A patient on clozapine develops agranulocytosis. The mechanism underlying clozapine-induced agranulocytosis is best described as:

• A Direct myelosuppression due to high affinity for D2 receptors in bone marrow
• B Inhibition of erythropoietin secretion from the kidney
• C Direct inhibition of folate metabolism required for myeloid cell proliferation
• D Immune-mediated destruction of granulocyte precursors, likely via reactive metabolite formation ✓

Explanation

Clozapine-induced agranulocytosis is believed to be immune-mediated, with reactive metabolites (norclozapine N-oxide, nitrenium ion) binding to granulocyte precursor proteins, triggering antibody formation and cell destruction; this is supported by the clinical pattern of delayed onset and occurrence with re-exposure. Mandatory weekly/fortnightly WBC monitoring is required under the Clozapine REMS program. It is not related to D2 receptor activity or folate metabolism.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.