A 35-year-old man comes to the emergency department due to acute onset coffee-ground emesis and lightheadedness. Three weeks ago, he developed lower back pain with stiffness and was started on naproxen and cyclobenzaprine. Past medical history is notable for moderate persistent asthma, hepatitis C, and HIV. His last CD4 count was 550/mm³. The patient has a remote history of intravenous drug use but currently does not use any illicit drugs. He has an allergy to penicillin that causes a rash and pruritus. Upper gastrointestinal endoscopy reveals gastric mucosal erythema and erosions. Which of the following best explains this patient's current symptoms?

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Quizplus · Accepted Answer

11ec160b_3c26_0ab0_9249_45ed4d463238_MD0001_00 This patient has acute upper gastrointestinal (GI) hemorrhage, which is likely an adverse reaction to his nonsteroidal anti-inflammatory drug (NSAID). Cyclooxygenase (COX) catalyzes the rate-limiting step in the conversion of arachidonic acid to prostaglandins, prostacyclin, and thromboxane. COX enzymes are involved in mediating inflammation but are also required for housekeeping functions (eg, platelet aggregation, gastric mucosal protection). COX enzymes are inhibited by NSAIDs such as naproxen. As a result, NSAIDs can cause impairment of prostaglandin-dependent GI mucosal protection, leading to mucosal erythema, erosions, and ulceration. Upper GI symptoms can occur within the first 24 hours of starting an NSAID, and changes to the mucosa can be seen within the first week. Most adverse drug reactions are predictable due to the known pharmacologic properties of the drug and usually occur after extended drug exposure. Unpredictable reactions are less common and occur due to immune processes or other mechanisms. In this case, upper GI bleeding due to an NSAID is a well-known and predictable adverse event. (Choice A) Exaggerated drug sensitivity refers to adverse reactions that occur due to known pharmacologic actions of the drug but at a lower dose than expected (eg, due to altered metabolism or increased end-organ susceptibility). Patients with deficiency of thiopurine methyltransferase, an enzyme that metabolizes azathioprine, are more likely to experience adverse effects of the drug. (Choice B) An idiosyncratic drug reaction is an unpredictable reaction due to genetic differences or complex metabolic interactions in certain patients. The use of trimethoprim-sulfamethoxazole in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency can lead to oxidative cellular injury and nonimmune hemolytic anemia. (Choice C) Immunologic drug reactions (drug allergies) are unpredictable antibody or T cell-mediated responses to medications. This patient's history of rash and pruritus with penicillin likely represents IgE-mediated type I hypersensitivity. (Choice E) Pseudoallergic drug reactions mimic immunologic reactions but occur via a nonimmunologic mechanism (eg, direct immune cell activation, inhibited prostaglandin synthesis). Vancomycin, opiates, and radioiodine contrast can directly activate mast cells to cause a pseudoallergic reaction that closely mimics IgE-mediated type I hypersensitivity. Educational objective: Most adverse drug reactions are predictable and due to known pharmacologic properties of the drug. Unpredictable reactions are less common and are typically driven by patient-specific genetics (eg, enzyme deficiency, immunologic idiosyncrasy).

A 35-Year-Old Man Comes to the Emergency Department Due to Acute