General Principles of Pharmacology第一篇 药 理 学 总 论 Part 1 General Principles of Pharmacology第一篇 药 理 学 总 论 Zhiqiang SHEN Department of Pharmacology, School of Pharmaceutical Science

Part 1 General Principles Chapter 1 Introduction 1 Chapter 2 Pharmacokinetics 2 3 Chapter 3 Receptor Theory & Pharmacodynamics

Chapter 1 Introduction 药理学的入门 www. What Why hoW

Important Concepts 药 品 Drug 药 物 Pharmacology 药效学 Pharmacodynamics 药动学 Pharmaceutical drug 药 品 Drug 药 物 Pharmacology 药效学 Pharmacodynamics 药动学 Pharmacokinetics

Source of drugs 药物的来源 Plants（植 物） Animals（动 物） Minerals（矿 物） 古代—Natural products Plants（植 物） Animals（动 物） Minerals（矿 物）

人 参 金银花 银杏白果

Sources of drugs Drugs from animals 《神农本草经》67种；《本草纲目》461种 《中药大辞典》有740种 1618年的《伦敦药典》 目前市售中药

蜈蚣 穿山甲 蟋 蟀 美洲大蠊

Sources of drugs Drugs from minerals 《本草纲目》的金、石部载有161种 《中国中药资源》药用矿物约有80种

朱 砂 硫 磺 明 矾 石 膏 雄 黄

Sources of drugs 现 代 Active principles from natural products（活性成分） Artificial synthetics（合成药） Semi-synthetic drugs—耐药青霉素，辛伐他汀等 full-synthetic drugs —磺胺、钙拮抗剂等 Genetic engineering drugs—rtPA, rhPTH，

What is drug Drug（药 物） 接种疫苗— prevention 扑热息痛—解热镇痛— treatment 钡餐—造影— diagnosis 避孕药— altering physiological function

What is drug 化学物质。 可以改变机体的生理功能、生化反应及 病理状态，用于预防、治疗、诊断疾病 药 物 可以改变机体的生理功能、生化反应及 病理状态，用于预防、治疗、诊断疾病 和计划生育， 安全有效、质量可控的 化学物质。 Drug A chemical substance that can modulate the physiological status and is utilized for the diagnosis, prevention and cure of an unwanted health condition.

Pharmaceutical drug（药品） 药物制剂 Drug 化学物质 药 品—有适应症或功能主治，标明用法和用量，临床可直接使用的药物制剂。

Difference Drug A chemical substance: modulating the physiological status and diagnosing, preventing and curing diseases. Pharmaceutical drug Pharmaceutical preparation: having indications, showing usage and dosage, directly applied in clinic.

Drug & Poison (药 物与毒 物) 三分毒！ 药物两重性: 治 病 及 致 病 药 物 双刃剑

药食同源，药毒难分 药物与毒物的界限？ Food （drug） Poison Example 1. fluid infusion 糖盐水 Chronic heart failure（心衰） Renal dysfunction （肾功能障碍） Hypertension （高血压） fluid infusion 糖盐水 Food （drug） Poison 药食同源，药毒难分

Thalidomide disaster（反应停事件） Example 2. 沙利度胺  20世纪十大科学错误之一 N-（2，6- 二氧代-3-哌啶基）-邻苯二甲酰亚胺 Developed by Germany in 1956 Calm and stop vomiting(镇静和止吐药) Ideal selection of pregnant women “孕妇的理想选择”

Thalidomide disaster Phocomelia（海豹肢畸形）

Toxicity of traditional Chinese medicine中药的毒性 砒霜 苦杏仁（生） 人参 甘草 中药安全无毒，有病治病，无病强身－不科学！ 中药走向世界的主要障碍之一 －毒性！

药 物 Drug & Poison 双刃剑 How to rationally use drugs ? How to R & D new drugs with higher therapeutic effect and lower toxic and side effects? 药 物 三分毒！ 治病或致病 双刃剑

学好药理 才是硬道理

药理学是研究药物和机体（或病原体、肿瘤细胞）相互作用及其规律的一门科学。 What is Pharmacology Pharmacology is the science of studying the interactions between drugs and the body（or pathogen, tumour cells）. 药理学是研究药物和机体（或病原体、肿瘤细胞）相互作用及其规律的一门科学。

Studying object of Pharmacology（研究对象） Drug Body

Pharmacodynamics Pharmacokinetics 研究药物对机体的作用及其作用机制 Contents of study（药理学的研究内容） Pharmacodynamics 药效学 Pharmacokinetics 药动学 Drug acts on body 研究药物对机体的作用及其作用机制 Body acts on drug 研究机体如何对药物进行处置, 即药物的吸收、分布、转化、排泄及药浓-时间的变化规律

效 应 --------- 药 理 学 --------- 转化 组织器官 细 胞 吸收 药物 分布 排泄 药效学过程 --------- 药 理 学 --------- 转化 组织器官 细 胞 吸收 药物 分布 效 应 排泄 ------- 药动学过程 -------- 药效学过程

Why to learn Pharmacology 性质与地位：桥梁学科，转化医学的经典 Basic medicine Clinical medicine Pharmacology Medicine Pharmacy R & D Pharmac- eutical enterprise

Major phases of new drug R & D New chemical entity 新化学实体 Lead compound 先导化合物 活性成分 发现与筛选 药理学 毒理学 药物化学 制剂学 药物分析 临床前研究 临床研究

Major phases of new drug R & D Ⅰ- Ⅲ期临床试验 售后临床监测 临床研究 Ⅱ期 Ⅲ期 Ⅰ期 Ⅳ期 健康志愿者 （20-50例） 安全性评价 药代学研究 患者 Small scale (200-300例) 有效性 安全性 患者 Large scale （>300例) 有效性 安全性 利益与风险评价 不良反应 (>2000例)

Phase III clinical trial Phase II Clinical trial The Long Road to a New Medicine Application Marketing Phase III clinical trial Phase I clinical trial Animal PK/PD/Tox Phase II Clinical trial 25) Idea-to-new medicine road - Full Development phase In this Full Development stage, known as Phase lll, several thousand patients with the particular disease receive the drug in carefully controlled studies to test its safety, tolerability, and efficacy. Finally, if the compound has proved its worth in all these tests, it enters the Registration phase in which the data of its entire history are compiled and analyzed in a regulatory submission. This New Drug Application, or NDA, is submitted to the FDA for review. In parallel, a Marketing Authorization Application (MAA) is filed in Europe, followed by a Japanese NDA. Only after a successful regulatory review does the candidate become a new medicine. Dosage form Candidate chemicals Design synthesis Screen

Steps in Drug Approval Process High Risk Process 11-15 Years, $800MM+ ~100 design proposals Steps in Drug Approval Process Isolation or development of new chemical Animal studies Human studies New Drug Application Screen MMs chemicals Pre-clinical Clinical 1 – 2 product 27) High attrition To turn out just one to two products requires about a hundred discovery projects or approaches, involving upwards of 7 million compound tests in early screening assays. This level of screening produces about a thousand compounds with some of the criteria we are looking for. Follow-up molecular design and sophisticated biological testing narrows the number of development candidates. Once safety is confirmed in animal studies, compounds are advanced into human clinical trials where efficacy, safety and toleration are confirmed. Pre-clinical Phase I Phase II Phase III Phase Ⅳ 5 10 15 Idea Drug 11 - 15 Years

How to learn pharmacology Particularity of Pharmacology 实践性、实用性很强的专业课 “六多” 课程：药名多、别名多、作用多、用途多、不良反应多、知识点多

Chemical name (化学名 ) Generic name (通用名) Brand name (商品名) N-(4-羟基苯基)乙酰胺，C8H9NO2 Generic name (通用名) 对乙酰氨基酚 Brand name (商品名) 泰诺林、百服宁、必理通 Another name (别名) 扑热息痛

How to learn Pharmacology Representative drugs: major pharmacological effects, clinical application, and adverse reactions. Be good at comparison, conclusion, and summary. Half-doctor, half-pharmacist.

Summary 药 品 Drug 药 物 Pharmacology 药效学 Pharmacodynamics 药动学 Pharmaceutical drug 药 品 Drug 药 物 Pharmacology 药效学 Pharmacodynamics 药动学 Pharmacokinetics

Preclinical Trials Clinical Trials Major phases of  new drug R & D Ⅰ-Ⅲ三期 临床研究 Preclinical Trials Clinical Trials Ⅳ期 售后临床监测 药物化学 药理学 制剂学毒理学 Ⅱ期 期

Chapter 1 Introduction www. What Why hoW

Thanks I am glad to share my knowledge with you, and I hope you become a master of pharmacology Thanks

Questions 1.Please distinguish drug from Pharmaceutical drug？ 2. What is Pharmacology？ 3.Please explain Pharmacokinetics and Pharmacodynamics. 4.试述新药研究的主要阶段及其内容(Major phases of new drug R & D, and their contents)。