第六编 药物治疗学基础 Section VI Pharmacological basis of drug therapeutics

教师介绍： 魏尔清 Wei Er-Qing Department of Pharmacology, School of Medicine, Zhujiang University Research field: Neuropharmacology Focusing on stroke therapeutic drugs Tel:

GeneralPrinciples General Principles General Concepts History The Nature of Drugs Methodology of Pharmacology New Drug Research and Development

General Concepts Human disease: prevention and treatment Drug therapy Drug therapy Surgery Surgery Radiotherapy Radiotherapy Physical therapy Physical therapy Psychological therapy Psychological therapy 药理学是药物治疗学的基础理论

General Concepts Pharmacology can be defined as the study of substances that interact with living systems through chemical processes, especially by binding to regulatory molecules and activating or inhibiting normal body processes. Medical Pharmacology is often defined as the science of substances used to prevent, diagnose, and treat disease. － － Katzung BG (Ed). Basic & Clinical Pharmacology (11th Edition). New York: McGraw-Hill, 药理学是研究药物与机体（包括人体和病原体）相互作用的规 律及其原理，是一门为临床合理用药防治疾病提供基本理论的 医学基础学科。

What is Pharmacology studied? Pharmacodynamics （药效动力学，药效学） : the actions of the drug on the body and the mechanisms Pharmacokinetics （药代动力学，药动学） : the actions of the body on the drugs Factors （影响因素） ： influencing the processes of pharmacodynamics and pharmacokinetics

Drugs Human Body Pharmacodynamics （药效学） Action and mechanism Pharmacokinetics （药动学） Absorption, distribution, metabolism, excretion, and drug concentration in the body Interaction between drug and human body 药物与人体的相互作用

HumanPathogens Drug Interactions between drug, human body, and pathogens 药物、人体和病原体之间的相互作用

Pharmacy药学 Pharmacology药理学 Therapeutics治疗学 Basic Research 基础研究 New Drug 新药研制 Clinical Pharmacology Life Science Screening and Evaluation The Goals of Pharmacology Drugs

History Remedies in China and Egypt,recognized and recorded the beneficial and toxic effects of many plant and animal materials. > 2500 years ago ～ 17th century. — 本草学 Remedies in China and Egypt, recognized and recorded the beneficial and toxic effects of many plant and animal materials. > 2500 years ago ～ 17th century. — 本草学 Materia medica,the science of drug preparation and the medical use of drugs: the precursor pharmacology. End of 17th cetury ～ 18th century. —— 药物学 Materia medica, the science of drug preparation and the medical use of drugs: the precursor pharmacology. End of 17th cetury ～ 18th century. —— 药物学

2 History Traditional pharmacology:developing the methods of experimental physiology and pharmacology; advances in chemistry. 18th century ～ early of 20th century. —— 经典药理学 Traditional pharmacology: developing the methods of experimental physiology and pharmacology; advances in chemistry. 18th century ～ early of 20th century. —— 经典药理学 Modern pharmacology:concepts of rational therapeutics, especially that of the controlled clinical trials; a major expansion of research efforts in all areas of biology, 20th century ～ ; rapid growth of information and understanding of the molecular basis for drug action, last 3 decades. Modern pharmacology: concepts of rational therapeutics, especially that of the controlled clinical trials; a major expansion of research efforts in all areas of biology, 20th century ～ ; rapid growth of information and understanding of the molecular basis for drug action, last 3 decades. —— 现代药理学

Rudolf Buchheim ( ) Founder of experimental pharmacology

药物： 影响机体生理、生化功能，能够用于诊断、预防 和治疗疾病的物质。 药品： 指用于预防、治疗、诊断人的疾病，有目的地调 节人的生理机能并规定有适应证、用法和用量的物质包 括中药材、中药饮片、中成药、化学原料药及其制剂、抗 生素、生化药品、放射性药品、血清疫苗、血液制品和诊 断药品等。 药品： 指用于预防、治疗、诊断人的疾病，有目的地调 节人的生理机能并规定有适应证、用法和用量的物质，包 括中药材、中药饮片、中成药、化学原料药及其制剂、抗 生素、生化药品、放射性药品、血清疫苗、血液制品和诊 断药品等。 药物和药品的概念

The Nature of Drugs 3.1 The physical nature of drugs 药物的理化特性 Solid: e.g. aspirin, atropine Solid: e.g. aspirin, atropine Liquid: e.g. nicotine, ethanol Liquid: e.g. nicotine, ethanol Gaseous: e.g. ether, nitrous oxide Gaseous: e.g. ether, nitrous oxide

The Nature of Drugs 3.2 Drug size 药物的大小 Very small: lithium ion (MW 7) Very small: lithium ion (MW 7) Very large: t-PA (MW 59,050) Very large: t-PA (MW 59,050) Most: MW between 100 – 1,000 Most: MW between 100 – 1,000

The Nature of Drugs 3.3 Drug reactivity and drug-receptor bonds 药物反应性及药物 - 受体作用力 药物反应性及药物 - 受体作用力 Chemical forces: Chemical forces: covalent, electrostatic, hydrophobic covalent, electrostatic, hydrophobic

The Nature of Drugs 3.4 Drug shape 药物的形状 Optimally, the shape of a drug is complementary to that of the receptor site in the same way that a key is complementary to a lack. The phenomenon of chirality ( 手性） (steroisomerism) is so common in biology that more than half of all useful drugs are chiral molecles, i.e. they exist as enantiomeric pairs.

The Nature of Drugs 3.5 Rational drug design 基于分子结构的药物设计 As more becomes known about target structures and computer programs are now available, rational drug design based on computer will become more feasible. As more becomes known about target structures and computer programs are now available, rational drug design based on computer will become more feasible.

The Nature of Drugs 3.6 Drug resources and preparation Nature sources 天然来源 Synthesis合成 Bioengineering生物工程 Dose Forms 剂型 Human Pharmacy药学 Pharmacology药理学

 新药定义： 未曾在中国境内上市销售的药品 。  旧定义： 我国尚未生产过的药品。已生产的药品改 变剂型、改变给药途径、增加新的适应证或制成新的 复方制剂，亦按新药管理 。 Pharmacology and the Research and Development (R&D) of New Drug

Pharmacology and the Research and Development of New Drug (R&D) 1. Preclinical testing 临床前研究 2. Approval for clinical testing 临床研究审批 3. Clinical testing (clinical pharmacology) 临床试 验（临床药理学） 4. Approval for production and marketing 生产和 销售审批

Pharmacology and the Research and Development (R&D) of New Drug 1. Preclinical testing Efficacy 有效性 (screening and evaluation by pharmacological methods) Safety 安全性 (evaluation by toxicological methods) Safety 安全性 (evaluation by toxicological methods) Quantity 质量可控性 (pharmacy) Quantity 质量可控性 (pharmacy) good laboratory practice （ GLP ） good laboratory practice （ GLP ）

Pharmacology and the Research and Development (R&D) of New Drug 2. Clinical testing – Phase I, II, III & IV Efficacy 疗效 (therapeutic effects) Efficacy 疗效 (therapeutic effects) Safety 安全性 (adverse effects) Safety 安全性 (adverse effects) Pharmacokinetics 药动学 (PK parameter or bioavaibility) good clinical practice (GCP) good clinical practice (GCP)

The phases of drug development 新药研究分期