药理学总论-绪言 Pharmacology A Very Basic Intro

1. 药理学总论-绪言 Pharmacology A Very Basic Intro

2. What is a drug? • any chemical agent which • affects any biological process

3. Sources of Drugs Animals Plants Minerals Synthetic Microbes Genetic engineering drugs

4. ③ ②限制酶截取DNA片断 ① ④ ③分离大肠杆菌中的质粒 ② ④ DNA重组 ⑤ ⑤用重组质粒转化大肠杆菌 ⑥ ⑥培养大肠杆菌克隆大量基因 基因工程药物过程示意图 ①从细胞中分离出DNA

6. A goal of Genomics is to find and express genes that code for unknown peptides with significant biological properties, like receptors or enzymes. In a reverse Pharmacology approach this peptide, e.g. a receptor, is then used to "fish" for a natural ligand . With receptor and ligand in hand the biological role of the receptor needs to be determined. Finally, screening for synthetic ligands as well as lead optimization can lead to new drug candidates. In contrast, the classical approach to drug discovery starts with the identification of a ligand that has biological activity that in turn is used to "fish" for the corresponding receptor.

7. One example for a Genomics strategy aims at identifying drug targets based on molecular homology within Gene-families. One of the most important families of drug-targets for the pharmaceutical industry is the family of G-protein coupled receptors (GPCRs). Of the top 200 best selling prescription drugs, more than 20% interact with GPCRs, providing worldwide sales of over $20 billion. The characteristic motif of the GPCR family is the seven distinct hydrophobic regions, each of 20 to 30 amino acids that form the transmembrane domain of these integral membrane proteins. This key amino-acid sequence motif can be found within all types of GPCRs and can be used to identify DNA-sequences that code for GPCRs.

8. What is pharmacology ? • the study of how drugs • effect biological systems

9. What is Pharmacology ? Pharmacokinetics Pharmacodynamics What the body does to drug What the drug does to body Pharmacology Pharmacotherapeutics Pharmacocognosy The study of the use of drugs Identifying crude materials as drugs Toxicology

10. Pharmacokinetics What the body does to the drug - Absorption - Distribution - Metabolism (Biotransformation) - Excretion Half-life (t1/2) - the time required for the plasma concentration of a drug to be reduced by 50 %

11. DRUG CLASSIFICATION • Based on the chemical structure • - Based on the main effect (e.g. analgesics). • - Based on the therapeutic use (e.g. antipsychotic 安定药). • Based on mechanism of action (e.g. serotonin agonist).

12. From Chemist to First In Man …approximately 7 – 10 years How a Drug becomes a drug…

13. Basic & Clinical Evaluation of New Drugs • Drug discovery & Drug screening • Chemistry • In Vitro Studies • Function in cells, tissues, and at receptors • 2. Preclinical safety & toxicity testing • In Vivo - Animal studies • Pharmacology and Behavioral Pharmacology • Potency and Efficacy – ED50 • Tolerance and Tachyphylaxis(快速耐受) • Toxicity – Acute and Chronic • LD50 • Teratogenicity = birth defects • Carcinogenicity = cancerous • 3. Evaluation of drug in humans H. Haarmann University of Maryland, 2002

14. Evaluating Drugs in Humans The Food and Drug Administration (FDA) Phases of a Clinical Trials Phase I Phase II Phase III Phase IV

15. Evaluating Drugs in Humans • Phase I – Healthy adult volunteers • Evaluation of safety, Pharmacokinetics (PK), side effects??? • Phase II - Patients • Evaluation of efficacy, safety, PK, and side effects • Double-blind placebo controlled • Phase III – Specific patient subpopulations • Determine efficacy for specific indications • Large sample of specific patients (1,000) • Randomized double-blind placebo controlled • Phase IV – Post FDA Approval • Determine efficacy for specific indication • Determine drug utilization patterns and additional efficacy • Monitor rare, severe side effects/toxicity

16. Drug Nomenclature • Chemical name（化学名）- *Generic name （非专利名） • Trade name （商品名） Chemical Name: 2-(4-isobutylphenyl)-propionic acid Generic Name: ibuprofen（布洛芬） Trade Names: Advil, Aches-N-Pain, Brufen, Emodin, Haltran, Medipren, Midol 200, Motrin, Nuprin, Rufen, Trendar, Wal-Profen *preclinical nomenclature = company abbrev-123456 (e.g. WAY-100635, MK-869)