Repeated USMLE Questions Step 1- Pharmacology-1

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Q- 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.

 

Q- 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.

 

Q- 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.

 

Q- 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.

 

Q- 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.

 

Q- 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.

 

Q- 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.

 

Q- 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.

 

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Dr Ray Makar
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12 thoughts on “Repeated USMLE Questions Step 1- Pharmacology-1”

  1. Thank you Dr. Mohamednor, I hope your success in your future medical career.

  2. I really appreciate your helping to me
    I thank you indeed Dr Ray
    Continue your efforts

  3. Thanks for knowledge to us medical students during corona holiday

  5. Thank you so much dear doctor Manzoor

  7. You are welcome. Thank you

  8. Thanks sir

  9. Cyclophosphamide is best known for bladder complications which are more common than pulmonary complications while bleomycin is known for pulmonary fibrosis which starts as lung inflammation leading to fibrosis in up to 10% of long term users. Thank you for your question.

  10. What about cyclophosphamide? It also causes pulmonary fibrosis,,, why bleomycin is the best answer to choose? Thank u

  11. Thank you

  12. Very Helpful

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