Metabolism of Drugs - Exam 3 Flashcards
definition of metabolism of drugs
chemical alteration of the drug molecule by the cells of the animal
bioinactivation
detoxification, most common, parent drug -> inactivate
bioactivation
lethal synthesis, “prodrug” -> active drug
liver as a site of biotransformation
most common site, sER, hepatocyte cytoplasm, mitochondria, lysosomes, nuclear envelope, plasma membrane
other tissue sites of biotransformation
nervous tissue, kidney, GI epithelium, lungs, skin, plasma
example of active drug -> active metabolite
aspirin converted to salicylic acid
example of inactive drug -> active metabolite
cortisone -> cortisol
prenisone -> prednisolone
example of nontoxic drug -> toxic metabolite
parathion -> paroxon
ethylene glycol -> glyoxylic acid “lethal transformation”
antifreeze toxicity is an example of ________ ; includes what 2 toxic metabolites
biotransformation; glycoaldehyde & glycoxylate
microsomal enzymes
non-specific, large groupings of enzymes, cause oxidation, reduction, hydrolysis, & conjugation to glucuronic acid
T/F: enzymatic reactions are saturable
true
T/F: enzymes can inhibited or induced by drugs
true
Phase I reactions include
oxidation, reduction, hydrolysis; non-synthetic
Phase II reactions include
conjugation; synthetic
definition of oxidation
loss of one or more electrons by a substance, gain O2, remove H+; most common biotransformation reaction
definition of reduction
gain of one or more electrons by a substance, gain H+, remove O2
definition of hydrolysis
splitting of a molecule into fragments by the addition of H2O
microsomal oxidation phase I
sER
nonmicrosomal oxidation phase I
cytoplasm, mitochondria
microsomal reduction phase I
reduction of chloramphenicol
nonmicrosomal reduction phase I
aldehyde reduction of chloral hydrate
lipid soluble drugs must go to phase ____ prior to excretion
II
conjugation reactions phase II
combination of a drug or its metabolite with an endogenous substance
conjugation is deficient in
neonates & cats
metabolite conjugates are usually
inactive, water soluble, and non toxic
most common & microsomal conjugation reaction
glucuronic acid (glucurodination)
cats are deficient in
glucuronyl transferases
dogs are deficient in
acetylating enzymes
ruminants have less
plasma pseudocholerestinase
ruminants and horses have high levels of
oxidative enzymes
pigs are deficient in
sulfate conjugating enzymes
birds lack
oxidative enzymes
first pass effect occurs with which type of drug administration
oral
hepatic first pass metabolism criteria
liver before systemic circulation
metabolized by liver
high hepatic extraction ratio
results of hepatic first pass metabolism
drug metabolized before distribution
decrease oral bioavailability
enzyme inducers
drugs that stimulate the liver to produce more metabolic enzymes
only what enzymes are inducible by drugs
microsomal
T/F enzyme induction is irreversible
false
examples of drug enzyme inducers
phenobarbital, phenylbutazone, griseofulvin, rifampin
enzyme inhibitors
drugs that inhibit liver production of metabolic enzymes
examples of drug enzyme inhibitors
chloramphenicol, cimetidine, ketoconazole
decreased distribution = decreased
metabolism because less drug can get to the liver
what tissue is common site for drug storage
adipose
drug storage in other tissues can lead to
re-distribution & delayed clinical effects
food enzyme inducer
charbroiled
food enzyme inhibitor
grapefruit juice
animals in the tropics may have less
biotransformation
