Flashcards in Pharmacogenetics Deck (100)
NAT Gene effects which drug?
Isoniazid for TB
NAT Gene effects the pharmacology of Isoniazid for tuberculosis
Rate of acetylation is determined by genetic polymorphisms
What is NAT gene for?
N-Acetyltransferase enzyme is important in which pathway?
Phase II Pathway
What is phase II pathway again?
Drug metabolism - attachment of a sugar/acetyl group to detoxify drug and make easier to excrete
What variation is seen for NAT polymorphisms?
Fast vs Slow acetylators of the drug Isoniazid
Asian - fast metabolizers
White - slower
What is Isoniazid used to treat?
Fast isoniazid are at lower risk for
Toxic effects of liver but lower effectiveness for TB
Low isoniazid are at higher risk for
Toxic effects of liver but higher potency for TB
Isoniazid metabolism is associated with which gene?
Drugs influenced by CYP3A
What is cyclosporine
CYP3A and Mechanism of Mutation?
Genetically is less important than other drug metabolism genes because the population distribution is continuous and unimodal
So using logic, if CYP3A is a gene that is responsible for drug metabolism, and one of the drugs it targets is cyclosporine,
What should we think about when perscribing cyclosporine to patients on Ketoconazole or Grapefruit juice?
These inhibit CYP3A which metabolizes Cyclosporine (clears) thus, we may have a buildup of immunosuppressant and oversuppress our immune system?
What should we think about when perscribing Rifampin and Cyclosporine simultaneously?
Rifampin is a CYP3A inducer, so we may be excreting cyclospobyrine more rapidly than normal, thus reducing is immunosuppressive activity? may need to perscribe more?
Ketocanazole - a drug to treat fungal infection (topical) - let's say you want to perscribe it to your patient and your patient is also taking cyclosporine, what would be your concern?
Well, cycosporine is an immunosuppressant that is detoxified/cleared from the body in part by CYP3A - However, ketoconazole is an inhibitor of CY3PA thus, it would seem that if my patient was goint to also start taking ketoconazole, we would need to lower her dose of cyclosporine because she would not be clearing it as fast?
What three specific factors should we be thinking about when we perscribe cyclosporine for immunosuppressant agent?
Grapefruit juice and
Ketoconazole inhibits CYP3A
Graprefuit juice inhibitbs CYP3A
and Rifampin induces CYP3A
Your patient loves Grapefruit juice and you perscribe her cyclosporine, what should you consider in terms of dosing?
Maybe a wee bit less because Grapefruit juice is an inhibitor or the enzyme (CYP3A) that clears the cyclosporine from the body?
Your patient is taking Rifampin for a fungal infection... You also want to perscribe Cyclosporine for an immunosuppressant drug... what should you consider?
Rifampin is an inducer of CYP3A - the eznyme that clears cyclosporine - thus you might want to consider a little bit more cyclosporine in this patient
What specific substrates of CYP2D6 should we be aware of?
What makes CYP2D6 unique?
It is an activator - unlike most of the enzymes that we are looking at - CYP2D6 is not so much required to clear drugs as it is to activate them?
Let's say you had a patient that was on a tricyclic antidepressant and you wanted to perscribe them quinidine (antiarrhythmic) what should you take under consideration?
quinidine is an inhibitor of CYP2D6
CYP2D6 is an metabolizer of tricyclic antidepressants
May need to perscribe lower dose Tricyclic antidepressant to account for quinidine inhibition of CYP2D6 clearance
Let's say you had a patient who was taking fluoxtine (for depression/ocd) and you needed to perscribe them codeine, what should you consider?
Well, Codeine is activated by CYP2D6
CYP2D6 is inhibited by Fluoixitine
Thus, activation of codeine by CYP2D6 may be diminished due to CYP2D6 inhibition, so perscribe a little more codeine?
What are the substrates of CYP2D6 that we should know? (2)
Tricyclic antidepressant - metabolism
Codeine - acitvation
What are the inhibitors of CYP2D6 that we should know? (3)
CYP2C9 - which drug is associated with this gene?
Warfarin is a substrate of an enzyme encoded by which gene?
CYP2C9 and VKORC1