A patient with diabetes takes metoclopramide for gastroparesis. After 3 months of daily use, she develops involuntary repetitive jaw movements and tongue protrusion. The mechanism of this adverse effect is:
- A Metoclopramide's anticholinergic action directly causes basal ganglia dysfunction
- B Chronic D2 receptor blockade in the nigrostriatal pathway causes upregulation of dopamine receptors leading to tardive dyskinesia ✓
- C Peripheral 5-HT4 agonism causes extrapyramidal sensitization via the gut-brain axis
- D Dopamine release from nigrostriatal terminals triggered by 5-HT3 blockade in the brainstem
Correct answer: B. Chronic D2 receptor blockade in the nigrostriatal pathway causes upregulation of dopamine receptors leading to tardive dyskinesia
Explanation
Metoclopramide blocks D2 dopamine receptors to enhance gastric motility (prokinetic) and suppress the CTZ (antiemetic). Chronic D2 blockade in the nigrostriatal pathway causes compensatory upregulation and supersensitivity of dopamine receptors. When dopamine intermittently overcomes blockade, stimulation of the supersensitive receptors causes abnormal involuntary movements known as tardive dyskinesia — typically oral-buccal-lingual movements. This is a serious long-term adverse effect; the risk increases with duration of treatment beyond 12 weeks.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.