Toxicokinetics Flashcards
Most common route of exposure in toxicology
oral
____ route important in toxic gases and insecticides
inhalation
____ route important in insecticides
dermal
____ is where a metabolite is more toxic/important than the parent compound
Lethal synthesis
The transfer of the toxin from site of administration to systemic circulation is the
absorption
T/F: the smaller the molecular size, the faster the penetration through cell membrane pores
true
T/F: increased lipid solubility decreases absorption
false, it increases it
T/F: the more non-ionized, the greater the absorption
true
T/f: the lower the concentration of the drug at absorptive site, the faster the absorption
False
What is first pass effect?
drugs absorbed from GIT –> liver for metabolism
some drugs metabolized before distribution to other tissues
drugs with high first-pass metabolism have less distribution
The transport of drugs from plasma to tissues is
distribution
Factors that affect distribution
physicochemical properties (lipid solubility, degree of ionization) concentration gradient plasma protein binding blood flow tissue barriers affinity to certain tissues
what protein do acidic compounds bind to?
albumin
what proteins do basic compounds bind to?
a1-glycoproteins and lipoproteins
T/F: plasma protein binding shortens a compounds half life
false, it prolongs it
T/F: a plasma protein bound compound is inactive
true
highly perfused tissues
brain, liver, kidney, endocrine glands
poorly perfused tissues
bone, adipose
moderately perfused tissues
muscle, skin
tissue barriers
BBB, eye, testicles, placenta, mammary gland
the chemical alteration of the drug molecule by the cells of the animal
biotransformation
main site of biotransformation
liver
phase 1 biotransformation reactions
oxidation, reduction, hydrolysis
phase II biotransformation reactions
conjugation (synthetic)
most common form of biotransformation reaction
oxidation
most common conjugation reaction
to glucuronic acid
T/F: neonates have a lot of conjugation activity
false it is deficient
what species is deficient in glucuronyl transferases?
cats
what species is deficient in hydroxylation and dealkylation?
cats
what species lack acetylating enzymes?
dogs
_____ have high levels of oxidative enzymes
ruminants and horses
which species is deficient in methylates?
horses
___ lack oxidative enzymes
birdss
___ have low levels of drug metabolizing enzymes
fish
List some enzyme inducers
phenobarbital, phenylbutazone, griseofulvin, rifampin, chlorinated hydrocarbon insecticides
T/F: all enzymes are inducible by drugs
False - only microsomal enzymes are
List some enzyme inhibitors
chloramphenicol, cimetidine, ketoconazole
T/F: biotransformation continues to increase with age
False, both newborns and geriatrics may have less biotransformation than adults
T/F: grapefruit juice is an enzyme inhibitor
True
Plasma protein binding ______ biotransformation
decreases
Effect of hypothermia on biotransformation
decreases it
removal of drug from the body
excretion
3 aspects of renal excretion
glomerular filtration
active tubular secretion
tubular reabsorption
4 factors that affect glomerular filtration
GFR, molecular size, molecular charge, protein binding
T/F: negative charged particles pass through the glomerulus easier than positive
false - they’re inhibited by negatively charged proteins in capillary wall
T/F only unbound drugs can be filtered by the glomerulus
true
OCTs transport bases and OATs transport acids in active tubular secretion
true
4 factors affecting tubular reabsorption
physicochemical properties of the drugs
degree of ionization
GFR
active tubular reabsorption
The second most important organ for drug excretion (kidney is first) is: A) sweat glands B) spleen C) liver D) tears
liver
T/F: enterohepatic circulation shortens the half life of a drug
false, it prolongs it
