These seven pharmacology questions cover high-yield topics that USMLE Step 1 tests again and again: drug toxicities, drug interactions, pharmacokinetics, autonomic drugs and teratogens. Pick your answer first, then open the explanation.
Question 1: Heart failure after chemotherapy
A 58-year-old woman completed chemotherapy for breast cancer 8 months ago. She now has shortness of breath on exertion, orthopnea and ankle swelling. Echocardiography shows a dilated left ventricle with an ejection fraction of 30%. She had a normal echocardiogram before treatment. Giving which of the following drugs together with her chemotherapy would most likely have reduced the risk of this complication?
A. Leucovorin B. Mesna C. Dexrazoxane D. Amifostine E. Filgrastim
Correct answer: C. Dexrazoxane
This patient has dilated cardiomyopathy caused by an anthracycline such as doxorubicin, a standard breast cancer drug. Anthracycline cardiotoxicity is dose-dependent and often irreversible. It is caused by iron-dependent free radical formation that damages heart muscle. Dexrazoxane is an iron chelator that lowers this free radical injury and protects the heart. Other ways to reduce risk are limiting the total cumulative dose and monitoring ejection fraction during treatment.
Why the other options are wrong:
Leucovorin (folinic acid) rescues normal cells from methotrexate toxicity.
Mesna prevents hemorrhagic cystitis from cyclophosphamide and ifosfamide.
Amifostine is a free radical scavenger that protects the kidneys from cisplatin.
Filgrastim (G-CSF) treats chemotherapy-induced neutropenia; it does not protect the heart.
Question 2: Severe hypotension after an erectile dysfunction drug
A 62-year-old man with stable angina uses sublingual nitroglycerin when needed. One evening he takes a medication for erectile dysfunction. Two hours later he develops chest pain and takes nitroglycerin. Within minutes he becomes dizzy, and his blood pressure is 72/40 mm Hg. Which of the following best explains this reaction?
A. Both drugs increase cAMP in vascular smooth muscle B. The erectile dysfunction drug blocks alpha-1 receptors C. The erectile dysfunction drug inhibits CYP3A4 and raises nitroglycerin levels D. The erectile dysfunction drug inhibits PDE-5 and prevents breakdown of cGMP E. Nitroglycerin directly activates potassium channels in arterioles
Correct answer: D. The erectile dysfunction drug inhibits PDE-5 and prevents breakdown of cGMP
Nitrates release nitric oxide (NO), which activates guanylyl cyclase and increases cGMP in vascular smooth muscle, causing vasodilation. Sildenafil and other PDE-5 inhibitors block the enzyme that breaks down cGMP. Together, the two drugs cause a large rise in cGMP and severe, sometimes fatal, hypotension. For this reason, nitrates are contraindicated within 24 hours of sildenafil (48 hours for tadalafil).
Why the other options are wrong:
These drugs work through cGMP, not cAMP.
PDE-5 inhibitors do not block alpha-1 receptors. Alpha-1 blockers (such as tamsulosin) can also lower blood pressure with PDE-5 inhibitors, but that is a different mechanism.
The interaction is pharmacodynamic (additive effects on cGMP), not a change in nitroglycerin levels.
Potassium channel openers (such as minoxidil) are a different drug class; nitroglycerin works through NO and cGMP.
Question 3: Stent thrombosis on dual antiplatelet therapy
A 55-year-old man has a drug-eluting coronary stent placed after a myocardial infarction. He is discharged on aspirin and clopidogrel and takes both exactly as prescribed. Two weeks later he returns with chest pain, and angiography shows thrombosis of the stent. Genetic testing shows two loss-of-function alleles of a hepatic cytochrome P450 enzyme. Which of the following best explains the treatment failure?
A. Increased clearance of aspirin B. Reduced conversion of clopidogrel to its active metabolite C. A mutation in the platelet thromboxane receptor D. Increased activity of platelet COX-1 E. Clopidogrel is a reversible GP IIb/IIIa inhibitor
Correct answer: B. Reduced conversion of clopidogrel to its active metabolite
Clopidogrel is a prodrug. It must be activated by the liver enzyme CYP2C19 before it can irreversibly block the P2Y12 ADP receptor on platelets. People with loss-of-function CYP2C19 alleles (“poor metabolizers”) make little active drug, so their platelets are not inhibited and they have a higher risk of stent thrombosis. Options for these patients include ticagrelor (not a prodrug) or prasugrel (activated by other enzymes). Drugs that inhibit CYP2C19, such as omeprazole, can also reduce clopidogrel’s effect.
Why the other options are wrong:
Aspirin is not activated by CYP2C19, and its clearance does not explain this genetic finding.
Clopidogrel acts on the P2Y12 (ADP) receptor, not the thromboxane receptor.
Aspirin irreversibly inhibits COX-1; a change in COX-1 activity would not involve a hepatic enzyme gene.
Clopidogrel is an irreversible P2Y12 blocker. GP IIb/IIIa inhibitors are abciximab, eptifibatide and tirofiban.
Question 4: Toxicity after a small dose increase
A 30-year-old man with epilepsy takes phenytoin 300 mg daily. His serum level is 12 µg/mL (therapeutic range 10–20 µg/mL), but he still has occasional seizures, so the dose is increased to 400 mg daily. Two weeks later he has nystagmus, slurred speech and an unsteady gait, and his phenytoin level is 35 µg/mL. Which of the following best explains the large rise in drug level?
A. Saturation of the liver enzymes that metabolize phenytoin B. Phenytoin induces its own metabolism C. First-order elimination of phenytoin D. Decreased renal excretion of unchanged phenytoin E. Increased oral bioavailability at higher doses
Correct answer: A. Saturation of the liver enzymes that metabolize phenytoin
At therapeutic doses, the liver enzymes that metabolize phenytoin are close to saturation. Once they are saturated, the body removes a fixed amount of drug per hour instead of a fixed fraction. This is called zero-order kinetics. As a result, a small dose increase can cause a large, disproportionate rise in serum level and toxicity (nystagmus first, then ataxia and confusion). Other drugs with zero-order elimination: ethanol and high-dose aspirin (mnemonic: “PEA” — Phenytoin, Ethanol, Aspirin).
Why the other options are wrong:
Phenytoin induces other drugs’ metabolism (CYP3A4), but autoinduction would lower, not raise, its level.
With first-order elimination, levels rise in proportion to the dose (a 33% increase, not almost tripling).
Phenytoin is mainly cleared by the liver, not the kidneys.
Bioavailability does not explain this pattern; enzyme saturation does.
Question 5: Blood pressure response to epinephrine after an alpha blocker
In an experiment, an intravenous dose of epinephrine raises a subject’s mean arterial pressure. The subject is then given phentolamine. When the same dose of epinephrine is given again, mean arterial pressure falls. Which of the following best explains the fall in blood pressure after the second dose?
A. Epinephrine becomes a selective alpha-1 agonist B. Phentolamine directly stimulates beta-1 receptors C. Activation of muscarinic receptors in blood vessels D. Inhibition of norepinephrine reuptake E. Unopposed beta-2 receptor–mediated vasodilation
Correct answer: E. Unopposed beta-2 receptor–mediated vasodilation
Epinephrine stimulates alpha-1 (vasoconstriction), beta-1 (heart) and beta-2 (vasodilation in skeletal muscle) receptors. Normally the alpha-1 effect wins, so blood pressure rises. Phentolamine is a nonselective alpha blocker. With alpha receptors blocked, only the beta-2 vasodilation remains, so blood pressure falls. This is called epinephrine reversal. Norepinephrine does not show this reversal because it has little beta-2 activity.
Why the other options are wrong:
Epinephrine’s receptor activity does not change; its alpha effects are simply blocked.
Phentolamine is an alpha antagonist, not a beta agonist.
Epinephrine does not act on muscarinic receptors.
Reuptake inhibition (as with cocaine) would increase, not decrease, the pressor response.
Question 6: Screening before a biologic for Crohn disease
A 34-year-old woman with moderate to severe Crohn disease is going to start infliximab. She was born in the Philippines and has no symptoms other than her bowel disease. Which of the following tests should be done before starting this drug?
A. Hepatitis A antibody B. Thiopurine methyltransferase (TPMT) activity C. Interferon-gamma release assay D. Antinuclear antibody E. Baseline audiogram
Correct answer: C. Interferon-gamma release assay
Infliximab is a monoclonal antibody against TNF-alpha. TNF-alpha is essential for forming and maintaining granulomas, which keep latent tuberculosis contained. Blocking it can cause reactivation of latent TB, often outside the lungs. All patients must be screened for latent TB before anti-TNF therapy with an interferon-gamma release assay or a tuberculin skin test. This patient’s birth in a TB-endemic country makes screening even more important. Hepatitis B screening is also recommended before anti-TNF drugs.
Why the other options are wrong:
Hepatitis A does not reactivate; screening is not required before anti-TNF therapy.
TPMT activity is checked before azathioprine or 6-mercaptopurine, not infliximab.
Infliximab can cause drug-induced lupus, but routine ANA testing is not the key safety screen.
Audiograms monitor ototoxic drugs such as aminoglycosides and cisplatin.
Question 7: An anticonvulsant in pregnancy
A 26-year-old woman has generalized epilepsy that is well controlled on a drug that is also used for bipolar disorder and migraine prevention. She was not taking a folic acid supplement. Her pregnancy test is now positive at 7 weeks of gestation. Her fetus is at greatest risk for which of the following malformations?
A. Ebstein anomaly B. Phocomelia C. Discolored teeth D. Neural tube defect E. Vaginal clear cell adenocarcinoma later in life
Correct answer: D. Neural tube defect
The drug is valproic acid, a broad-spectrum anticonvulsant that is also used for bipolar disorder and migraine prevention. Valproate is one of the most teratogenic anticonvulsants. It interferes with folate metabolism and causes neural tube defects such as spina bifida (about 1–2% of exposed pregnancies), plus heart defects and developmental delay. Valproate should be avoided in women who can become pregnant whenever possible. Women taking anticonvulsants are advised to take folic acid before conception.
Why the other options are wrong:
Ebstein anomaly is linked to lithium.
Phocomelia (limb defects) is linked to thalidomide.
Tooth discoloration is linked to tetracyclines.
Clear cell adenocarcinoma of the vagina is linked to DES (diethylstilbestrol).
Key takeaways
Doxorubicin: dilated cardiomyopathy; prevent with dexrazoxane.
Never give nitrates with PDE-5 inhibitors (sildenafil, tadalafil).
Clopidogrel is a prodrug activated by CYP2C19; poor metabolizers get less benefit.
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Written and reviewed by Dr. Ray Makar, MD, dermatologist with 20 years of clinical practice. Last reviewed: October 2026. For exam preparation only, not medical advice.
