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RANG AND DALE’S

Pharmacology
Content Strategist: Meghan Ziegler
Content Development Specialist: Alexandra Mortimer
Content Coordinator: Sam Crowe, Trinity Hutton
Project Manager: Joanna Souch
Design: Christian Bilbow
Illustration Manager: Brett MacNaughton
Illustrator: Peter Lamb, Antbits, Jason McAlexander
Marketing Manager: Melissa Darling
Pharmacology
RANG AND DALE’S

EIGHTH EDITION

H P Rang MB BS MA DPhil Hon FBPharmacolS FMedSci FRS

Emeritus Professor of Pharmacology,
University College London, London, UK

J M Ritter DPhil FRCP FBPharmacolS FMedSci

Emeritus Professor of Clinical Pharmacology,
King’s College London, and Medical Research Director, Quintiles,
London, UK

R J Flower PhD DSc FBPharmacolS FMedSci FRS

Professor, Biochemical Pharmacology,
The William Harvey Research Institute,
Barts and the London School of Medicine and Dentistry,
Queen Mary University of London, London, UK

G Henderson BSc PhD FBPharmacolS FSB

Professor of Pharmacology, University of Bristol, Bristol, UK

For additional online content visit

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an imprint of Elsevier Limited

© 2016, Elsevier Ltd. All rights reserved.

First edition 1987

Second edition 1991
Third edition 1995
Fourth edition 1999
Fifth edition 2003
Sixth edition 2007
Seventh edition 2012

The right of H P Rang, J M Ritter, R J Flower and G Henderson to be identified as authors of this
work has been asserted by them in accordance with the Copyright, Designs and Patents Act 1988.

No part of this publication may be reproduced or transmitted in any form or by any means,
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broaden our understanding, changes in research methods, professional practices, or medical
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Practitioners and researchers must always rely on their own experience and knowledge in
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ISBN:
Main edition
ISBN-13 978-0-7020-5362-7

International edition
ISBN-13 978-0-7020-5363-4

Printed in China
Last digit is the print number: 9 8 7 6 5 4 3 2 1
 Contents

Preface xv
Acknowledgements xv
4. How drugs act: cellular aspects – excitation,
contraction and secretion 50
Section 1: General principles Overview 50
Regulation of intracellular calcium 50
Calcium entry mechanisms 50
1. What is pharmacology? 1 Calcium extrusion mechanisms 53
Overview 1 Calcium release mechanisms 53
What is a drug? 1 Calmodulin 53
Origins and antecedents 1 Excitation 54
Pharmacology in the 20th and 21st centuries 2 The ‘resting’ cell 55
Alternative therapeutic principles 2 Electrical and ionic events underlying the action
The emergence of biotechnology 3 potential 55
Pharmacology today 3 Channel function 56
Muscle contraction 60
2. How drugs act: general principles 6 Skeletal muscle 60
Cardiac muscle 60
Overview 6
Smooth muscle 61
Introduction 6
Release of chemical mediators 63
Protein targets for drug binding 6
Exocytosis 63
Drug receptors 6
Non-vesicular release mechanisms 64
Drug specificity 7
Epithelial ion transport 64
Receptor classification 8
Drug–receptor interactions 8 5. Cell proliferation, apoptosis, repair and
Competitive antagonism 10
Partial agonists and the concept of efficacy 12 regeneration 67
Other forms of drug antagonism 15 Overview 67
Desensitisation and tolerance 17 Cell proliferation 67
Change in receptors 17 The cell cycle 67
Translocation of receptors 17 Interactions between cells, growth factors and
Exhaustion of mediators 17 the extracellular matrix 69
Altered drug metabolism 18 Angiogenesis 70
Physiological adaptation 18 Apoptosis and cell removal 71
Quantitative aspects of drug–receptor interactions 18 Morphological changes in apoptosis 71
The binding reaction 18 The major players in apoptosis 71
Binding when more than one drug is present 19 Pathways to apoptosis 72
The nature of drug effects 20 Pathophysiological implications 73
Repair and healing 74
3. How drugs act: molecular aspects 22 Hyperplasia 74
Overview 22 The growth, invasion and metastasis of
Targets for drug action 22 tumours 74
Receptors 22 Stem cells and regeneration 74
Ion channels 22 Therapeutic prospects 75
Enzymes 23 Apoptotic mechanisms 75
Transporters 23 Angiogenesis and metalloproteinases 75
Receptor proteins 24 Cell cycle regulation 75
Cloning of receptors 24
Types of receptor 24
6. Cellular mechanisms: host defence 78
Molecular structure of receptors 25 Overview 78
Type 1: Ligand-gated ion channels 26 Introduction 78
Type 2: G protein-coupled receptors 27 The innate immune response 78
Type 3: Kinase-linked and related receptors 39 Pattern recognition 78
Type 4: Nuclear receptors 42 The adaptive immune response 83
Ion channels as drug targets 45 The induction phase 84
Ion selectivity 45 The effector phase 85
Gating 45 Systemic responses in inflammation 88
Molecular architecture of ion channels 46 The role of the nervous system in inflammation 88
Pharmacology of ion channels 47 Unwanted inflammatory and immune
Control of receptor expression 47 responses 88
Receptors and disease 48 The outcome of the inflammatory response 89 v
 CONTENTS • SECTIONS 1 AND 2

7. Method and measurement in pharmacology 91 Drug elimination expressed as clearance 126

Single-compartment model 127
Overview 91 Effect of repeated dosing 127
Bioassay 91 Effect of variation in rate of absorption 128
Biological test systems 91 More complicated kinetic models 128
General principles of bioassay 92 Two-compartment model 129
Animal models of disease 94 Saturation kinetics 130
Genetic and transgenic animal models 95 Population pharmacokinetics 131
Pharmacological studies in humans 96 Limitations of pharmacokinetics 131
Clinical trials 96
Avoidance of bias 97 11. Individual variation, pharmacogenomics and
The size of the sample 98
Clinical outcome measures 98
personalised medicine 133
Placebos 99 Overview 133
Meta-analysis 99 Introduction 133
Balancing benefit and risk 99 Epidemiological factors and inter-individual variation
of drug response 134
8. Absorption and distribution of drugs 101 Ethnicity 134
Age 134
Overview 101
Pregnancy 135
Introduction 101 Disease 136
Physical processes underlying drug Drug interactions 136
disposition 101 Genetic variation in drug responsiveness 137
The movement of drug molecules across Relevant elementary genetics 137
cell barriers 101 Single-gene pharmacokinetic disorders 138
Binding of drugs to plasma proteins 106 Therapeutic drugs and clinically available
Partition into body fat and other tissues 107 pharmacogenomic tests 139
Drug absorption and routes of administration 108 HLA gene tests 140
Oral administration 109 Drug metabolism-related gene tests 140
Sublingual administration 110 Drug target-related gene tests 141
Rectal administration 110 Combined (metabolism and target) gene tests 141
Application to epithelial surfaces 110 Conclusions 141
Distribution of drugs in the body 112
Body fluid compartments 112
Volume of distribution 113
Special drug delivery systems 114
Section 2: Chemical mediators

9. Drug metabolism and elimination 116 12. Chemical mediators and the autonomic
Overview 116 nervous system 143
Introduction 116 Overview 143
Drug metabolism 116 Historical aspects 143
Phase 1 reactions 116 The autonomic nervous system 144
Phase 2 reactions 118 Basic anatomy and physiology 144
Stereoselectivity 118 Transmitters in the autonomic nervous system 145
Inhibition of P450 118 Some general principles of chemical
Induction of microsomal enzymes 119 transmission 147
First-pass (presystemic [‘first-pass’] metabolism) 119 Dale’s principle 147
Pharmacologically active drug Denervation supersensitivity 147
metabolites 119 Presynaptic modulation 148
Drug interactions due to enzyme induction or Postsynaptic modulation 149
inhibition 120 Transmitters other than acetylcholine and
Drug and metabolite excretion 122 noradrenaline 149
Biliary excretion and enterohepatic Co-transmission 149
circulation 122 Termination of transmitter action 151
Renal excretion of drugs and metabolites 122 Basic steps in neurochemical transmission: sites of
Drug interactions due to altered drug drug action 153
excretion 123
13. Cholinergic transmission 155
10. Pharmacokinetics 125 Overview 155
Overview 125 Muscarinic and nicotinic actions of
Introduction: definition and uses of acetylcholine 155
pharmacokinetics 125 Acetylcholine receptors 155
Uses of pharmacokinetics 125 Nicotinic receptors 155
vi Scope of this chapter 126 Muscarinic receptors 157
 SECTION 2 • CONTENTS

Physiology of cholinergic transmission 158 Histamine receptors 213

Acetylcholine synthesis and release 158 Actions 213
Electrical events in transmission at fast cholinergic Eicosanoids 214
synapses 160 General remarks 214
Effects of drugs on cholinergic transmission 161 Structure and biosynthesis 214
Drugs affecting muscarinic receptors 161 Prostanoids 214
Drugs affecting autonomic ganglia 165 Leukotrienes 218
Drugs that act presynaptically 170 Leukotrienes receptors 219
Drugs that enhance cholinergic Leukotrienes actions 219
transmission 171 Lipoxins and resolvins 220
Other drugs that enhance cholinergic Platelet-activating factor 220
transmission 176 Biosynthesis 220
Actions and role in inflammation 220
14. Noradrenergic transmission 177 Concluding remarks 220
Overview 177
Catecholamines 177 18. Local hormones 2: peptides and proteins 222
Classification of adrenoceptors 177 Overview 222
Physiology of noradrenergic transmission 178 Introduction 222
The noradrenergic neuron 178 General principles of protein and peptide
Uptake and degradation of catecholamines 181 pharmacology 222
Drugs acting on noradrenergic Structure 222
transmission 182 Types of protein and peptide mediator 222
Drugs acting on adrenoceptors 182 Biosynthesis and regulation of peptides 223
Drugs that affect noradrenergic neurons 192 Peptide precursors 223
Diversity within peptide families 224
15. 5-Hydroxytryptamine and the pharmacology Peptide trafficking and secretion 224
of migraine 197 Bradykinin 224
Source and formation of bradykinin 224
Overview 197 Metabolism and inactivation of bradykinin 225
5-Hydroxytryptamine 197 Bradykinin receptors 225
Distribution, biosynthesis and degradation 197 Actions and role in inflammation 225
Pharmacological effects 197 Neuropeptides 226
Drugs acting at 5-HT receptors 201 Cytokines 226
Migraine and other clinical conditions in which Interleukins and related compounds 228
5-HT plays a role 203 Chemokines 228
Migraine and antimigraine drugs 203 Interferons 228
Carcinoid syndrome 205 The ‘cytokine storm’ 228
Pulmonary hypertension 206 Proteins and peptides that downregulate
inflammation 229
16. Purines 207 Concluding remarks 229
Overview 207
Introduction 207 19. Cannabinoids 231
Purinergic receptors 207 Overview 231
Adenosine as a mediator 207 Plant-derived cannabinoids and their
Adenosine and the cardiovascular system 209 pharmacological effects 231
Adenosine and asthma 209 Pharmacological effects 231
Adenosine in the CNS 210 Pharmacokinetic and analytical aspects 231
ADP as a mediator 210 Adverse effects 231
ADP and platelets 210 Tolerance and dependence 232
ATP as a mediator 210 Cannabinoid receptors 232
ATP as a neurotransmitter 210 Endocannabinoids 233
ATP in nociception 210 Biosynthesis of endocannabinoids 233
ATP in inflammation 210 Termination of the endocannabinoid signal 234
Future prospects 211 Physiological mechanisms 235
Pathological involvement 235
17. Local hormones 1: histamine and the biologically Synthetic cannabinoids 235
active lipids 212 Clinical applications 235
Overview 212
Introduction 212
20. Nitric oxide and related mediators 237
What is a ‘mediator’? 212 Overview 237
Histamine 212 Introduction 237
Synthesis and storage of histamine 212 Biosynthesis of nitric oxide and its control 237
Histamine release 213 Degradation and carriage of nitric oxide 239 vii
 CONTENTS • SECTIONS 2 AND 3

Effects of nitric oxide 240 Prevention of atheromatous disease 288

Biochemical and cellular aspects 240 Lipid-lowering drugs 289
Vascular effects 241 Statins: HMG-CoA reductase inhibitors 289
Neuronal effects 241 Fibrates 290
Host defence 241 Drugs that inhibit cholesterol absorption 290
Therapeutic aspects 242 Nicotinic acid 291
Nitric oxide 242 Fish oil derivatives 291
Nitric oxide donors/precursors 242
Inhibition of nitric oxide synthesis 242 24. Haemostasis and thrombosis 293
Nitric oxide replacement or potentiation 243 Overview 293
Clinical conditions in which nitric oxide may Introduction 293
play a part 243 Blood coagulation 293
Related mediators 244 Coagulation cascade 293
Vascular endothelium in haemostasis and
Section 3: Drugs affecting major thrombosis 295
Drugs that act on the coagulation cascade 296
organ systems Coagulation defects 296
Thrombosis 297
21. The heart 247 Platelet adhesion and activation 301
Overview 247 Antiplatelet drugs 302
Introduction 247 Fibrinolysis (thrombolysis) 304
Physiology of cardiac function 247 Fibrinolytic drugs 304
Antifibrinolytic and haemostatic drugs 307
Cardiac rate and rhythm 247
Cardiac contraction 250
Myocardial oxygen consumption and coronary
25. Haemopoietic system and treatment
blood flow 251 of anaemia 308
Autonomic control of the heart 252 Overview 308
Sympathetic system 252 Introduction 308
Parasympathetic system 253 The haemopoietic system 308
Cardiac natriuretic peptides 254 Types of anaemia 308
Ischaemic heart disease 254 Haematinic agents 309
Angina 254 Iron 309
Myocardial infarction 255 Folic acid and vitamin B12 311
Drugs that affect cardiac function 255 Haemopoietic growth factors 312
Antidysrhythmic drugs 255 Erythropoietin 313
Drugs that increase myocardial Haemolytic anaemia 315
contraction 259 Drugs used to treat haemolytic anaemias 315
Antianginal drugs 260

22. The vascular system 265 26. Anti-inflammatory and immunosuppressant

Overview 265
drugs 317
Introduction 265 Overview 317
Vascular structure and function 265 Cyclo-oxygenase inhibitors 317
Control of vascular smooth muscle tone 266 Mechanism of action 318
The vascular endothelium 266 Pharmacological actions 320
The renin–angiotensin system 269 Therapeutic actions 320
Vasoactive drugs 271 Some important NSAIDs and coxibs 322
Vasoconstrictor drugs 271 Antirheumatoid drugs 325
Vasodilator drugs 272 Disease-modifying anti-rheumatic drugs 326
Clinical uses of vasoactive drugs 276 Immunosuppressant drugs 327
Systemic hypertension 276 Anticytokine drugs and other
Heart failure 279 biopharmaceuticals 329
Shock and hypotensive states 280 Drugs used in gout 330
Peripheral vascular disease 282 Antagonists of histamine 331
Raynaud’s disease 282 Possible future developments 333
Pulmonary hypertension 282
27. Skin 335
23. Atherosclerosis and lipoprotein metabolism 285 Overview 335
Overview 285 Introduction 335
Introduction 285 Structure of skin 335
Atherogenesis 285 Common diseases of the skin 337
Lipoprotein transport 286 Acne 337
viii Dyslipidaemia 286 Rosacea 338
 SECTION 3 • CONTENTS

Baldness and hirsutism 338 Gastric secretion 367

Eczema 338 The regulation of acid secretion by
Pruritus 338 parietal cells 367
Urticaria 338 The coordination of factors regulating acid
Psoriasis 338 secretion 368
Warts 339 Drugs used to inhibit or neutralise gastric acid
Other infections 339 secretion 339
Drugs acting on skin 339 Treatment of Helicobacter pylori infection 371
Formulation 339 Drugs that protect the mucosa 372
Principal drugs used in skin disorders 339 Vomiting 372
Antimicrobial agents 339 The reflex mechanism of vomiting 372
Glucocorticoids and other anti-inflammatory Antiemetic drugs 373
agents 340 The motility of the gastrointestinal tract 375
Drugs used to control hair growth 340 Purgatives 376
Retinoids 341 Drugs that increase gastrointestinal motility 376
Vitamin D analogues 341 Antidiarrhoeal agents 376
Agents acting by other mechanisms 342 Drugs for chronic bowel disease 378
Concluding remarks 342 Drugs affecting the biliary system 378
Future directions 378
28. Respiratory system 344
Overview 344 31. The control of blood glucose and drug treatment
The physiology of respiration 344 of diabetes mellitus 380
Control of breathing 344 Overview 380
Regulation of musculature, blood vessels and Introduction 380
glands of the airways 344 Control of blood glucose 380
Pulmonary disease and its treatment 345
Pancreatic islet hormones 380
Bronchial asthma 345
Insulin 380
Drugs used to treat and prevent
Glucagon 384
asthma 348
Somatostatin 384
Severe acute asthma (status asthmaticus) 351
Amylin (islet amyloid polypeptide) 385
Allergic emergencies 352
Incretins 385
Chronic obstructive pulmonary disease 352
Diabetes mellitus 385
Surfactants 353
Treatment of diabetes mellitus 386
Cough 353
Potential new antidiabetic drugs 391
29. The kidney and urinary system 355 32. Obesity 393
Overview 355 Overview 393
Introduction 355 Introduction 393
Outline of renal function 355 Definition of obesity 393
The structure and function of the Obesity as a health problem 393
nephron 355 Homeostatic mechanisms controlling
Tubular function 356 energy balance 394
Acid–base balance 360 The role of gut and other hormones in body
Potassium balance 360 weight regulation 394
Excretion of organic molecules 360 Neurological circuits that control body weight and
Natriuretic peptides 361 eating behaviour 394
Prostaglandins and renal function 361 The pathophysiology of human obesity 397
Drugs acting on the kidney 361 Food intake and obesity 397
Diuretics 361 Physical exercise and obesity 398
Drugs that alter the pH of the urine 365 Obesity as a disorder of the homeostatic control of
Drugs that alter the excretion of organic energy balance 398
molecules 365 Genetic factors and obesity 398
Drugs used in renal failure 365 Pharmacological approaches to the problem
Hyperphosphataemia 365 of obesity 399
Hyperkalaemia 366 Centrally acting appetite suppressants 399
Drugs used in urinary tract disorders 366 Orlistat 399
New approaches to obesity therapy 400
30. The gastrointestinal tract 367
Overview 367 33. The pituitary and the adrenal cortex 402
The innervation and hormones of the gastrointestinal Overview 402
tract 367 The pituitary gland 402
Neuronal control 367 The anterior pituitary gland 402
Hormonal control 367 Hypothalamic hormones 402 ix
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 CONTENTS • SECTIONS 3 AND 4

Anterior pituitary hormones 403 Bone remodelling 439

Posterior pituitary gland 407 The action of cells and cytokines 439
The adrenal cortex 408 The turnover of bone minerals 441
Glucocorticoids 409 Hormones involved in bone metabolism
Mineralocorticoids 414 and remodelling 441
New directions in glucocorticoid therapy 415 Disorders of bone 444
Drugs used in bone disorders 444
34. The thyroid 418 Bisphosphonates 444
Overview 418 Oestrogens and related compounds 445
Synthesis, storage and secretion of Parathyroid hormone and teriparatide 446
thyroid hormones 418 Strontium 446
Uptake of plasma iodide by the follicle cells 418 Vitamin D preparations 446
Oxidation of iodide and iodination of Biologicals 447
tyrosine residues 418 Calcitonin 447
Secretion of thyroid hormone 418 Calcium salts 447
Regulation of thyroid function 418 Calcimimetic compounds 447
Actions of the thyroid hormones 420 Potential new therapies 447
Effects on metabolism 420
Effects on growth and development 420 Section 4: Nervous system
Mechanism of action 420
Transport and metabolism of thyroid
hormones 420 37. Chemical transmission and drug action in
Abnormalities of thyroid function 421 the central nervous system 449
Hyperthyroidism (thyrotoxicosis) 421
Overview 449
Simple, non-toxic goitre 421
Hypothyroidism 421 Introduction 449
Drugs used in diseases of the thyroid 421 Chemical signalling in the nervous system 449
Hyperthyroidism 421 Targets for drug action 450
Hypothyroidism 423 Drug action in the central nervous system 451
Blood–brain barrier 452
35. The reproductive system 425 The classification of psychotropic drugs 452
Overview 425
Introduction 425
38. Amino acid transmitters 454
Endocrine control of reproduction 425 Overview 454
Neurohormonal control of the female Excitatory amino acids 454
reproductive system 425 Excitatory amino acids as CNS transmitters 454
Neurohormonal control of the male reproductive Metabolism and release of excitatory amino
system 426 acids 454
Behavioural effects of sex hormones 427 Glutamate 455
Drugs affecting reproductive function 428 Glutamate receptor subtypes 455
Oestrogens 428 Synaptic plasticity and long-term potentiation 458
Antioestrogens 429 Drugs acting on glutamate receptors 459
Progestogens 429 γ-Aminobutyric acid (GABA) 462
Postmenopausal hormone replacement Synthesis, storage and function 462
therapy 430 GABA receptors: structure and pharmacology 462
Androgens 430 Drugs acting on GABA receptors 463
Anabolic steroids 431 Glycine 465
Antiandrogens 431 Concluding remarks 465
Gonadotrophin-releasing hormone: agonists
and antagonists 432 39. Other transmitters and modulators 467
Gonadotrophins and analogues 432 Overview 467
Drugs used for contraception 433 Introduction 467
Oral contraceptives 433 Noradrenaline 467
Other drug regimens used for contraception 434 Noradrenergic pathways in the CNS 467
The uterus 435 Functional aspects 467
The motility of the uterus 435 Dopamine 468
Drugs that stimulate the uterus 435 Dopaminergic pathways in the CNS 469
Drugs that inhibit uterine contraction 436 Dopamine receptors 470
Erectile dysfunction 436 Functional aspects 471
5-Hydroxytryptamine 472
36. Bone metabolism 439 5-HT pathways in the CNS 473
Overview 439 5-HT receptors in the CNS 473
Introduction 439 Functional aspects 473
x Bone structure and composition 439 Clinically used drugs 474
 SECTION 4 • CONTENTS

Acetylcholine 474 Analgesic drugs 515

Cholinergic pathways in the CNS 474 Opioid drugs 515
Acetylcholine receptors 475 Paracetamol 526
Functional aspects 476 Treatment of neuropathic pain 527
Purines 476 Other pain-relieving drugs 528
Histamine 477 New approaches 529
Other CNS mediators 477
Melatonin 477 43. Local anaesthetics and other drugs affecting
Nitric oxide 478 sodium channels 530
Lipid mediators 478
Overview 530
A final message 479
Local anaesthetics 530
40. Neurodegenerative diseases 482 Chemical aspects 530
Mechanism of action 530
Overview 482 Pharmacokinetic aspects 533
Protein misfolding and aggregation in chronic New approaches 533
neurodegenerative diseases 482 Other drugs that affect sodium channels 534
Mechanisms of neuronal death 482 Tetrodotoxin and saxitoxin 534
Excitotoxicity 484 Agents that affect sodium channel gating 535
Apoptosis 484
Oxidative stress 485 44. Anxiolytic and hypnotic drugs 536
Ischaemic brain damage 486 Overview 536
Pathophysiology 486 The nature of anxiety and its treatment 536
Therapeutic approaches 487 Measurement of anxiolytic activity 536
Alzheimer’s disease 487 Animal models of anxiety 536
Pathogenesis of Alzheimer’s disease 487 Tests on humans 537
Therapeutic approaches 489 Drugs used to treat anxiety 538
Parkinson’s disease 491 Benzodiazepines and related drugs 538
Features of Parkinson’s disease 491 Buspirone 543
Pathogenesis of Parkinson’s disease 492 Other potential anxiolytic drugs 543
Drug treatment of Parkinson’s disease 493 Drugs used to treat insomnia (hypnotic drugs) 544
Huntington’s disease 496
Neurodegenerative prion diseases 496 45. Antiepileptic drugs 546
41. General anaesthetic agents 498 Overview 546
Introduction 546
Overview 498 The nature of epilepsy 546
Introduction 498 Types of epilepsy 546
Mechanism of action of anaesthetic Neural mechanisms and animal models
drugs 498 of epilepsy 548
Lipid solubility 498 Antiepileptic drugs 549
Effects on ion channels 499 Carbamazepine 552
Effects on the nervous system 500 Phenytoin 553
Effects on the cardiovascular and respiratory Valproate 554
systems 500 Ethosuximide 554
Intravenous anaesthetic agents 501 Phenobarbital 554
Propofol 501 Benzodiazepines 555
Thiopental 501 Newer antiepileptic drugs 555
Etomidate 502 Development of new drugs 556
Other intravenous agents 502 Other uses of antiepileptic drugs 557
Inhalation anaesthetics 503 Antiepileptic drugs and pregnancy 557
Pharmacokinetic aspects 503 Muscle spasm and muscle relaxants 557
Individual inhalation anaesthetics 506
Isoflurane, desflurane, sevoflurane, enflurane and 46. Antipsychotic drugs 559
halothane 506 Overview 559
Nitrous oxide 507 Introduction 559
Balanced anaesthesia 507
The nature of schizophrenia 559
Aetiology and pathogenesis of schizophrenia 560
42. Analgesic drugs 509 Antipsychotic drugs 562
Overview 509 Classification of antipsychotic drugs 562
Neural mechanisms of pain 509 Clinical efficacy 562
Nociceptive afferent neurons 509 Pharmacological properties 565
Modulation in the nociceptive pathway 510 Unwanted effects 566
Neuropathic pain 511 Pharmacokinetic aspects 567
Chemical signalling in the nociceptive pathway 512 Future developments 568 xi
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Results 1: Key terms and definitions

Learning Objective 1: Research findings and conclusions
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
[Figure 1: Diagram/Chart/Graph]
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• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 2: Diagram/Chart/Graph]
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• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
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• Current trends and future directions
- Sub-point: Additional details and explanations
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- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
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- Sub-point: Additional details and explanations
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- Note: Important consideration
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• Key terms and definitions
- Sub-point: Additional details and explanations
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- Example: Practical application scenario
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- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
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- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Ethical considerations and implications
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Key Concept: Theoretical framework and methodology
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Definition: Historical development and evolution
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Practice Problem 17: Literature review and discussion
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Important: Best practices and recommendations
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Key Concept: Problem-solving strategies and techniques
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 20: Diagram/Chart/Graph]
Background 3: Study tips and learning strategies
Definition: Best practices and recommendations
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Best practices and recommendations
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Example 22: Assessment criteria and rubrics
• Comparative analysis and synthesis
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Note: Literature review and discussion
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Study tips and learning strategies
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
Important: Case studies and real-world applications
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 26: Diagram/Chart/Graph]
Important: Critical analysis and evaluation
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 27: Diagram/Chart/Graph]
Note: Current trends and future directions
• Theoretical framework and methodology
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Note: Historical development and evolution
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Experimental procedures and results
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Module 4: Key terms and definitions
Example 30: Theoretical framework and methodology
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Key Concept: Experimental procedures and results
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Assessment criteria and rubrics
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Research findings and conclusions
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Remember: Fundamental concepts and principles
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Important: Problem-solving strategies and techniques
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Learning outcomes and objectives
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Definition: Case studies and real-world applications
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Ethical considerations and implications
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Study tips and learning strategies
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Abstract 5: Current trends and future directions
Remember: Ethical considerations and implications
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Practice Problem 41: Fundamental concepts and principles
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Remember: Historical development and evolution
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Definition: Case studies and real-world applications
• Case studies and real-world applications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Assessment criteria and rubrics
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Note: Best practices and recommendations
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 46: Diagram/Chart/Graph]
Note: Interdisciplinary approaches
• Best practices and recommendations
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Key Concept: Historical development and evolution
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 48: Literature review and discussion
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 49: Comparative analysis and synthesis
• Critical analysis and evaluation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
Abstract 6: Assessment criteria and rubrics
Note: Case studies and real-world applications
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Practice Problem 51: Study tips and learning strategies
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 52: Diagram/Chart/Graph]
Note: Practical applications and examples
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Remember: Comparative analysis and synthesis
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Definition: Literature review and discussion
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Definition: Research findings and conclusions
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Important: Key terms and definitions
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
[Figure 57: Diagram/Chart/Graph]
Important: Case studies and real-world applications
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Definition: Practical applications and examples
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Important: Literature review and discussion
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 60: Diagram/Chart/Graph]
Discussion 7: Historical development and evolution
Practice Problem 60: Literature review and discussion
• Learning outcomes and objectives
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Current trends and future directions
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Important: Literature review and discussion
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 63: Experimental procedures and results
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 64: Ethical considerations and implications
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Practice Problem 65: Historical development and evolution
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
[Figure 66: Diagram/Chart/Graph]
Example 66: Research findings and conclusions
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Definition: Research findings and conclusions
• Assessment criteria and rubrics
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Note: Statistical analysis and interpretation
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 69: Theoretical framework and methodology
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Appendix 8: Current trends and future directions
Definition: Interdisciplinary approaches
• Experimental procedures and results
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
Example 71: Literature review and discussion
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 72: Diagram/Chart/Graph]
Example 72: Assessment criteria and rubrics
• Comparative analysis and synthesis
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 73: Historical development and evolution
• Research findings and conclusions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Definition: Experimental procedures and results
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Formula: [Mathematical expression or equation]
[Figure 75: Diagram/Chart/Graph]
Remember: Theoretical framework and methodology
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
[Figure 76: Diagram/Chart/Graph]
Key Concept: Historical development and evolution
• Study tips and learning strategies
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 77: Statistical analysis and interpretation
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Definition: Best practices and recommendations
• Literature review and discussion
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 79: Fundamental concepts and principles
• Ethical considerations and implications
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Discussion 9: Fundamental concepts and principles
Example 80: Problem-solving strategies and techniques
• Historical development and evolution
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 81: Assessment criteria and rubrics
• Practical applications and examples
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 82: Historical development and evolution
• Current trends and future directions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Example 83: Assessment criteria and rubrics
• Interdisciplinary approaches
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
Practice Problem 84: Critical analysis and evaluation
• Key terms and definitions
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Formula: [Mathematical expression or equation]
[Figure 85: Diagram/Chart/Graph]
Definition: Best practices and recommendations
• Problem-solving strategies and techniques
- Sub-point: Additional details and explanations
- Example: Practical application scenario
[Figure 86: Diagram/Chart/Graph]
Example 86: Key terms and definitions
• Fundamental concepts and principles
- Sub-point: Additional details and explanations
- Example: Practical application scenario
Key Concept: Learning outcomes and objectives
• Statistical analysis and interpretation
- Sub-point: Additional details and explanations
- Example: Practical application scenario
- Note: Important consideration
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