Parkinsonism Overview
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Questions and Answers

Which of the following is a notable side effect associated with ropinirole?

  • Weight gain
  • Dry mouth
  • Hallucinations (correct)
  • Increased appetite

What is the starting dose for pramipexole in treating early Parkinson's disease?

  • 1.0 mg TDS
  • 0.25 mg TDS
  • 0.125 mg TDS (correct)
  • 0.5 mg TDS

What therapeutic effect does selegiline have when administered with levodopa?

  • Decreases hallucinations
  • Increases frequency of on-off effect
  • Prolongs levodopa action (correct)
  • Enhances peripheral metabolism

Which of the following medications is FDA approved for restless leg syndrome?

<p>Ropinirole (D)</p> Signup and view all the answers

What does the term ‘wearing off’ effect refer to?

<p>Reduction in the effectiveness of dosage over time (B)</p> Signup and view all the answers

How does pramipexole compare to ropinirole in terms of potency?

<p>Twice as potent (C)</p> Signup and view all the answers

Which of the following is a common side effect of advanced doses of levodopa?

<p>Dyskinesias (C)</p> Signup and view all the answers

What is the primary reason for neuronal death in parkinsonism related to glutamate?

<p>Excitotoxic neuronal death due to Ca2+ overload (D)</p> Signup and view all the answers

What symptom is characteristic of the later stages of untreated Parkinson's disease?

<p>Severe rigidity and inability to move (C)</p> Signup and view all the answers

Which drug is primarily known for causing drug-induced temporary parkinsonism due to dopaminergic blockage?

<p>Metoclopramide (A)</p> Signup and view all the answers

What was a significant breakthrough in the treatment of Parkinson's disease in 1967?

<p>Introduction of levodopa producing dramatic improvement (D)</p> Signup and view all the answers

Which area of the brain is primarily affected in Parkinson's disease?

<p>Substantia nigra pars compacta (B)</p> Signup and view all the answers

Which condition is a rare cause of Parkinsonism due to chronic copper poisoning?

<p>Wilson’s disease (B)</p> Signup and view all the answers

What effect does reserpine have on dopamine in the brain?

<p>Depletes dopamine along with other monoamines (C)</p> Signup and view all the answers

What is a common manifestation accompanying Parkinson's disease?

<p>Cognitive decline or dementia (A)</p> Signup and view all the answers

What does an 'all or none' response in patients indicate regarding their condition?

<p>Fluctuating levels of disability (A)</p> Signup and view all the answers

Which of the following statements is true regarding the use of peripheral decarboxylase inhibitors?

<p>They enhance the effectiveness of levodopa by reducing its peripheral conversion. (A)</p> Signup and view all the answers

What is typically the starting dose of levodopa for a patient?

<p>0.25 g twice daily (C)</p> Signup and view all the answers

How does pyridoxine affect the therapeutic effect of levodopa?

<p>It abolishes the therapeutic effect of levodopa. (D)</p> Signup and view all the answers

What might the combination of carbidopa and levodopa lead to regarding patient symptoms?

<p>Minimized cardiac complications. (A)</p> Signup and view all the answers

For which condition is cautious use of levodopa especially important?

<p>Ischaemic heart disease (A)</p> Signup and view all the answers

What typically occurs to systemic dopamine levels with the use of levodopa?

<p>They are significantly reduced. (B)</p> Signup and view all the answers

What is the approximate usual daily dose of levodopa?

<p>2–3 g/day (B)</p> Signup and view all the answers

What happens to levodopa's half-life in the periphery when doses are reduced?

<p>It is prolonged to approximately 1/4th. (C)</p> Signup and view all the answers

What response may exemplify the progression of a disorder in patients on levodopa?

<p>Alternating periods of being well and disabled. (C)</p> Signup and view all the answers

What is the role of Levodopa in treating Parkinson's Disease?

<p>It serves as a precursor to dopamine and provides symptomatic relief. (B)</p> Signup and view all the answers

Which of the following is a side effect associated with the use of Glutamate antagonists such as Amantadine?

<p>Frank psychosis and increased sexual activity (A)</p> Signup and view all the answers

How do D1 like receptors primarily affect neuronal signaling?

<p>By increasing cAMP formation and mobilizing calcium (B)</p> Signup and view all the answers

Which MAO-B inhibitor is commonly used in the management of Parkinson's Disease?

<p>Selegiline (B)</p> Signup and view all the answers

What characterizes D2 like receptors in the dopamine receptor family?

<p>They inhibit adenylyl cyclase and promote potassium channel opening. (D)</p> Signup and view all the answers

Which of the following central anticholinergics is used to manage extrapyramidal symptoms?

<p>Trihexyphenidyl (D)</p> Signup and view all the answers

What is a major concern when using COMT inhibitors like Entacapone?

<p>Potential liver toxicity and interaction with Levodopa (D)</p> Signup and view all the answers

Which of the following statements about MPTP-like chemicals is accurate?

<p>They may be present in some patients and can induce Parkinsonian symptoms. (A)</p> Signup and view all the answers

Which drug is associated with an 'awakening' effect in hepatic coma?

<p>Levodopa (B)</p> Signup and view all the answers

What is a direct consequence of using antihistaminics like Promethazine in treating neurological conditions?

<p>They create adverse effects similar to those caused by cholinergic blockers. (A)</p> Signup and view all the answers

What is an advantage of using ropinirole or pramipexole over levodopa in Parkinson's treatment?

<p>They do not contribute to neuronal damage via oxidative metabolism. (B), They reduce the incidence of dyskinesias and motor fluctuations. (D)</p> Signup and view all the answers

Which specific type of MAO does selegiline inhibit?

<p>MAO-B (C)</p> Signup and view all the answers

What is the primary route of metabolism for ropinirole?

<p>Hepatic metabolism via CYP1A2 (D)</p> Signup and view all the answers

How long is the terminal half-life of ropinirole?

<p>6 hours (D)</p> Signup and view all the answers

What is the main effect of the drug bromocriptine in Parkinson’s disease?

<p>It acts as a potent agonist on D2 receptors. (A)</p> Signup and view all the answers

What condition is associated with the use of levodopa that newer DA agonists attempt to mitigate?

<p>Dopaminergic neuronal damage (B)</p> Signup and view all the answers

What percentage of ropinirole is bound to plasma proteins after oral absorption?

<p>40% (C)</p> Signup and view all the answers

Which of the following is true regarding the side effects associated with levodopa compared to DA agonists?

<p>Levodopa is associated with a greater risk of motor fluctuations. (D)</p> Signup and view all the answers

What is the implication of using ropinirole or pramipexole for Parkinson's patients considering neuronal degeneration?

<p>They may slow the rate of neuronal degeneration. (C)</p> Signup and view all the answers

What is the purpose of differentiating between MAO-A and MAO-B in pharmacology?

<p>To understand their relevance in Parkinson's disease treatment. (A)</p> Signup and view all the answers

Flashcards

Parkinson's Disease (PD)

A progressive neurological disorder characterized by rigidity, tremors, and slow movements due to loss of dopamine-producing cells in the brain.

Tremor

The most common symptom of PD, it is a rhythmic trembling in a body part, typically in the hands.

Rigidity

Stiffness and resistance to movement in the muscles, often seen in the limbs.

Hypokinesia

Slowness of movement and difficulty initiating movement, also known as Bradykinesia.

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Substantia Nigra

The area in the brain where dopamine-producing cells are located, which is affected in Parkinson's disease.

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Dopamine

A vital neurotransmitter that plays a crucial role in movement, mood, and cognition.

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Nigrostriatal Pathway

The main pathway in the brain that is affected in Parkinson's disease, connecting the substantia nigra to the striatum and responsible for dopamine transmission.

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Levodopa

A drug that is frequently used to treat Parkinson's disease, helping to replenish dopamine levels in the brain.

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All or none response

A state where Parkinson's patients experience alternating periods of good motor function ('on' phase) and severe disability ('off' phase). This pattern emerges as the disease progresses.

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Peripheral decarboxylation

The breakdown of levodopa outside the brain, reducing its effectiveness. This process is enhanced by pyridoxine (vitamin B6).

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Peripheral decarboxylase inhibitors

Medications like carbidopa and benserazide that block the enzyme responsible for breaking down levodopa outside the brain, increasing its availability to reach the brain.

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Levodopa + Carbidopa (or Benserazide)

The combination of levodopa with a peripheral decarboxylase inhibitor, such as carbidopa. This combination increases levodopa's effectiveness and reduces side effects.

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Half-life (t½)

The time it takes for a drug's concentration in the body to decrease by half.

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Drug elimination

The process of breaking down and eliminating a drug from the body.

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Dyskinesia

A condition characterized by uncontrolled, involuntary movements.

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Loss of dopamine regulation

The inability to regulate the release of dopamine, leading to unpredictable fluctuations in motor control.

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Bioavailability

The process of making a drug available for use, often by transforming it into a different but active form.

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Dopamine Agonists

A class of drugs that prevent the breakdown of dopamine, increasing its concentration in the brain and improving symptoms in Parkinson's disease.

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Ergot-Derived Dopamine Agonists

A type of dopamine agonist that works by mimicking the effects of dopamine at specific dopamine receptors in the brain, alleviating symptoms of Parkinson's disease.

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Non-Ergot Dopamine Agonists

A type of dopamine agonist that works by stimulating dopamine receptors in the brain, providing relief from symptoms of Parkinson's Disease, and being synthesized in the lab.

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MAO-B

An enzyme that breaks down dopamine in the brain. Medications targeting this enzyme can increase dopamine levels, helping with Parkinson's treatment.

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MAO-B inhibitors

Drugs that inhibit the activity of MAO-B, an enzyme that breaks down dopamine. They help increase dopamine levels in the brain as a treatment for Parkinson's disease.

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COMT

An enzyme involved in the metabolism of dopamine and some medications used to treat Parkinson's disease. Inhibiting this enzyme can improve the effectiveness of Levodopa.

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COMT inhibitors

Drugs that block the activity of the enzyme COMT, which breaks down dopamine, increasing its availability in the brain and enhancing the effects of Levodopa in Parkinson's disease treatment.

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Amantadine

A medication used to treat Parkinson's disease by mimicking the effects of dopamine at specific receptors in the brain. It can also 'wake up' the brain during times of sedation.

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Drugs Affecting the Cholinergic System

A class of medications that work in the brain's cholinergic system, influencing the levels of acetylcholine, a neurotransmitter also involved in movement. They are used to treat tremors and rigidity in Parkinson's disease.

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Ropinirole and Pramipexole

Ropinirole and pramipexole are dopamine agonists. They are used to treat Parkinson's disease symptoms like tremors and stiffness, but can cause side effects like nausea, dizziness and hallucinations.

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On-Off Effect

The 'on-off' effect in Parkinson's refers to sudden fluctuations in movement control, where patients experience periods of good movement ('on') followed by periods of stiffness and difficulty moving ('off').

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Selegiline and Dopamine Breakdown

Selegiline, a drug used to manage Parkinson's, inhibits the breakdown of dopamine in the brain. It helps to increase the amount of available dopamine for communication between brain cells.

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Sleepiness as Side Effect

Ropinirole and pramipexole are dopamine agonists used to treat Parkinson's, but they may increase sleepiness. This can be risky, especially for those who drive.

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Selegiline and Levodopa

Selegiline is a medication for Parkinson's. When combined with levodopa, it can improve the effectiveness of levodopa, make it last longer and reduce side effects.

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Selegiline Interactions

Higher doses of selegiline can interact negatively with drugs like levodopa, leading to potentially serious side effects.

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Ropinirole

A type of dopamine agonist used to treat Parkinson's, known for its long-lasting effects.

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Monoamine Oxidase B (MAO-B)

An enzyme that breaks down dopamine, leading to a decrease in dopamine levels in the brain.

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Selegiline (Deprenyl)

A type of MAO-B inhibitor used to treat Parkinson's, helping to increase dopamine levels.

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Bromocriptine

A type of ergot derivative that acts as a potent agonist on dopamine receptors, used in treating Parkinson's.

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Metabolism

The process by which a drug is broken down and eliminated from the body.

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Study Notes

Parkinsonism

  • Parkinsonism is an extrapyramidal motor disorder, characterized by rigidity, tremor, and hypokinesia
  • Secondary symptoms include impaired posture and gait, a mask-like face, and excessive saliva production (sialorrhoea)
  • Dementia is sometimes associated with parkinsonism
  • Untreated, symptoms progressively worsen over several years, leading to a rigid state, difficulty breathing, and susceptibility to infections or embolisms
  • Parkinson's Disease (PD) is a progressive degenerative disorder primarily affecting the elderly. It was first described in 1817.
  • Most cases are idiopathic, some are arteriosclerotic, and postencephalitic cases are now rare.
  • Wilson's disease, a rare cause, is due to chronic copper poisoning.
  • The main pathological feature of Parkinson's Disease is neuronal degeneration in the substantia nigra pars compacta and the nigrostriatal dopaminergic pathway.
  • This causes a dopamine deficiency in the striatum, which subsequently creates an imbalance between inhibitory dopaminergic and excitatory cholinergic systems controlling muscle tone and coordination.

Antiparkinsonian Drugs - Classification

  • Drugs affecting brain dopaminergic system include:
    • Dopamine precursors (e.g., levodopa)
    • Peripheral decarboxylase inhibitors (e.g., carbidopa, benserazide)
    • Dopamine agonists (e.g., bromocriptine, ropinirole, pramipexole)
    • MAO-B inhibitors (e.g., selegiline, rasagiline)
    • COMT inhibitors (e.g., entacapone, tolcapone)

Levodopa

  • Levodopa is a specific and effective treatment for PD
  • It's a precursor to dopamine, and crosses the blood-brain barrier to alleviate dopamine deficiency
  • Levodopa is decarboxylated in peripheral tissues (primarily the gut and liver) into dopamine
  • About 1-2% of administered levodopa crosses to the brain converting to DA, stored as a neurotransmitter.

Actions of Levodopa

  • Levodopa primarily improves symptoms in Parkinsonian patients, especially hypokinesia and rigidity, then tremor
  • It normalizes secondary symptoms, such as posture, gait, speech, facial expression, mood, and self-care
  • While effective initially, its effect gradually diminishes as the disease progresses

Adverse Effects of Levodopa

  • Common side effects include nausea, vomiting, postural hypotension (often asymptomatic)
  • Cardiac arrhythmias, exacerbation of angina are also possible
  • Alterations in taste sensation are possible from levodopa therapy

Classification of Dopaminergic Agonists

  • Non-ergot dopamine agonists (e.g., ropinirole, pramipexole): fewer gastrointestinal side effects, better tolerated compared to bromocriptine
  • Ergot dopamine agonists (e.g., bromocriptine): effective but more likely to produce side effects such as nausea, vomiting, hallucinations, hypotension.

Other Drugs used in Parkinsonism

  • Peripheral decarboxylase inhibitors (carbidopa/benserazide): combined with levodopa to increase levodopa bioavailability
  • MAO-B inhibitors: selegiline and rasagiline prolong the effects of levodopa and may have mild neuroprotective benefits
  • COMT inhibitors (entacapone and tolcapone): enhance levodopa action by inhibiting COMT, the enzyme that breaks down levodopa, prolonging its effects

Anticholinergics

  • These drugs reduce the unbalanced cholinergic activity in the striatum of Parkinsonian patients
  • Commonly used drugs include Trihexyphenidyl, Procyclidine, Biperiden, Orphenadrine, Promethazine
  • Side effects mimicking atropine-like effects are possible, but less severe than levodopa or MAO inhibitors

MAO-B Inhibitors

  • Selegiline and rasagiline selectively inhibit MAO-B, reducing the breakdown of dopamine
  • This can be beneficial in early-stage PD and sometimes in combination with levodopa

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Anti-Parkinsonian Drugs PDF

Description

Explore the symptoms, causes, and progression of Parkinsonism, a motor disorder characterized by rigidity, tremor, and hypokinesia. This quiz covers the pathophysiology behind Parkinson’s Disease, including neuronal degeneration and the role of dopamine. Test your knowledge on this progressive condition and its associated factors.

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