P450 Flashcards
overview of the lecture
- different CYPs involved in drug metabolism
- mech of CYP action
- effects of mutations and polymorphisms in CYPs on drug metabolism
what are the major characteristics of cytochrome?
- perfrom RedOx rxn (phase 1)
- bound to the lipid membranes of the smooth endoplasmic reticulum
- most are found in the liver, but exist in lung, kidney, heart, and brain also
CYP enzymes are an important biotransforming system,
utilizing mostly oxidation and reduction
what is a prodrug?
a medication that is administered in an inactive or less than fully active form, and is then converted to its active from through a normal metabolic process.
what is an example of prodrug?
codeine (inactive) becomes morphine via CYP2D6.
codeine is a prodrug that is metabolized by CYP2D6, when Rifampin was given what happens?
Rifampin induce CYP2D6, thus converts more codeine to morphine
Define prodrug
a medication that is administered in an inactive or less than fully active form, and is then converted to its active form through a normal metabolic process
Define induction
biotransformation by induced CYP enzmyes results in either increased activity of prodrugs or enhanced elimination of drugs
what is it called that a genetic change that exists for at least 1% of population?
polymorphism
when does CYP polymorphism occur?
when the biotransforming properties of an enzyme are altered
warfarin is taken for
artrial fibrilation
warfarin is used to inhibit
factors 2, 7, 9, and 10, thus anticoagulating the blood
warfarin is measured in
INR
what are the substrates for CYP2C9?
Warfarin, Phenytoin
warfarin is a substrate for CYP2C9 and is
metabolized at a satisfactory rate for the patient’s blood to be adequately anticoagulated
what is the consequenc of induction?
results in either increased activity of prodrugs or enhanced elimination of drugs
what are some inducers of P450?
- smoking
- charred food
- Barbiturates
- Rifampins
- St. John’s wort
What will happen if you take Verapamil for HTN and St. John’s wort at the same time?
St. John induces P450 and thus will weaken the drug effecitveness
what are some inhibitors of P450?
- grapefruit juice
- macrolides
- fluoxetine
- Quinidine
- Haloperidol
- Ketoconazol
what happens if you take ferfenadine and ketoconazole at the same time?
may develop Torsades de Pointes
what are the 2 major types of CYP enzyme?
- poor
2. extensive
what are two types of P450 that are poor metabolizers?
CYP 2C9, CYP 2C19
what is the type of P450 that is both poor metabolizers and extensive metabolizers?
CYP 2D6
caffeine, theophyillie
1A2
phenytoin, warfarin
2C9
diazepam, codeine
2D6
paracetamol
2E1
verapamil
3A4
which 3 types of P450 have polymorphism?
2C9, 2C19, 2D6
