WBR0413

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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 that is associated with sulfa allergy.]]
Answer E AnswerE::Chlorthalidone
Answer E Explanation AnswerEExp::Chlorthalidone is also a thiazides-type diuretic that is associated 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 only with sulfa antibiotics due to the presence of N-1 substituents in the antibiotic formula. On the other hand, non-antibiotic sulfa 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 allergy 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 clinical manifestations until complete resolution is attained. 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 for symptomatic relief of fluid overload. Compared with other loop diuretics, ethacrynic acid is associated with higher rates of ototoxicity and is usually only reserved for patients with sulfa allergy who cannot tolerate other commonly used loop or thiazide diuretics.
Educational Objective: Ethacrynic acid is a loop diuretic often prescribed to patients with sulfa allergy who cannot tolerate other commonly used diuretics. 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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