Antiparkinsonian Drugs

On this page

Parkinson's Pathophys & Levodopa - Brain Balancers

  • Pathophysiology: Dopamine (DA) depletion in nigrostriatal pathway (substantia nigra pars compacta → striatum); Lewy bodies. Imbalance: ↓DA, relative ↑Acetylcholine (ACh). Pathophysiology of Parkinson's Disease
  • Levodopa (L-DOPA):
    • MOA: Metabolic precursor of DA; crosses Blood-Brain Barrier (BBB); converted to DA by DOPA decarboxylase in brain. Most effective drug.
  • Carbidopa/Benserazide:
    • MOA: Peripheral DOPA decarboxylase inhibitors.
    • Benefits: ↓ L-DOPA dose required, ↓ peripheral side effects (Nausea/Vomiting, arrhythmias), ↑ L-DOPA reaching brain.
  • L-DOPA Adverse Effects:
    • Peripheral: Nausea/Vomiting, postural hypotension, cardiac arrhythmias.
    • Central: Dyskinesias (chorea, dystonia), psychosis (hallucinations), 'on-off' phenomenon (📌 like a faulty switch), 'wearing-off' phenomenon.
  • Interactions:
    • Pyridoxine (Vitamin B6): Enhances peripheral L-DOPA metabolism (if L-DOPA given alone), ↓ efficacy.
    • Non-selective MAOIs: Risk of hypertensive crisis.

⭐ The 'on-off' phenomenon, characterized by unpredictable fluctuations between mobility and immobility, is a significant challenge in long-term Levodopa therapy.

Dopamine Agonists - Dopamine's Deputies

  • MOA: Directly stimulate DA receptors in striatum.
  • Types & Key Drugs:
    CategoryExamplesKey Features
    Non-ErgotPramipexole (D2/D3), Ropinirole (D2), Rotigotine (D1-3 patch), Apomorphine (D1/D2 SC rescue)Preferred; lower fibrosis risk
    ErgotBromocriptine (D2)Less used; ⚠️ risk of fibrosis (cardiac, pulmonary)
  • Pros vs. Levodopa: Longer action; potentially ↓ motor fluctuations/dyskinesias (early).
  • Cons: Less potent (motor); ↑ somnolence (sleep attacks), hallucinations, edema, 📌 impulse control disorders.
  • Use: Early PD monotherapy (<65-70 yrs); adjunct in advanced PD (↓ 'off' time, ↓ L-DOPA dose).

⭐ Impulse control disorders (e.g., pathological gambling, compulsive shopping, hypersexuality) are a distinctive and serious adverse effect class associated with dopamine agonists.

Enzyme Inhibitors & Amantadine - Helper Crew Drugs

  • MAO-B Inhibitors (Selegiline, Rasagiline, Safinamide):
    • MOA: Inhibit MAO-B → ↑brain DA. Safinamide: also ↓glutamate.
    • Use: Early PD; adjunct to L-DOPA (↓'wearing-off').
    • SE: Nausea, insomnia (Selegiline). Serotonin syndrome risk (SSRIs/TCAs). Rare tyramine reaction.
  • COMT Inhibitors (Entacapone, Tolcapone, Opicapone):
    • MOA: Inhibit COMT → ↓L-DOPA metabolism (Entacapone/Opicapone: peripheral; Tolcapone: P+C) → ↑L-DOPA bioavailability & t½.
    • Use: With L-DOPA for 'wearing-off'.
    • SE: Dyskinesias (↑L-DOPA), N/D. Brownish-orange urine (Entacapone).

    ⭐ Tolcapone, a COMT inhibitor, carries a significant risk of hepatotoxicity, necessitating regular liver function monitoring, unlike Entacapone.

  • Amantadine:
    • MOA: ↑DA release, ↓DA reuptake, NMDA antagonist, anticholinergic.
    • Use: Mild early PD; L-DOPA-induced dyskinesia.
    • SE: Livedo reticularis, ankle edema, confusion.

Pharmacology of Antiparkinsonian Drugs

Anticholinergics & Management - Tremor Tamers & Tactics

  • Anticholinergics (Central Muscarinic Receptor Antagonists)
    • MOA: Block striatal muscarinic receptors; restore Dopamine/Acetylcholine balance. ↓ tremor, rigidity.
    • Examples: Trihexyphenidyl, Benztropine, Procyclidine, Biperiden.
    • Use: Younger patients (<65-70 yrs) with predominant tremor. Drug-induced parkinsonism (not tardive dyskinesia).
    • Side Effects: Dry mouth, blurred vision, constipation, urinary retention, tachycardia, confusion (elderly). 📌 Mnemonic: 'Can't see, can't pee, can't spit, can't shit'.
    • Contraindications: Narrow-angle glaucoma, prostatic hyperplasia, paralytic ileus.

⭐ Central anticholinergics are particularly effective against tremor in Parkinson's disease but are poorly tolerated in elderly patients due to cognitive side effects and other peripheral anticholinergic effects.

  • Overall Management Strategy
    • Initial: MAO-B inh, Amantadine, DA agonist, Levodopa (age, symptoms, preference).
    • Motor Complications ('wearing-off', 'on-off', dyskinesias): Adjust L-DOPA; add COMT/MAO-B inh, DA agonist; Amantadine (dyskinesia); Apomorphine rescue.
    • Refractory: Deep Brain Stimulation (DBS).

High‑Yield Points - ⚡ Biggest Takeaways

  • Levodopa: Most effective drug, but efficacy wanes with motor fluctuations ("on-off" phenomenon).
  • Carbidopa/Benserazide: Peripheral decarboxylase inhibitors; ↓ Levodopa's side effects, ↑ brain availability.
  • Dopamine Agonists (e.g., Pramipexole, Ropinirole): Monotherapy in early PD or adjuncts to Levodopa.
  • MAO-B Inhibitors (e.g., Selegiline, Rasagiline): Prevent dopamine breakdown; mild symptomatic relief.
  • COMT Inhibitors (e.g., Entacapone): Prolong Levodopa's action; Tolcapone: hepatotoxicity risk.
  • Amantadine: Useful for Levodopa-induced dyskinesia; modest antiparkinsonian effects.
  • Anticholinergics (e.g., Trihexyphenidyl): Best for tremor and rigidity; less for bradykinesia.

Practice Questions: Antiparkinsonian Drugs

Test your understanding with these related questions

Which of the following drugs is primarily used for the treatment of Parkinson's disease?

1 of 5

Flashcards: Antiparkinsonian Drugs

1/10

The _____ receptor antagonism of amantadine is responsible for its antidyskinetic properties in parkinsonism

TAP TO REVEAL ANSWER

The _____ receptor antagonism of amantadine is responsible for its antidyskinetic properties in parkinsonism

NMDA glutamate

browseSpaceflip

Enjoying this lesson?

Get full access to all lessons, practice questions, and more.

Start Your Free Trial