MBBS 52 SDL: Drug Therapy for Neurodegenerative Disorders

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Questions and Answers

Which of the following drugs is classified as a dopamine receptor agonist used in the treatment of Parkinson’s disease?

Pramipexole (correct)

Comtan

Benserazide

Memantine

What is a common adverse effect of L-dopa treatment in Parkinson’s disease?

Cognitive impairment

Tardive dyskinesia

Nausea (correct)

Severe hypertension

Which class of drugs used in Parkinson’s disease works by preventing dopamine degradation?

MAO-B inhibitors (correct)

Dopamine releasing agents

Anticholinergics

COMT inhibitors

What is the primary action of carbidopa and benserazide when used with L-dopa?

Prevent peripheral L-dopa conversion Signup and view all the answers

Which of the following is an NMDA receptor antagonist used in Alzheimer's disease treatment?

Memantine Signup and view all the answers

Which drug is NOT commonly used in Huntington’s chorea?

Bromocriptine Signup and view all the answers

How do centrally acting anticholinergics help in drug-induced parkinsonism?

By restoring the DA-ACh balance Signup and view all the answers

Which of the following is a decarboxylase inhibitor used with L-dopa?

Benserazide Signup and view all the answers

What is the role of COMT inhibitors in Parkinson’s disease therapy?

Prevent dopamine degradation Signup and view all the answers

What is the primary action of centrally acting anticholinergics in the treatment of drug-induced parkinsonism?

They block muscarinic receptors. Signup and view all the answers

Which symptom is most effectively managed by centrally acting anticholinergics like benztropine?

Tremor Signup and view all the answers

Why are other anti-parkinsonian drugs not effective in treating drug-induced parkinsonism?

They primarily act through dopamine receptors. Signup and view all the answers

What peripheral symptom is controlled by the action of centrally acting anticholinergics?

Sialorrhoea Signup and view all the answers

Which of the following is a major limitation of using dopamine receptor agonists in drug-induced parkinsonism?

They have little effect due to blocked receptors. Signup and view all the answers

When treating drug-induced parkinsonism, which class of medication is predominantly preferred?

Centrally acting anticholinergics Signup and view all the answers

What percentage of levodopa crosses the blood-brain barrier (BBB)?

3% Signup and view all the answers

What is the primary role of carbidopa in combination therapy with levodopa?

Inhibit peripheral dopa decarboxylase Signup and view all the answers

Which of the following is a limitation of the carbidopa and levodopa combination?

Accentuation of involuntary movements Signup and view all the answers

What is the end product of catechol-O-methyl transferase (COMT) mediated degradation of levodopa?

3-O-Methyldopa (3OMD) Signup and view all the answers

Which enzyme do COMT inhibitors primarily inhibit to enhance the effects of levodopa?

Catechol-O-methyl transferase (COMT) Signup and view all the answers

What is one effect of the combination of carbidopa and levodopa on levodopa dose requirements?

Reduced by 75% Signup and view all the answers

What effect does selegiline have in the treatment of Parkinson's disease?

Inhibit monoamine oxidase – B (MAO-B) Signup and view all the answers

What adverse effect is NOT resolved by the combination of carbidopa and levodopa?

Postural hypotension Signup and view all the answers

Which pathway does levodopa take after being converted in the brain due to the combination with carbidopa?

Converted to dopamine Signup and view all the answers

What happens to the systemic concentration of dopamine with the combination of carbidopa and levodopa?

Decreases significantly Signup and view all the answers

What is the primary function of levodopa in the treatment of Parkinson's disease?

To be converted into dopamine by dopa decarboxylase Signup and view all the answers

What peripheral adverse effect can occur due to the agonistic action of dopamine on the DA receptor in the CTZ?

Nausea and vomiting Signup and view all the answers

What phenomenon describes the rapid fluctuation in the efficacy of levodopa in patients?

On-off phenomenon Signup and view all the answers

Which of the following is a potential CNS adverse effect of levodopa?

Hallucinations Signup and view all the answers

How does pyridoxine (Vitamin B6) interact with levodopa?

It increases extracerebral metabolism of levodopa Signup and view all the answers

What effect can levodopa have on patients with existing heart conditions?

Exacerbation of angina Signup and view all the answers

What is one of the common movements associated with dyskinesias due to levodopa?

Tremors Signup and view all the answers

Which of the following describes a tolerance effect that may occur with prolonged levodopa treatment?

Postural hypotension stabilizing Signup and view all the answers

What is the mechanism of action of carbidopa in combination with levodopa?

It enables more levodopa to cross the blood-brain barrier Signup and view all the answers

What is a significant reason for the wearing-off effect in patients on levodopa therapy?

Rapid fluctuation in levodopa plasma levels Signup and view all the answers

What is the primary mechanism by which amantadine provides symptomatic relief in parkinsonism?

Facilitating presynaptic DA release Signup and view all the answers

Which of the following actions does selegiline NOT possess?

Enhancing serotonin levels Signup and view all the answers

Dopamine agonists are particularly useful in which situation?

Advanced patients with diminished DA synthesis Signup and view all the answers

What additional effect does amantadine have beyond facilitating dopamine release?

Weak antimuscarinic action Signup and view all the answers

The rationale for using centrally acting anticholinergics in drug-induced parkinsonism involves which mechanism?

Restoring balance between ACh and DA levels Signup and view all the answers

Which dopamine receptor agonist is known for having a longer duration of action compared to levodopa?

Cabergoline Signup and view all the answers

What effect does drug-induced parkinsonism primarily occur through?

Blocking dopamine receptors Signup and view all the answers

Which of the following properties is NOT associated with dopamine receptor agonists?

Short duration of action Signup and view all the answers

How does selegiline contribute to the management of Parkinson’s disease?

By inhibiting monoamine oxidase Signup and view all the answers

What is a common effect of both amantadine and dopamine agonists in treating parkinsonism?

Increasing the availability of dopamine Signup and view all the answers

Study Notes

Drug Therapy of Neurodegenerative Disorders

Parkinson’s Disease Drug Classification:
- Dopamine level increasers:
  - Levodopa (dopamine precursor)
  - Carbidopa and Benserazide (decarboxylase inhibitors)
  - Tolcapone and Entacapone (COMT inhibitors)
  - Amantadine (dopamine releasing agent)
- Dopamine degradation preventers:
  - Selegiline and Rasagiline (MAO-B inhibitors)
- Dopamine receptor agonists:
  - Bromocriptine, Cabergoline, Ropinirole, Pramipexole
- DA-ACh balance restorers:
  - Benztropine and Benzhexol (centrally acting anticholinergics)

Alzheimer's Disease and Huntington's Chorea Drugs

Alzheimer’s Disease:
- Anticholinesterases: Donepezil, Rivastigmine, Galantamine
- NMDA receptor antagonist: Memantine
Huntington’s Chorea:
- Chlorpromazine, Haloperidol, Olanzapine, Tetrabenazine

Adverse Effects of Levodopa

Peripheral Effects:
- Nausea and vomiting due to dopamine stimulation in CTZ
- Arrhythmias from beta receptor agonism
- Postural hypotension, altered taste and smell
CNS Effects:
- Fluctuations: Wearing-off and on-off phenomena
- Dyskinesias: Abnormal movements (tics, tremors)
- Psychiatric symptoms: Hallucinations, confusion, insomnia

Drug Interaction: Levodopa and Pyridoxine

Pyridoxine enhances peripheral decarboxylase activity, increasing levodopa metabolism before crossing the BBB and diminishing its therapeutic effects.

Benefits of Levodopa and Carbidopa Combination

Maximizes levodopa crossing into the brain, allowing for better dopamine levels.
Prolonged plasma half-life and increased bioavailability of dopamine in the brain.
Significant reduction in levodopa dosage, minimizing peripheral side effects.
Helps maintain stable dopamine levels, reducing the on-off effect.

Limitations of Levodopa and Carbidopa Combination

Does not eliminate postural hypotension.
May exacerbate involuntary movements and behavioral abnormalities.

Antiparkinsonian Actions of Various Drugs

COMT Inhibitors (e.g., Tolcapone):
- Prevent peripheral degradation of levodopa, enhancing dopamine delivery to the brain.
MAO-B Inhibitors (e.g., Selegiline):
- Inhibit MAO-B to increase dopamine levels and provide neuroprotective effects.
Amantadine:
- Increases presynaptic DA release and inhibits DA reuptake, also has weak antimuscarinic effects.
Dopamine Agonists:
- Stimulate postsynaptic dopamine receptors directly, beneficial for advanced parkinsonism with less risk of dyskinesias.

Centrally Acting Anticholinergics in Drug-Induced Parkinsonism

Used to rebalance cholinergic activity when dopamine receptors are blocked (e.g., by Metoclopramide).
Drugs like Benztropine and Benzhexol target muscarinic receptors in the basal ganglia, effectively reducing tremors and rigidity.

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Description

This quiz focuses on the drug therapy strategies used for treating neurodegenerative disorders, particularly Parkinson’s disease. It covers drug classification, important adverse effects of L-dopa, and drug interactions involving L-dopa and pyridoxine. Additionally, it explores the pharmacokinetics of L-dopa and the synergistic effects of carbidopa and benserazide.