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藥理學(xué)
本書系統(tǒng)地介紹了藥理學(xué)的基本知識(shí),包括常用藥物的作用和原理、臨床應(yīng)用、不良反應(yīng)以及藥物相互作用等。
Pharmacology is one of indispensable basic courses in medical colleges, and also is one of
professional basic courses for students in various majors of clinical medicine, pharmaceutics and nursing. Pharmacological science provides an important theoretical basis and experimental methods for revealing the therapeutic principle to diseases, expounding the innate character of life activity, promoting the development of biological science. Pharmacology is the study of interaction between drugs and the body, the bridge between basic medicine and clinical medicine, the sharing resource between medicine and pharmacy. In recent decades, it appears new advances in change of disease spectrum, in requirement of public health, in research and development of new drug. With these advances, pharmacology shows the more and more importance and applicability. The goal of this textbook is to provide a succinct, accurate, up-to-date, clinically relevant introduction to drug action, mechanism of action, clinical uses, adverse drug reaction, drug interaction, et al., on which rational therapeutics is based. The authors have aimed to make the textbook readable and useful in learning Pharmacology for the foreign medical student studying in China, and also suitable for five-year program medical students. In our long-term teaching for international medical students and on the basis of the first four editions textbook of pharmacology, this textbook not only affords students basic knowledge and theories, but also lays a foundation for clinical courses. According to the development of pharmacology and drug research, many chapters have been updated. At the same time, it introduces some new drugs and new mechanisms of actions, especially the trends of pharmacology. The content of this textbook includes six sections, i.e., general introduction, autonomic nervous system drugs, central nervous system drugs, cardiovascular system drugs, internal organ and endocrine system drugs, and chemotherapeutic drugs. The reference books used are as follows: Brunton L L, et al. 2011. Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 12th Edi; Katzung B G, et al. 2012. Basic and Clinical Pharmacology 12th Edi; Rang H P, et al. 2011. Rang and Dale’s Pharmacology 7th Edi; Yang B F. 2009. Pharmacology 7th Edi; Lin Z B, et al. 2008. Basis of Medical Pharmacology. 6th Edi; Finkel R, et al. 2009. Lippincott’s Illustrated Reviews: Pharmacology, 4th Edi. This textbook is written by faculty members of the Department of Pharmacology, Tianjin Medical University. Since our ability and level are limited, there maybe some mistakes and shortcomings in this textbook. I hope the readers give valuable opinions and comments. Any suggestion and comment are always welcome at anytime to send to author’s E-mail. We have the capacity and ingenuity to correct these mistakes and shortcomings in next edition. LOU Jianshi Department of Pharmacology School of Basic Medicine Tianjin Medical University Tianjin 300070, P.R.China jianshilou@tijmu.edu.cn November 2014
Chapter 1 Introduction…………………………………………………………………………………1
Ⅰ. Development of Pharmacology………………………………………………………………1 Ⅱ. New Drug Research……………………………………………………………………………2 Chapter 2 Pharmacodynamics…………………………………………………………………………3 Ⅰ. General Classification of Drug Effects………………………………………………………3 Ⅱ. Dose-Effect Relationship………………………………………………………………………4 Ⅲ. Receptor Theory and Drug Receptor Interaction……………………………………………6 Ⅳ. Receptor Families and Their Transducer and Effector Molecules…………………………9 Ⅴ. Relationship Between Regulatory Mechanisms of Receptors and the Pharmacological Action…………………………………………………………………11 Ⅵ. Mechanism of Action…………………………………………………………………………12 Chapter 3 Pharmacokinetics……………………………………………………………………………13 Ⅰ. Drug Transport across Membranes…………………………………………………………13 Ⅱ. The Dynamics of Drug Absorption, Distribution, and Elimination………………………14 Ⅲ. General Principles of Pharmacokinetics……………………………………………………19 Chapter 4 Pharmacogenetics…………………………………………………………………………24 Ⅰ. The Objectives of Research in Pharmacogenetics……………………………………………24 Ⅱ. The Effect of Genetic Factors on Drug Reactions……………………………………………25 Ⅲ. The Racial Difference of Drug Reaction and Metabolism…………………………………29 Chapter 5 Autonomic Pharmacology…………………………………………………………………31 Ⅰ. Anatomy and Neurotransmitter Chemistry of the Autonomic Nervous System………31 Ⅱ. Biosynthesis and Metabolism of Transmitters………………………………………………32 Ⅲ. Locations of Autonomic Receptors……………………………………………………………35 Ⅳ. Presynaptic Regulation of Transmitter Release……………………………………………36 Ⅴ. Functional Organization of Autonomic Activity……………………………………………38 Ⅵ. Coupling Mechanism of Receptor-effect……………………………………………………39 Ⅶ. Mode of Action of Autonomic Nervous System Drugs……………………………………40 Ⅷ. Classification of Autonomic Nervous System Drugs………………………………………41 Chapter 6 Cholinoceptor-Activating and Cholinesterase-Inhibiting Drugs………………………42 Ⅰ. Direct-acting Cholinoceptor Stimulants……………………………………………………42 Ⅱ. Cholinesterase Inhibitors………………………………………………………………………44 Chapter 7 Organophosphates Anticholinesterase Intoxication and Cholinesterase Reactivators……47 Ⅰ. Organophosphates Anticholinesterase Intoxication………………………………………47 Ⅱ. Cholinesterase Reactivator……………………………………………………………………48 Chapter 8 M Cholinoceptor Antagonists………………………………………………………………50 Ⅰ. Natural M Cholinoceptor Blocking Drugs…………………………………………………50 Ⅱ. Synthetic Spasmolytic Drugs…………………………………………………………………53 Chapter 9 N Cholinoceptor Antagonists………………………………………………………………54 Ⅰ. N1 Cholinoceptor Blocking Drugs……………………………………………………………54 Ⅱ. N2 Cholinoceptor Blocking Drugs……………………………………………………………55 Chapter 10 Adrenoceptor-Activating Drugs…………………………………………………………58 Ⅰ. Chemical Structure……………………………………………………………………………58 Ⅱ. Classification……………………………………………………………………………………59 Ⅲ. Mixed α and β Receptor Agonists……………………………………………………………60 Ⅳ. α Receptor Agonists……………………………………………………………………………63 Ⅴ. β Receptor Agonists ……………………………………………………………………………64 Ⅵ. Dopaminergic Receptor Agonists……………………………………………………………66 Chapter 11 Adrenoceptor Blocking Drugs……………………………………………………………69 Ⅰ. α Receptor Antagonists…………………………………………………………………………69 Ⅱ. β Receptor Antagonists ………………………………………………………………………73 Ⅲ. α, β Receptor Antagonists……………………………………………………………………76 Chapter 12 Sedative-Hypnotics Drugs…………………………………………………………………78 Ⅰ. Introduction……………………………………………………………………………………78 Ⅱ. Benzodiazepines………………………………………………………………………………79 Ⅲ. Barbiturates……………………………………………………………………………………83 Ⅳ. Other Sedative-Hypnotics……………………………………………………………………85 Chapter 13 Antiepileptic Drugs………………………………………………………………………88 Ⅰ. Classification of Seizure Types………………………………………………………………88 Ⅱ. Drugs Used in Seizures………………………………………………………………………89 Ⅲ. Selectivity and Withdrawal of Antiepileptic Drugs…………………………………………94 Ⅳ. Anticonvulsant Drugs…………………………………………………………………………95 Chapter 14 Psychotropic Drugs………………………………………………………………………97 Ⅰ. Antipsychotic Drugs……………………………………………………………………………97 Ⅱ. Antimanic Drugs……………………………………………………………………………103 Ⅲ. Antidepressants………………………………………………………………………………105 Chapter 15 Antiparkinsonism Drugs………………………………………………………………108 Ⅰ. Dopaminergic Drugs………………………………………………………………………108 Ⅱ. Anticholinergic Drugs………………………………………………………………………111 Ⅲ. Others…………………………………………………………………………………………112 Chapter 16 Antipyretic-Analgesic and Antiinflammatory Drugs…………………………………113 Ⅰ. Introduction…………………………………………………………………………………113 Ⅱ. Salicylates……………………………………………………………………………………115 Ⅲ. Anilines………………………………………………………………………………………117 Ⅳ. Pyrazolones…………………………………………………………………………………117 Ⅴ. Others…………………………………………………………………………………………118 Ⅵ. Analgesic Compounds………………………………………………………………………120 Ⅶ. Slow Acting Antirheumatic Drugs…………………………………………………………120 Ⅷ. Antigout Drugs………………………………………………………………………………121 Chapter 17 Narcotic Analgesics……………………………………………………………………123 Ⅰ. Introduction…………………………………………………………………………………123 Ⅱ. Opioid Receptor Agonists…………………………………………………………………125 Ⅲ. Opioid Receptor Antagonists………………………………………………………………130 Chapter 18 Central Stimulants………………………………………………………………………132 Ⅰ. Cerebral Stimulants…………………………………………………………………………132 Ⅱ. Medullary Stimulants………………………………………………………………………135 Chapter 19 Drugs Used in the Treatment of Heart Failure………………………………………136 Ⅰ. Pathophysiology of Congestive Heart Failure……………………………………………136 Ⅱ. Diuretics………………………………………………………………………………………138 Ⅲ. Aldosterone Antagonists……………………………………………………………………138 Ⅳ. Inhibitors of RAAS: ACEI and AT1 Receptor Antagonists………………………………138 Ⅴ. β Adrenergic Receptor Blocking Agents…………………………………………………139 Ⅵ. Vasodilators…………………………………………………………………………………139 Ⅶ. Cardiac Glycosides…………………………………………………………………………139 Ⅷ. β Adrenergic Receptor Stimulators………………………………………………………146 Ⅸ. Phosphodiesterase Inhibitors………………………………………………………………147 Chapter 20 Antihypertensive Drugs…………………………………………………………………148 Ⅰ. Introduction…………………………………………………………………………………148 Ⅱ. Drugs that Alter Sodium and Water Balance……………………………………………150 Ⅲ. Drugs that Alter Sympathetic Nervous System Function………………………………152 Ⅳ. Vasodilators…………………………………………………………………………………156 Ⅴ. Drugs that Interfere with the Renin-Angiotensin System………………………………160 Ⅵ. Clinical Pharmacology of Antihypertensive Drugs………………………………………162 Chapter 21 Anti-Angina Pectoris Drugs……………………………………………………………164 Ⅰ. Introduction…………………………………………………………………………………164 Ⅱ. Nitrates and Nitrites…………………………………………………………………………165 Ⅲ. Calcium Channel Blockers…………………………………………………………………167 Ⅳ. β Receptor Antagonists……………………………………………………………………167 Chapter 22 Antiarrhythmic Drugs…………………………………………………………………170 Ⅰ. Introduction…………………………………………………………………………………170 Ⅱ. Class ⅠA………………………………………………………………………………………174 Ⅲ. Class ⅠB………………………………………………………………………………………176 Ⅳ. Class ⅠC………………………………………………………………………………………178 Ⅴ. Class Ⅱ………………………………………………………………………………………178 Ⅵ. Class Ⅲ………………………………………………………………………………………179 Ⅶ. Class Ⅳ………………………………………………………………………………………180 Ⅷ. Others…………………………………………………………………………………………181 Chapter 23 Antihyperlipidemic Drugs………………………………………………………………184 Ⅰ. Atherogenesis………………………………………………………………………………184 Ⅱ. Lipoprotein Transport………………………………………………………………………185 Ⅲ. Dyslipidaemia………………………………………………………………………………186 Ⅳ. Antihyperlipidemic Drugs…………………………………………………………………186 Chapter 24 Diuretic and Dehydrant Drugs…………………………………………………………191 Ⅰ. Kidney Structure and Function……………………………………………………………191 Ⅱ. Diuretics………………………………………………………………………………………193 Ⅲ. Osmotic Diuretics (Mannitol, Sorbitol, Glucose, Urea)…………………………………198 Chapter 25 Antiasthmatic Drugs……………………………………………………………………199 Ⅰ. Bronchodilators………………………………………………………………………………199 Ⅱ. Anti-Inflammatory Drugs…………………………………………………………………203 Chapter 26 Drugs Used in Gastrointestinal Diseases………………………………………………206 Ⅰ. Drugs Used to Treat Peptic Ulcer…………………………………………………………206 Ⅱ. Antiemetic Drugs……………………………………………………………………………210 Ⅲ. Antidiarrheal Drugs…………………………………………………………………………212 Ⅳ. Laxatives………………………………………………………………………………………212 Chapter 27 Drugs Affecting Uterine Motility………………………………………………………214 Ⅰ. Drugs that Stimulate Uterine Contraction………………………………………………214 Ⅱ. Drugs that Inhibit Uterine Contraction……………………………………………………216 Chapter 28 Anticoagulants and Coagulants………………………………………………………217 Ⅰ. Introduction…………………………………………………………………………………217 Ⅱ. Anticoagulants………………………………………………………………………………219 Ⅲ. Antiplatelet Drugs……………………………………………………………………………223 Ⅳ. Fibrinolytic Drugs……………………………………………………………………………225 Ⅴ. Coagulants……………………………………………………………………………………226 Chapter 29 Histamine and Antihistamine Drugs…………………………………………………228 Ⅰ. Histamine……………………………………………………………………………………228 Ⅱ. H1 Receptor Antagonists……………………………………………………………………231 Ⅲ. H2 Receptor Antagonists……………………………………………………………………232 Chapter 30 Adrenocorticosteroids…………………………………………………………………234 Ⅰ. Introduction…………………………………………………………………………………234 Ⅱ. Glucocorticoids………………………………………………………………………………235 Ⅲ. Mineralocorticoids…………………………………………………………………………243 Chapter 31 Drugs Affecting the Thyroid Gland…………………………………………………245 Ⅰ. Thyroid Hormone (TH)……………………………………………………………………245 Ⅱ. Antithyroid Drugs……………………………………………………………………………247 Chapter 32 Antidiabetic Drugs………………………………………………………………………250 Ⅰ. Insulin…………………………………………………………………………………………250 Ⅱ. Oral Hypoglycemic Drugs…………………………………………………………………254 Ⅲ. Current Treatment Options…………………………………………………………………258 Chapter 33 Introduction to Antibacterial Drugs…………………………………………………259 Ⅰ. Specialty Terms………………………………………………………………………………259 Ⅱ. Antimicrobial Mechanisms…………………………………………………………………260 Ⅲ. Mechanism of Resistance to Antibiotics…………………………………………………261 Chapter 34 Synthetic Antimicrobial Drugs…………………………………………………………263 Ⅰ. Sulfonamides…………………………………………………………………………………263 Ⅱ. Trimethoprim…………………………………………………………………………………265 Ⅲ. Quinolones……………………………………………………………………………………268 Chapter 35 β-Lactam Antibiotics…………………………………………………………………272 Ⅰ. Penicillins……………………………………………………………………………………272 Ⅱ. Cephalosporins………………………………………………………………………………278 Ⅲ. Other β-Lactam Drugs………………………………………………………………………281 Chapter 36 Macrolides, Lincosamides and Glycopeptides………………………………………284 Ⅰ. Macrolides……………………………………………………………………………………284 Ⅱ. Lincosamides…………………………………………………………………………………288 Ⅲ. Glycopeptides………………………………………………………………………………290 Chapter 37 Broad-Spectrum Antibiotics……………………………………………………………292 Ⅰ. Tetracyclines…………………………………………………………………………………292 Ⅱ. Chloramphenicols……………………………………………………………………………296 Chapter 38 Aminoglycosides and Polypeptides……………………………………………………299 Ⅰ. Aminoglycosides……………………………………………………………………………299 Ⅱ. Polypeptides…………………………………………………………………………………305 Chapter 39 Antifungal Drugs………………………………………………………………………306 Ⅰ. Antibiotics……………………………………………………………………………………306 Ⅱ. Azole Antifungal Drugs……………………………………………………………………307 Ⅲ. Allylamine Antifungal Drugs………………………………………………………………308 Ⅳ. Pyrimidine Antifungal Drugs………………………………………………………………308 Chapter 40 Antiviral Drugs…………………………………………………………………………310 Ⅰ. Anti-Human Immunodeficiency Virus Drugs……………………………………………311 Ⅱ. Anti-Herpersvirus Drugs……………………………………………………………………318 Ⅲ. Anti-Influenza Drugs………………………………………………………………………324 Ⅳ. Anti-Hepacivirus Drugs……………………………………………………………………328 Chapter 41 Antimycobacterial Drugs………………………………………………………………332 Ⅰ. Introduction…………………………………………………………………………………332 Ⅱ. First-Line Drugs Used in Tuberculosis……………………………………………………332 Ⅲ. Alternative Second-Line Drugs in Treatment of Tuberculosis…………………………337 Ⅳ. Combination Chemotherapy of Tuberculosis……………………………………………339 Chapter 42 Antimalarial Drugs……………………………………………………………………340 Ⅰ. Plasmodium Life Cycles and Action of Antimalarial Drugs……………………………340 Ⅱ. Antimalarial Drugs Mainly Applied to Control Symptoms……………………………341 Ⅲ. Antimalarial Drugs Mainly Applied to Control Relapse and Transmission…………351 Ⅳ. Antimalarial Drugs Mainly Applied to Causal Prophylaxis……………………………352 Chapter 43 Amebicides………………………………………………………………………………355 Ⅰ. Life Cycles of Entamoeba Histolytica and Action of Amebicides…………………………355 Ⅱ. Luminal Amebicides…………………………………………………………………………356 Ⅲ. Extraintestinal Amebicides…………………………………………………………………359 Ⅳ. Luminal and Simultaneously Extraintestinal Amebicides………………………………360 Chapter 44 Anthelmintic Drugs……………………………………………………………………364 Ⅰ. Nematocides…………………………………………………………………………………364 Ⅱ. Taeniacides……………………………………………………………………………………366 Ⅲ. Anti-Trematode Drugs………………………………………………………………………366 Chapter 45 Antineoplastic Drugs……………………………………………………………………369 Ⅰ. Introduction…………………………………………………………………………………369 Ⅱ. Cytotoxic Drugs………………………………………………………………………………372 Ⅲ. Non-Cytotoxic Drugs………………………………………………………………………378 References………………………………………………………………………………………………382
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