. pylori): an occasionally silent killer | 529 | ||
| NSAIDs: enemies of the gut | 529 | ||
| Drugs affecting oesophageal motility and the lower oesophageal sphincter | 530 | ||
| Drugs to reduce or neutralise gastric acid | 530 | ||
| Proton pump inhibitors (PPIs) | 530 | ||
| Pharmacology | 530 | ||
| Pharmacokinetics | 530 | ||
| Adverse reactions and interactions | 530 | ||
| H2 receptor antagonists (H2RAs) | 531 | ||
| Pharmacology | 531 | ||
| Pharmacokinetics and dosage | 531 | ||
| Section 8: Endocrine system, metabolic conditions | 557 | ||
| Chapter 35: Adrenal corticosteroids, antagonists, corticotropin | 558 | ||
| Synopsis | 558 | ||
| Adrenal steroids and their synthetic analogues | 558 | ||
| Mechanism of action | 559 | ||
| On inorganic metabolism | 559 | ||
| On organic metabolism | 559 | ||
| Individual adrenal steroids | 562 | ||
| Hydrocortisone | 562 | ||
| Prednisolone | 563 | ||
| Methylprednisolone | 563 | ||
| Fluorinated corticosteroids (triamcinolone, fludrocortisone) | 563 | ||
| Triamcinolone | 563 | ||
| Fludrocortisone | 563 | ||
| Dexamethasone and betamethasone | 563 | ||
| Aldosterone | 563 | ||
| Spironolactone | 563 | ||
| Beclometasone, budesonide, fluticasone, mometasone and ciclesonide | 563 | ||
| Pharmacokinetics of corticosteroids | 563 | ||
| Dosage schedules | 563 | ||
| Adverse effects of systemic adrenal steroid pharmacotherapy | 564 | ||
| Endocrine | 564 | ||
| Musculoskeletal | 564 | ||
| Immune | 564 | ||
| Gastrointestinal | 564 | ||
| Central nervous system | 564 | ||
| Ophthalmic effects | 564 | ||
| Other effects | 564 | ||
| Adrenal steroids and pregnancy | 564 | ||
| Precautions during chronic adrenal steroid therapy | 565 | ||
| Treatment of intercurrent illness | 565 | ||
| Dosage and routes of administration | 565 | ||
| Systemic commencing doses: | 565 | ||
| Topical applications | 565 | ||
| Contraindications | 565 | ||
| Long-term use of adrenal steroids in children | 566 | ||
| Uses of adrenocortical steroids | 566 | ||
| Replacement therapy | 566 | ||
| Acute adrenocortical insufficiency (Addisonian crisis) | 566 | ||
| Chronic primary adrenocortical insufficiency (Addison's disease) | 566 | ||
| Chronic secondary adrenocortical insufficiency | 566 | ||
| Iatrogenic adrenocortical insufficiency: abrupt withdrawal | 566 | ||
| Pharmacotherapy | 568 | ||
| Suppression of adrenocortical function | 568 | ||
| Use in inflammation and for immunosuppression | 568 | ||
| Further specific uses | 568 | ||
| Use in diagnosis | 569 | ||
| Withdrawal of pharmacotherapy | 569 | ||
| Inhibition of synthesis of adrenal and other steroid hormones | 569 | ||
| Competitive antagonism of adrenal steroids | 570 | ||
| Adrenocorticotrophic hormone (ACTH) (corticotropin) | 570 | ||
| Natural corticotropin | 570 | ||
| Synthetic corticotropins | 570 | ||
| Actions | 570 | ||
| The effects | 570 | ||
| Uses | 570 | ||
| Diagnostic use | 570 | ||
| Therapeutic use | 570 | ||
| Preparations | 570 | ||
| Guide to further reading | 571 | ||
| Chapter 36: Diabetes mellitus, insulin, oral antidiabetes agents, obesity | 572 | ||
| Synopsis | 572 | ||
| Diabetes overview | 572 | ||
| History of insulin therapy in diabetes | 572 | ||
| Sources of insulin | 573 | ||
| Insulin receptors | 573 | ||
| Actions of insulin | 573 | ||
| Uses | 573 | ||
| Pharmacokinetics | 574 | ||
| Preparations of insulin (Table 36.1) | 574 | ||
| Notes for prescribing insulin | 574 | ||
| Allergy | 574 | ||
| Antibodies | 574 | ||
| Compatibility | 574 | ||
| Intravenous insulin | 574 | ||
| The standard strength | 576 | ||
| Choice of insulin regimen | 576 | ||
| Dose and injection technique | 577 | ||
| Adverse effects of insulin | 577 | ||
| Hypoglycaemia | 577 | ||
| Oral antidiabetes drugs | 578 | ||
| (i) Insulin secretagogues | 578 | ||
| Meglitinides | 579 | ||
| Incretin analogues and mimetics | 579 | ||
| Dipeptidyl peptidase-4 (DPP-4) inhibitors | 579 | ||
| (ii) Insulin sensitisers | 579 | ||
| Biguanides | 579 | ||
| Thiazolidinediones | 580 | ||
| (iii) Agents which reduce glucose absorption | 580 | ||
| Acarbose | 580 | ||
| Dietary fibre and diabetes | 580 | ||
| Choice of oral antidiabetic drugs in type 2 diabetes | 580 | ||
| Diet and diabetes | 581 | ||
| Interactions with non-diabetes drugs | 581 | ||
| Adrenal steroids, | 581 | ||
| Growth hormone | 581 | ||
| Oral contraceptives | 581 | ||
| Thyroid hormone | 581 | ||
| Drug-induced diabetes | 582 | ||
| Diazoxide | 582 | ||
| Pregnancy and diabetes | 582 | ||
| Surgery in diabetic patients | 582 | ||
| Principles of management | 582 | ||
| Type 1 diabetes | 582 | ||
| Elective major surgery | 582 | ||
| Minor surgery/ procedures | 583 | ||
| Emergency surgery | 583 | ||
| Type 2 diabetes | 583 | ||
| Diabetic ketoacidosis | 583 | ||
| Intravenous fluid | 583 | ||
| Soluble insulin | 583 | ||
| Potassium | 583 | ||
| Bicarbonate | 583 | ||
| Success in treatment | 583 | ||
| Diabetic ketosis without acidosis | 583 | ||
| Hyperosmolar diabetic coma | 583 | ||
| Preventing complications other than by glucose lowering | 584 | ||
| Obesity and appetite control | 585 | ||
| Orlistat | 585 | ||
| Adverse effects | 585 | ||
| Leptin | 585 | ||
| Obesity and diabetes | 585 | ||
| Guide to further reading | 586 | ||
| Chapter 37: Thyroid hormones, antithyroid drugs | 587 | ||
| Synopsis | 587 | ||
| Thyroid hormones | 587 | ||
| Calcitonin | 587 | ||
| Physiology and pharmacokinetics | 587 | ||
| T4 (levothyroxine) | 587 | ||
| T3 (liothyronine) | 588 | ||
| Pharmacodynamics | 588 | ||
| Levothyroxine for hypothyroidism | 588 | ||
| Treatment of hypothyroidism | 588 | ||
| Levothyroxine tablets | 588 | ||
| Liothyronine tabs | 588 | ||
| Subclinical hypothyroidism | 588 | ||
| Adverse effects | 588 | ||
| In pregnancy | 589 | ||
| Antithyroid drugs and hyperthyroidism | 589 | ||
| Thionamides (thiourea derivatives) carbimazole, methimazole, propylthiouracil | 589 | ||
| Mode of action (Fig.37.1) | 589 | ||
| Carbimazole and methimazole | 589 | ||
| Propylthiouracil | 589 | ||
| Immunosuppression | 589 | ||
| Doses | 590 | ||
| Use | 590 | ||
| Adverse reactions | 590 | ||
| Pregnancy | 590 | ||
| Control of antithyroid drug therapy | 590 | ||
| Ī²-Adrenergic blockade | 590 | ||
| Iodine (iodide and radioactive iodine) | 591 | ||
| Effects | 591 | ||
| Uses | 591 | ||
| Potassium iodate | 591 | ||
| As an antiseptic | 591 | ||
| Bronchial secretions | 591 | ||
| Organic compounds | 591 | ||
| Adverse reactions | 591 | ||
| Symptoms of iodism | 591 | ||
| Radioiodine (131I) | 592 | ||
| Risks | 592 | ||
| Radioisotope tests | 592 | ||
| Preparation for surgery | 592 | ||
| Thyroid storm | 593 | ||
| Graves' ophthalmopathy | 593 | ||
| Treatment of subclinical hyperthyroidism | 593 | ||
| Drugs that cause hypothyroidism | 593 | ||
| Amiodarone | 594 | ||
| Miscellaneous | 595 | ||
| Treatment of thyroiditis | 595 | ||
| Calcitonin | 595 | ||
| Guide to further reading | 595 | ||
| Chapter 38: Hypothalamic, pituitary and sex hormones | 596 | ||
| Synopsis | 596 | ||
| Hypothalamic and anterior pituitary hormones | 596 | ||
| Corticotropin releasing hormone (CRH) | 596 | ||
| Adrenocorticotrophic hormone (ACTH) | 596 | ||
| Thyrotrophin releasing hormone (TRH) | 596 | ||
| Thyroid stimulating hormone (TSH) thyrotrophin, | 597 | ||
| Sermorelin | 597 | ||
| Octreotide | 597 | ||
| Growth hormone, somatrophin | 597 | ||
| Pegvisomant | 598 | ||
| Gonadotrophin releasing hormone (GnRH), | 598 | ||
| Follicle stimulating hormone (FSH) | 598 | ||
| Chorionic gonadotrophin | 598 | ||
| Prolactin | 598 | ||
| Hypopituitarism | 599 | ||
| Posterior pituitary hormones and analogues | 599 | ||
| Vasopressin: antidiuretic hormone (ADH) | 599 | ||
| Desmopressin | 599 | ||
| Diabetes insipidus: vasopressin deficiency | 599 | ||
| Desmopressin replacement therapy | 600 | ||
| Syndrome of inappropriate antidiuretic hormone secretion (SIADH) | 600 | ||
| Emergency treatment of hyponatraemia | 600 | ||
| Oxytocin | 600 | ||
| Sex (gonadal) hormones and antagonists: steroid hormones | 600 | ||
| Steroid hormone receptors | 600 | ||
| Selectivity | 600 | ||
| Pharmacokinetics | 600 | ||
| Androgens | 601 | ||
| Indications for androgen therapy | 601 | ||
| Preparations and choice of androgens | 601 | ||
| Oral preparations | 601 | ||
| Parenteral preparations | 601 | ||
| Transdermal preparations | 601 | ||
| Buccal preparations | 601 | ||
| Testosterone implants | 601 | ||
| Adverse effects | 602 | ||
| Antiandrogens (androgen antagonists) | 602 | ||
| Cyproterone | 602 | ||
| Uses | 602 | ||
| Anabolic steroids | 602 | ||
| Oestrogens | 603 | ||
| Pharmacokinetics | 603 | ||
| Preparations of oestrogens | 603 | ||
| Choice of oestrogen | 603 | ||
| Oestrogen formulations and routes of administration | 603 | ||
| Oral | 603 | ||
| Transdermal | 603 | ||
| Subcutaneous implants | 603 | ||
| Vaginal (ring, cream, tablet or pessary) | 603 | ||
| Others | 603 | ||
| Indications for oestrogen therapy | 603 | ||
| Replacement therapy in hypo-oestrogenaemia | 603 | ||
| Post-menopausal hormone replacement therapy (HRT) | 603 | ||
| Preparations used for HRT | 604 | ||
| Contraception | 604 | ||
| Adverse effects of HRT | 604 | ||
| Contraindications | 604 | ||
| Anti-oestrogens | 604 | ||
| Clomifene | 605 | ||
| Cyclofenil | 605 | ||
| Tamoxifen | 605 | ||
| Progesterone and progestogens | 605 | ||
| Uses | 605 | ||
| Preparations | 605 | ||
| Adverse effects | 605 | ||
| Antiprogestogens | 605 | ||
| Mifepristone | 606 | ||
| Other progesterone derivatives | 606 | ||
| Fertility regulation | 606 | ||
| Infertility | 606 | ||
| For women, | 606 | ||
| For men, | 606 | ||
| Polycystic ovary syndrome (PCOS) | 606 | ||
| Contraception by drugs and hormones | 607 | ||
| Hormonal contraception in women | 607 | ||
| Combined contraceptives (the `pillĀ“) | 607 | ||
| Combined oestrogen-progestogen | 607 | ||
| Important aspects | 607 | ||
| Subsequent fertility | 607 | ||
| Effect on an existing pregnancy | 607 | ||
| Carcinomas | 607 | ||
| The effect on menstruation | 607 | ||
| Libido | 607 | ||
| Cardiovascular complications | 607 | ||
| Major surgery | 608 | ||
| Plasma lipoproteins | 608 | ||
| Plasma proteins | 608 | ||
| Other adverse effects | 608 | ||
| Absolute contraindications | 608 | ||
| Relative contraindications | 608 | ||
| Duration of use | 608 | ||
| Benefits additional to contraception | 608 | ||
| Formulations of oestrogen-progestogen combination | 609 | ||
| Oestrogen: | 609 | ||
| Progestogen: | 609 | ||
| Combined oral contraceptives | 609 | ||
| Choice of oestrogen-progestogen combination | 609 | ||
| Common problems | 609 | ||
| Missed pill | 609 | ||
| Intercurrent gut upset | 609 | ||
| Changing of preparation | 609 | ||
| Breakthrough bleeding | 609 | ||
| Progestogen-only contraception | 609 | ||
| Postcoital (`morning after pillĀ“) and emergency contraception | 610 | ||
| Progestogen-only treatment | 610 | ||
| Drug interaction with steroid contraceptives | 610 | ||
| Enzyme induction | 610 | ||
| Hypothalamic/pituitary hormone approach to contraception | 610 | ||
| Other methods of contraception | 610 | ||
| Copper intrauterine devices | 610 | ||
| The intrauterine levonorgestrel system | 610 | ||
| Vaginal preparations, | 610 | ||
| Oil-based lubricants | 610 | ||
| Risks of contraception in relation to benefit | 611 | ||
| Menstrual disorders | 611 | ||
| Amenorrhoea, | 611 | ||
| Menorrhagia | 611 | ||
| The timing of menstruation | 611 | ||
| Endometriosis | 611 | ||
| Dysmenorrhoea | 612 | ||
| Premenstrual tension syndrome | 612 | ||
| Cyclical breast pain | 612 | ||
| Myometrium | 612 | ||
| Oxytocics | 612 | ||
| Oxytocin | 612 | ||
| Ergometrine | 612 | ||
| Prostaglandins | 612 | ||
| Dinoprost | 612 | ||
| Gemeprost | 613 | ||
| Carboprost | 613 | ||
| Induction of abortion | 613 | ||
| Induction and augmentation of labour | 613 | ||
| Prevention and treatment of uterine haemorrhage | 613 | ||
| Uterine relaxants | 613 | ||
| Guide to further reading | 614 | ||
| Chapter 39: Vitamins, calcium, bone | 615 | ||
| Synopsis | 615 | ||
| Vitamin A: retinol | 615 | ||
| Therapeutic uses | 616 | ||
| Psoriasis | 616 | ||
| Acne | 616 | ||
| Acute promyelocytic leukaemia | 616 | ||
| Vitamin A deficiency | 616 | ||
| Adverse effects | 616 | ||
| Teratogenicity | 616 | ||
| Vitamin B complex | 616 | ||
| Thiamine (B1) | 616 | ||
| Cobalamins (B12) | 616 | ||
| Folic acid | 616 | ||
| Pyridoxine (B6) | 616 | ||
| Niacin (nicotinic acid, B3) | 616 | ||
| Vitamin C: ascorbic acid | 617 | ||
| Indications | 617 | ||
| Scurvy | 617 | ||
| Methaemoglobinaemia | 617 | ||
| Adverse effects | 617 | ||
| Vitamin D, calcium, parathyroid hormone, calcitonin, bisphosphonates, bone | 617 | ||
| Vitamin D | 617 | ||
| Pharmacokinetics | 618 | ||
| Actions | 619 | ||
| Indications | 619 | ||
| Vitamin D deficiency | 619 | ||
| Osteoporosis | 619 | ||
| Hypoparathyroidism | 619 | ||
| Psoriasis | 619 | ||
| Renal osteodystrophy | 619 | ||
| Index | 627 |