Exam II: Drug Metabolism Flashcards
Who performed the first biochemical study showing the passage of waste into urine (himself and his dog) in early 1880s?
Friedrich Wohler
What are the possible outcomes of biotransformation
decrease in activity (detoxication)
increase in polarity
increase in activity/bioactivation (prodrug)
increase in toxicity (toxication)
T/F a prodrug can be either lipid or water soluble
true
do prodrugs increase or decrease bioavailability?
increase
define xenobiotic
something not naturally produced by body (aka a drug)
Who discovered the first class of antibiotics and which antibiotic was it?
Gerhard Domagk
sulfa drugs
which organ is the main site of biotransformation?
where else does biotransformation occur?
liver
intestinal mucosa cells
renal tubular cells
other organs
colon (microbiota)
Name the different metabolic pathways of phase I
oxidation
hydrolysis
reduction
add/expose functional group for phase II conjugation
Name the different metabolic pathways of phase II
conjugative (inc mass and hydrophilicity)
What makes newborns/infants metabolize drugs differently?
which phase II enzyme in particular?
why does chloramphenicol toxicity occur more in newborns?
why does bilirubin toxicity occur more in newborns?
- may not have developed all necessary enzymes for metabolism or not have enough enzymes to properly metabolize
- glucuronosyltransferases
- lack of glucuronidation
- lack of glucuronidation
Which diseases primarily affect drug metabolism (organs/drugs)
liver disease
kidney disease
drug-drug interactions
Which phase I enzyme do rats lack that is found in humans?
CYP3A4
how can certain drugs affect other drug metabolism?
some drugs can induce/inhibit enzymes and thus reduce efficacy of another drug
how can certain foods affect drug metabolism?
example with grapefruit:
some foods can inhibit drug enzymes
grapefruit juice can inhibit CYP enzymes
Name the phase I hydrolysis enzymes
Carboxylesterase
Peptidase
Name the phase I reduction enzymes
Azo-reductase carbonyl reductase disulfide reductase sulfoxide reductase quinine reductase
Name the phase I oxidation enzymes
Alcohol dehydrogenase aldehyde oxidase Xanthine oxidase monoamine oxidase Diamine oxidase Cytochromes P450 Flavin monooxygenase
What does hydrolysis do?
uses water to break chemical bonds
typically attacks oxygen and breaks the bond leaving OH
what does oxidation do?
removes electrons and hydrogens from compound typically by adding something (mainly oxygen)
what is N-demethylation
removal of methyl group (CH3) and replacing with a hydrogen on a nitrogen
what does reduction do?
adds electrons and hydrogen to compound typically by removing something (mainly oxygen)
Why is chloramphenicol toxic in newborns?
what syndrome does it cause?
they lack glucuronidation (phase II) enzymes
grey baby syndrome
why does bilirubin toxicity occur in newborns?
they lack glucuronidation and develop temporary jaundice due to lack of excretion of bilirubin
to be more easily excreted, acetaminophen turns into a sulfate by what process?
removal of OH replaced by sulfa group
