Contents
General Pharmacology 1History of Pharmacology. . . . . . . . 2
The Idea . . . . . . . . . . . . . . . . 2
The Impetus . . . . . . . . . . . . . . 2
Early Beginnings. . . . . . . . . . . . 3
Foundation. . . . . . . . . . . . . . . 3
Consolidation—General Recognition . 3
Status Quo . . . . . . . . . . . . . . . 3
Drug Sources . . . . . . . . . . . . . . 4
Drug and Active Principle. . . . . . . . 4
The Aims of Isolating Active
Principles . . . . . . . . . . . . . . . . . 4
European Plants as Sources of
Effective Medicines . . . . . . . . . . . 6
Drug Development . . . . . . . . . . . 8
Congeneric Drugs and Name
Diversity . . . . . . . . . . . . . . . . . 10
Drug Administration . . . . . . . . . . 12
OralDosage Forms. . . . . . . . . . . . 12
Drug Administration by Inhalation . . . 14
Dermatological Agents . . . . . . . . . 16
Skin Protection (A). . . . . . . . . . . . 16
Dermatological Agents as Vehicles (B). 16
From Application to Distribution in
the Body . . . . . . . . . . . . . . . . . 18
Cellular Sites of Action . . . . . . . . . 20
Potential Targets of Drug Action . . . . 20
Distribution in the Body . . . . . . . . 22
External Barriers of the Body . . . . . . 22
Blood–Tissue Barriers . . . . . . . . . . 24
Membrane Permeation . . . . . . . . . 26
Possible Modes of Drug Distribution . . 28
Binding to Plasma Proteins . . . . . . . 30
Drug Elimination . . . . . . . . . . . . 32
The Liver as an Excretory Organ . . . . 32
Biotransformation ofDrugs. . . . . . . 34
Drug Metabolism by Cytochrome
P450. . . . . . . . . . . . . . . . . . . . 38
The Kidney as an Excretory Organ . . . 40
Presystemic Elimination . . . . . . . . . 42
Pharmacokinetics . . . . . . . . . . . . 44
Drug Concentration in the Body as
a Function of Time—First Order
(Exponential) Rate Processes . . . . . . 44
Time Course of Drug Concentration
in Plasma . . . . . . . . . . . . . . . . . 46
Time Course of Drug Plasma Levels
during Repeated Dosing (A) . . . . . . . 48
Time Course of Drug Plasma Levels
during Irregular Intake (B). . . . . . . . 48
Accumulation: Dose, Dose Interval,
and Plasma Level Fluctuation (A) . . . . 50
Change in Elimination Characteristics
duringDrug Therapy (B). . . . . . . . . 50
Quantification of Drug Action . . . . . 52
Dose–Response Relationship . . . . . . 52
Concentration–Effect Relationship (A) . 54
Concentration–Effect Curves (B) . . . . 54
Drug–Receptor Interaction. . . . . . . 56
Concentration–Binding Curves . . . . . 56
Types of Binding Forces . . . . . . . . . 58
Covalent Bonding . . . . . . . . . . . 58
Noncovalent Bonding . . . . . . . . . 58
Agonists—Antagonists . . . . . . . . . . 60
Models of the Molecular Mechanism
of Agonist/Antagonist Action (A) . . . . 60
Other Forms of Antagonism. . . . . . . 60
Enantioselectivity of Drug Action . . . . 62
Receptor Types . . . . . . . . . . . . . . 64
Mode of Operation of G-Proteincoupled
Receptors . . . . . . . . . . . . 66
Time Course of Plasma Concentration
and Effect . . . . . . . . . . . . . . . . . 68
Adverse Drug Effects . . . . . . . . . . 70
Undesirable Drug Effects, Side
Effects . . . . . . . . . . . . . . . . . . . 70
VI Contents
Causes of Adverse Effects. . . . . . . . 70
Drug Allergy . . . . . . . . . . . . . . . 72
Cutaneous Reactions . . . . . . . . . . 74
Drug Toxicity in Pregnancy and
Lactation . . . . . . . . . . . . . . . . . 76
Genetic Variation of Drug Effects . . . 78
Pharmacogenetics . . . . . . . . . . . . 78
Drug-independent Effects . . . . . . . 80
Placebo (A) . . . . . . . . . . . . . . . . 80
Systems Pharmacology 83
Drugs Acting on the Sympathetic
Nervous System. . . . . . . . . . . . . 84
Sympathetic Nervous System. . . . . . 84
Structure of the Sympathetic
Nervous System . . . . . . . . . . . . . 86
Adrenergic Synapse . . . . . . . . . . . 86
Adrenoceptor Subtypes and
Catecholamine Actions . . . . . . . . . 88
SmoothMuscle Effects . . . . . . . . . 88
Cardiostimulation . . . . . . . . . . . . 88
Metabolic Effects. . . . . . . . . . . . . 88
Structure–Activity Relationships
of Sympathomimetics. . . . . . . . . . 90
Indirect Sympathomimetics. . . . . . . 92
α-Sympathomimetics,
α-Sympatholytics . . . . . . . . . . . . 94
β-Sympatholytics (β-Blockers) . . . . . 96
Types of β-Blockers . . . . . . . . . . . 98
Antiadrenergics . . . . . . . . . . . . . 100
Drugs Acting on the Parasympathetic
Nervous System. . . . . . . . . . . . . 102
Parasympathetic Nervous System . . . 102
Cholinergic Synapse . . . . . . . . . . . 104
Parasympathomimetics . . . . . . . . . 106
Parasympatholytics . . . . . . . . . . . 108
Nicotine. . . . . . . . . . . . . . . . . . 112
Actions ofNicotine . . . . . . . . . . . 112
Localization of Nicotinic ACh
Receptors. . . . . . . . . . . . . . . . . 112
Effects of Nicotine on Body Function . 112
Aids for Smoking Cessation. . . . . . . 112
Consequences of Tobacco Smoking . . 114
Biogenic Amines. . . . . . . . . . . . . 116
Dopamine. . . . . . . . . . . . . . . . . 116
Histamine Effects and Their
Pharmacological Properties. . . . . . . 118
Serotonin . . . . . . . . . . . . . . . . . 120
Vasodilators . . . . . . . . . . . . . . . 122
Vasodilators—Overview . . . . . . . . . 122
OrganicNitrates . . . . . . . . . . . . . 124
Calcium Antagonists . . . . . . . . . . . 126
I. Dihydropyridine Derivatives . . . . . . 126
II. Verapamil and Other Catamphiphilic
Ca2+ Antagonists . . . . . . . . . . . . . 126
Inhibitors of the Renin–Angiotensin–
Aldosterone System. . . . . . . . . . . 128
ACE Inhibitors. . . . . . . . . . . . . . . 128
Drugs Acting on Smooth Muscle . . . 130
Drugs Used to Influence Smooth
MuscleOrgans . . . . . . . . . . . . . . 130
Cardiac Drugs . . . . . . . . . . . . . . 132
Cardiac Glycosides . . . . . . . . . . . . 134
AntiarrhythmicDrugs . . . . . . . . . . 136
I. Drugs for Selective Control of
Sinoatrial and AVNodes. . . . . . . . 136
II. Nonspecific Drug Actions on
Impulse Generation and Propagation 136
Electrophysiological Actions of
Antiarrhythmics of the Na+-Channel
Blocking Type. . . . . . . . . . . . . . . 138
Antianemics . . . . . . . . . . . . . . . 140
Drugs for the Treatment of Anemias . . 140
Erythropoiesis (A) . . . . . . . . . . . 140
Vitamin B12 (B) . . . . . . . . . . . . 140
Folic Acid (B) . . . . . . . . . . . . . . 140
Iron Compounds . . . . . . . . . . . . . 142
Antithrombotics . . . . . . . . . . . . . 144
Prophylaxis and Therapy of Thromboses 144
Vitamin K Antagonists and Vitamin K . 146
Possibilities for Interference (B) . . . . . 146
Heparin (A) . . . . . . . . . . . . . . . . 148
Contents VII
Hirudin and Derivatives (B) . . . . . . . 148
Fibrinolytics. . . . . . . . . . . . . . . . 150
Intra-arterial Thrombus
Formation (A) . . . . . . . . . . . . . . 152
Formation, Activation, and
Aggregation of Platelets (B). . . . . . . 152
Inhibitors of Platelet
Aggregation (A) . . . . . . . . . . . . . 154
Presystemic Effect of ASA. . . . . . . . 154
Plasma Volume Expanders. . . . . . . 156
Drugs Used in Hyperlipoproteinemias 158
Lipid-lowering Agents. . . . . . . . . . 158
Diuretics . . . . . . . . . . . . . . . . . 162
Diuretics—AnOverview . . . . . . . . . 162
NaCl Reabsorption in the Kidney (A) . . 164
Aquaporins (AQP) . . . . . . . . . . . . 164
Osmotic Diuretics (B) . . . . . . . . . . 164
Diuretics of the Sulfonamide Type . . . 166
Potassium- sparing Diuretics and
Vasopressin. . . . . . . . . . . . . . . . 168
Potassium- sparing Diuretics (A) . . . . 168
Vasopressin and Derivatives (B) . . . . 168
Drugs for the Treatment of Peptic
Ulcers . . . . . . . . . . . . . . . . . . . 170
Drugs for Gastric and Duodenal
Ulcers . . . . . . . . . . . . . . . . . . . 170
I. Lowering of Acid Concentration . . 170
II. Protective Drugs . . . . . . . . . . 172
III. Eradication of Helicobacter
pylori (C) . . . . . . . . . . . . . . . . 172
Laxatives . . . . . . . . . . . . . . . . . 174
1. Bulk Laxatives. . . . . . . . . . . . 174
2. Irritant Laxatives . . . . . . . . . . 176
2a. Small-Bowel Irritant Purgative . . 178
2b. Large-Bowel Irritant Purgatives . 178
3. Lubricant laxatives . . . . . . . . . 178
Antidiarrheals . . . . . . . . . . . . . . 180
Antidiarrheal Agents. . . . . . . . . . . 180
Drugs Acting on the Motor System . 182
Drugs Affecting Motor Function . . . . 182
Muscle Relaxants. . . . . . . . . . . . . 184
Nondepolarizing Muscle Relaxants . . . 184
Depolarizing Muscle Relaxants . . . . . 186
AntiparkinsonianDrugs . . . . . . . . . 188
Antiepileptics . . . . . . . . . . . . . . . 190
Drugs for the Suppression of Pain . . 194
Pain Mechanisms and Pathways . . . . 194
Antipyretic Analgesics . . . . . . . . . 196
Eicosanoids . . . . . . . . . . . . . . . . 196
Antipyretic Analgesics vs. NSAIDs. . . . 198
Nonsteroidal Anti- inflammatory
Drugs (NSAIDs) . . . . . . . . . . . . . . 198
Nonsteroidal Anti- inflammatory
Drugs . . . . . . . . . . . . . . . . . . . 200
Cyclooxygenase (COX) Inhibitors . . . . 200
Local Anesthetics . . . . . . . . . . . . 202
Opioids . . . . . . . . . . . . . . . . . . 208
Opioid Analgesics—Morphine Type . . . 208
General Anesthetics . . . . . . . . . . . 214
General Anesthesia and General
Anesthetic Drugs . . . . . . . . . . . . . 214
Inhalational Anesthetics . . . . . . . . . 216
Injectable Anesthetics . . . . . . . . . . 218
Psychopharmacologicals . . . . . . . . 220
Sedatives,Hypnotics . . . . . . . . . . . 220
Benzodiazepines . . . . . . . . . . . . . 222
Benzodiazepine Antagonist . . . . . . 222
Pharmacokinetics of Benzodiazepines . 224
Therapy of Depressive Illness . . . . . . 226
Mania . . . . . . . . . . . . . . . . . . . 230
Therapy of Schizophrenia . . . . . . . . 232
Neuroleptics . . . . . . . . . . . . . . 232
Psychotomimetics (Psychedelics,
Hallucinogens) . . . . . . . . . . . . . . 236
Hormones. . . . . . . . . . . . . . . . . 238
Hypothalamic and Hypophyseal
Hormones. . . . . . . . . . . . . . . . . 238
ThyroidHormone Therapy. . . . . . . . 240
Hyperthyroidism and Antithyroid
Drugs . . . . . . . . . . . . . . . . . . . 242
Glucocorticoid Therapy . . . . . . . . . 244
I. Replacement Therapy . . . . . . . . . 244
VIII Contents
II. Pharmacodynamic Therapy with
Glucocorticoids (A) . . . . . . . . . . . 244
Androgens, Anabolic Steroids,
Antiandrogens . . . . . . . . . . . . . . 248
Inhibitory Principles . . . . . . . . . . 248
Follicular Growth and Ovulation,
Estrogen and Progestin Production . . 250
Oral Contraceptives . . . . . . . . . . . 252
Antiestrogen and Antiprogestin
Active Principles . . . . . . . . . . . . . 254
Aromatase Inhibitors . . . . . . . . . . 256
Insulin Formulations . . . . . . . . . . . 258
Variations in Dosage Form . . . . . . 258
Variation in Amino Acid Sequence. . 258
Treatment of Insulin-dependent
Diabetes Mellitus. . . . . . . . . . . . . 260
Undesirable Effects . . . . . . . . . . 260
Treatment of Maturity-Onset
(Type II) Diabetes Mellitus. . . . . . . . 262
Oral Antidiabetics . . . . . . . . . . . . 264
Drugs for Maintaining Calcium
Homeostasis . . . . . . . . . . . . . . . 266
Antibacterial Drugs . . . . . . . . . . . 268
Drugs for Treating Bacterial
Infections . . . . . . . . . . . . . . . . . 268
Inhibitors of Cell Wall Synthesis . . . . 270
Inhibitors of Tetrahydrofolate
Synthesis . . . . . . . . . . . . . . . . . 274
Inhibitors ofDNA Function . . . . . . . 276
Inhibitors of Protein Synthesis . . . . . 278
Drugs for Treating Mycobacterial
Infections . . . . . . . . . . . . . . . . . 282
Antitubercular drugs (1) . . . . . . . 282
Antileprotic drugs (2) . . . . . . . . . 282
Antifungal Drugs . . . . . . . . . . . . 284
Drugs Used in the Treatment of
Fungal Infections . . . . . . . . . . . . . 284
Antiviral Drugs. . . . . . . . . . . . . . 286
Chemotherapy of Viral Infections. . . . 286
Drugs for the Treatment of AIDS . . . . 290
I. Inhibitors of Reverse
Transcriptase—Nucleoside Agents . . 290
Nonnucleoside Inhibitors . . . . . . . 290
II.HIV protease Inhibitors . . . . . . . 290
III. Fusion Inhibitors . . . . . . . . . . 290
Antiparasitic Drugs . . . . . . . . . . . 292
Drugs for Treating Endoparasitic
and Ectoparasitic Infestations . . . . . . 292
Antimalarials . . . . . . . . . . . . . . . 294
Other TropicalDiseases . . . . . . . . . 296
Anticancer Drugs . . . . . . . . . . . . 298
Chemotherapy of Malignant
Tumors . . . . . . . . . . . . . . . . . . 298
Targeting of Antineoplastic Drug
Action (A) . . . . . . . . . . . . . . . . . 302
Mechanisms of Resistance to
Cytostatics (B) . . . . . . . . . . . . . . 302
Immune Modulators . . . . . . . . . . 304
Inhibition of Immune Responses . . . . 304
Antidotes . . . . . . . . . . . . . . . . . 308
Antidotes and Treatment of
Poisonings. . . . . . . . . . . . . . . . . 308
Therapy of Selected Diseases 313
Hypertension. . . . . . . . . . . . . . . 314
Angina Pectoris . . . . . . . . . . . . . 316
Antianginal Drugs . . . . . . . . . . . . 318
Acute Coronary Syndrome—
Myocardial Infarction . . . . . . . . . . 320
Congestive Heart Failure . . . . . . . . 322
Hypotension . . . . . . . . . . . . . . . 324
Gout. . . . . . . . . . . . . . . . . . . . 326
Obesity—Sequelae and
Therapeutic Approaches. . . . . . . . . 328
Osteoporosis . . . . . . . . . . . . . . . 330
Rheumatoid Arthritis. . . . . . . . . . . 332
Migraine. . . . . . . . . . . . . . . . . . 334
Common Cold . . . . . . . . . . . . . . 336
Atopy and Antiallergic Therapy . . . . . 338
Bronchial Asthma. . . . . . . . . . . . . 340
Emesis . . . . . . . . . . . . . . . . . . . 342
Alcohol Abuse. . . . . . . . . . . . . . . 344
Local Treatment of Glaucoma. . . . . . 346
Contents IX
Further Reading 349
Drug Indexes 351
Trade Name – Drug Name . . . . . . . 352 Drug Name – Trade Name. . . . . . . . 369
Subject Index 381
You want ebook?? massage on my facebook
my number +6285749696020
0 komentar:
Post a Comment