Pharmacology
Anti-Parkinsonian drugs
Pharmacology

Anti-Parkinsonian drugs

Levodopa-carbidopa, dopamine agonists, MAO-B and COMT inhibitors, anticholinergics — when each helps and what they break.

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Levodopa-carbidopa (gold standard)

  • Levodopa crosses BBB → converted to dopamine in CNS
  • Carbidopa = peripheral decarboxylase inhibitor → prevents peripheral conversion → less nausea, more drug to brain
  • Best for the bradykinesia and rigidity components
  • After 5–10 years: 'on-off' fluctuations + dyskinesias (peak-dose chorea)
  • AVOID protein with doses (large amino acids compete for transport)
  • AVOID first-generation antipsychotics in Parkinson (D2 blockade worsens motor); use quetiapine or clozapine if psychosis

Dopamine agonists

  • Pramipexole, ropinirole — non-ergot; first-line in younger patients (delays levodopa)
  • Side effects: somnolence, impulse control (gambling, hypersexuality), peripheral edema, hallucinations
  • Ergot-derived (bromocriptine, pergolide) — rarely used (cardiac valve fibrosis)
  • Rotigotine — transdermal patch
  • Apomorphine — rescue for off-episodes

MAO-B inhibitors

  • Selegiline, rasagiline, safinamide
  • ↑ dopamine in synapse by blocking breakdown
  • Mild monotherapy in early disease; adjunct to levodopa for off-episodes
  • Watch for serotonin syndrome with SSRIs, TCAs, tramadol, meperidine
  • Tyramine hypertensive crisis at higher doses (lose B-selectivity)

COMT inhibitors

  • Entacapone, tolcapone, opicapone
  • ↑ levodopa half-life by blocking peripheral breakdown
  • Tolcapone: hepatotoxicity (need LFTs)
  • Always given WITH levodopa (no benefit alone)

Anticholinergics

  • Benztropine, trihexyphenidyl
  • Useful for TREMOR (especially young patients)
  • AVOID in elderly (confusion, urinary retention, dry mouth, falls)
  • Also rapidly reverses acute dystonia from antipsychotics

Amantadine

  • Mild antiparkinsonian + reduces levodopa-induced dyskinesias
  • NMDA antagonist + dopamine release
  • Side effects: livedo reticularis (mottled skin), ankle edema

Deep brain stimulation

  • Subthalamic nucleus or globus pallidus interna
  • For motor fluctuations + dyskinesias refractory to medications
  • Does NOT slow disease progression
  • Best candidate: good levodopa response, no dementia, intact cognition

Parkinson drug picker

PatientBest initial
Young (<65), motor symptomsDopamine agonist (pramipexole)
Older or severeLevodopa-carbidopa
Tremor-predominant, youngAnticholinergic (trihexyphenidyl)
Refractory dyskinesiasAmantadine
End-of-dose 'off' periodsCOMT or MAO-B inhibitor add
Psychosis in ParkinsonQuetiapine or clozapine (NEVER haloperidol)

High-yield pearls

  • Antipsychotic + Parkinson patient → use QUETIAPINE or CLOZAPINE (low D2 affinity); NEVER haloperidol
  • Pramipexole/ropinirole impulse control disorders — ASK about gambling, hypersexuality
  • Selegiline + SSRI → serotonin syndrome risk
  • Anticholinergics for Parkinson are AVOIDED in elderly (worsens cognition, falls)
  • Stalevo = levodopa + carbidopa + entacapone (triple combo pill)
Quick check

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