All are true about Ifosfamide except
Correct Answer: Less neurotoxic than cyclophosphamide
Description: Less neurotoxic than cyclophosphamide Ifosfamide is a synthetic analogue of cyclophosphamide. It is a nitrogen mustard alkylating agent. Ifosfamide is a cyclophosphamide analogue thus it has all the potential adverse effects of cyclophosphamide. Ifosfamide metabolite, rather than the parent drug is responsible for toxicity of Ifosfamide. Ifosfamide is a prodrug that requires metabolic activation by microsomal liver enzymes to produce biologically active compounds. Activation is mediated by cytochrome p450 - CYP3A4 and deactivated by CYP3A-4 AND CYP2B6. The metabolic activation of Ifosfamide is an autoinducible process and besides producing active cytotoxic metabolites it also results in generation of some toxic metabolic byproducts that are responsible for its side effects. The two well known toxic nzetabolities of Ifosfamide are acrolein and chloracetaldehyde. - "Acrolein is responsible for Ifosfamide induced hemorrhagic cystitis where as chloroacetaldehyde is responsible for renal tubular damage and neutrotoxicity". Acrolein - Hemorrhagic cystitis Chloroacetaldehyde - Nephrotoxicity (Renal tubular danage) - Neurotoxicity At equivalent doses, the rate of chloroacetaldehyde generation with ifosfamide is 40 times greater than with cyclophosphamide. -This explains why cyclophosphamide although structurally related has viually no nephrotoxicity and less neurotoxic. Goodman Gilman Says - At equivalent doses, the rate of chloroacetaldehyde generation with ifosfamide is 40 times greater than with cyclophosphamide therefore it produces more platelet suppression, neurotoxicity, urothelial damage. Neurotoxicity in ifosfamide Neurotoxity in ifosfamide is caused by the active metabolite of ifosfamide i.e., chloralacetaldehyde These metabolites enter brain and produce neurological symptoms which are encephalopathy and seizure. These symptoms almost always resolve with discontinuation of the drug. Patients who have mild to moderate symptoms can continue to receive the drug.
Category:
Pharmacology
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