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Pharmacology 2060A/B
Angela Nissen

Module 10 Adverse Drug Reactions (ADRs) - unintended/undesired response from drugs - enormous societal health problem (8% hospital admissions185,000) o side effects  somewhat expected  occur at therapeutic doses, secondary  unavoidable  due to poor specificity or selectivity of drug  ex. Antihistamine (block Hi histamine receptors to prevent symptoms of allergy)  side effects antihistamine works other parts of body, BRAIN...dry mouth, drowsiness o drug toxicity  severe ADR  too much of drug, drug overdose  extensions of therapeutic effect  too much insulin, glucose levels too low, patient could go ocma o allergic reaction  mediated by immune system  requires prior sensitization, no allergic reaction first exposure  second exposure to drug = allergic reaction  ex. Mast cell sensitization causes antibodies , second time exposed to drug, histamine released from mast cells = symptoms of allergy (itching, rash, anaphylaxis, bronchospasm, edema, hypotension)  intensity does NOT = dose, even small doses = allergy  10% ADRs are drug allergy  very few drugs, PENICILLINS, sulfonamides and nonsteroidal anti-inflammatory drugs  MOST COMMON = TRUNK AREA (chest, stomach, thighs  common = legs, arms, spine  uncommon = feet, hands, neck  rare = head o idiosyncratic reactions  rarely and unpredictably  genetic polymorphisms in drug metabolism enzymes and drug transport proteins  warfarin (cyp2c9) and 6-mercaptopurine (TPMT)  cyp2c9 15%, decrease metabolism  cyp2d6 10% no pain relief from codeine (metab to morphine)  thiopurine methyltranferase (TPMT) 10% decrease activity , 0.3% no activity, if low/absent – bone marrow supression  oat1b1 15% uptake drug transporter, increase plasma conc, decrease function, myopathy (muscle toxicity)  glucose 6-phosphate dehydrogenase (G6PDH) o carcinogenic effects  cause cancer, relatively few drugs, takes years after initial dose  diethylstilbestrol (DES) used to prevent spontaneous abortion  female offspring develop vaginal or uterine cancer o mutagenic effect  alter DNA , also carginogenic/teratogenic  Ames test = ability of drug to cause mutation in bacteria o Teratogenic effects  Birth d
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