Parkinsonism and Parkinson's Disease Overview
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Questions and Answers

What is a potential side effect of using selegiline with levodopa?

  • Nausea (correct)
  • Hypertension
  • Diarrhoea (correct)
  • Hypersensitivity

    • Why is tolcapone's use restricted in Europe and Canada?

  • It causes chronic insomnia.
  • It is ineffective for Parkinson's disease.
  • It has been associated with acute fatal hepatitis. (correct)
  • It leads to severe respiratory depression.

    • Which medication is known to interact with pethidine, enhancing its effects?

  • Entacapone
  • Rasagiline
  • Tolcapone
  • Selegiline (correct)

    • Which of the following is a characteristic of Rasagiline compared to selegiline?

    <p>Longer acting</p> Signup and view all the answers

    What is the recommended dose for entacapone when taken with levodopa-carbidopa?

    <p>200 mg with each dose</p> Signup and view all the answers

    What type of drug is selegiline classified as?

    <p>MAO-B inhibitor</p> Signup and view all the answers

    What is a prominent side effect reported in patients taking tolcapone?

    <p>Diarrhoea</p> Signup and view all the answers

    Which of the following statements is true regarding entacapone?

    <p>It helps reduce off time when administered with levodopa.</p> Signup and view all the answers

    What is one of the therapeutic effects of ropinirole in patients with Parkinson's disease?

    <p>Decreases the 'wearing off' effect of levodopa</p> Signup and view all the answers

    What common side effect should patients be cautioned about when taking ropinirole?

    <p>Nausea and dizziness</p> Signup and view all the answers

    How does pramipexole compare to ropinirole in terms of potency?

    <p>It is twice as potent as ropinirole.</p> Signup and view all the answers

    What should patients taking higher doses of ropinirole be cautious of?

    <p>Hypertensive interactions with levodopa</p> Signup and view all the answers

    What may worsen in advanced cases when taking pramipexole?

    <p>Peak dose levodopa side effects</p> Signup and view all the answers

    What is the starting dose of ropinirole in managing restless leg syndrome?

    <p>0.25 mg TDS</p> Signup and view all the answers

    What is the effect of selegiline when administered with levodopa?

    <p>Prolongs levodopa action and attenuates motor fluctuations</p> Signup and view all the answers

    What is a potential side effect of pramipexole?

    <p>Visual hallucinations</p> Signup and view all the answers

    What is the primary effect of dopaminergic action in the striatum regarding SN-PR and GP-I?

    <p>Inhibitory influence</p> Signup and view all the answers

    How does levodopa affect prolactin levels during therapy?

    <p>Decreases prolactin levels</p> Signup and view all the answers

    What physiological process affects the bioavailability of levodopa?

    <p>Gastric emptying speed</p> Signup and view all the answers

    What condition results from the degenerative lesion in SN-PC in Parkinson’s disease?

    <p>Imbalance between dopamine and acetylcholine</p> Signup and view all the answers

    What major neurotransmitter actions are inhibited by endocrine dopamine on pituitary mamotropes?

    <p>Inhibits prolactin release</p> Signup and view all the answers

    What role does the GABAergic link play in the output from SN-PR and GP-I?

    <p>Inhibitory feedback</p> Signup and view all the answers

    Which neurotransmitter is primarily affected by therapeutic doses of levodopa in Parkinson’s patients?

    <p>Acetylcholine</p> Signup and view all the answers

    What is one of the side effects commonly experienced by patients undergoing therapy with levodopa?

    <p>Nausea and vomiting</p> Signup and view all the answers

    What is the primary symptom improvement observed in parkinsonian patients treated with levodopa?

    <p>Reduced rigidity</p> Signup and view all the answers

    What effect does excess dopamine (DA) and norepinephrine (NA) formed in the brain have on sympathetic outflow?

    <p>Reduces sympathetic outflow</p> Signup and view all the answers

    Which secondary symptoms gradually normalize with treatment using levodopa?

    <p>Mood and interest in life</p> Signup and view all the answers

    How is the therapeutic benefit of levodopa affected as the disease advances in parkinsonian patients?

    <p>It declines</p> Signup and view all the answers

    What kind of receptors are present in the Chemoreceptor Trigger Zone (CTZ) and how does dopamine (DA) function there?

    <p>Dopaminergic, acting as an excitatory transmitter</p> Signup and view all the answers

    What type of pathways do striatal GABAergic neurons follow to interact with the basal ganglia?

    <p>Direct and indirect pathways</p> Signup and view all the answers

    What gradual effect does levodopa have on the cardiovascular system?

    <p>Develops tolerance to hypotensive actions</p> Signup and view all the answers

    What is the primary neurotransmitter action in the direct pathway modulated by D1 receptors?

    <p>Excitatory action</p> Signup and view all the answers

    What is a common side effect associated with high doses of bromocriptine?

    <p>Nausea and vomiting</p> Signup and view all the answers

    Which of the following symptoms may worsen when using bromocriptine?

    <p>Involuntary movements</p> Signup and view all the answers

    What are the newer D2/D3 receptor agonists mentioned as alternatives to bromocriptine?

    <p>Ropinirole and Pramipexole</p> Signup and view all the answers

    When combining levodopa with carbidopa, what is the name given to this combination?

    <p>Co-careldopa</p> Signup and view all the answers

    What potential issue can arise with the 'first dose' of medications that lower blood pressure?

    <p>Marked fall in blood pressure</p> Signup and view all the answers

    Which of the following statements about levodopa is true?

    <p>Levodopa is generally combined with a decarboxylase inhibitor.</p> Signup and view all the answers

    What does excessive daytime sleepiness indicate in some patients?

    <p>Potential side effects of treatment</p> Signup and view all the answers

    What is the initial dosage of bromocriptine recommended for use at night?

    <p>1.25 mg once at night</p> Signup and view all the answers

    What was amantadine originally developed for?

    <p>Prophylaxis of influenza A2</p> Signup and view all the answers

    What is the role of COMT inhibitors like entacapone and tolcapone in Parkinson's disease therapy?

    <p>They prolong the half-life of levodopa.</p> Signup and view all the answers

    Which property of amantadine contributes to its benefits in parkinsonism?

    <p>Antagonism of NMDA receptors</p> Signup and view all the answers

    What happens to the efficacy of levodopa when combined with carbidopa and COMT inhibitors over time?

    <p>Tolerance develops and efficacy is gradually lost.</p> Signup and view all the answers

    Which statement is true regarding the action of entacapone?

    <p>It mainly affects peripheral pathways.</p> Signup and view all the answers

    Which group of patients is most likely to benefit from amantadine?

    <p>Patients with mild cases or those with advanced disease</p> Signup and view all the answers

    What effect does COMT have on dopamine in the brain?

    <p>It enhances the degradation of dopamine.</p> Signup and view all the answers

    Why might amantadine be considered less efficacious compared to levodopa?

    <p>Amantadine is not a dopamine agonist.</p> Signup and view all the answers

    Study Notes

    Parkinsonism

    • Parkinsonism is an extrapyramidal motor disorder, characterized by rigidity, tremor and hypokinesia
    • Secondary manifestations include posture and gait problems, a mask-like face, and excessive saliva.
    • Dementia may accompany the condition.
    • Untreated symptoms can progress over years, leading to severe rigidity, immobility, breathing issues, and susceptibility to infections or embolism.

    Parkinson's Disease (PD)

    • PD is a progressive degenerative disorder, primarily affecting older individuals.
    • Idiopathic cases are most common, some may be related to arteriosclerosis, and postencephalitic cases are rare.
    • Wilson's disease, a rare copper poisoning disorder, can be a cause.
    • The primary pathological lesion is the degeneration of substantia nigra pars compacta (SN-PC) neurons and the nigrostriatal dopaminergic tract.
    • This leads to reduced dopamine (DA) in the striatum, impacting muscle tone and movement coordination.
    • An imbalance arises between dopaminergic and cholinergic systems.
    • The exact cause of the neuronal degeneration is uncertain, but it likely involves multiple factors like oxidation of DA by MAO-B and aldehyde dehydrogenase, leading to free radical formation, age-related or acquired defects in protective mechanisms, mitochondrial dysfunction, and potential environmental toxins or genetic factors.

    Antiparkinsonian Drugs

    • These drugs effectively treat symptoms of parkinsonism.
    • Levodopa was a significant breakthrough in 1967 for its role in restoring dopamine levels.
    • DA itself cannot cross the blood-brain barrier, so Levodopa (a precursor) is used.
    • Drugs are classified into ones impacting the brain's dopaminergic system:
      • Dopamine precursor: Levodopa (l-dopa)
      • Peripheral decarboxylase inhibitors: Carbidopa, Benserazide.
      • Dopaminergic agonists: Bromocriptine, Ropinirole, Pramipexole.
      • MAO-B inhibitor: Selegiline, Rasagiline
      • COMT inhibitors: Entacapone, Tolcapone.

    Drug Actions

    • Levodopa has a specific beneficial effect in PD, outperforming other treatments.
    • It's inactive by itself, acting as a precursor to DA.
    • Peripheral metabolism degrades over 95% of an oral levodopa dose.
    • DA formed crosses the blood-brain barrier.
    • Levodopa can improve hypokinesia, rigidity, and tremor, impacting posture, gait, and speech.

    Classification of Drugs

    • Drugs affecting brain cholinergic system:
      • Central anticholinergics: Trihexyphenidyl, Procyclidine, Biperiden.
      • Antihistaminics: Orphenadrine, Promethazine

    Levodopa adverse effects

    • Early effects: nausea, vomiting, postural hypotension.
    • Long-term effects: dyskinesias (abnormal movements), behavioural changes (depression, psychosis), and fluctuations in motor control (on-off phenomenon).

    Dopamine agonists

    • Act on DA receptors, even in advanced PD.
    • Bromecriptine, a potent D2 agonist, is used in advanced cases.
    • Ropinirole and Pramipexole are newer, non-ergot DA agonists, preferred for their tolerability and reduced risk of long-term side effects.

    MAO-B inhibitors

    • Selegiline (Deprenyl) is a selective MAO-B inhibitor.
    • Used in early PD cases and with Levodopa to improve symptoms, extend 'on' time and reduce motor fluctuations.
    • Rasagiline is a newer MAO-B inhibitor, potentially slowing neuronal degeneration.

    COMT inhibitors

    • Entacapone and Tolcapone enhance levodopa's action in advanced and fluctuating PD.
    • Tolcapone has a higher incidence of side effects (hepatitis).
    • Increasing 'on' time, decreasing 'off' time, improving daily living activities, and reducing levodopa dose are potential benefits.

    Other drugs

    • Amantadine acts as a glutamate NMDA receptor antagonist, offering additional benefits and acting to maintain and enhance levodopa effectiveness, particularly in milder cases.
    • Central anticholinergics
      • Improve symptoms, particularly tremor, in early PD.
      • Commonly used drug is Trihexyphenidyl.
      • Not as effective as levodopa and have more side effects.

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    Description

    This quiz examines the characteristics and pathology of Parkinsonism and Parkinson's Disease (PD). It covers the symptoms, progression, and underlying neurological changes associated with these conditions. Test your knowledge on the causes and effects of this neurodegenerative disorder.

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