Additional Information
Book Details
Abstract
This book covers all the pharmacology you need, from basic science pharmacology and pathophysiology, through to clinical pharmacology to therapeutics, in line with the integrated approach of new medical curricula. The first section covers the basic principles, and the rest is organised by body systems. The book ends with sections on toxicity and prescribing practice.
- Integrates basic science pharmacology, clinical pharmacology and therapeutics
- Brief review of pathophysiology of major diseases
- Case histories and multiple choice questions (and answers)
- Tabular presentation of all common drugs within each class
- Section on further reading
- Kinetics chapter simplified with more practical examples
- Includes more on genetic issues
- Drug tables made more concise to make information more accessible
- Fully updated to reflect current clinical practice
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front cover | cover | ||
| Half title page | i | ||
| Dedication | ii | ||
| Medical Pharmacology and Therapeutics | iii | ||
| Copyright page | iv | ||
| Table of Contents | v | ||
| Preface | vii | ||
| Drug dosage and nomenclature | ix | ||
| Drug nomenclature | ix | ||
| Drug dosages | ix | ||
| 1 General Principles | 1 | ||
| 1 Principles of pharmacology and mechanisms of drug action | 3 | ||
| Studying pharmacology | 3 | ||
| Receptors and receptor-mediated mechanisms | 4 | ||
| Actions of drugs at binding sites (receptors) | 4 | ||
| Major types of receptors | 4 | ||
| Transmembrane ion channels | 5 | ||
| Seven-transmembrane receptors | 6 | ||
| The G-protein system | 6 | ||
| Second messenger systems | 6 | ||
| Cyclic nucleotide system | 6 | ||
| The phosphatidylinositol system | 6 | ||
| Protease-activated receptors | 8 | ||
| Enzyme-linked transmembrane receptors | 8 | ||
| Intracellular (nuclear) receptors | 10 | ||
| Other sites of drug action | 11 | ||
| Properties of receptors | 12 | ||
| Receptor binding | 12 | ||
| Receptor selectivity | 13 | ||
| Drug stereochemistry and activity | 14 | ||
| Receptor numbers | 14 | ||
| Properties of drug action | 15 | ||
| Dose–response relationships | 15 | ||
| Selectivity | 15 | ||
| Potency | 15 | ||
| Efficacy | 16 | ||
| Types of drug action | 16 | ||
| Agonists | 16 | ||
| Affinity and intrinsic activity | 16 | ||
| Spare receptors | 17 | ||
| Antagonists | 17 | ||
| Partial agonists | 17 | ||
| Inverse agonists | 17 | ||
| Allosteric modulators | 18 | ||
| Enzyme inhibitors/activators | 18 | ||
| Non-specific actions | 18 | ||
| Physiological antagonists | 18 | ||
| Tolerance to drug effects | 18 | ||
| Genetic variation in drug responses | 19 | ||
| Conclusions | 20 | ||
| Self-assessment | 20 | ||
| True/false questions | 20 | ||
| True/false answers | 20 | ||
| Further reading | 21 | ||
| 2 Pharmacokinetics | 31 | ||
| Pharmacokinetics of biological drugs | 31 | ||
| The biological basis of pharmacokinetics | 31 | ||
| General considerations | 32 | ||
| Passage across membranes | 32 | ||
| Passive diffusion | 32 | ||
| Passage through membrane pores or ion channels | 33 | ||
| Carrier-mediated processes | 33 | ||
| Pinocytosis | 34 | ||
| Drug ionisation and membrane diffusion | 34 | ||
| Absorption | 35 | ||
| Absorption from the gut | 35 | ||
| Drug structure | 35 | ||
| Drug formulation | 36 | ||
| Gastric emptying | 36 | ||
| First-pass metabolism | 36 | ||
| Intestinal lumen | 36 | ||
| Intestinal wall | 36 | ||
| Liver | 36 | ||
| Lung | 36 | ||
| Absorption from other routes | 36 | ||
| Percutaneous (transcutaneous) administration | 36 | ||
| Intradermal and subcutaneous injection | 36 | ||
| Intramuscular injection | 37 | ||
| Intranasal administration | 37 | ||
| Inhalation | 37 | ||
| Minor routes | 37 | ||
| Distribution | 37 | ||
| Reversible protein binding | 38 | ||
| Irreversible protein binding | 38 | ||
| Distribution to specific organs | 38 | ||
| Brain | 38 | ||
| Fetus | 39 | ||
| Elimination | 39 | ||
| Metabolism | 39 | ||
| Phase 1 | 40 | ||
| Phase 2 | 42 | ||
| Factors affecting drug metabolism | 43 | ||
| Excretion | 43 | ||
| Excretion via the urine | 44 | ||
| Glomerular filtration | 44 | ||
| Reabsorption | 44 | ||
| Tubular secretion | 44 | ||
| Excretion via the faeces | 44 | ||
| The mathematical basis of pharmacokinetics | 45 | ||
| General considerations | 45 | ||
| Zero-order reactions | 45 | ||
| First-order reactions | 45 | ||
| Absorption | 47 | ||
| Rate of absorption | 47 | ||
| Extent of absorption | 47 | ||
| Distribution | 48 | ||
| Rate of distribution | 48 | ||
| Extent of distribution | 49 | ||
| Elimination | 50 | ||
| Rate of elimination | 50 | ||
| The activity of the organ of elimination | 50 | ||
| Reversible passage of drug from the blood into tissues | 50 | ||
| Extent of elimination | 51 | ||
| Chronic administration | 51 | ||
| Time to reach steady-state | 51 | ||
| Plasma concentration at steady-state | 52 | ||
| Oral administration | 52 | ||
| Loading dose | 53 | ||
| Pharmacokinetics of biological drugs | 53 | ||
| Genetic variation and drug kinetics | 53 | ||
| Self-Assessment | 55 | ||
| True/false questions | 55 | ||
| One-best-answer (OBA) questions | 55 | ||
| Descriptive question | 55 | ||
| Case-based questions | 55 | ||
| Case 1 | 55 | ||
| Case 2 | 56 | ||
| Case 3 | 56 | ||
| True/false answers | 56 | ||
| OBA answers | 57 | ||
| Descriptive answers | 57 | ||
| Case-based answers | 57 | ||
| Case 1 | 57 | ||
| Case 2 | 58 | ||
| Case 3 | 58 | ||
| Further reading | 58 | ||
| 3 Drug discovery, safety and efficacy | 59 | ||
| Drug discovery | 59 | ||
| Drug approval | 60 | ||
| Safety | 61 | ||
| Quality | 61 | ||
| Efficacy | 61 | ||
| Establishing safety and efficacy | 61 | ||
| Preclinical studies | 62 | ||
| Toxicity testing | 62 | ||
| Clinical trials: phases I–III | 63 | ||
| Phase I studies | 63 | ||
| Phase II studies | 63 | ||
| Phase III studies | 63 | ||
| Post-marketing surveillance: phase IV (pharmacovigilance) | 65 | ||
| Self-Assessment | 66 | ||
| One-best-answer (OBA) questions | 66 | ||
| OBA answers | 66 | ||
| Further reading | 66 | ||
| 4 Neurotransmission and the peripheral autonomic nervous system | 67 | ||
| Arrangement of the central and peripheral nervous systems | 67 | ||
| Principles of neurotransmission | 67 | ||
| Presynaptic receptors and modulation of transmitter release | 69 | ||
| The peripheral autonomic nervous system | 69 | ||
| The sympathetic nervous system and noradrenergic transmission | 72 | ||
| Synthesis and storage of catecholamines: noradrenaline, adrenaline and dopamine | 72 | ||
| Noradrenaline release | 74 | ||
| Uptake and metabolism of released noradrenaline | 74 | ||
| Monoamine oxidase | 74 | ||
| Catechol-O-methyltransferase | 75 | ||
| Sympathetic nervous system receptors | 75 | ||
| The parasympathetic nervous system and cholinergic transmission | 75 | ||
| Synthesis of acetylcholine | 75 | ||
| Storage of acetylcholine | 75 | ||
| Release of acetylcholine | 75 | ||
| Metabolism and inactivation of released acetylcholine | 76 | ||
| Cholinergic receptors | 78 | ||
| Nicotinic (N1) receptors | 78 | ||
| Nicotinic (N2) receptors | 78 | ||
| Muscarinic (M) receptors | 78 | ||
| Other transmitters in the peripheral nervous system | 78 | ||
| Amines | 78 | ||
| Dopamine | 78 | ||
| Synthesis and storage of dopamine | 78 | ||
| Release of dopamine | 78 | ||
| Removal of activity of released dopamine | 78 | ||
| Dopamine receptors | 79 | ||
| Serotonin (5-hydroxytryptamine) | 79 | ||
| Synthesis of serotonin | 79 | ||
| Storage of serotonin | 79 | ||
| Release of serotonin | 79 | ||
| Metabolism and removal of serotonin activity | 79 | ||
| Serotonin receptors | 80 | ||
| Histamine | 80 | ||
| Synthesis of histamine | 80 | ||
| Storage of histamine | 80 | ||
| Release of histamine | 80 | ||
| Removal of histamine activity | 80 | ||
| Histamine receptors | 81 | ||
| Amino acids | 81 | ||
| Gamma-aminobutyric acid | 81 | ||
| Synthesis and storage of GABA | 81 | ||
| Release of GABA | 81 | ||
| Removal of GABA activity | 81 | ||
| GABA receptors | 81 | ||
| Glutamate | 81 | ||
| Synthesis and storage of glutamate | 81 | ||
| Release of glutamate | 81 | ||
| Removal of glutamate activity | 81 | ||
| Glutamate receptors | 81 | ||
| Glycine | 82 | ||
| Synthesis and storage of glycine | 82 | ||
| Release of glycine | 82 | ||
| Removal of glycine activity | 82 | ||
| Glycine receptors | 82 | ||
| Imidazoline receptor ligands | 82 | ||
| Peptides | 82 | ||
| Purines | 82 | ||
| Self-Assessment | 82 | ||
| True/false questions | 82 | ||
| One-best-answer (OBA) question | 83 | ||
| True/false answers | 83 | ||
| OBA answer | 83 | ||
| Further reading | 84 | ||
| 2 The Cardiovascular System | 85 | ||
| 5 Ischaemic heart disease | 87 | ||
| Clinical manifestations of myocardial ischaemia | 88 | ||
| Stable angina | 88 | ||
| Acute coronary syndromes (unstable angina, myocardial infarction and sudden death) | 89 | ||
| Unstable angina | 89 | ||
| Myocardial infarction and sudden cardiac death | 89 | ||
| Drug treatment of angina | 90 | ||
| Organic nitrates | 90 | ||
| Mechanism of action and effects | 90 | ||
| Pharmacokinetics | 91 | ||
| Unwanted effects | 91 | ||
| Beta-adrenoceptor antagonists (β-blockers) | 91 | ||
| Mechanism of action and effects in angina | 91 | ||
| Pharmacokinetics | 92 | ||
| Unwanted effects | 92 | ||
| Calcium channel blockers | 93 | ||
| Mechanism of action and effects | 93 | ||
| Pharmacokinetics | 95 | ||
| Unwanted effects | 95 | ||
| Potassium channel openers | 95 | ||
| 3 The Respiratory System | 185 | ||
| 12 Asthma and chronic obstructive pulmonary disease | 187 | ||
| Asthma | 187 | ||
| Chronic obstructive pulmonary disease | 188 | ||
| Drugs for asthma and chronic obstructive pulmonary disease | 189 | ||
| Drug delivery to the lung | 189 | ||
| Pressurised metered-dose inhaler | 191 | ||
| Pressurised metered-dose inhaler with a spacer | 191 | ||
| Breath-actuated metered-dose inhaler | 191 | ||
| Dry-powder inhaler | 191 | ||
| Multi-dose liquid inhaler | 191 | ||
| Nebulisers | 191 | ||
| Symptom-relieving drugs for airflow obstruction (bronchodilators; ‘relievers’) | 191 | ||
| Beta2-adrenoceptor agonists | 191 | ||
| Mechanism of action and effects | 192 | ||
| Pharmacokinetics | 192 | ||
| Unwanted effects | 192 | ||
| Antimuscarinic agents | 192 | ||
| 4 The Renal System | 211 | ||
| 14 Diuretics | 213 | ||
| Functions of the kidney | 213 | ||
| The kidney and maintenance of salt and water balance | 213 | ||
| The proximal convoluted tubule | 213 | ||
| The loop of Henle | 213 | ||
| The proximal (cortical) diluting segment of the distal convoluted tubule | 215 | ||
| The distal part of the distal convoluted tubule and the collecting duct | 216 | ||
| Diuretic drugs | 216 | ||
| Carbonic anhydrase inhibitors | 216 | ||
| 5 The Nervous System | 239 | ||
| 17 General anaesthetics | 241 | ||
| Mechanisms of action of general anaesthetics | 241 | ||
| Drugs used in anaesthesia | 243 | ||
| Intravenous anaesthetics | 243 | ||
| Pharmacokinetics | 244 | ||
| Unwanted effects | 244 | ||
| Intravenous opioids | 244 | ||
| 6 The Musculoskeletal System | 347 | ||
| 27 The neuromuscular junction and neuromuscular blockade | 349 | ||
| Neuromuscular transmission | 349 | ||
| Drugs acting at the neuromuscular junction | 349 | ||
| Acetylcholinesterase inhibitors | 349 | ||
| Inhibitors of acetylcholine release | 349 | ||
| Antagonists/blockers at the neuromuscular junction | 350 | ||
| Competitive N2 receptor antagonists (non-depolarising blockers) | 351 | ||
| 7 The Gastrointestinal System | 389 | ||
| 32 Nausea and vomiting | 391 | ||
| Nausea and vomiting | 391 | ||
| Anti-emetic agents | 391 | ||
| Antihistamines | 391 | ||
| Mechanism of action and clinical use | 391 | ||
| Pharmacokinetics | 391 | ||
| Unwanted effects | 391 | ||
| Antimuscarinic agent | 392 | ||
| Mechanism of action and clinical use | 392 | ||
| 8 The Immune System | 437 | ||
| 38 The immune response and immunosuppressant drugs | 439 | ||
| Biological basis of the immune response | 439 | ||
| Innate immunity | 439 | ||
| Adaptive immunity | 439 | ||
| Cell-mediated immunity | 441 | ||
| Humoral immunity | 441 | ||
| Unwanted immune reactions | 442 | ||
| Hypersensitivity reactions | 442 | ||
| Type 1 (acute, immediate) | 442 | ||
| Type 2 (cytotoxic) | 442 | ||
| Type 3 (complex-mediated) | 442 | ||
| Type 4 (cell-mediated, delayed-type hypersensitivity) | 442 | ||
| Transplant rejection | 442 | ||
| Autoimmunity | 442 | ||
| Immunosuppressant drugs | 442 | ||
| Calcineurin inhibitors | 443 | ||
| Ciclosporin | 443 | ||
| Mechanism of action | 443 | ||
| Pharmacokinetics | 443 | ||
| Unwanted effects | 443 | ||
| Tacrolimus | 444 | ||
| 9 The Endocrine System and Metabolism | 455 | ||
| 40 Diabetes mellitus | 457 | ||
| Control of blood glucose | 457 | ||
| Diabetes mellitus | 458 | ||
| Type 1 diabetes mellitus | 458 | ||
| Type 2 diabetes mellitus | 458 | ||
| Insulins and insulin analogues | 459 | ||
| Natural insulin formulations | 459 | ||
| Pharmacokinetics | 459 | ||
| Unwanted effects | 460 | ||
| Insulin analogues | 460 | ||
| Mechanism of action and effects | 460 | ||
| Short-acting insulin analogues | 460 | ||
| Long-acting insulin analogues | 460 | ||
| 10 The Skin and Eyes | 557 | ||
| 49 Skin disorders | 559 | ||
| Vehicles for topical skin applications | 559 | ||
| Atopic and contact dermatitis | 559 | ||
| Atopic dermatitis (eczema) | 559 | ||
| Contact dermatitis | 560 | ||
| Other types of dermatitis | 560 | ||
| Treatment of atopic dermatitis | 560 | ||
| Treatment of contact dermatitis | 560 | ||
| Psoriasis | 560 | ||
| Topical therapy | 560 | ||
| Emollients | 560 | ||
| Keratolytics | 560 | ||
| Vitamin D analogues | 560 | ||
| Topical retinoids | 561 | ||
| Dithranol | 561 | ||
| Coal tar preparations | 561 | ||
| Phototherapy | 561 | ||
| Topical corticosteroid preparations | 561 | ||
| Systemic treatments | 561 | ||
| Methotrexate | 561 | ||
| Retinoids | 561 | ||
| Ciclosporin or tacrolimus | 562 | ||
| Biologic agents | 562 | ||
| Fumaric acid esters | 562 | ||
| Acne | 562 | ||
| Treatment of acne | 562 | ||
| Topical treatments | 562 | ||
| Systemic treatments | 562 | ||
| Choice of treatment for acne | 563 | ||
| Self-Assessment | 563 | ||
| True/false questions | 563 | ||
| One-best-answer (OBA) question | 563 | ||
| Case-based questions | 563 | ||
| True/false answers | 563 | ||
| OBA answer | 563 | ||
| Case-based answers | 564 | ||
| Further reading | 564 | ||
| 50 The eye | 569 | ||
| Accommodation | 569 | ||
| Pupil size | 569 | ||
| Drainage of aqueous humour | 569 | ||
| Topical application of drugs to the eye | 570 | ||
| Glaucoma | 570 | ||
| Drugs for glaucoma | 571 | ||
| Beta-adrenoceptor antagonists | 571 | ||
| Sympathomimetics | 571 | ||
| Carbonic anhydrase inhibitors | 571 | ||
| Prostaglandin analogues | 571 | ||
| Miotic drugs (muscarinic agonists) | 571 | ||
| Treatment of glaucoma | 571 | ||
| Mydriatic and cycloplegic drugs | 572 | ||
| Antimuscarinics | 572 | ||
| Sympathomimetics | 572 | ||
| Other topical applications for the eye | 572 | ||
| Antibacterial agents | 572 | ||
| Antiviral agents | 572 | ||
| Corticosteroids | 572 | ||
| Antiallergic agents | 572 | ||
| Local anaesthetics | 572 | ||
| Non-steroidal anti-inflammatory drugs | 573 | ||
| Artificial tears | 573 | ||
| Age-related macular degeneration | 573 | ||
| Treatment of age-related macular degeneration | 573 | ||
| Self-Assessment | 573 | ||
| True/false questions | 573 | ||
| Extended-matching-item questions | 573 | ||
| Case-based questions | 573 | ||
| True/false answers | 574 | ||
| Extended-matching-item answers | 574 | ||
| Case-based answers | 574 | ||
| Further reading | 574 | ||
| 11 Chemotherapy | 579 | ||
| 51 Chemotherapy of infections | 581 | ||
| Bacterial infections | 581 | ||
| Classification of antibacterial drugs | 581 | ||
| Antimicrobial resistance | 582 | ||
| Antibacterial drug resistance | 582 | ||
| Spontaneous mutation | 582 | ||
| Conjugation | 582 | ||
| Transduction | 583 | ||
| Transformation | 583 | ||
| Antibacterial drugs | 583 | ||
| Drugs affecting the cell wall: β-lactam antibacterials | 583 | ||
| Mechanism of action of β-lactam antibacterials | 583 | ||
| Penicillins | 583 | ||
| Spectrum of activity | 583 | ||
| Resistance | 584 | ||
| Pharmacokinetics | 584 | ||
| Unwanted effects | 585 | ||
| Cephalosporins | 585 | ||
| Spectrum of activity | 585 | ||
| Resistance | 587 | ||
| Pharmacokinetics | 587 | ||
| Unwanted effects | 587 | ||
| Monobactams | 587 | ||
| Carbapenems | 587 | ||
| Other drugs affecting the cell wall | 587 | ||
| Glycopeptides | 587 | ||
| Mechanism of action | 587 | ||
| 12 General Features: Toxicity and Prescribing | 659 | ||
| 53 Drug toxicity and overdose | 661 | ||
| Drug toxicity and adverse effects | 661 | ||
| Types of unwanted effect | 662 | ||
| Pharmacological toxicity | 662 | ||
| Biochemical toxicity | 663 | ||
| Paracetamol | 664 | ||
| Cyclophosphamide | 664 | ||
| Isoniazid | 665 | ||
| Spironolactone | 665 | ||
| Aromatic amines and nitrites | 666 | ||
| Methaemoglobinaemia | 666 | ||
| Haemolysis | 666 | ||
| Immunological toxicity | 666 | ||
| Self-poisoning and drug overdose | 668 | ||
| Management principles | 668 | ||
| Managing adverse effects | 668 | ||
| Immediate measures | 668 | ||
| Supportive measures | 669 | ||
| Cardiac or respiratory arrest | 669 | ||
| Hypotension | 669 | ||
| Arrhythmias | 670 | ||
| Seizures | 670 | ||
| Renal failure | 670 | ||
| Hepatic failure | 670 | ||
| Impaired temperature regulation | 670 | ||
| Reducing toxicity | 670 | ||
| Prevention of absorption of poisons | 670 | ||
| Gastric aspiration and lavage | 670 | ||
| Activated charcoal | 670 | ||
| Elimination of poisons | 670 | ||
| Activated charcoal | 671 | ||
| Renal elimination | 671 | ||
| Haemodialysis | 671 | ||
| Specific antidotes | 671 | ||
| Competitive receptor antagonists | 671 | ||
| Chelating agents | 671 | ||
| Compounds that affect drug metabolism | 671 | ||
| Antibodies | 671 | ||
| Some specific common poisonings | 671 | ||
| Paracetamol | 671 | ||
| Salicylates | 672 | ||
| Tricyclic antidepressants | 673 | ||
| Opioid analgesics | 673 | ||
| Beta-adrenoceptor antagonists | 673 | ||
| Ecstasy | 673 | ||
| Self-Assessment | 673 | ||
| True/false questions | 673 | ||
| Case-based questions | 673 | ||
| True/false answers | 673 | ||
| Case-based answers | 673 | ||
| Further reading | 674 | ||
| 54 Substance abuse and dependence | 677 | ||
| The biological basis of dependence | 677 | ||
| Acute activation of the mesolimbic dopamine reward pathways | 677 | ||
| Chronic stimulation of the mesolimbic dopamine reward pathways | 677 | ||
| Drugs of abuse | 678 | ||
| Psychomotor stimulants | 678 | ||
| Cocaine | 679 | ||
| Index | 707 | ||
| A | 707 | ||
| B | 710 | ||
| C | 711 | ||
| D | 713 | ||
| E | 715 | ||
| F | 715 | ||
| G | 716 | ||
| H | 717 | ||
| I | 718 | ||
| J | 719 | ||
| K | 719 | ||
| L | 719 | ||
| M | 720 | ||
| N | 721 | ||
| O | 722 | ||
| P | 723 | ||
| Q | 725 | ||
| R | 725 | ||
| S | 725 | ||
| T | 727 | ||
| U | 728 | ||
| V | 728 | ||
| W | 728 | ||
| X | 729 | ||
| Y | 729 | ||
| Z | 729 |