68 Questions
Which of the following resources provides graded recommendations for medication use?
CPIC
What is the primary role of drug-metabolizing enzymes?
To transform compounds into more hydrophilic entities
Which enzyme is responsible for the metabolism of most drugs?
CYP450
What is the consequence of genetic polymorphisms in drug-metabolizing enzymes?
Either increased or decreased activity of the enzyme
What is the consequence of being a poor metabolizer (PM) of CYP2C19?
Reduced levels of the active metabolite
What is the recommended dose of citalopram in poor metabolizers (PMs)?
20 mg
What is the primary aim of pharmacogenomics?
To predict how an individual may respond to a drug based on their genetics
What is the consequence of being an ultrarapid metabolizer (UM) of CYP2C19?
Increased enzyme activity
What is a haplotype in the context of pharmacogenomics?
A group of inherited variations
What is the term for the observable trait that is predicted by pharmacogenomics?
Phenotype
What is phenoconversion?
A change from the predicted phenotype
Which of the following SSRIs is metabolized by CYP2D6?
Paroxetine
According to the Clinical Pharmacogenomics Implementation Consortium (CPIC), how many drugs have been identified with pharmacogenomic implications?
Over 250
What is the recommended dose adjustment for poor metabolizers (PMs) of CYP2D6 taking fluvoxamine?
50% decrease
What is the term for a variant form of a gene?
Allele
What is the functional status of an allele based on in pharmacogenomics?
Based on the level of activity associated with the allele
What is the recommendation for UM individuals according to the CPIC guidelines when using paroxetine?
Avoid using paroxetine due to pharmacotherapy failure
What is the effect of CYP2D6 on the metabolism of tramadol and codeine in UM individuals?
Increased concentrations of active metabolites, leading to increased risk of toxicity
What is the recommendation for PM individuals according to the CPIC guidelines when using warfarin?
Use a lower dose to achieve desired therapeutic effect
What is the effect of CYP2C9 on the metabolism of NSAIDs in IM individuals?
Decreased metabolism of NSAIDs, leading to increased exposure to concentrations
What is the recommendation for PM individuals according to the CPIC guidelines when using meloxicam and piroxicam?
Use an alternative agent to avoid adverse effects
What is the effect of CYP2C19 genotype on the metabolism of voriconazole?
Decreased metabolism of voriconazole, leading to increased risk of toxicity
What is the main purpose of drug transporters in the body?
To promote the influx or efflux of drug molecules across biologic membranes
What is the primary function of ATP-binding cassette transporters?
To bind ATP and use the energy to drive the transport of molecules across the membrane
Which of the following is NOT a type of solute carrier transporter?
PGP – P-Glycoprotein
What is the primary function of OATP1B1?
To move drugs from the blood into the hepatocyte
According to CPIC guidelines, what is the recommended approach for patients with poor SLCO1B1 function?
Recommend alternative agents
What is the effect of genetic polymorphisms on OATP1A2?
Reduced ability of the drug to get through the intestine to the blood
What is the primary function of HLA-encoded cell surface proteins?
To present intracellular antigens to the immune system
What is the association between HLA-B*15:02 and carbamazepine?
Increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis
What is the recommendation for carriers of HLA-A*31:01 who need to take carbamazepine?
They should avoid taking carbamazepine unless the benefit outweighs the risk
What is the consequence of having HLA-A*31:01 and taking certain medications?
All of the above
What is the association between HLA-B*15:02 and phenytoin?
Increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis
What is the recommendation for patients with HLA-B*15:02 who need to take phenytoin?
They should avoid taking phenytoin and fosphenytoin unless benefits clearly outweigh risks
What percentage of the Caucasian population are ultrarapid metabolizers of CYP2C19?
5%
What is the risk associated with poor metabolizers of CYP2C19?
Supratherapeutic troughs and adverse events
What percentage of the East Asian population are poor metabolizers of CYP2C19?
15%
What is the recommendation for patients who are poor metabolizers of CYP2C19?
Alternative medication
What is the percentage of the Caucasian population that are normal metabolizers of CYP2C19?
39%
What is the risk associated with ultrarapid metabolizers of CYP2C19?
Subtherapeutic levels and decreased efficacy
Which type of transporters requires adenosine triphosphate (ATP) to drive the transport of molecules across the membrane?
ATP-binding cassette transporters
What is the primary function of the OATP1B1 transporter in the liver?
To move drugs from the bloodstream into the hepatocyte
What is the effect of decreased OATP1B1 expression in the liver?
Increased plasma concentrations and increased adverse effects
What is the primary function of the OATP1A2 transporter in the intestine?
To move drugs from the intestine into the bloodstream
What is the consequence of genetic polymorphisms that result in decreased OATP1A2 activity?
Decreased absorption of drugs into the bloodstream
What is the primary function of HLA-encoded cell surface proteins?
To distinguish between self and foreign proteins in the immune system
What is the recommendation for patients with poor SLCO1B1 function according to CPIC guidelines?
Use lower doses of simvastatin or alternative agents
What is the consequence of having HLA-B*15:02 and taking carbamazepine?
Increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis
If a patient is considered to be at risk of non-response with standard dosing, what is the recommended approach?
Consider alternative agent (e.g.isavuconazole for treatment and posaconazole for prophylaxis)
What is the association between HLA-A*31:01 and certain medications?
Increased risk of cutaneous adverse reactions
What is the recommended approach for patients with HLA-B*15:02 who need to take carbamazepine?
Avoid the use of carbamazepine unless benefits clearly outweigh risks
What is the recommended approach if voriconazole is considered most appropriate for a patient?
Initiate voriconazole at a lower dose for prophylaxis or treatment
What is the consequence of having HLA-A*31:01 and taking certain medications?
Increased risk of cutaneous adverse reactions
What is the consideration for patients with normal metabolism and no increased risk?
Initiate standard of care dosing
What is the association between HLA-B*15:02 and phenytoin?
Increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis
What is the consideration for patients with higher trough concentrations compared to normal metabolizers?
Consider alternative agent (e.g.liposomal amphotericin B, and posaconazole)
What is the consideration for patients with a small probability of attaining therapeutic concentrations with standard dosing?
Consider alternative agent (e.g.liposomal amphotericin B, and posaconazole)
What is the recommended approach for patients with a modest probability of attaining therapeutic concentrations with standard dosing?
Consider alternative agent (e.g.isavuconazole for treatment and posaconazole for prophylaxis)
What is the primary goal of pharmacogenomic resources like CPIC and PharmGKB?
To provide evidence-based clinical guidelines for medication use
What is the consequence of genetic polymorphisms in CYP2C19?
Decreased enzyme activity
What is the function of CYP450 enzymes?
To metabolize most drugs
What is the effect of being an intermediate metabolizer (IM) of CYP2C19?
Decreased active metabolite levels
What is the recommended alternative agent for poor metabolizers (PMs) of CYP2C19?
An alternative SSRI
What is the consequence of being an ultrarapid metabolizer (UM) of CYP2C19?
Enhanced platelet inhibition
What is the function of the 'Table of Pharmacogenetic Associations' published by the FDA?
To categorize gene-drug pairs into three sections
What is the consequence of genetic polymorphisms in CYP2D6?
Decreased enzyme activity
What is the recommended dose adjustment for poor metabolizers (PMs) of CYP2C19 taking citalopram?
50% dose reduction
What is the consequence of phenoconversion in CYP2C19?
Altered predicted phenotype
This quiz covers pharmacogenomics resources including CPIC guidelines, PharmGKB, and AMP recommendations. It discusses the role of genetic variation on drug response and testing panels.
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