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Definition: it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function. pharmacodynamics pharmacokinetics unwanted effects caused by normal therapeutic doses. any noxious or unintended reaction to a drug that is administered in standard doses by the proper route for the purpose of prophylaxis, diagnosis, or treatment. Standard dose Proper route Circumstances such as misuse, noncompliance, abuse and drug quality are excluded Type A Type B Large proportion dose-related and mild consequence of the drug’s pharmacological effect predictable Words for video clip CDC : Center for Disease Control emergency department: 急诊 adverse events clinical placebo respiratory Ingredient Questions: 1. What is the CDC warning about? 2. What is the basis for the warning from CDC? 3. What are the suggestion from CDC ? not predictable not dose-related and severe, a genetic or immunological basis Low frequency Allergic reactions: An immunologically mediated reaction, characterised by specificity, transferability by antibodies or lymphocytes, and recurrence on re-exposure type C --continuous reactions due to long-term drug use analgesic nephropathy: injury to the kidney caused by analgesic medications such as aspirin and paracetamol kidney function—adequate blood flow--prostaglandins Type D: delayed reaction these reactions refer to carcinogenic and teratogenic effects. These reactions are delayed and are very rare since extensive mutagenicity and carcinogenicity studies have been conducted before drug is licensed. Type E: end-of-use reactions (withdrawal reactions) Abnormal physical or psychological features that follow the abrupt discontinuation of a drug. Eg. Sudden cessation of the use of an antidepressant can deepen the feel of depression significantly Large population being exposed to drugs 3% of acute hospital admissions are resulted from type A reaction ADRs complicate 10-20% of all admissions patient factors Prescriber factors Drug factors Gene polymorphism and ADR CYP2D6 (common enzyme in drug metabolism) 弱代谢型 (poor metabolizer, PM) 中间代谢型(intermediate Metabolizer,IM) 强代谢型(extensive metabolizer, EM) 超快代谢型(Ultra rapid metabolizer) ADR monitoring/ PVG Clinical trials in new drug R&D Pharmacovigilance (PV) is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem (overdose, abuse, misuse, unqualified products, acute and chronic intoxication report, interactions between drug and food) 1. 2. 3. Questions for reviewing Try to summarize the characteristics of type A and type B reactions. Please paraphrase other types adverse reactions. Please discuss briefly about the significance of ADR monitoring.