【正文】 . Requires changing the drug therapy 3. Requires modifying the dose 4. Necessitates admission to a hospital 5. Prolongs stay in a health care facility 6. Necessitates supportive treatment 7. Significant plicates diagnosis 8. Negatively affects prognosis, or 9. Results in temporary or permanent harm, disability, or death Type A reactions ? Extensions of the drug’s known pharmacology 。 responsible for the majority of ADRs ? usually dosedependent and predictable, but can be due to conitant disease states, drugdrug interactions , or fooddrug interactions ? ways to minimize such reactions: monitoring drugs with a narrow therapeutic window。 avoiding polypharmacy when possible Type B reactions ? Idiosyncratic reactions, immunologic or allergic reactions。 carcinogenic/teratogenic reactions ? seem to be a function of patient susceptibility ? Rarely predictable ? usually not dosedependent ? seem to concentrate in certain body systems such as liver, blood, skin, kidney, nervous system, and others ? unmon, generally very serious, can be lifethreatening Type B reactions ? except for immediate hypersensitivity reactions, they usually take 5 days before the patient demonstrates hypersensitivity to a drug ? there is no maximum time for the occurrence of a reaction, but most occur within 12 weeks of therapy Allergic vs idiosyncratic reaction ? Allergic reaction: an immunologic hypersensitivity, occurring as the results of unusual sensitivity to a drug ? idiosyncratic reaction: abnormal susceptibility to a drug that is peculiar to the individual Type of reaction mnemonic examples A： doserelated augmented digoxin toxicity、 serotonin syndrome with SSRI B： nondoserelated bizarre penicillin hypersensitivity、 acute porphyria、 malignant hyperthermia C： doserelated ＆ timerelated chronic HPAaxis suppression by steroid、benzodiazepine dependence、analgesic nephropathy D： timerelated delayed teratogenesis、 carcinogenesis E： withdrawal end of use opiate withdrawal syndrome F： unexpected failure of therapy failure inadequate dosage of oral contraceptives used with specific enzyme inducers Case 1: Imipramine ? 15 monthold boy, suffered from cons disturbance ＆frequent seizurelike movement ? Brain CT was performed, mannitol IV was used under the impression of brain edema ? Cons disturbance was not improved ? Transferred to our ER, admitted to NCU ? Fell down from 3040cm height chair 4 days ago ( no seizure, no cons disturbance, no vomiting or irritable crying ) ? EKG: QRS prolongation, QTc widening ? Imipramine level: 1389μg/l （ therapeutic range: 150250, toxic level:＞ 500） Case 2: acetaminophen ? 22 y/o lady, suffered from migraine since her childhood, it became worse 56 years ago, acetaminophen was given since then at LMD ? She stated that she took more than 10 tablets per day ? About one week ago, nausea, vomiting and diarrhea attacked her for 1 day , then subsided ? But the condition became serious, she was send to ER ? GOT/GPT： 6058/ 8732 ? HBS Ag, anti HBCIgM, anti HCV, anti HAVIgM：（ ） ? Abdominal echo： fatty liver, hepatomegaly ? Concurrent medication： unknown Case