PHARMA EXAM 2

CARDIOVASCULAR — Which gene-drug class pair is the statin transporter example?

SLCO1B1 and statins.

CARDIOVASCULAR — What does SLCO1B1 encode?

SLCO1B1 encodes OATP1B1, a transporter that helps move certain statins from the blood into the liver.

CARDIOVASCULAR — What happens to statin levels when SLCO1B1 function is reduced?

Less statin may enter the liver, so more can remain in the blood.

CARDIOVASCULAR — What is the main clinical concern when reduced SLCO1B1 function raises statin exposure?

Increased exposure can raise the risk of muscle toxicity, including myopathy.

CARDIOVASCULAR — What does the SLCO1B1 phenotype table help guide?

It helps guide statin choice and dosing based on expected transporter function and risk of side effects.

CARDIOVASCULAR — What is the key exam chain for reduced SLCO1B1 function?

Reduced transporter function → less statin enters the liver → more statin remains in the blood → increased myopathy risk.

CARDIOVASCULAR — Which gene affects warfarin clearance?

CYP2C9 affects warfarin metabolism and clearance; this is a pharmacokinetic (PK) effect.

CARDIOVASCULAR — Which gene affects warfarin sensitivity?

VKORC1 affects warfarin's target and the body's sensitivity to the drug; this is a pharmacodynamic (PD) effect.

CARDIOVASCULAR — What are the two main warfarin gene associations?

CYP2C9 affects clearance (PK); VKORC1 affects sensitivity (PD).

CARDIOVASCULAR — Which gene helps activate clopidogrel (Plavix)?

CYP2C19 helps activate clopidogrel.

CARDIOVASCULAR — What can reduced CYP2C19 function mean for clopidogrel response?

Less active drug may be formed, leading to weaker platelet inhibition.

CARDIOVASCULAR — Which gene-drug pair affects metoprolol metabolism?

CYP2D6 and metoprolol.

CARDIOVASCULAR — What can reduced CYP2D6 function do to metoprolol exposure?

It can slow metoprolol metabolism and increase exposure, potentially increasing bradycardia or low blood pressure risk.

CARDIOVASCULAR — Which gene is associated with hydralazine metabolism in the class notes?

NAT2; slower acetylation can reduce hydralazine inactivation.

CARDIOVASCULAR — What is the possible effect of slower hydralazine inactivation?

Higher exposure may increase adverse-effect risk, including low blood pressure and reflex tachycardia.

CARDIOVASCULAR — Which statin is especially emphasized with SLCO1B1 in the notes?

Simvastatin.

CARDIOVASCULAR — How can reduced SLCO1B1 function affect simvastatin?

It can reduce liver uptake, increase circulating simvastatin exposure, and raise myopathy risk.

CARDIOVASCULAR — What is the difference between pharmacokinetics and pharmacodynamics?

PK is what the body does to a drug, including metabolism and clearance. PD is what the drug does to the body, including its target effects.

CARDIOVASCULAR — Short answer: A patient has reduced SLCO1B1 function. What happens to statin levels, and what is the concern?

Less statin may enter the liver, so more remains in the blood; increased exposure can raise myopathy risk.

CARDIOVASCULAR — Short answer: Explain the two gene associations for warfarin.

CYP2C9 affects warfarin clearance (PK), while VKORC1 affects sensitivity to warfarin (PD).

CARDIOVASCULAR — Short answer: Compare the CYP2C19 and CYP2C9 examples.

CYP2C19 helps activate clopidogrel; CYP2C9 helps clear warfarin.

CARDIOVASCULAR — Short answer: What does the SLCO1B1 phenotype table help a clinician consider?

It helps guide statin choice and dose based on expected transporter function and risk.

CARDIOVASCULAR — Short answer: Which gene-drug pair is the transporter example emphasized for the exam?

SLCO1B1 and statins.

PSYCH & NEURO — Which HLA variants are associated with carbamazepine-related skin reactions?

HLA-B*15:02 and HLA-A*31:01 are associated with increased risk of serious immune-mediated skin reactions.

PSYCH & NEURO — Why might a patient be tested for HLA-B*15:02 and HLA-A*31:01 before carbamazepine treatment?

Testing can identify increased risk of serious, potentially life-threatening skin reactions.

PSYCH & NEURO — Do the carbamazepine HLA associations mainly affect drug transport or metabolism?

No. They are associated with immune response and drug safety, rather than how the body transports or metabolizes the drug.

PSYCH & NEURO — Which gene helps metabolize secondary and tertiary amine antidepressants?

CYP2D6 helps metabolize both types through hydroxylation, according to the class notes.

PSYCH & NEURO — What can CYP2C19 do to some tertiary amine antidepressants?

It can convert some tertiary amines into secondary amines.

PSYCH & NEURO — What can happen to the amitriptyline-to-nortriptyline balance in CYP2C19 poor metabolizers?

Conversion of amitriptyline to nortriptyline may be reduced, increasing the amitriptyline-to-nortriptyline ratio.

PSYCH & NEURO — Why can higher amitriptyline concentrations matter in CYP2C19 poor metabolizers?

Higher parent-drug concentrations may increase the risk of side effects.

PSYCH & NEURO — What is the class-note dosing point for CYP2C19 intermediate metabolizers taking amitriptyline?

Although the ratio may shift modestly, the notes say evidence does not support an alternate dose solely for CYP2C19 intermediate metabolizers.

PSYCH & NEURO — Short answer: What does CYP2D6 do to secondary and tertiary amine antidepressants?

It helps metabolize both through hydroxylation; CYP2C19 can convert some tertiary amines into secondary amines.

PSYCH & NEURO — Short answer: How can CYP2C19 poor-metabolizer status affect amitriptyline and nortriptyline?

It can reduce conversion of amitriptyline to nortriptyline, raising the parent-drug-to-metabolite ratio and potentially increasing side-effect risk.

INFECTIOUS DISEASE — Which gene-drug pair involves NAT2?

NAT2 and isoniazid.

INFECTIOUS DISEASE — What does NAT2 do to isoniazid?

NAT2 metabolizes isoniazid.

INFECTIOUS DISEASE — What type of enzyme is NAT2?

A Phase II transferase enzyme.

INFECTIOUS DISEASE — What can happen in NAT2 slow acetylators taking isoniazid?

They may metabolize isoniazid more slowly, increasing drug exposure and toxicity risk.

INFECTIOUS DISEASE — Which gene-drug pair is associated with abacavir hypersensitivity?

HLA-B*57:01 and abacavir.

INFECTIOUS DISEASE — What does HLA-B*57:01 testing help assess before abacavir treatment?

It helps identify patients at risk of abacavir hypersensitivity.

INFECTIOUS DISEASE — What does G6PD do to protect red blood cells?

G6PD supports NADPH production, which helps maintain glutathione protection against oxidative damage.

INFECTIOUS DISEASE — How can G6PD deficiency affect drug safety?

It can leave red blood cells more vulnerable to oxidative damage and hemolysis with certain drugs.

INFECTIOUS DISEASE — Why may G6PD-related problems be more noticeable in men?

G6PD is X-linked, so a harmful variant in a man's single X chromosome can affect him.

INFECTIOUS DISEASE — Short answer: Which enzyme metabolizes isoniazid, and what kind of enzyme is it?

NAT2, a Phase II transferase.

INFECTIOUS DISEASE — Short answer: Give a gene-drug example that affects immune response rather than drug metabolism.

HLA-B*57:01 and abacavir.

INFECTIOUS DISEASE — Short answer: Why can G6PD deficiency make some drugs dangerous?

Red blood cells may be less protected from oxidative stress and can be damaged or destroyed.

CANCER — What is Tarceva?

Tarceva is erlotinib, a small-molecule EGFR tyrosine kinase inhibitor.

CANCER — What tumor testing is relevant before erlotinib treatment?

Tumor testing for specific EGFR mutations helps determine whether erlotinib may be appropriate.

CANCER — Where does a small-molecule EGFR inhibitor act?

It enters the cell and blocks the receptor's intracellular tyrosine kinase domain.

CANCER — Where does an anti-EGFR monoclonal antibody bind?

It binds the receptor's extracellular domain.

CANCER — What is the key difference between a small-molecule EGFR inhibitor and an anti-EGFR antibody?

The small molecule acts inside the cell at the kinase domain; the antibody binds outside the cell at the extracellular domain.

CANCER — What does EGFR-family receptor dimerization mean?

Two receptor molecules pair together.

CANCER — Why can receptor dimerization matter in cancer?

Pairing can activate tyrosine kinase signaling and promote cell growth.

CANCER — What can gene amplification do to receptor signaling?

Extra gene copies can increase receptor production and signaling.

CANCER — What does DPYD encode?

DPYD encodes DPD, the enzyme that breaks down 5-fluorouracil (5-FU).

CANCER — Why can severe DPD deficiency make 5-FU dangerous?

Reduced DPD function can cause 5-FU to build up and lead to severe, potentially life-threatening toxicity.

CANCER — What does the DPYD activity score help estimate?

It estimates DPD function and can help guide 5-FU dosing or avoidance.

CANCER — Short answer: Compare an anti-EGFR antibody with a small-molecule EGFR inhibitor.

The antibody binds the extracellular domain; the small molecule enters the cell and blocks the intracellular kinase domain.

CANCER — Short answer: What is Tarceva, and what tumor feature may be tested before treatment?

Tarceva is erlotinib, a small-molecule EGFR inhibitor; specific EGFR mutations may be tested to help guide treatment.

CANCER — Short answer: Why can standard-dose 5-FU be dangerous for someone with severe DPD deficiency?

They may break down 5-FU too slowly, causing dangerous exposure and severe toxicity.

CANCER — Short answer: What is receptor dimerization, and why does it matter?

It is the pairing of two receptors, which can activate tyrosine kinase signaling and promote cell growth.

CANCER — Short answer: What is gene amplification, and how can it affect cancer?

Extra copies of a gene can increase receptor production and signaling.

GENERAL EXAM CONCEPTS — What is an off-target drug effect?

It occurs when a drug binds to an unintended target as well as its intended target.

GENERAL EXAM CONCEPTS — Why can off-target binding cause side effects?

Interactions with unintended targets can produce harmful effects beyond the drug's intended action.

GENERAL EXAM CONCEPTS — What type of gene-drug association is SLCO1B1 with statins?

A transporter association that can affect drug levels.

GENERAL EXAM CONCEPTS — What type of gene-drug association is CYP2C9 with warfarin?

A pharmacokinetic association affecting metabolism and clearance.

GENERAL EXAM CONCEPTS — What type of gene-drug association is VKORC1 with warfarin?

A pharmacodynamic association affecting the drug target and sensitivity.

GENERAL EXAM CONCEPTS — What type of gene-drug association is CYP2C19 with clopidogrel?

A drug-activation association; clopidogrel is a prodrug.

GENERAL EXAM CONCEPTS — What type of gene-drug association are HLA variants with drug hypersensitivity?

An immune-response association that can affect safety without primarily changing drug levels.

GENERAL EXAM CONCEPTS — Name one example of a drug response association that is not primarily PK or PD.

HLA-associated immune hypersensitivity, such as HLA-B*57:01 with abacavir.

TCA class — What are the main pharmacogenes for tricyclic antidepressants (TCAs)?

CYP2C19 affects demethylation, including conversion of some tertiary amines to secondary amines; CYP2D6 affects hydroxylation and overall clearance.

Amitriptyline — What does CYP2C19 do?

CYP2C19 helps convert amitriptyline, a tertiary amine, to nortriptyline, a secondary amine.

Amitriptyline — What can happen in CYP2C19 poor metabolizers?

Less amitriptyline may be converted to nortriptyline, increasing the amitriptyline-to-nortriptyline ratio and potentially increasing side-effect risk.

Amitriptyline and nortriptyline — What does CYP2D6 do?

CYP2D6 helps hydroxylate and clear both drugs.

Amitriptyline and nortriptyline — What can happen in CYP2D6 poor metabolizers?

Drug levels may be higher because clearance is reduced, increasing the chance of side effects.

Amitriptyline and nortriptyline — What can happen in CYP2D6 ultrarapid metabolizers?

Drug levels may be too low for treatment to work well.

Tertiary-amine TCAs — Which drugs are examples?

Amitriptyline, clomipramine, doxepin, imipramine, and trimipramine.

Secondary-amine TCAs — Which drugs are examples?

Desipramine, nortriptyline, and protriptyline.

Tertiary- vs secondary-amine TCAs — What is the general difference in effect?

Tertiary amines tend to have a stronger serotonin reuptake effect; secondary amines tend to have a stronger norepinephrine reuptake effect.

SSRIs — What transporter do this class of drugs inhibit?

SLC6A4 encodes the serotonin transporter targeted by SSRIs.

SSRIs and SLC6A4 — What does the lecture say about genetic effects on response?

Findings about SLC6A4 variants and SSRI response are contradictory.

Citalopram — Which gene affects its exposure, and what is the key concern?

CYP2C19 affects citalopram exposure. Poor metabolizers may have higher exposure and increased risk of QT-prolongation-related arrhythmias.

Escitalopram — Which gene affects its exposure?

CYP2C19. Variation in CYP2C19 activity may alter escitalopram exposure.

Sertraline — Which gene affects its exposure?

CYP2C19. Variation in CYP2C19 activity can contribute to differences in sertraline levels.

Paroxetine — Which gene metabolizes it, and what can happen in poor metabolizers?

CYP2D6 metabolizes paroxetine. Poor metabolizers may have greater exposure.

Paroxetine — What can happen in CYP2D6 ultrarapid metabolizers?

Paroxetine levels may be very low or undetectable, which can contribute to treatment failure.

Fluvoxamine — Which gene metabolizes it, and what can happen in poor metabolizers?

CYP2D6 contributes to its metabolism. Poor metabolizers may have greater exposure.

Fluoxetine — Which genes contribute to its metabolism?

CYP2D6 and CYP2C9 both contribute to formation of active norfluoxetine.

Atomoxetine (Strattera) — Which gene affects its metabolism?

CYP2D6.

Atomoxetine — What can happen in CYP2D6 poor metabolizers?

Exposure can be much higher, which may improve treatment response but also increase side-effect risk.

Atomoxetine — What side effects may be more likely with increased exposure?

Increased heart rate and diastolic blood pressure.

Atomoxetine — Which transporter does the drug inhibit?

SLC6A2 encodes the norepinephrine transporter that atomoxetine inhibits.

Antipsychotics — What is the main target of many first-generation antipsychotics?

DRD2 encodes the dopamine D2 receptor, which many first-generation antipsychotics block.

Antipsychotics — What is the general difference between first- and second-generation drugs?

First-generation drugs mainly block D2 receptors; second-generation drugs act on both serotonin and dopamine signaling.

Clozapine — What does the lecture say about its pharmacogenes?

The lecture says antipsychotics are metabolized by CYP enzymes, but it does not specify one CYP gene for clozapine.

Carbamazepine — Which genes help metabolize it?

CYP3A4 forms the active carbamazepine-10,11-epoxide; EPHX1 helps convert that metabolite to another form.

Carbamazepine — What does auto-induction mean?

Carbamazepine can increase its own metabolism over time.

Carbamazepine — Which HLA variants are associated with serious skin reactions?

HLA-B*15:02 is associated mainly with SJS/TEN; HLA-A*31:01 is associated with SJS/TEN, DRESS, and other skin reactions.

Carbamazepine — Do HLA-B*15:02 and HLA-A*31:01 affect drug metabolism?

No. They are associated with immune-mediated drug reactions, not how the body metabolizes or transports carbamazepine.

Phenytoin — Which genes metabolize it?

CYP2C9 and CYP2C19.

Phenytoin — What can reduced CYP2C9 function cause?

Slower metabolism, higher phenytoin levels, and increased toxicity risk.