An elderly patient on chlorpromazine for schizophrenia develops parkinsonian features and tardive dyskinesia after 18 months. The receptor mechanism MOST responsible for tardive dyskinesia is:

• A Accumulation of toxic metabolites that directly damage nigrostriatal dopaminergic neurons
• B Dopamine D2 receptor supersensitivity in the nigrostriatal pathway due to chronic blockade ✓
• C Cholinergic receptor upregulation in the basal ganglia
• D Serotonin 5-HT2A receptor activation in the mesocortical pathway

Explanation

Tardive dyskinesia (TD) arises from chronic D2 receptor blockade in the nigrostriatal system, leading to compensatory upregulation and supersensitivity of dopamine D2 receptors in the striatum. When the antipsychotic is continued or dose is reduced, the supersensitive receptors are overstimulated even by normal dopamine levels, producing involuntary orofacial and choreiform movements. This is distinct from acute extrapyramidal effects (D2 blockade) and is often irreversible. VMAT2 inhibitors (valbenazine, tetrabenazine) reduce presynaptic dopamine release and are approved treatments for TD.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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