A 58-year-old man with Parkinson's disease on levodopa-carbidopa 25/100 mg four times daily develops predictable 'wearing-off' phenomena. Which pharmacological strategy most specifically targets motor fluctuations from wearing-off?
- A Adding an anticholinergic agent
- B Switching to immediate-release levodopa at higher doses
- C Addition of entacapone (COMT inhibitor) ✓
- D Adding amantadine
Correct answer: C. Addition of entacapone (COMT inhibitor)
Explanation
Entacapone (or tolcapone) inhibits COMT, reducing peripheral metabolism of levodopa and extending its plasma half-life, thereby smoothing motor fluctuations during wearing-off. Safinamide (MAO-B inhibitor) and dopamine agonists are also effective for wearing-off. Amantadine specifically reduces levodopa-induced dyskinesias rather than wearing-off. Anticholinergics are used for tremor-dominant PD and worsen cognition. Increasing levodopa dose raises dyskinesia risk without addressing the pharmacokinetic issue.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.