Pharmacokinetics: Drug Metabolism Flashcards
Metabolism definition
thhe processes by which a drug is chemically altered in a way that facilitates its action or enhances its elimination from the body
Metabolism slide
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There are no specific enzymes for the biotransformation of drugs.
True or False?
True
The enzymes are involved are the same that are involved in the synthesis and biotransformation of other endogenous and exogenous compounds
Phase 1 reactions (oxidation and reduction): catalysed by
Cytochrome P450 enzyme family
CP450 enzyme family catalyse phase II reactions.
True or False?
False
multiple enzyme types
Factors affecting metabolism:
- functional capacity: age, sex, pathologies **8
- interactions: induction/inhibition ***
- genetics (pharmacogenetics/genomics) ***
- environment
- race and ethnicity
Induction effect on metabolism
faster
Inhibition of CP450
- erythromycin/ clarithromycin
- grapefruit juice
- ciprofloxacin
Inducers of CP450:
- rifampicin
- chronic alcohol
Enzymatic induction effect on bioavailbility
bioavailability decrease
Enzymatic inhibition effect on bioavailability
increases
Effect of enzymatic induction of metabolism on a prodrug?
Metabolised faster
hence quicker therapeutic effect, quicker sub-therapeutic
62-year-oldman presented to his GP with a 2-day history of muscle aches and pain. He was treated with clarithromycin for a chest infection a week ago. He also takes atorvastatin daily.
What is the cause of his joint pain?
Clarithromycin is an inhibitor of metabolism, hence atorvastatin not metabolised and can reach toxic levels
Genetics and Drug Metabolism
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What is the CP450?
1) A specific enzyme of Phase I metabolism
2) A superfamily of enzymes mainly synthesised in the
kidney
3) A superfamily of enzymes responsible for
conjugation/hydrolysis/Phase II reactions
4) A superfamily of enzymes responsible for
oxidation/reduction/Phase I reactions
5) Specific enzymes formed for the biotransformation
of drugs
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