Anti-Parkinsonian Therapy & Drug Options

As the name suggests, anti-Parkinson’s drugs are used to treat Parkinson’s disease. Anti-Parkinson’s drugs are an important part of Pharmacology. Read this entire blog post to know everything about these drugs and elevate your NEET PG preparation. 

Parkinson’s Disease

• Seen in the elderly population.
• Symptoms:
  • Bradykinesia (slowing of movements)
  • Rigidity
  • Tremors
• The Dopamine decreases, and the activity of Acetylcholine increases in the Substantia Nigra.

Aim of Anti-Parkinsonian Therapy

1. ↑ Dopamine level
2. ↓ Acetylcholine level
3. MAO-B Inhibitor
4. COMT Inhibitors
5. D2 Agonist

Increase the level of Dopamine.

• Dopamine acts on the D2 receptor.
• Dopamine can not be given orally due to Dopamine can not cross BBB (Blood-brain barrier). Due to that, Dopamine is given with levodopa (Pro-drug). Inhibit Enzyme COMT and MOA-B to increase the level of Dopamine. Giving a D2 agonist drug increases the Dopamine level.

Drugs

Levodopa (Pro-drug)

• It has a very short half-life (t ½ = 1-2 hr). Levodopa ⇒ crosses BBB ⇒ Dopamine. In central levodopa is metabolized to dopamine with the help of Central decarboxylase enzyme. Levodopa metabolized in the periphery ⇒ Dopamine with the help of peripheral decarboxylase enzyme.

Drug Interaction L-Dopa

• Levodopa should not combine with D2 blockers. 

Ex. Typical Anti-psychotic, Metoclopramide

• Levodopa + Vitamin B6 ⇒ ↓ Levodopa efficacy

Contraindication of L-Dopa

• L-dopa is not used in a patient with acute psychosis.
• Not used in a patient with gastric ulcer.
• Not used in a patient with Angle-closure glaucoma.

 Why is carbidopa combined given with L-dopa? 

• Diminished peripheral metabolism of L-dopa in GIT and other tissues (thus increasing t₁/2). Increase availability of levodopa to CNS. Reduce the dose of levodopa and its side effects.
• Important ⇒ Levodopa: carbidopa: 4:1

Advantages of The Combination of Carbidopa With L-Dopa

• Levodopa becomes long acting in brain. Peripheral adverse effects not seen. Decreases the episode of Parkinson.

Disadvantages of the Combination of Carbidopa With L-Dopa 

• No ↓ psychosis. No ↓ dyskinesis. No ↓ Postural hypotension

MAO-B Inhibitor (Monoamine Oxidase)

Drugs Acting On MAO

Selegiline (Doprenyl)

• Pk ⇒ Metabolized ⇒ Amphetamine ⇒ Seizures. It increases Dopamine activity ⇒ develops psychosis symptoms. Advantage is neuroprotective effect.

Rasagiline

• It has 5 times more potent. It is not metabolized to amphetamine.

Safinamide

• New MAO Inhibitor approved for Parkinson’s disease.

COMT Inhibitors (Catechol Ortho Methyltransferase)

• Levodopa can be metabolized by COMT into 3-O -methyldopa. Entacapon Does not cross BBB. Tolcapone ⇒ BBB (Inhibit in periphery and central COMT). Tolcapone shows Hepatotoxicity.

D2 Agonist

Ergot Derived 

• Drugs: Bromocriptine, Cabergoline, Pergolide
• Adverse Effects

• Vasoconstriction ⇒ Gangrene
• Fibrosis

Non- Ergot derived. 

• Drugs: Ropinorole, Pramipexole, Rotigotine [Available as transdermal patch]
• Uses

• Parkinson’s disease
• Restless Lung syndrome 
• Adverse Effect
• Increase Compulsive behaviour like Hypersexuality, Gambling, Kleptomania

Apomorphine

• It is a non-ergot derived drug. Given as S.C. Injection
• Rx: Acute off Episodes
• Adverse Effects
  • Nausea 
  • Vomiting

Decreased ACH Level

Drugs ↓ Ach level is called Central anticholinergics.

Drugs Lowering Ach Level

Amantadine

• Amantadine produces Anti-dyskinetic properties. It Produces NMDA Antagonism. It has Anti-cholinergic properties.
• Adverse effects

• Livedo reticularis
• Ankle oedema

Newer Drugs For Parkinson Disease

• Opicapone ⇒ COMT Inhibitor: To decrease off episodes of Parkinson disease.
• Istradephylline ⇒ Adenosine antagonist: To decrease episodes Off Parkinson Disease.

And that is everything you need to know about anti-Parkinson’s drugs for your Pharmacology paper. For more informative and interesting blog posts like this, download the PrepLadder App and keep following our blog!