A 72-year-old patient with Parkinson's disease on carbidopa-levodopa develops unpredictable off episodes despite multiple daily doses. Which adjunct therapy targets the COMT enzyme to extend levodopa's half-life and reduce off time?

• A Opicapone or entacapone (COMT inhibitors) ✓
• B Pramipexole (dopamine agonist)
• C Selegiline (MAO-B inhibitor)
• D Amantadine (NMDA antagonist)

Explanation

COMT (catechol-O-methyltransferase) inhibitors — entacapone and opicapone — block peripheral degradation of levodopa and 3-OMD (3-O-methyldopa), extending levodopa's plasma half-life and improving CNS delivery. They are indicated for motor fluctuations (wearing-off/on-off phenomenon) as adjuncts to levodopa. Opicapone (once daily) is preferred over entacapone (given with each levodopa dose) for convenience. Tolcapone (an older COMT inhibitor) is restricted due to hepatotoxicity. MAO-B inhibitors (rasagiline, selegiline) reduce central dopamine breakdown and can also reduce off time.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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Written and medically reviewed by the StethoPrep medical team.