COMSAE - Comprehensive Osteopathic Medical Self-Assessment Examination Pharmacology Questions and Answers — Questions and Answers
Question 1: A 68-year-old male with a history of heart failure with reduced ejection fraction and concurrent atrial fibrillation is being managed medically. His physician adds a medication that works by inhibiting the Na+/K+-ATPase pump in myocardial cells. This action leads to an increase in intracellular calcium. Which of the following effects is the primary therapeutic goal of this medication in this patient?
- Increased myocardial contractility and decreased atrioventricular (AV) node conduction (Correct answer)
- Coronary artery vasodilation and decreased platelet aggregation
- Decreased systemic vascular resistance and increased heart rate
- Inhibition of the renin-angiotensin-aldosterone system and potassium retention
Correct answer: Increased myocardial contractility and decreased atrioventricular (AV) node conduction
The medication described is digoxin. Its primary mechanism is the inhibition of the Na+/K+-ATPase pump, which increases intracellular sodium. This, in turn, reduces the activity of the Na+/Ca2+ exchanger, leading to increased intracellular calcium and thus stronger myocardial contractions (positive inotropy). Additionally, digoxin has a parasympathomimetic effect that slows conduction through the AV node, which is therapeutic for controlling the ventricular rate in atrial fibrillation.
Question 2: A 45-year-old male is being treated for a severe MRSA infection with intravenous vancomycin. During the infusion, he develops diffuse erythema and flushing of his face, neck, and upper torso, accompanied by pruritus and mild hypotension. What is the most likely direct cause of this reaction?
- An IgE-mediated type I hypersensitivity reaction
- Direct degranulation of mast cells and basophils (Correct answer)
- Formation of drug-hapten complexes leading to immune activation
- A cytokine storm induced by bacterial lysis
Correct answer: Direct degranulation of mast cells and basophils
This patient is experiencing Vancomycin Infusion Reaction (VIR), also known as red man syndrome. This is an anaphylactoid reaction, not a true allergic (IgE-mediated) reaction. It is caused by the rapid infusion of vancomycin, which directly stimulates mast cells and basophils to release histamine, leading to the characteristic flushing, erythema, and pruritus.
Question 3: A 55-year-old female with type 2 diabetes mellitus is started on empagliflozin. Which of the following best describes the primary mechanism of action of this medication?
- It increases insulin secretion from pancreatic beta cells.
- It decreases hepatic glucose production.
- It increases insulin sensitivity in peripheral tissues.
- It inhibits glucose reabsorption in the proximal convoluted tubule. (Correct answer)
Correct answer: It inhibits glucose reabsorption in the proximal convoluted tubule.
Empagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor. SGLT2 is responsible for reabsorbing the majority of filtered glucose from the tubular fluid back into the blood in the proximal convoluted tubule of the kidney. By inhibiting this transporter, empagliflozin promotes the excretion of glucose in the urine, thereby lowering blood glucose levels.
Question 4: A farmworker is brought to the emergency department with confusion, pinpoint pupils, profuse sweating, and muscle fasciculations. He is bradycardic and hypotensive. These symptoms are characteristic of poisoning by an agent that causes which of the following?
- Blockade of muscarinic acetylcholine receptors
- Inhibition of acetylcholinesterase (Correct answer)
- Blockade of nicotinic acetylcholine receptors at the neuromuscular junction
- Increased release of norepinephrine from sympathetic nerve terminals
Correct answer: Inhibition of acetylcholinesterase
This clinical presentation is classic for organophosphate poisoning, which is common in agricultural settings. Organophosphates are irreversible inhibitors of acetylcholinesterase (AChE). Inhibition of AChE leads to an accumulation of acetylcholine at both muscarinic and nicotinic synapses, causing a cholinergic crisis with symptoms like miosis, salivation, lacrimation, urination, defecation, GI distress, emesis (DUMBELS), as well as muscle fasciculations and weakness.
Question 5: A 62-year-old male with chronic back pain has been managed with long-term, high-dose opioid therapy. While patients typically develop tolerance to many side effects of opioids, which of the following adverse effects is least likely to diminish over time?
- Sedation
- Nausea and vomiting
- Constipation (Correct answer)
- Respiratory depression
Correct answer: Constipation
While tolerance develops to most of the central nervous system effects of opioids, such as sedation, euphoria, and respiratory depression, tolerance to the gastrointestinal effects, particularly constipation, develops very slowly or not at all. Opioids decrease GI motility and secretions, leading to persistent constipation that often requires proactive management throughout the duration of therapy.
Question 6: A patient stabilized on warfarin for atrial fibrillation is prescribed a new medication. Several weeks later, their INR is found to be dangerously elevated without any change in diet or warfarin dose. The new medication is most likely a potent inhibitor of which cytochrome P450 enzyme?
- CYP1A2
- CYP2D6
- CYP2C9 (Correct answer)
- CYP3A4
Correct answer: CYP2C9
Warfarin is a substrate for several CYP enzymes, but its more potent S-enantiomer is primarily metabolized by CYP2C9. Inhibition of CYP2C9 by another drug (such as amiodarone, fluconazole, or trimethoprim-sulfamethoxazole) will decrease the metabolism of S-warfarin, leading to higher plasma levels and an increased anticoagulant effect, reflected by a dangerously elevated INR.
