Pharmacology of Parkinson's Disease Treatment

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

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

Levodopa serves as a dopamine precursor that is converted into dopamine in the brain to help alleviate symptoms.

How do peripheral decarboxylase inhibitors like Carbidopa enhance the effectiveness of Levodopa?

Carbidopa prevents the premature conversion of Levodopa to dopamine outside the brain, ensuring more reaches the central nervous system.

Name two types of dopaminergic agonists and briefly describe their categories.

Ergot (like Bromocriptine) and Non-ergot (like Ropinirole and Pramipexole) are the two categories of dopaminergic agonists.

What are MAO-B inhibitors and give an example?

MAO-B inhibitors are drugs that inhibit the monoamine oxidase B enzyme, prolonging dopamine action; an example is Selegiline. Signup and view all the answers

What role do central anticholinergics play in Parkinson's treatment?

Central anticholinergics help reduce muscle tremors and rigidity by blocking acetylcholine, which is often elevated in Parkinson's. Signup and view all the answers

What is the primary function of COMT inhibitors like Entacapone and Tolcapone?

To enhance the effects of dopamine in the brain by inhibiting the COMT enzyme. Signup and view all the answers

How does Amantadine function as a dopamine facilitator?

Amantadine increases dopamine release and may also block its reuptake. Signup and view all the answers

In what context is Amantadine used besides being a dopamine facilitator?

It is also used as an antiviral agent to treat infections such as influenza. Signup and view all the answers

What is the mechanism by which COMT inhibitors like Entacapone and Tolcapone work?

They inhibit the enzyme catechol-O-methyltransferase (COMT) to prevent dopamine breakdown. Signup and view all the answers

Name two COMT inhibitors mentioned in the content.

Entacapone and Tolcapone. Signup and view all the answers

What are the primary therapeutic goals of Parkinson's disease treatment?

The primary goals are to alleviate symptoms, improve quality of life, and maintain functional independence. Signup and view all the answers

How can anti-parkinsonian drugs be classified based on their mechanism of action?

Anti-parkinsonian drugs can be classified into categories such as dopaminergic agents, anticholinergics, and MAO-B inhibitors. Signup and view all the answers

Why is it important to personalize Parkinson's disease treatment?

Personalizing treatment is vital due to individual variations in symptoms, response to medications, and side effects. Signup and view all the answers

What role do lifestyle changes play in the management of Parkinson's disease?

Lifestyle changes can enhance treatment effectiveness by improving physical health, mobility, and emotional well-being. Signup and view all the answers

What is the function of dopaminergic agents in Parkinson's disease treatment?

Dopaminergic agents aim to replenish or mimic dopamine to reduce motor symptoms of Parkinson's disease. Signup and view all the answers

What is the most appropriate initial treatment for the patient’s symptoms based on her concerns?

MAO-B inhibitor. Signup and view all the answers

Which neurotransmitter deficiency is primarily associated with Parkinson’s Disease?

Dopamine. Signup and view all the answers

List two alternative treatment options for managing Parkinson's Disease symptoms.

Anticholinergic medication and Dopamine agonist. Signup and view all the answers

Why might an MAO-B inhibitor be preferred over levodopa/carbidopa as the initial treatment?

It has a lower risk of side effects and is better suited for early-stage symptoms. Signup and view all the answers

What role does dopamine play in the context of Parkinson’s Disease?

Dopamine is crucial for regulating movement and coordination. Signup and view all the answers

What is the primary action of dopamine agonists in relation to dopamine levels?

They restore dopamine levels. Signup and view all the answers

Which option among the provided choices indicates a possible enhancement of neurotransmitter activity related to movement?

Increase acetylcholine levels. Signup and view all the answers

How do dopamine agonists affect the activity concerning MAO-B?

They inhibit MAO-B. Signup and view all the answers

What neurotransmitter levels might be decreased due to the side effects of dopamine agonists?

Serotonin levels. Signup and view all the answers

What side effect could be expected from blocking dopamine receptors in patients using dopamine agonists?

Extrapyramidal symptoms. Signup and view all the answers

What is a common symptom in younger patients that anticholinergic drugs are primarily used to treat?

Hallucinations Signup and view all the answers

Which of the following is NOT a symptom commonly associated with anticholinergic drug use: weight gain, hallucinations, or hypotension?

Hypotension Signup and view all the answers

How might anticholinergic drugs affect sleep patterns in patients?

They can cause insomnia. Signup and view all the answers

Identify a common side effect of anticholinergic medications apart from hallucinations.

Dry mouth Signup and view all the answers

What potential weight-related side effect is associated with anticholinergic drug use?

Weight gain Signup and view all the answers

Study Notes

Level 2 Semester 5 Module

Module title: Central Nervous System & Special Senses Module (CNS 412)
Topic: Anti-Parkinsonian Drugs

Instructor Information

Name: Samah M. Elaidy, MD, PhD, JMHPE
Position: Professor of Clinical Pharmacology
Department: Pharmacology
Email: [email protected]
Mobile/WhatsApp: +201005265925
Office hours: Saturday & Monday
Office: 315, 3rd floor

Learning Outcomes

Identify therapeutic goals of Parkinson's disease treatment
Classify anti-parkinsonian drugs by mechanism of action
Explain mechanisms of action, pharmacokinetics, therapeutic uses, and adverse effects of antiparkinsonian drugs
Discuss potential drug-drug interactions of levodopa/carbidopa

Case Scenario

55-year-old woman with early-stage Parkinson's Disease, experiencing tremors
Started on trihexyphenidyl
Common side effect: dry mouth

Dopamine Pathways in the Brain

Nigrostriatal Pathway: motor control (Dopamine 2 Receptor (D2R)), cell death causes Parkinson's disease.
Mesolimbic-Mesocortical Pathways: motivation, emotional response, reward, addiction, hyperactivation causes schizophrenia
Tuberoinfundibular pathway: Prolactin regulation, blockade of D2 receptor causes hyperprolactinemia

Normal Balance in the Nigrostriatal Pathway

Movement: initiation & modulation
Muscle tone: inhibition of muscle tone, balance between excitatory and inhibitory input to skeletal muscles

Loss of Dopamine in Nigrostriatal Pathway

Bradykinesia (slow movement)
Rigidity (stiffness)
Tremor (shaking)

Dopamine in the Nigrostriatal Pathway

Decreased dopamine
Increased acetylcholine
Imbalance leading to Parkinson's disease

Parkinsonism

Broad term for progressive clinical syndrome
Manifests with motor symptoms
Muscle movements (rigidity, tremors, bradykinesia)
Unstable posture
Gait impairment
Causes:
- Idiopathic (85% of cases)
- Secondary: stroke, viral infection, drug-induced (e.g., neuroleptic, antipsychotic drugs), environmental toxins

Learning Outcome 1 & 2

Identify therapeutic goals of Parkinson's disease treatment
Classify anti-parkinsonian drugs based on their mechanism of action

Goals of Anti-Parkinsonian Drugs

Restore balance between dopamine and acetylcholine
Increase dopamine levels
Block acetylcholine receptors

Dopamine Cannot Cross Blood-Brain Barrier

Reason why dopamine isn't used directly for Parkinson's disease therapy

Classification of Antiparkinsonian Drugs

Drugs acting on dopaminergic system
- Dopamine precursors (Levodopa, L-dopa)
- Peripheral Decarboxylase Inhibitors (Carbidopa)
- Dopaminergic Agonists (Ergot, Non ergot: Ropinirole, Pramipexole)
- MAO-B inhibitors (Selegiline, Rasagiline, Safinamide)
- COMT inhibitors (Entacapone, Tolcapone)
- Dopamine facilitator (Amantadine)
Drugs acting on cholinergic system
- Central anticholinergics (Trihexyphenidyl, Benztropine)

Levodopa/Carbidopa

Levodopa: precursor for dopamine, decarboxylated in the substantia nigra
Carbidopa: Inhibitor of DOPA decarboxylase
Benefits: ↓metabolism in the gut and peripheral tissues; ↑ concentration in CNS
Dose reduction: 30% reduced dose of Levodopa which leads to a reduction in side effects
Method of administration: together in clinical practice

Levodopa Pharmacokinetics

High first-pass effect: 95% is decarboxylated to dopamine in the gut and liver
Rapid absorption from small intestine
Short t1/2: 1-2 hours
1-2% crosses the blood-brain barrier, taken up by neurons
Proteins, especially leucine and isoleucine, compete with Levodopa absorption from the gut; therefore, take on an empty stomach.

Adverse Effects of Levodopa

Short-term: nausea and vomiting (N&V), saliva and urine turn brownish, loss of appetite, postural hypotension
Long-term: involuntary movements (dyskinesia), wearing-off phenomenon, unpredictable on/off periods, confusion, visual hallucinations, delusions

How to Decrease Levodopa Motor Fluctuations

Intervals between doses
Prescribe controlled-release Sinemet
Add one of the following:
- Selegiline
- Entacapone
- Dopamine agonists
- Adenosine A2 receptor antagonist (Istradefylline)

Levodopa Drug Interactions

High-protein diet: ↓absorption and ↑peripheral breakdown of Levodopa
Pyridoxine (Vitamin B6): ↑peripheral breakdown of Levodopa
Typical antipsychotic drugs (e.g., haloperidol): blocks the action of Levodopa by blocking dopamine receptors
MAOIs: hypertensive crisis due to ↓ catecholamine metabolism
Anticholinergic drugs: synergistic effect

D2 Receptor Agonists (Non-Ergot)

Pramipexole
Ropinirole
Apomorphine
Rotigotine
Indications: Mild cases and young patients as first-line drugs; combined with levodopa to lessen fluctuation, increased responsiveness
Adverse effects: nausea, postural hypotension, hallucinations, dyskinesia (less than levodopa), daytime sleepiness, impulsive control disorder (esp., gambling, hypersexuality).
Side effect comparison to Levodopa: decreased dyskinesia and less fluctuation, longer duration of action (t½)

Dopamine Facilitators: Amantadine

Antiviral agent
Presynaptic synthesis & release of DA in striatum
Blocks NMDA glutamate receptors (antidyskinesia)

Learning Outcome 3 & 4

Explain mechanisms of action, pharmacokinetics, therapeutic uses, and adverse effects of antiparkinsonian drugs
Discuss possible drug-drug interactions of levodopa/carbidopa

Anticholinergic Drugs (M2 Receptors)

Reduce cholinergic activity in striatum
Relieve tremor and sialorrhea more than rigidity and hypokinesia
Indications: Mild cases and when Levodopa is contraindicated for use
Adverse effects: memory loss, hallucinations, urine retention, delayed gastric emptying, dry mouth
Contraindications: glaucoma, elderly men with prostatic hyperplasia, gastric ulcers

References

Pharmacology (Lippincott Illustrated Reviews Series)
https://www.clinicalkey.com/student/institution-login

Learning Moments

A summary to help students reflect on the information they learned in the session.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

This quiz explores the pharmacological strategies used in treating Parkinson's disease, focusing on the roles of Levodopa, Carbidopa, dopaminergic agonists, and COMT inhibitors. It also discusses the importance of personalizing treatment and the impact of lifestyle changes. Test your knowledge on the various medications and their mechanisms of action in managing this condition.