Pathophysiology
Clinical meaning
Red flag ADRs are severe, potentially fatal medication reactions requiring immediate recognition. SJS/TEN: immune-mediated keratinocyte apoptosis triggered by medications (sulfonamides, allopurinol, carbamazepine, phenytoin, lamotrigine), progressing from prodromal flu symptoms to epidermal detachment — SJS (< 10% BSA), TEN (> 30%). Mortality: SJS 5-10%, TEN 25-35%. Serotonin syndrome: excessive 5-HT stimulation from combined serotonergic drugs (SSRIs + tramadol, SSRIs + MAOIs), with mental status changes, autonomic instability, neuromuscular excitability (clonus, hyperreflexia). NMS: idiosyncratic D2 blockade reaction (antipsychotics) with hyperthermia, lead-pipe rigidity, AMS, elevated CK. DRESS: onset 2-8 weeks post-drug with fever, facial edema, rash, eosinophilia, organ involvement. Agranulocytosis: ANC < 500 from clozapine, methimazole, carbamazepine.