Toxicology Principles

Question 1

graded dose response

Answer 1

toxic response on an individual to various doses

Question 2

quantal dose response

Answer 2

responsiveness in a population of individuals as dose increases

Question 3

Therapeutic index

Answer 3

TI=TD50/ED50

Toxic dose/effective dose in half population

Question 4

Margin of safety

Answer 4

MS=TD1/ED99

toxic dose in 1% population/ effective dose in 99%

higher MS, easier to use because larger window of usability for doses

Question 5

Risk

Answer 5

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

Question 6

Benefit-to-risk ratio

Answer 6

expression of adverse effects is more useful clinically than therapeutic index

Question 7

Hormesis

Answer 7

U shaped dose response from non-nutritional toxicants

lower doses- protective effects, higher doses-adverse effects

Question 8

Toxicity

Answer 8

dose related adverse effect of drugs
-overextension of pharmacological response- atropine induced dry mouth, propranolol induced heart block, etc.

-organ directed toxicity- aspirin induced GI toxicity, aminoglycoside induced renal toxicity, etc.

Question 9

Fetal toxicity

Answer 9

directly toxic (sulfonamide induced kernicterus, tetracycline induced teeth discoloration) or being teratogenic (effects pronounced during organogenesis in 1st trimester- thalidomide for antiemesis leading to significant malformations, fetal alcohol syndrome)

Question 10

Drug allergies (hypersensitivity)

Answer 10

abnormal response from previous sensitizing exposure activating immunologic mechanism

minute amt of otherwise safe drug elicits severe reaction

most drugs must bind to self-macromolecule to become immunogenic

Question 11

Immediate hsn

Answer 11

anaphylactic

via IgE

Question 12

Autoimmune hsn

Answer 12

cytotoxic
IgM, IgG
circulating blood cells
cause leukopenia, thrombocytopenia, hemolytic anemia, etc.

Question 13

Immune complex hsn

Answer 13

arthus
Ag-Ab complexes
serum sickness, vasculitis, arthritis

Question 14

Delayed hsn

Answer 14

Cell-mediated
allergic encephalitis, tb, contact nephritis
Sensitized T cells

Question 15

Idiosyncrasies

Answer 15

caused by genetic abnormalities in enzymes of receptors

ex. abnormal serum cholinesterase develop apnea when given normal doses of succinylcholine

Question 16

Isoniazid idiosyncrasy

Answer 16

fast and slow acetylators

-slow acetylators have low hepatic N-acetyltransferase activity- more prone to isoniazide induced vitamin B6 deficiency

Question 17

G6PD deficiency can lead to

Answer 17

hemolytic anemia elicited by primaquine in pts whose red cells are deficient in g6pd

Question 18

Abnormal heme biosynthesis

Answer 18

Barbiturate induced porphyria in those individuals

Question 19

Acetaminophen

Answer 19

Can cause GSH depletion and ROS
-Some acetaminophen is metabolized into NAPQI which is a toxic intermediate, which is gotten rid of via glutathione
if there is excess acetaminophen and depletion of glutathione, there is excess of NAPQI which will cause damage to mitochondria and stuff

-treatment with N-acetyl cysteine which will make more glutathione

Question 20

Organophosphates, carbamates

Answer 20

cholinesterase inhibiting insecticides

treat with atropine

Question 21

carbamates

Answer 21

cholinesterase inhibiting insecticides

carbamates- reversible: carbaryl, aldicarb, carbofuran, aminocarb
-2PAM contraindicated for carbamates

Question 22

organophosphates

Answer 22

cholinesterase inhibitors insectiside

Organophosphates- irreversible: parathion, malathion, sarin, soman

Question 23

Paraquat

Answer 23

undergoes redox cycling and causes free radical mediated injury to lungs, liver, kidney

the end point is pulmonary toxicity via lipid free radicals whether inhaled or oral, and this is fatal

Question 24

cyanide poisoning

Answer 24

blocks oxidative phosphorylation

CN binds heme iron in cyt A3 of complex IV- electrons not transported, blocks ATP formation

Question 25

bioterrorism

Answer 25

category A agents- anthrax, small pox, plague, botulism, tularemia, VHF

ricin, chemical terrorism (cyanide, nerve agents, pulmonary agents, blister agents), radiological terrorism, nuclear terrorism

Question 26

top 5 substance classes most frequently involved in all human exposures

Answer 26

analgesics
househood cleaning substances
cosmetics/personal care
sedatives/hypnotics/antipsychotics
antidepressants