Adverse effects of pharmacotherapeutics

Question 1

sulfonamides (kernicterus)
chloramphenicaol (Gray baby)
tetracyclines (retardation of bone growth)

Answer 1

direct fetal toxicity

Question 2

• 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

Answer 2

fetal teratogens

Question 3

abnormal response resulting from previous sensitizing exposure activating immunologic mechanism

Answer 3

drug hypersensitivity

Question 4

• anaphylactic, IgE mediated, binds Fc receptors on basophils
• targets GI tract, skin, lung, vasculature
• GI allergy, urticaria, asthma, anaphylactic shock

Answer 4

type I reaction

Question 5

• IgG/IgM, antibody dependent cytotoxicity
• targets circulating RBCs
• hemolytic anemia, thrombocytopenia, neutropenia
• activate complement
• ex: penicillin, methyldopa, quinidine, sulfonamides, cyclophosphamide

Answer 5

type 2 cytotoxic (autoimmune) reaction

Question 6

• Antigen antibody complex deposition
• target blood vessels, joints, skin, kidney
• serum sickness, vasculitis, arthritis, nephritis
• ex: sulfonamides, penicillin, thiouracil, anticonvulsnats, iodides, vaccines

Answer 6

type 3 reaction : immune complex deposition

Question 7

severe immune vasculitis induced by sulfonamides

Answer 7

Stevens Johnson syndrome

Question 8

• T cell mediated, delayed reaction
• targets skin, lungs, CNS
• contact dermatitis, Stevens Johnson, interstitial nephritis, drug induced hepatitis

Answer 8

type IV T cell mediated, delayed reaction

Question 9

abnormal response caused by genetic abnormalities instead of immune mediated, referred to as pharmacogenetic disorders

Answer 9

idiosyncracies

Question 10

patients with abnormal ________ develop apnea when given normal doses of succinylcholine

Answer 10

serum cholinesterase

Question 11

slow acetylators of _______ have low NAT activity, more prone to vitamin B6 deficiency, anemia and neuropathy

Answer 11

isoniazid

Question 12

hemolytic anemia elicited by _______ in patients whose red cells are deficient in G6PDH, 10% of black males in US

Answer 12

primaquine, sulfonamides, nitrofurantoin

Question 13

_______ induced porphyria in individuals with abnormal heme biosynthesis, mimics heme structure –> ALA synthase –> porphyrin production

Answer 13

barbiturate

Question 14

reduction in _____ of drug absorption may result in subtherapeutic serum levels

Answer 14

extent

Question 15

resin binds with drugs and prevents absorption

Answer 15

cholestyramine

Question 16

metals chelate tetracyclines and fluoroquinolones, preventing absorption

Answer 16

antacids

Question 17

decrease GI motility, slow absorption of drugs

Answer 17

anticholinergics (atropine)

Question 18

oral hypoglycemics, oral anticoags (warfarin), antimetabolites (methotrexate) displace drugs from _______

Answer 18

plasma protein binding sites

Question 19

alkalinization of urine with sodium bicarb enhances excretion of?

Answer 19

weak organic acids

Question 20

acidification with ammonium chloride of urine enhances excretion of?

Answer 20

weak organic bases

Question 21

_______ blocks tubular secretion of penicillin

Answer 21

probenicid

Question 22

single dose of the agent up to a lethal dose in 2 species

Answer 22

acute toxicity

Question 23

phase 1 human testing:

-goal is to find _______ dose, characterize adverse effects and define ________

Answer 23

max tolerated dose

pharmacokinetics

Question 24

phase 2 human testing: determine ______, use large subject pool

Answer 24

clinical effectiveness

Question 25

phase 3 testing: determine _____ and _____

Answer 25

efficacy and toxicity

Question 26

phase 4: post marketing surveillance to determine ______

Answer 26

adverse side effects