10 USMLE Pharmacology Mechanism Questions with Answers and Explanations (Set 3)

These 10 USMLE pharmacology practice questions (Set 3) focus on drug interactions, antidotes and adverse effects that are tested again and again: CYP450 interactions, beta-blocker and opioid overdose, ACE inhibitor cough, bleomycin lung toxicity, drugs to avoid in shock and the role of urine pH in drug excretion. Each question includes the correct answer and an explanation.

Written by Dr. Ray Makar, MD, author of the Repeated USMLE Questions eBook series.

Prefer video? Watch daily USMLE case questions on MedFocus by Dr. Ray on YouTube.

How to use this page: read the question, pick your answer, then tap Show Answer and Explanation.

Questions

Question 1. A 58-year-old woman with hyperlipidemia has been taking simvastatin for the past 6 months. She recently started drinking a large glass of grapefruit juice every morning. Two weeks later, she presents with diffuse muscle pain and weakness. Laboratory studies reveal a markedly elevated creatine kinase (CK) level. Which of the following best explains the mechanism underlying this patient’s presentation?

A- Grapefruit juice inhibits intestinal CYP3A4, increasing simvastatin plasma concentration
B- Grapefruit juice induces hepatic CYP3A4, decreasing simvastatin metabolism
C- Grapefruit juice chelates simvastatin, forming an insoluble complex
D- Grapefruit juice increases renal clearance of simvastatin metabolites
E- Grapefruit juice displaces simvastatin from plasma protein binding sites

A- Grapefruit juice inhibits intestinal CYP3A4, the enzyme responsible for first-pass metabolism of many statins (especially simvastatin, lovastatin, and atorvastatin). This raises statin plasma concentration and significantly increases the risk of myopathy and rhabdomyolysis.
The correct answer is A

 

Question 2. A 67-year-old man on chronic warfarin therapy for atrial fibrillation is prescribed a 10-day course of metronidazole for a dental infection. One week later, he presents with gum bleeding and easy bruising. His INR is found to be markedly elevated compared to his stable baseline. Which of the following best explains this interaction?

A- Metronidazole inhibits CYP2C9-mediated metabolism of warfarin
B- Metronidazole induces hepatic synthesis of vitamin K-dependent clotting factors
C- Metronidazole decreases intestinal absorption of warfarin
D- Metronidazole increases warfarin renal excretion
E- Metronidazole permanently displaces warfarin from albumin

A- Metronidazole inhibits CYP2C9, the enzyme responsible for metabolizing the more potent S-enantiomer of warfarin. This leads to elevated warfarin levels, an increased INR, and a higher risk of bleeding.
The correct answer is A

 

Question 3. A 24-year-old man is brought to the emergency department after intentionally ingesting a large number of propranolol tablets. On arrival, his heart rate is 42/min and blood pressure is 78/46 mmHg. Intravenous fluids and atropine fail to improve his heart rate or blood pressure. Which of the following is the most appropriate next step in management?

A- Glucagon
B- Calcium gluconate
C- Naloxone
D- Sodium bicarbonate
E- Flumazenil

A- Glucagon bypasses the blocked beta-adrenergic receptor by directly activating adenylate cyclase, increasing intracellular cAMP and improving heart rate and contractility. It is the treatment of choice for severe beta-blocker overdose refractory to fluids and atropine.
The correct answer is A

 

Question 4. A 29-year-old man is found unresponsive with pinpoint pupils and a respiratory rate of 4/min. He is given a medication that rapidly reverses his respiratory depression. Which of the following best describes the mechanism of action of the drug most likely administered?

A- Competitive antagonist at mu-opioid receptors
B- Irreversible inhibitor of opioid receptor synthesis
C- Partial agonist at kappa-opioid receptors
D- Inhibitor of acetylcholinesterase
E- Agonist at GABA-A receptors

A- Naloxone is a competitive antagonist at mu-opioid receptors. It rapidly displaces opioids from these receptors, reversing respiratory depression, sedation, and miosis. Because its duration of action is shorter than most opioids, repeat dosing or an infusion may be required.
The correct answer is A

 

Question 5. A 55-year-old man with hypertension started on lisinopril two months ago returns to clinic complaining of a persistent dry cough. Physical examination and chest x-ray are unremarkable. Which of the following best explains the mechanism of this adverse effect?

A- Decreased degradation of bradykinin
B- Increased angiotensin II levels
C- Direct irritation of the bronchial epithelium by lisinopril
D- Accumulation of aldosterone
E- Increased renin release

A- ACE (kininase II) normally degrades bradykinin. ACE inhibitors reduce bradykinin breakdown, leading to its accumulation in the respiratory tract, which is thought to cause the characteristic dry cough seen in up to 20% of patients on these medications.
The correct answer is A

 

Question 6. A 72-year-old man presents to the office for evaluation of new symptoms. He has a history of cancer and takes chemotherapeutic treatment. Now he complains of dyspnea and mild fatigue since last week. Examination reveals temperature of 98.3 F, pulse of 80/min, blood pressure of 140/86 and respiratory rate of 22/min. On chest auscultation, there are crackles on both lung bases with no wheezes. A chest x-ray shows bilateral diffuse interstitial markings. Which of the following agents is responsible for this patient’s new features?

A- Bleomycin
B- Cisplatin
C- Cyclophosphamide
D- Etoposide
E- Paclitaxel

A- Bleomycin- It is the only drug of the above list that causes pulmonary fibrosis. It is age- and dose-dependent.
The correct answer is A

 

Question 7. Which of these medications is contraindicated in a case of cardiogenic shock?

A- Dopamine
B- Intravenous fluids
C- Metoprolol
D- Norepinephrine

C- Metoprolol- The treatment of all types of shock should include supportive care, intravenous fluids and other medications depends on the cause of shock. Beta blockers are contraindicated in cardiogenic shock as it worsens hypotension. Dopamine and norepinephrine can be used in case of very low ejection fraction and hypotension.
The correct answer is C

 

Question 8. Which one of the following types of drug interactions occurs when aspirin is given with acetaminophen?

A- Additive
B- Permissive
C- Synergistic
D- Tachyphylactic

A- Additive- This occurs when the effect of the 2 medications is equal to the sum of their individual effects.
The correct answer is A

 

Question 9. Which one of the following amines is permanently charged?

A- Primary amines
B- Secondary amines
C- Tertiary amines
D- Quaternary amines

D- Quaternary amines- Quaternary amines are a type of amine compound where the nitrogen atom is bonded to four carbon atoms. In this arrangement, the nitrogen atom carries a positive charge (quaternary nitrogen). This positive charge makes quaternary amines permanently charged. Primary amines have one alkyl or aryl group attached to the nitrogen atom. Secondary amines have two alkyl or aryl groups attached to the nitrogen atom. Tertiary amines have three alkyl or aryl groups attached to the nitrogen atom. Unlike quaternary amines, primary, secondary, and tertiary amines do not have a permanent positive charge on the nitrogen atom because they can donate a pair of electrons to form a covalent bond with a proton (H+), resulting in the formation of a temporary positive charge. However, quaternary amines have all their valence electrons used in bonds, so they cannot donate any electrons, leading to a permanent positive charge on the nitrogen atom.
The correct answer is D

 

Question 10. Administration of which one of the following can increase the excretion of a weak acid i.e. Aspirin toxicity?

A- A weak base
B- A neutral salt
C- A weak acid
D- A strong acid

A- A weak base- Aspirin is a weak acid. When the urine becomes more alkaline (basic), it promotes the ionization of weak acids like aspirin. This ionization leads to increased solubility and excretion of aspirin in the urine, reducing its toxicity.
The correct answer is A

 

High-yield points from this set

  • Grapefruit juice inhibits intestinal CYP3A4 and raises simvastatin levels (myopathy).
  • Metronidazole inhibits CYP2C9 and raises warfarin levels (bleeding, high INR).
  • Beta-blocker overdose not responding to atropine and fluids: IV glucagon.
  • Naloxone is a competitive mu-opioid receptor antagonist.
  • ACE inhibitor cough comes from bradykinin accumulation.
  • Bleomycin causes dose-dependent pulmonary fibrosis.
  • Beta-blockers are contraindicated in cardiogenic shock.
  • Two drugs whose combined effect equals the sum of their effects = additive interaction.
  • Quaternary amines are permanently charged and cross membranes poorly.
  • Alkalinizing the urine traps weak acids such as aspirin and increases their excretion.

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