Adverse effects of pharmacotherapeutics Flashcards
sulfonamides (kernicterus)
chloramphenicaol (Gray baby)
tetracyclines (retardation of bone growth)
direct fetal toxicity
- physical defects in developing fetus
- effect most from day 20 to end of first trimester
- thalidomide, antifolates, phenytoin, warfarin, lithium, valproic acid, fetal alcohol syndrome
fetal teratogens
abnormal response resulting from previous sensitizing exposure activating immunologic mechanism
drug hypersensitivity
- anaphylactic, IgE mediated, binds Fc receptors on basophils
- targets GI tract, skin, lung, vasculature
- GI allergy, urticaria, asthma, anaphylactic shock
type I reaction
- IgG/IgM, antibody dependent cytotoxicity
- targets circulating RBCs
- hemolytic anemia, thrombocytopenia, neutropenia
- activate complement
- ex: penicillin, methyldopa, quinidine, sulfonamides, cyclophosphamide
type 2 cytotoxic (autoimmune) reaction
- Antigen antibody complex deposition
- target blood vessels, joints, skin, kidney
- serum sickness, vasculitis, arthritis, nephritis
- ex: sulfonamides, penicillin, thiouracil, anticonvulsnats, iodides, vaccines
type 3 reaction : immune complex deposition
severe immune vasculitis induced by sulfonamides
Stevens Johnson syndrome
- T cell mediated, delayed reaction
- targets skin, lungs, CNS
- contact dermatitis, Stevens Johnson, interstitial nephritis, drug induced hepatitis
type IV T cell mediated, delayed reaction
abnormal response caused by genetic abnormalities instead of immune mediated, referred to as pharmacogenetic disorders
idiosyncracies
patients with abnormal ________ develop apnea when given normal doses of succinylcholine
serum cholinesterase
slow acetylators of _______ have low NAT activity, more prone to vitamin B6 deficiency, anemia and neuropathy
isoniazid
hemolytic anemia elicited by _______ in patients whose red cells are deficient in G6PDH, 10% of black males in US
primaquine, sulfonamides, nitrofurantoin
_______ induced porphyria in individuals with abnormal heme biosynthesis, mimics heme structure –> ALA synthase –> porphyrin production
barbiturate
reduction in _____ of drug absorption may result in subtherapeutic serum levels
extent
resin binds with drugs and prevents absorption
cholestyramine
metals chelate tetracyclines and fluoroquinolones, preventing absorption
antacids
decrease GI motility, slow absorption of drugs
anticholinergics (atropine)
oral hypoglycemics, oral anticoags (warfarin), antimetabolites (methotrexate) displace drugs from _______
plasma protein binding sites
alkalinization of urine with sodium bicarb enhances excretion of?
weak organic acids
acidification with ammonium chloride of urine enhances excretion of?
weak organic bases
_______ blocks tubular secretion of penicillin
probenicid
single dose of the agent up to a lethal dose in 2 species
acute toxicity
phase 1 human testing:
-goal is to find _______ dose, characterize adverse effects and define ________
max tolerated dose
pharmacokinetics
phase 2 human testing: determine ______, use large subject pool
clinical effectiveness
phase 3 testing: determine _____ and _____
efficacy and toxicity
phase 4: post marketing surveillance to determine ______
adverse side effects
