WBR0413

Author	[[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pharmacology
Sub Category	SubCategory::Renal
Prompt	[[Prompt::A 72-year-old man presents to the physician's office with complaints of dyspnea and bilateral pitting edema. His past medical history is significant for diabetes mellitus, gout, and osteoarthritis. Upon further questioning, the patient explains that he is allergic to several medications. Among the list of medications that he has tried in the past, he recalls he developed skin rash when he was administered sulfonylurea, probenicid, celecoxib, and sulfonamide antibiotics. Following appropriate work-up, the patient is diagnosed with congestive heart failure. The physician decides to prescribe diuretic therapy to relieve the patient's symptoms. Which of the following diuretics is the optimal therapeutic option to treat this patient's congestive heart failure?]]
Answer A	AnswerA::Furosemide
Answer A Explanation	[[AnswerAExp::Furosemide is a loop diuretic that is associated with sulfa allergy.]]
Answer B	AnswerB::Acetazolamide
Answer B Explanation	[[AnswerBExp::Acetazolamide is carbonic anhydrase inhibitor that is associated with sulfa allergy.]]
Answer C	AnswerC::Ethacrynic acid
Answer C Explanation	[[AnswerCExp::Ethacrynic acid is a loop diuretic often prescribed to patients with sulfa allergy.]]
Answer D	AnswerD::Hydrochlorothiazide
Answer D Explanation	[[AnswerDExp::Hydrochlorothiazide is a thiazides-type diuretic. Some thiazide diuretics are associated with sulfa allergy.]]
Answer E	AnswerE::Chlorthalidone
Answer E Explanation	[[AnswerEExp::Chlorthalidone is also a thiazides-type diuretic. Some thiazide diuretics are associated with sulfa allergy.]]
Right Answer	RightAnswer::C
Explanation	[[Explanation::Sulfa allergy is a term that describes adverse drug reactions to sulfanamide-based (sulfa) medications. The following list of medications are common sulfa drugs: Sulfonamide antibiotics: sulfanilamide, sulfadiazine, sulfapyridine, sulfacetamide, sulfoxazole, sulfamylon, sulfamethoxazole-trimethoprim (associated with the most severe hypersensitivity reactions) Diuretics: Acetazolamide Loop diuretics: Furosemide, bumetanide Thiazide diuretics: Hydrochlorothiazide, chlorothiazide, chlorthalidone, indapamide Sulfonylureas: Glyburide, chlorpropamide, gliclazide, glimepiride, tolbutamide NSAIDs: Celecoxib and valdecoxib Uricosuric agents: Probenecid Antimigraine agents: Sumatriptan, naratriptan Anticonvulsants: Topiramate Antiarrhythmic agents: Sotalol, ibutilide Others: Dapsone, sulfasalazine Sulfa allergy has an incidence rate of approximately 3 to 5% among the general population. Only a minority of patients with reported sulfa allergy have true type I hypersensitivity reactions, which often occur with sulfa antibiotics only due to the presence of N-1 substituents in the antibiotic formula. On the other hand, non-antibiotic drugs do not usually contain N-1 substituents, and patients do not usually have true type I hypersensitivity. Instead, they present with delayed manifestations of immunologic or idiosyncratic drug reactions. Clinical manifestations range from a very mild clinical course to potentially fatal outcomes. Symptoms of sulfa hypersensitivity include fever, skin rash (maculopapular rash or fixed drug eruption that often develops 1 or 2 weeks following drug administration) along with hepatic, renal, pulmonary, and hematological (thrombocytopenia, leukopenia/agranulocytosis, hemolytic anemia) manifestations. The first step in the management of sulfa allergy is stopping the offending medications followed by symptomatic treatment of the hypersensitivity manifestations until complete resolution. Among patients who require dieresis (such as patients with advanced congestive heart failure), ethacrynic acid, a phenoxyacetic acid derivative, is a loop diuretic that is not associated with sulfa allergy and may be prescribed to patients with sulfa allergy to symptomatic relief of fluid overload. However, ethacrynic acid is associated with high rates of ototoxicity and is usually only reserved for patients who are known to have sulfa allergy. Educational Objective: Ethacrynic acid is a loop diuretic often prescribed to patients with sulfa allergy for symptomatic relief of fluid overload. Features of sulfa allergy include skin, visceral, hematological, and constitutional manifestations. References: Wall GC, Bigner D, Craig S. Ethacrynic acid and the sulfa-sensitive patient. Arch Intern Med. 2003;163(1):116-117. Kucera CM, Greenberger PA: Adverse drug reactions: treatment and prevention. Hosp Med. 1996;32:11-24. Knowles S, Shapiro L, Shear, NH. Should celecoxib be contraindicated in patients who are allergic to sulfonamides? Revisiting the meaning of ‘sulfa’ allergy. Drug Safety., 2001;24:239-247. First Aid 2014 page 255]]
Approved	Approved::Yes
Keyword	WBRKeyword::Sulfa allergy, WBRKeyword::Diuretics, WBRKeyword::Ethacrynic acid, WBRKeyword::Sulfa drug, WBRKeyword::Hypersensitivity, WBRKeyword::Congestive heart failure
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Order in Linked Questions	LinkedOrder::