Gurley Feb 5 pt. 2 (CYP1A2 & CYP2D6) Flashcards
he said to be sure and understand chart on p. 11 and 22-24
where is CYP1A2 expressed
primarily in the liver
what gender tends to express more CYP1A2
males more than females
CYP1A2 is very sensitive to what?
inhibition and induction
what is the classic CYP1A2 substrate
caffeine
list some inducers of CYP1A2
cigarette smoke charbroiled meat cruciferous vegetables Primidone Rifampin Omeprazole Phenobarbital
list the CYP1A2 substrates (major pathway)
Caffeine Clozapine R-Warfarin Riluzole Ropivicane Tacrine Theophylline Phenacetin Olanzipine
what is the most potent inhibitor of CYP1A2
fluvoxamine
what SSRI has the least amount of drug-drug interactions
citalopram
Fluvoxamine/Theophylline combinations result in how much of an increase in theophylline concentrations
3 fold increase
Fluvoxamine/Clozapine combinations can lead to how much of an increase in clozapine
5 fold increase
what class of drugs is known to inhibit theophylline increase via CYP1A2
fluoroquinolones
arrange these in most inhibitory to least inhibitory of theophylline clearance via CYP1A2 inhibition:
ofloxacin, enoxacin, ciprofloxacin, norfloxacin, perfloxacin
Enoxacin>ciprofloxqacin>perfloxacin>norfloxacin= ofloxacin
just remember enoxacin is most then huge drop
what nuclear receptor causes induction of CYP1A2?
AhR (arylhydrocarbon nuclear receptor)
list the important types of drugs substrates of CYP2D6
Antiarrhythmics Beta blockers Antipsychotics Opioid analgesics Tricyclic antidepressants SSRIs (note that not all of these types are substrates just some of them)
what are the inducers of 2D6
definite test Q
no inducers (don’t have to worry about drug drug interactions for 2d6 induction; can be inhibited)
what are the important inhibitors of CYP2D6
Fluoxetine
Paroxitine
Quinidine
what is interesting about quinidines CYP interactions
It most potent inhibitor of 2D6, but not a substrate (so not metabolized by it); primarily a 3A4 substrate
list the SSRIs that are the most problematic 2D6 inhibitors
list the SSRI’s that have little effect on 2D6
problematic = fluoxetine and paroxetine
little effect = citalopram and fluvoxamine
what is 2D6’s effect on codeine
metabolizes it to morphine (otherwise it doesn’t work)
extensive metabolizers of 2D6 have what genotype
heterozygous
or homozygous dominant
poor metabolizers via 2D6 have what genotype
homozygous for mutated alleles
what should you immediately think of if you see CYP2D6*2
Test q according to Gurley
potential ultra rapid metabolizer
means multiple wildtype copies of the gene
what CYP2D6 polymorphism designations indicate normal
CYP2D61
CYP2D62 (with exception of multiple wildtype copies)
CYP2D6*35
of P450’s what enzyme do polymorphisms effect the most
2D6
what is the “bottom line” of what the AmpliChip CYP450 is?
A microarray chip that with a blood sample parts become fluorescent showing which alleles someone has
what CYPs are “AmpliChip CYP450” used for
CYP2D6 and CYP2C19
what is the halflife of dsipramine in extensive metabolizers of 2D6?
poor metabolizers?
extensive = 17 hours
poor - 100 hours
what can occur with propefenone being taken by poor metabolizers?
can become arrhythmogenic
what occurs with poor metabolizers of CYP2D6 taking codeine; more analgesia or less analgesia
less analgesia (prodrug that must be metabolized to active form)
what is the max number of 2D6 gene copies can an individual have
up to 13 copies
