Flashcards in Drug Metabolism Deck (22):
What is the effect of metabolism
limits the life of a substance in the body, by rendering lipid soluble and non-polar compounds to water soluble and polar compounds so that they can be excreted
Production of toxic metabolites (direct toxicity, carcinogenesis)
Loss of pharmalogical activity
Increase in prodrug
What happens to lipid soluble substances instead of getting excreted?
Passively reabsorbed from renal or extra renal excretory sites back into the blood
Purpose of metabolism?
To increase water solubility and so aid excretion
or to deactivate compounds (may involve a number of steps).
What are prodrugs?
Drugs activated following metabolism
What are phase 1 reactions of metabolism?
What is the purpose of phase 1 metabolism?
Increases polarity of the compound
Provides active site for phase 2 metabolism
What is the most important super family of metabolising enzymes?
What is the main role of the CYP1-3 families (contained within the P-450 family)
Important in oxidative drug metabolism
Where are enzymes found that are responsible for the breakdown of SOME drugs
CYP3A4 - Liver + Gut
Why may 5-10% of the population may be immune to the analgesic actions of codeine?
Reduced expression of the enzyme responsible for conversion of codeine to morphine
Why do smokers require a higher dose of theophylline than non-smokers?
Enzyme responsible for the metabolism of theophylline is induced by smoking
What does phase 2 metabolism involve?
Attachment of glucoronic acid, glutathione, sulphate or acetate to the metabolite generated by phase 1 metabolism
Usually results in inactivation
What factors affect metabolism?
Other drugs/herbals/natural substances
Hepatic blood flow
What is the effect of induction of drug metabolising enzyme on metabolism?
Increased synthesis of the enzyme - increased activity - Decreased drug effect
What is the effect of inhibition of drug metabolising enzyme on metabolism?
Reversible or irreversible binding to the enzyme
What is the effect of decreased enzyme activity or lack of an enzyme responsible for drug metabolism?
(can be as a result of genetic polymorphism)
Increased drug toxicity
What are the four phenotype subpopulations of metabolizers?
Poor metabolizers (PM)
Intermediate metabolizers (IM)
Extensive metabolizers (EM)
Ultrarapid metabolizers (UM)
Describe the prevalence of drug metabolising enzymes in the fetus or premature infant?
Deficient or reduced, renal function is also deficient so drug and metabolites rapidly build up to toxic levels.
Who metabolises drugs faster - a teenager at puberty or an adult?
What areas in drug response does disparity occur between genders?
What can affect the metabolism of drugs in a pregnant woman?
The trimester she is in