Flashcards in pharmacokinetics -drug metabolism Deck (24)
biochemical modification of pharmaceutical substances by living organisms usually through specialized enzymatic activity.
what does metabolism do to lipid soluble and
converts them into water soluble and polar substances which are able to be excreted
what are prodrugs?
drugs that are activated by metabolism
what is the purpose of metabolism?
-increase water solubility and so aid excretion.
examples of prodrugs
codeine, enalapril, simvastatin, sacubitril
effects of metabolism in a drug
-Loss of pharmacological activity.
-Increase in activity, more active metabolites (prodrugs)
-Production of toxic metabolites
what are the effects of toxic metabolites of a drug
-teratogenesis (production of congenital abnormalities in an embryo or fetus)
phase 1 of drug metabolism
drug is either activated or inactivated by oxidation, reduction or hydrolysis
what does phase 1 do to the polarity of an organism?
what is the most important enzyme family for phase 1 metabolism?
the major constitutive enzyme in the liver, also found in the gut so responsible for pre-systemic metabolism
resposible for the metabolism of some antidepressants and codeine to morphine
induced by smoking and is important in the metabolism of theophylline
phase 2 of metabolism
involves conjugation, this increases water solubility which enhances excretion of metabolised compound.
factors which affect metabolism
-Other drugs/herbals/natural substances
-Hepatic blood flow
what is induction of drug metabolising enzymes?
increased synthesis and therefore increased activity of an enzyme
what effect does enzyme induction have on drug effect?
decreases it as there is increased metabolism
examples of enzyme inducers
what are drug enzyme inhibitors?
reduce the activity of drug metabolising enzymes
examples of drug enzyme inhibitors
calcium channel blockers
how can genetic variation affect drug metabolism?
-individuals may express different forms of a drug metabolising enzyme
-may also have abnormal levels of an enzyme. too high- reduced effect
too low- drug toxicity
what will lack or decreased activity of an enzyme result in ?
how does drug metabolism differ in children?
-often deficient of metabolising enzymes in fetus and premature infant renal function is reduced so drugs can build up.
-by two children can metabolise many drugs more rapidly than adults