Flashcards in drug metabolism Deck (25)
what is the purpose of metabolism of drugs?
increases water solubility so as to aid excretion
deactivation of compounds
can drugs be activated following metabolism?
what are some effects of metabolism?
loss of pharmacological activity
decrease in activity, with metabolites that show some activity
increase in activity, more active metabolites
activation of a prodrug
production of toxic metabolites
change to different pharmacological properties
what reactions are involved in phase 1 metabolism?
hydrolysis, oxidation or reduction
what are the most important family of metabolising enzymes?
what families of cytochrome p450 are important in drug metabolism?
what is the major constitutive enzyme in the human liver?
what does CYP2D6 metabolise?
some antidepressants, antipsychotics, also responsible for the conversion of codeine to morphine
what can the CYP2D6 enzyme be induced be?
what can CYP1A2 be induced by?
what is the effect of conjugation and where does it occur?
increases water solubilty and enhances excretion
happens in phase 2 metabolism
what factors can affect the rate of metabolism?
hepatic blood flow
what is enzyme induction?
increased synthesis of the enzyme, which results in increased activity
what is the effect of enzyme induction?
decreased drug effect
what factors can cause enzyme inhibition?
commonly used drugs can cause enzyme inhibition through a range of mechanisms including reversible and irreversible binding to the enzyme
what can gene mutations cause with regard to enzymes that metabolise drugs?
can cause deficiencies or complete absence of enzymes required to metabolise drugs
less commonly there may be multiple expressions of a particular metabolising enzyme, which increases enzyme activity, reduces drug effect
what effect does decreased enzyme activity have?
increased drug toxicity
in the fetus/infant, what is the state of drug metabolising enzymes?
what four phenotypic populations of metabolizers are there?
what are some enzymes that exhibit genetic variation?
cytochrome p450 2D6
cytochrome p450 2C19
what is the rate of metabolism in puberty compared to adulthood?
what is the effect of pregnancy on drug metabolism?
some enzymes are induced during second and third trimester
why are the elderly more likely to be on multiple drug therapy?
chronic disease is more common
what effect does ethnicity have on drug metabolism?
many incidences of racial differences in the genetic expression of cytochrome p-450 isoforms