Netter's Illustrated Pharmacology

Netter's Illustrated Pharmacology

By Robert B. Raffa, PhD; Scott M. Rawls; and Elena Portyansky Beyzarov

Chapter 1. Basic Principles of Pharmacology

Overview 1
Major Ways in Which Drugs Work
Eliminate External and Internal Threats 2
Replenish or Neutralize Endogenous Chemicals 4
Modulate Physiologic Processes 5
Chemical Communication
Chemical Transmission at the Synapse 6
Synapse Morphology 7
Pharmacodynamics Receptors and Signaling 8
Receptor Subtypes 9
Agonists 10
Antagonists 11
Stereochemistry and 3-Dimensional Fit 12
Receptor-Effector Coupling 13
Signal Transduction and Cross Talk 14
Second-Messenger Pathways 15
Ligand-Gated Ion Channels 16
G Protein?Coupled Receptors 17
Trk Receptors 18
Nuclear Receptors 19
Up-regulation and Down-regulation of Receptors 20
Dose-Response Curves 21
Potency 22
Efficacy 22
Inverse Agonists 23
Antagonists: Surmountable (Reversible) and Nonsurmountable (Irreversible) 24
Routes of Administration 25
First-Pass Effect 26
Membrane Transport 27
Distribution 28
Barriers 29
Metabolism (Biotransformation) of Drugs 30
Cytochrome P-450 (CYP450) Enzymes 31
Metabolic Enzyme Induction and Inhibition 32
Elimination 33

Chapter 2. Drugs Used to Affect the Autonomic and Somatic Nervous Systems

Overview 35
Organization of the Nervous System
Organization of the Nervous System 36
Action of Drugs on Nerve Excitability 37
Somatic Nervous System
Interface of the Central and Peripheral Nervous Systems
and Organization of the Somatic Division 38
Neuromuscular Transmission 39
Nicotinic Acetylcholine Receptor 40
Physiology of the Neuromuscular Junction 41
Pharmacology of the Neuromuscular Junction 42
Mechanism of Action of Acetylcholinesterase Inhibitors 43
Neuromuscular Blocking Agents: Nondepolarizing and Depolarizing 44
Autonomic Nervous System
Autonomic Nervous System: Schema 45
Sympathetic Fight or Flight Response 46
Cholinergic and Adrenergic Synapses 47
Example of Cholinergic and Adrenergic Drug Treatment: Glaucoma 48
Cholinergic Receptors 49
Cholinergic Drugs 50
Example of Cholinergic Drug Treatment: Myasthenia Gravis 52
Adrenergic Receptors 53
Adrenergic Drugs 54
Drugs That Act on the Autonomic Nervous System 55
Drug Side Effects 56

Chapter 3. Drugs Used in Disorders of the Central Nervous System and Treatment of Pain

Overview 57
Introduction to the CNS and Drug Action
Development of the Nervous System 58
Anatomy of the Nervous System 59
Functional Correlations and Visualization of Brain Structures 60
Resting Membrane and Action Potentials 61
Excitatory and Inhibitory Postsynaptic Potentials 62
Central Nervous System Neurotransmitters, Receptors, and Drug Targets 63
Sedative-Hypnotic Drugs
GABAA Receptor Complex and Sedative-Hypnotic Drugs 64
Anxiolytic Agents
Clinical Anxiety 65
Anxiolytic Agents 66
Antiepileptic Agents
Causes of Seizures and Their Treatment 67
Epilepsy: Generalized Seizures and Status Epilepticus 68
Epilepsy: Partial and Absence Seizures 69
Clinical Depression 71
Antidepressants: Mechanisms of Action 72
Drugs Affecting Bipolar Disorder and OCD
Bipolar Disorder and Compulsive Behavior 73
Antipsychotic Agents
Psychosis and Dopamine Pathways 74
Drugs Affecting Movement Disorders and Other Neurodegenerative Disorders
Motor Tracts, Basal Ganglia, and Dopamine Pathways 75
Parkinsonism: Symptoms and Defect 77
Parkinsonism: Levodopa, Carbidopa, and Other Drugs 78
Huntington Disease and Tourette Syndrome 79
Alzheimer Disease: Symptoms, Course, and Pathology 80
Alzheimer Disease: Cholinergic Involvement and Drugs 81
Stroke: Symptoms and Drug Treatment 83
CNS Skeletal Muscle Relaxants
Motor Neurons and Drugs 84
Analgesics and Anesthetics
Pain Pathways 85
Local Anesthetics: Spinal Afferents and Local Anesthetic Mechanisms of Action 86
General Anesthetics: Properties 87
Opioids: Endogenous Opioid Pathway 88
Opioids: Receptor-Transduction Mechanisms 89
Nonopioids: NSAIDs, Selective Cyclooxygenase-2 Inhibitors, and Acetaminophen 90
Sumatriptans and Reuptake Inhibitors 91

Chapter 4. Drugs Used in Disorders of the Cardiovascular System

Overview 93
Cardiovascular System: Anatomy, Function, and Regulation of the Heart
Cardiovascular Function: Anatomy 94
Cardiovascular Function: Definition of Terms and Regulation 95
Role of Catecholamines in Heart Function 96
Sympathetic and Parasympathetic Regulation of Heart Function 97
Synthesis and Storage of Catecholamines 98
Regulation of Norepinephrine Release 99
Inactivation of Norepinephrine 100
Hypercholesterolemia and Atherosclerosis
Hypercholesterolemia: Causes 101
Hypercholesterolemia: Pharmacologic Therapy 102
Angina Overview 103
Nitrates for Angina Treatment: Classes, Administration Routes,
Pharmacology, and Adverse Effects 104
Nitroglycerin in Angina Treatment 105
Nitroglycerin: Mechanism of Action 106
Calcium Channel Antagonists 107
Drug Summary for Angina 108
Heart Failure
Heart Failure Overview 109
Heart Failure: Treatment 110
Heart Failure Treatment: b-Adrenergic Stimulators and Blockers 111
Heart Failure Treatment: Cardiac Glycosides 112
Cardiac Arrhythmias: General 113
Cardiac Arrhythmias: Treatment 115
Cardiac Arrhythmias: Drug Classification 117
Hypertension Overview 118
Hypertension: Causes 119
Hypertension Treatment: Diuretics 120
Hypertension Treatment: Angiotensin-Converting Enzyme Inhibitors 121
Hypertension Treatment: b and a Blockers 122
Hypertension Treatment: Minoxidil 123
Hypertension Treatment: Clonidine 124
Hypertension in Elderly Patients 125
Pheochromocytoma-Induced Hypertension 126
Hypertension in Cushing Syndrome 127
Peripheral Vascular Disease
Peripheral Vascular Disease 128

Chapter 5. Drugs Used in Disorders of the Endocrine System

Overview 129
Hypothalamic and Pituitary Disorders
Regulation of Hypothalamic and Pituitary Hormones 130
Hypopituitarism 132
Growth Hormone Deficiency and Treatment 133
Growth Hormone Excess (Acromegaly) and Treatment 134
Thyroid Disorders
Thyroid Hormones 135
Thyroid Hormones: Synthesis, Release, and Regulation 136
Hypothyroidism 137
Hypothyroidism: Treatment of Choice 138
Liothyronine and T4/T3 Combinations 139
Hyperthyroidism 140
Hyperthyroidism: Treatment 141
Thioamides 142
Thioamides: Adverse Effects 143
Radioactive Iodine 144
Iodide 145
Adrenergic Antagonists 146
Corticosteroids and Adrenocortical Dysfunction
Regulation of Adrenal Hormones 147
Mineralocorticoids and Glucocorticoids 148
Corticosteroids 149
Cushing Syndrome 150
Ketoconazole 151
Metyrapone 152
Aminoglutethimide 153
Addison Disease, or Primary Adrenal Insufficiency 154
Diabetes Mellitus
The Pancreas and Insulin Production 155
Insulin Secretion 156
Lack of Insulin 157
Type 1 Diabetes Mellitus 158
Type 2 Diabetes Mellitus 159
Insulin Therapy 160
Reactions to Insulin: Hypoglycemia and Adipose Tissue Changes 161
Sulfonylureas 162
Biguanides 163
Meglitinides 164
a-Glucosidase Inhibitors 165
Thiazolidinediones 166
Thiazolidinediones: Clinical Rationale and Adverse Effects 167

Chapter 6. Drugs Used in Disorders of the Gastrointestinal System

Overview 169
Function and Regulation of the GI System
Enteric Nervous System 170
Integration of the Autonomic and Enteric Nervous Systems 171
Gastrointestinal Motility 172
Control of Peristalsis 174
Hormones of the Gastrointestinal Tract 175
Parietal Cell Function Regulation 176
Pancreatic Secretion 177
Defecation 178
Protein Digestion 179
Fat Digestion 180
Disorders of Colonic Motility
Colonic Motility and Treatment of Diarrhea 181
Antidiarrheal Drugs and Their Adverse Effects 182
Causes of Constipation 183
Treatment of Constipation 184
Functional Disorder of the Large Intestine
Treatment of Irritable Bowel Syndrome 185
Protozoal GI Infection
Giardiasis 187
Peptic Ulcer
Helicobacter pylori Infection Overview 188
Treatment of Helicobacter pylori Infection 189
Peptic Ulcer Treatment 190
Gastroesophageal Reflux Disease
Gastroesophageal Reflux Disease Overview 191
Gastroesophageal Reflux Disease Treatment 192
Treatment of Pancreatitis 193
Pathologic Features of Gallstones 195
Gallstone Pathogenesis and Treatment 196
Liver Physiology and Pathology
Liver Function 197
Bilirubin Production and Excretion 198
Cirrhosis 199
Ascites 200
Nausea and Vomiting
Physiology of Emesis 202
Antiemetics 204

Chapter 7. Drugs Used in Disorders of the Respiratory System

Overview 205
Respiration: Introduction to Physiology and Pathology
Respiration Overview 206
Respiratory Diseases 207
Allergy 208
Leukocyte Function 209
Allergic Rhinitis 210
Introduction to Asthma 211
Extrinsic and Intrinsic Asthma 212
Asthma Pharmacotherapy 214
Anti-IgE Antibodies 215
Mast Cell Degranulation Blockers 216
Bronchodilators 217
Methylxanthines 218
Methylxanthine: Adverse Effects 219
b-Adrenergic Agonists 220
Nonselective b-Adrenergic Agonists 221
Selective b2-Adrenergic Agonists 222
Antimuscarinic Antagonists 223
Antiinflammatory Agents: Corticosteroids
Corticosteroids 224
Corticosteroids: Clinical Uses 225
Corticosteroids: Adverse Effects 226
Antiinflammatory Agents: Leukotriene Antagonists
Leukotrienes 227
Leukotriene Antagonists 228
Cough 229
Cough Suppressants (Antitussive Agents) 230
Chronic Obstructive Pulmonary Disease 231
Emphysema 232
Emphysema: Causes 233
Inherited Emphysema 234
Chronic Bronchitis 235
COPD: General Treatment Measures 236
COPD: Specific Drug Treatments 237
Restrictive Pulmonary Disease 238
Pneumonia 239
Viral Pneumonia 241
Bacterial Pneumonia 243

Chapter 8. Drugs Used in Disorders of the Reproductive System

Overview 245
Organization and Function of the Reproductive System
Organization of the Reproductive System 246
Regulation of Estrogen and Testosterone 247
Events of the Normal Menstrual Cycle 248
Combination Oral Contraceptives 249
Major Adverse Effects of Combination Oral Contraceptives 250
Estrogen and Coagulation 251
Progestin-Only Contraceptives 252
The Morning-After Pill 253
The Abortion Pill 254
Endometriosis and Treatment
Endometriosis 255
Danazol 256
Gonadotropin-Releasing Hormone Agonists, Combination
Oral Contraceptives, and Progestin 257
Postmenopausal Hormone Changes and Therapy
Estrogen Decline 258
Vasomotor Symptoms 259
Genitourinary Atrophy 260
Osteoporosis and Estrogen 261
Role of Progestins in Hormone Replacement Therapy 262
Route of Hormone Administration 263
General Adverse Effects 264
Cardiovascular and Neurologic Risks 265
Cancer Risks 266
Selective Estrogen Receptor Modulators 267
Antiestrogens 268
Hypogonadism 269
Hypogonadism Treatment and Adverse Effects 270

Chapter 9. Drugs Used to Affect Renal Function

Overview 271
Organization and Functions of the Renal System Macroscopic Anatomy 272
The Nephron 273
Blood Vessels Surrounding Nephrons 274
The Glomerulus 275
Practical Application: Measuring the Glomerular Filtration Rate 276
Tubular Segments 277
Ion and Water Reabsorption 278
Bicarbonate Reabsorption 279
Potassium Excretion 280
Volume Regulation
Antidiuretic Hormone 281
Renin-Angiotensin-Aldosterone System 282
General Considerations: Volume Homeostasis 283
Mercurial Diuretics 285
Carbonic Anhydrase Inhibitors 286
Thiazide Diuretics 287
Potassium-Sparing Agents 288
Loop (High-Ceiling) Diuretics 289
Osmotic Agents 290
Summary of Therapeutics 291
Urinary Incontinence
Urinary Incontinence 293
Urinary Tract Calculi
Urinary Tract Calculi (Kidney Stones) 294
Renal Insufficiency and Dialysis
Effect of Renal Insufficiency on Drug Action 295
Effect of Hemodialysis on Drug Action 296

Chapter 10. Drugs Used in Infectious Disease

Overview 297
Bacterial Infections: Antibiotics
Classification of Antibiotics 298
Definitions: Bacteriostatic Versus Bactericidal 299
Spectrum of Activity 300
Mechanisms of Resistance 301
Examples of Resistance 302
Natural Penicillins: Penicillin G and Penicillin V 303
Aminopenicillins: Amoxicillin and Ampicillin 304
Antipseudomonal Penicillins: Carbenicillin, Piperacillin, and Ticarcillin 305
b-Lactamase Inhibitors 306
b Lactamase?Resistant Penicillins: Cloxacillin, Dicloxacillin, Oxacillin, and Nafcillin 307
Adverse Effects of Penicillins 308
Cephalosporins 309
Carbapenems: Imipenem-Cilastatin, Ertapenem, and Meropenem 310
Monobactams: Aztreonam 311
Vancomycin 312
Vancomycin Treatment Difficulties: Resistance and Adverse Effects 313
Tetracyclines 314
Aminoglycosides 315
Macrolides: Erythromycin, Azithromycin, and Clarithromycin 316
Clindamycin 317
Quinolones 318
New-Generation Quinolones 319
Quinupristin/Dalfopristin 321
Linezolid 322
Sulfonamides 323
Fungal Infections: Antifungal Drugs
Nature of Fungal Infections and Therapy 324
Amphotericin B 325
Azole Antifungal Agents and Other Antifungal Agents 326
Viral Infections and Antiviral Agents
Nature of Viral Infections 327
Herpesviruses 328
Acyclovir and Famciclovir 329
Ganciclovir 330
Influenza and Its Treatment 331
HIV Infection: Antiretroviral Agents
HIV Infection 332
Nucleoside Reverse Transcriptase Inhibitors (NRTIs) and Non-NRTIs 333
Protease Inhibitors 334
Other Antiretroviral Agents for AIDS: Tenofovir and Enfuvirtide 335

Chapter 11. Drugs Used in Neoplastic Disorders

Overview 337
Introduction to Chemotherapy
Cell Cycle 338
Combination Chemotherapy 339
Adverse Effects of Chemotherapy 340
Folate Analogs: Methotrexate 341
Purine Analogs: Mercaptopurine and Thioguanine 342
Pyrimidine Analogs: 5-Fluorouracil 343
Pyrimidine Analogs: Capecitabine 344
Pyrimidine Analogs: Cytarabine and Fludarabine 345
Pyrimidine Analogs: Gemcitabine 346
Substituted Ureas: Hydroxyurea 347
Alkylating Agents
Nitrogen Mustards: Mechlorethamine and Melphalan 348
Cyclophosphamide and Ifosfamide 349
Nitrosoureas: Carmustine and Lomustine 350
Platinum Compounds: Cisplatin, Carboplatin, and Oxaliplatin 351
Microtubule Inhibitors
Vinca Alkaloids: Vincristine, Vinblastine, and Vinorelbine 352
Taxanes 353
Anthracyclines: Doxorubicin and Daunorubicin 354
Hormonal Therapies
Estrogen Antagonists: Tamoxifen and Toremifene 355
Aromatase Inhibitors: Anastrozole, Letrozole, and Exemestane 356
Gonadotropin-Releasing Hormone Analogs: Leuprolide and Goserelin 357
Antiandrogens: Flutamide, Bicalutamide, and Nilutamide 358
Monoclonal Antibodies
Unconjugated Antibodies: Trastuzumab, Alemtuzumab, and Rituximab 359
Conjugated Antibodies: Ibritumomab Tiuxetan and Tositumomab
and Iodine I 131 Tositumomab 360
Newer Miscellaneous Agents
Imatinib Mesylate .361
Gefinitib 362
Bortezomib 363

Chapter 12. Drugs Used for Skin Disorders

Overview 365
Organization of the Skin
Anatomy of the Skin 366
Hair Loss
Alopecia 367
Blister Diseases
Bullous (Blister) Skin Diseases 368
Common Dermatoses Including Eczema 369
Psoriasis 370
Mite and Louse Infestations
Scabies and Pediculosis 371
Urticaria 372

Chapter 13. Vitamins: Deficiencies and Drug Interactions

Overview 373
Fat-Soluble Vitamins
Deficiency of Vitamin A (Retinol) and Other Fat-Soluble Vitamins 374
Water-Soluble Vitamins
Deficiency of Thiamine (B1) and Other B Vitamins 375
Niacin or Nicotinic Acid Deficiency (Pellagra) 376
Vitamin C Deficiency (Scurvy) 377
Vitamin-Drug Interactions
Fat-Soluble Vitamin-Drug Interactions 378
Water-Soluble Vitamin-Drug Interactions 379

Chapter 14. Drug Allergy, Abuse, and Poisoning or Overdose

Overview 381
Drug Allergy
Allergic Reactions to Drugs 382
Type I (Acute, Anaphylactic) Reactions 383
Type II (Cytotoxic, Autoimmune) Reactions 384
Type III (Immune Complex, Serum Sickness, Arthus) Reactions 385
Type IV (Cell-Mediated, Delayed-Hypersensitivity, Contact Dermatitis) Reactions 386
Drug Abuse
Brain Reward Circuit 387
Ethanol: Deleterious Effects 388
Ethanol Abuse: Treatment 389
Withdrawal: Opioids, Benzodiazepines, and Barbiturates 390
Poisoning or Overdose
Sympathomimetic Drugs 392
Cholinergic Drugs 393
Anticholinergic Drugs 394
Serotonergics 395
Opioids 396
Over-the-Counter Products 397
Management of Poisoning and Overdose 398

Index 399