Cyclophosphamide is an alkylating agent that requires hepatic activation. The metabolite responsible for its antineoplastic effect and its dose-limiting hemorrhagic cystitis is:

• A Chloroethylaziridine (both effects)
• B Phosphoramide mustard (antineoplastic) and acrolein (bladder toxicity) ✓
• C Nornitrogen mustard (antineoplastic) and chloroacetaldehyde (bladder toxicity)
• D 4-hydroxycyclophosphamide (bladder toxicity) and carboxyphosphamide (antineoplastic)

Explanation

Cyclophosphamide is activated by hepatic CYP2B6 to 4-hydroxycyclophosphamide, which spontaneously decomposes to phosphoramide mustard (the alkylating moiety that cross-links DNA) and acrolein. Acrolein accumulates in the bladder urothelium causing hemorrhagic cystitis. Mesna (2-mercaptoethane sulfonate sodium) is given prophylactically to detoxify acrolein in the bladder by conjugation. Adequate hydration and frequent urination also help. This highlights the clinical importance of this two-product activation scheme.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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