Toxic Principles

Question 1

1 to 2 days, single or multiple exposures

Answer 1

acute toxicity

Question 2

repeated exposure, less than 3 months

Answer 2

subacute toxicity

Question 3

repeated exposure, greater than 3 months

Answer 3

chronic toxicity

Question 4

-measures toxic response on an individual to various doses, response for each toxxic effect or molecular interaction will be different

Answer 4

individual/graded dose response

Question 5

-measures responses in a population of individuals as dose increases

Answer 5

quantal response

Question 6

LD50/ED50 (animals) or toxic dose over therapeutic dose in humans

Answer 6

therapeutic index

Question 7

LD1/ED99 or TD/ED99 for humans

Answer 7

margin of safety

Question 8

the probability that injury will result from exposure to a substance under specified conditions of dose and route of administration

Answer 8

risk

Question 9

expression of adverse effects, more clinically useful than therapeutic index

Answer 9

benefit to risk ratio

Question 10

• lower doses have protective effects, higher doses have adverse effects
• alochol: lower dose good, chronic high dose leads to alcoholic liver disease
• U shaped curve for non nutritional toxicants

Answer 10

hormesis

Question 11

• dose related adverse effects of drugs
• overextension of pharmacological response (atropine induced dry mouth, propanolol heart block, diazepam drowsiness)
• organ directed toxicities (aspirin GI, aminoglycoside renal, acetaminophen hepatotoxicity, doxorubicin)

Answer 11

toxicity

Question 12

• directly toxic or teratogenic
• direct toxic: sulfonamide kernicterus, chloramphenicol gray baby, tetracycline teeth discoloration and retarded bone growth
• teratogenic: physical defects in developing fetus: effects most pronounced during day 20 to end of first trimester during organogenesis, thalidomide, fetal alchol syndrome, phenytion, warfarin, lithium, valproic acid

Answer 12

fetal toxicity

Question 13

-abnormal response resulting from previous sensitizing exposure activating immunologic mechanism

Answer 13

drug allergy (hypersensitivity)

Question 14

• altered reaction occurs only in fraction of population
• dose response is unusual
• manifestations different from usual pharmacological and tox effects of drug
• requires primary sensitization
• most drugs themselves are not immunogenic, must become hapten

Answer 14

drug allergies (hypersensitivity)

Question 15

• anaphylactic
• GI, skin, lung, vasculature
• urticaria, asthma, anaphylactic shock
• IgE mediated

Answer 15

type 1 anaphylactic rxn

Question 16

• circulating blood cells
• leukopenia, thrombocytopenia, hemolytic anemia, granulocytopenia
• IgM, IgG

Answer 16

type 2 cytotoxic (autoimmune) hypersensitivity

Question 17

• affects blood vessels, skin, joints, kidney
• serum sickness, vasculitis, arthritis, glomerular nephritis
• antigen antibody complexes

Answer 17

type 3 immune complex rxn

Question 18

• abnormal response not immunologically mediated

- often caused by genetic abnormalities in enzymes or receptors (pharmacogenomics)

Answer 18

drug idiosyncracies

Question 19

idiosyncracies: patents with abnormal ________ develop apnea when given normal doses of succinylcholine

Answer 19

serum cholinesterase

Question 20

slow acetylators of isoniazid have low hepatic ______ activity, more prone to B6 deficiency

Answer 20

N-acetyltransferase

Question 21

hemolytic anemia elicited by _______ in patients whose red cells are deficient in G6PDH, affects about 10% of black men

Answer 21

primaquine

Question 22

barbiturate induce __________ occurs in individuals with abnormal heme biosynthesis, mimics part of heme structure occupying portion of protein that regulates ALA synthetase, inhibits production

Answer 22

barbiturate

Question 23

• undergoes redox cycling, causes free radical mediated injury to lungs
• oral or inhalation, fatal

Answer 23

paraquat

Question 24

-binds heme iron in cytochrome A3 of complex 4, blocks ATP formation

Answer 24

cyanide poisoning

Question 25

analgesics, household cleaning, cosmetics, sedatives/hypnotics/antipsychotics, antidepressants

Answer 25

top 5 substances involved in posioning

Question 26

- anthrax - smallpox - plague - botulism - tularemia - VHF

Answer 26

category A bioterrorism agents