Pharmacogenomics- FINAL Flashcards
What is Pharmacogenetics?
The study of how genetic variations influence an individual’s response to specific drugs.
What is Pharmacogenomics?
The broader application of genomic technologies to drug discovery and characterization, considering all genes’ influence on drug response.
What reactions occur in Phase I drug metabolism?
Oxidation, reduction, and hydrolysis reactions.
What is the primary role of Phase I metabolism?
Creates a more polar compound to prepare for Phase II.
What reactions occur in Phase II drug metabolism?
Conjugation reactions like adding glucuronide.
What is the result of Phase II metabolism?
Makes the drug water-soluble and ready for elimination through kidneys or bile.
What can genetic variations influence in pharmacogenetics?
Enzyme activity, receptor sensitivity, and drug transporter efficiency.
What does CYP2D6 metabolize?
About 25% of all drugs including beta blockers and antidepressants.
What happens in CYP2D6 ultra-rapid metabolizers?
They may convert prodrugs too quickly, leading to excess active drug and toxicity.
What does CYP2C19 metabolize?
Proton pump inhibitors and clopidogrel.
What is the clinical significance of CYP2C19 poor metabolizers?
They may have reduced drug effectiveness.
What drugs does CYP2C9 metabolize?
NSAIDs, warfarin, and phenytoin.
How do CYP2C9 variants affect warfarin?
Decrease metabolism, leading to higher warfarin levels and increased bleeding risk.
What does CYP3A4/5 metabolize?
The largest number of drugs including statins and calcium channel blockers.
What happens in poor metabolizers?
Increased drug levels causing toxicity and side effects; prodrugs may be ineffective.
What happens in ultra-rapid metabolizers?
Subtherapeutic drug levels and potential excess active drug production.
What genetic variants affect Coumadin (warfarin) response?
CYP2C9, VKORC1, and CYP4F2 variants.
Which 5 drugs have common adverse drug events related to genetics?
Warfarin, Clopidogrel, Codeine, Carbamazepine, Thiopurines.
What risk is associated with Clopidogrel in CYP2C19 poor metabolizers?
Reduced activation and lower effectiveness.
What risk is associated with Codeine in CYP2D6 ultra-rapid metabolizers?
Excess morphine production and risk of respiratory depression.
What is the risk of Carbamazepine in HLA-B*1502 carriers?
Serious skin reactions like Stevens-Johnson Syndrome.
Which genetic variants affect Thiopurines?
TPMT and NUDT15 variants causing bone marrow suppression.
What does CYP450 enzyme system do?
Performs Phase I metabolism (oxidation), increasing polarity and preparing drugs for elimination.
Which CYP enzyme metabolizes 50% of drugs?
CYP3A4.
Which CYP enzyme metabolizes 20% of drugs and has over 70 variants?
CYP2D6.
Which CYP enzymes are inducible?
CYP3A4, CYP2C9, CYP2C19.
What is the function of Phase II metabolism?
Conjugation reactions to make drugs more water-soluble for excretion.
What are SNPs?
Single Nucleotide Polymorphisms, the most common genetic variation.
What are INDELs?
Insertions and deletions in DNA.
What gene variants affect Warfarin response?
CYP2C9 and VKORC1.
What population requires lower Warfarin doses?
Asians.
What converts Codeine into Morphine?
CYP2D6 enzyme.
What activates Clopidogrel?
CYP2C19 enzyme.
Why is Clopidogrel less effective in some people?
Poor metabolizers of CYP2C19 have reduced drug activation.
What gene mutation improves Pegasys response?
IL28B gene mutation.
What is Warfarin’s mechanism of action?
Inhibits Vitamin K via VKORC1.
What are examples of targeted drugs?
Herceptin (Her2/neu), Erbitux (EGFR), Tarceva (EGFR).
What drugs require genetic testing before use?
Warfarin, Clopidogrel, Herceptin, Erbitux, 6-Mercaptopurine.
What are challenges in pharmacogenetics implementation?
Clinician education, EHR integration, and lab equipment costs.
What is the most commonly occuring genetic difference?
SNP’s
