Toxicology Principles Flashcards
graded dose response
toxic response on an individual to various doses
quantal dose response
responsiveness in a population of individuals as dose increases
Therapeutic index
TI=TD50/ED50
Toxic dose/effective dose in half population
Margin of safety
MS=TD1/ED99
toxic dose in 1% population/ effective dose in 99%
higher MS, easier to use because larger window of usability for doses
Risk
probability that injury will result from exposure to a substance under specified conditions of dose and route of administration
Benefit-to-risk ratio
expression of adverse effects is more useful clinically than therapeutic index
Hormesis
U shaped dose response from non-nutritional toxicants
lower doses- protective effects, higher doses-adverse effects
Toxicity
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.
Fetal toxicity
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)
Drug allergies (hypersensitivity)
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
Immediate hsn
anaphylactic
via IgE
Autoimmune hsn
cytotoxic
IgM, IgG
circulating blood cells
cause leukopenia, thrombocytopenia, hemolytic anemia, etc.
Immune complex hsn
arthus
Ag-Ab complexes
serum sickness, vasculitis, arthritis
Delayed hsn
Cell-mediated
allergic encephalitis, tb, contact nephritis
Sensitized T cells
Idiosyncrasies
caused by genetic abnormalities in enzymes of receptors
ex. abnormal serum cholinesterase develop apnea when given normal doses of succinylcholine
Isoniazid idiosyncrasy
fast and slow acetylators
-slow acetylators have low hepatic N-acetyltransferase activity- more prone to isoniazide induced vitamin B6 deficiency
G6PD deficiency can lead to
hemolytic anemia elicited by primaquine in pts whose red cells are deficient in g6pd
Abnormal heme biosynthesis
Barbiturate induced porphyria in those individuals
Acetaminophen
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
Organophosphates, carbamates
cholinesterase inhibiting insecticides
treat with atropine
carbamates
cholinesterase inhibiting insecticides
carbamates- reversible: carbaryl, aldicarb, carbofuran, aminocarb
-2PAM contraindicated for carbamates
organophosphates
cholinesterase inhibitors insectiside
Organophosphates- irreversible: parathion, malathion, sarin, soman
Paraquat
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
cyanide poisoning
blocks oxidative phosphorylation
CN binds heme iron in cyt A3 of complex IV- electrons not transported, blocks ATP formation
bioterrorism
category A agents- anthrax, small pox, plague, botulism, tularemia, VHF
ricin, chemical terrorism (cyanide, nerve agents, pulmonary agents, blister agents), radiological terrorism, nuclear terrorism
top 5 substance classes most frequently involved in all human exposures
analgesics househood cleaning substances cosmetics/personal care sedatives/hypnotics/antipsychotics antidepressants
