WBR0162

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Author PageAuthor::William J Gibson
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Pharmacology
Sub Category SubCategory::Hematology, SubCategory::Oncology
Prompt [[Prompt::A 74 year old woman with Chronic lymphocytic leukemia presents to her oncologist for worsening fever and weight loss over the past month. The oncologist initiates therapy with fludarabine, cyclophosphamide, and rituximab. Two weeks later, the patient experiences bloody urine with suprapubic tenderness and a slight burning sensation. Which of the following drugs could have prevented this condition?]]
Answer A AnswerA::Acrolein
Answer A Explanation AnswerAExp::Acrolein is urotoxic metabolite of cyclophosphamide that is responsible for hemorrhagic cystitis.
Answer B AnswerB::Leucovorin
Answer B Explanation AnswerBExp::Leucovorin is equivalent to activated folinic acid. It can be administered to “rescue” the effects of Methotrexate.
Answer C AnswerC::Mesna
Answer C Explanation AnswerCExp::Mesna binds to a urotoxic metabolite of cyclophosphamide called acrolein in the bladder and can prevent hemorrhagic cystitis.
Answer D AnswerD::Methylene Blue
Answer D Explanation AnswerDExp::Methylene blue is the antidote for cyanide poisoning.
Answer E AnswerE::N-acetyl Cysteine
Answer E Explanation AnswerEExp::N-acetyl cysteine can be administered for acetominophen overdose.
Right Answer RightAnswer::C
Explanation [[Explanation::The patient in this vignette has developed hemorrhagic cystitis as a consequence of cyclophosphamide therapy. Chronic lymphocytic leukemia is an indolent, slowly evolving hematopoetic malignancy that primarily affects the elderly. Chemotherapy is withheld until the patient is symptomatic. One of the drugs used in treating CLL is cyclophosphamide. Cyclophosphamide is an alkylating agent that covalently cross-links guanine nucleotides at the N-7 nitrogen. Cyclophosphamide is notorious for causing hemorrhagic cystitis. A small portion of the original drug is metabolized to arolein. Acrolein is toxic to the bladder epithelium and can lead to hemorrhagic cystitis. This can be prevented through the use of aggressive hydration and/or mesna. Mesna binds acrolein in the bladder, barring it from exerting its toxic effects. Cyclophosphamide itself is a carcinogen and may cause AML or transitional cell carcinoma of the bladder.

Mnemonic: Cyclophosphamide is A SCAM

Anti-neoplastic

SIADH

Cystitis

Alkylating agent

Myelosuppression.
Educational Objective: Cyclophosphamide should be administered along with mesna to prevent hermorrhagic cystitis.
References: First Aid 2014 page 407]]

Approved Approved::Yes
Keyword WBRKeyword::Cancer, WBRKeyword::Chemotherapy, WBRKeyword::CLL, WBRKeyword::Chronic lymphocytic leukemia, WBRKeyword::Leukemia, WBRKeyword::Hematopoetic, WBRKeyword::Antidote, WBRKeyword::Chemotherapeutic
Linked Question Linked::
Order in Linked Questions LinkedOrder::