A patient with tardive dyskinesia develops this condition after prolonged use of a first-generation antipsychotic. The pathophysiological mechanism most widely accepted is:

• A Upregulation and supersensitivity of D2 receptors in the nigrostriatal pathway ✓
• B D2 receptor downregulation in the mesolimbic pathway
• C Excess serotonin activity in the basal ganglia
• D Cholinergic excess in the striatum due to muscarinic receptor upregulation

Explanation

Prolonged D2 receptor blockade by typical antipsychotics causes compensatory upregulation and supersensitivity of striatal D2 receptors in the nigrostriatal pathway. This sensitised pathway responds abnormally even to physiological dopamine, producing involuntary choreiform movements (tardive dyskinesia). This condition is often irreversible and distinct from drug-induced parkinsonism (which is due to D2 blockade per se). Valbenazine and deutetrabenazine (VMAT2 inhibitors) are used in treatment.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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