Neurology: Levodopa and Restless Legs Syndrome
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Questions and Answers

What percentage of patients may experience postural hypotension as a symptom?

  • 33% (correct)
  • 1%
  • 50%
  • 10%
  • Which of the following is a common side effect of long-term levodopa therapy?

  • Hypertension
  • Cognitive decline
  • Tachycardia
  • Abnormal movements (dyskinesias) (correct)
  • What is the effect of phenothiazines on levodopa therapy?

  • They enhance the therapeutic effects of levodopa
  • They reverse the therapeutic effect of levodopa (correct)
  • They do not interact with levodopa
  • They increase plasma levels of levodopa
  • Which factor significantly contributes to postural hypotension occurring in patients?

    <p>Concurrent use of antihypertensives (C)</p> Signup and view all the answers

    What role does pyridoxal play concerning levodopa?

    <p>It serves as a cofactor for dopa-decarboxylase (D)</p> Signup and view all the answers

    What happens to blood pressure in patients after prolonged treatment with levodopa?

    <p>It normalizes with continued treatment (D)</p> Signup and view all the answers

    Which of the following symptoms is least likely to be associated with excessive levodopa levels?

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

    What pathway is utilized to increase the uptake of levodopa into the brain?

    <p>Amino acid carrier-mediated transport (C)</p> Signup and view all the answers

    What is the primary characteristic of Restless Legs Syndrome (RLS)?

    <p>An irresistible urge to move the legs during relaxation (C)</p> Signup and view all the answers

    Which of the following is most likely a cause of secondary Restless Legs Syndrome?

    <p>Iron deficiency anemia (B)</p> Signup and view all the answers

    What effect does walking have on the symptoms of Restless Legs Syndrome?

    <p>It temporarily reduces symptoms (B)</p> Signup and view all the answers

    Which class of medications is considered most effective for treating Restless Legs Syndrome?

    <p>Nonergot dopaminergic agonists (A)</p> Signup and view all the answers

    What is a potential adverse effect of selegiline treatment?

    <p>Postural hypotension and confusion (D)</p> Signup and view all the answers

    What is the significance of the recent data regarding rasagiline in treating parkinsonism?

    <p>It supports a neuroprotective effect against cell degeneration (C)</p> Signup and view all the answers

    Which scenario best describes when symptoms of Restless Legs Syndrome typically occur?

    <p>During periods of relaxation or sleep (D)</p> Signup and view all the answers

    What is the primary effect of peripheral decarboxylase inhibitors like carbidopa and benserazide?

    <p>They prevent levodopa from converting to dopamine in the periphery. (C)</p> Signup and view all the answers

    Which of the following statements about selegiline is accurate?

    <p>It enhances dopamine levels by preventing its metabolism (A)</p> Signup and view all the answers

    When starting levodopa treatment, what is the initial recommended dose?

    <p>0.25 g BD after meals (D)</p> Signup and view all the answers

    What is the impact of pyridoxine on the therapeutic effect of levodopa when not combined with carbidopa?

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

    What is a significant side effect of dopamine fluctuations when treating with levodopa?

    <p>Rapid and unpredictable fluctuations in motor control (A)</p> Signup and view all the answers

    Which population requires cautious use of levodopa due to potential complications?

    <p>Elderly patients and those with ischemic heart disease (B)</p> Signup and view all the answers

    What is the overall benefit of administering levodopa with decarboxylase inhibitors?

    <p>They minimize the on-off effect of levodopa. (B)</p> Signup and view all the answers

    What is the usual prescribed dose of levodopa for optimal response?

    <p>2-3 g per day (A)</p> Signup and view all the answers

    What cardiovascular effect is minimized by the use of levodopa and carbidopa together?

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

    Which statement accurately describes the effect of domperidone in relation to levodopa?

    <p>Domperidone reduces levodopa-induced nausea but does not affect its antiparkinsonian effect. (B)</p> Signup and view all the answers

    What is a primary reason for dose limitation when using domperidone?

    <p>It does not cross the blood-brain barrier. (D)</p> Signup and view all the answers

    What behavioral effect can excessive DA action in the limbic system cause?

    <p>Severe depression and hallucinations. (D)</p> Signup and view all the answers

    Which of the following describes the 'end of dose' phenomenon in parkinsonian therapy?

    <p>Symptoms worsen gradually between doses leading to rapid 'on-off' switches. (C)</p> Signup and view all the answers

    What is the effect of nonselective MAO inhibitors when combined with levodopa?

    <p>They cause hypertensive crises by preventing the degradation of dopamine. (A)</p> Signup and view all the answers

    How do antihypertensive drugs affect patients taking levodopa?

    <p>They intensify postural hypotension and may require dose adjustments. (C)</p> Signup and view all the answers

    Why might atropine and antiparkinsonian anticholinergic drugs be prescribed with levodopa?

    <p>For their additive therapeutic effect at low doses. (A)</p> Signup and view all the answers

    What are the potential severe motor effects that can develop from long-term levodopa therapy?

    <p>Abnormal movements that may be as disabling as the disease. (B)</p> Signup and view all the answers

    What primarily characterizes the motor defects associated with parkinsonism?

    <p>Imbalance between dopaminergic and cholinergic systems (A)</p> Signup and view all the answers

    Which substance is used to alleviate dopamine deficiency in Parkinson's disease?

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

    What is the consequence of an acquired defect in protective mechanisms against free radicals in the brain?

    <p>Damage to lipid membranes and DNA (B)</p> Signup and view all the answers

    What can potentially accentuate defects in mitochondrial function in the context of Parkinson's disease?

    <p>Environmental toxins or genetic factors (A)</p> Signup and view all the answers

    What role do free radicals play in the degeneration of dopaminergic neurons in Parkinson's disease?

    <p>They contribute to neuronal degeneration (D)</p> Signup and view all the answers

    Which drug type serves as a precursor for dopamine in treating Parkinson's disease?

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

    Which substance is known as an environmental toxin that can induce symptoms similar to Parkinson's disease?

    <p>N-methyl-4-phenyl tetrahydropyridine (MPTP) (A)</p> Signup and view all the answers

    What is the effect of anticholinergic drugs in the treatment of Parkinson's disease?

    <p>Restore balance between dopamine and acetylcholine (D)</p> Signup and view all the answers

    What is the primary benefit of anticholinergics in managing parkinsonian symptoms?

    <p>They produce an improvement in symptoms lasting 4–8 hours. (A)</p> Signup and view all the answers

    What is a potential reason to delay the use of levodopa in treating parkinsonism?

    <p>To avoid the early onset of dyskinesias associated with higher doses. (C)</p> Signup and view all the answers

    Which statement is true regarding the use of anticholinergics in older patients?

    <p>They may impair memory and cause urinary retention, particularly in males. (D)</p> Signup and view all the answers

    Which drug acts as a standard therapy and replaces the use of levodopa alone?

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

    What is a significant side effect associated with the use of anticholinergics primarily in older patients?

    <p>Impairment of memory and organic confusional states. (B)</p> Signup and view all the answers

    Which adjunctive treatment can be utilized with levodopa to manage the 'wearing off' effect?

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

    Which combination of drugs is generally recommended for younger patients with early/mild symptoms of parkinsonism?

    <p>Anticholinergics/amantadine/selegiline/direct DA agonists. (A)</p> Signup and view all the answers

    What effect do dopaminergic agonists like ropinirole or pramipexole have in early treatment of parkinsonism?

    <p>They are associated with fewer motor complications. (B)</p> Signup and view all the answers

    Flashcards

    Dopamine (DA)

    A neurotransmitter that plays a crucial role in movement, motivation, and reward.

    Striatum

    A brain structure involved in motor control, learning, and habit formation. It is particularly important for smooth, coordinated movements.

    Parkinson's Disease (PD)

    A disorder characterized by a lack of dopamine in the striatum, leading to tremors, rigidity, and slow movements.

    Dopamine Oxidation

    The process of breaking down dopamine by the enzyme Monoamine Oxidase B (MAO-B).

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    Free Radicals

    Harmful molecules that can damage cells and contribute to the degeneration of neurons in Parkinson's Disease.

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    Levodopa (L-dopa)

    A drug used to treat Parkinson's disease by increasing dopamine levels in the brain. It is a precursor to dopamine and can cross the blood-brain barrier.

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    Levodopa Potentiators

    Drugs that enhance the effects of levodopa by preventing its breakdown in the periphery, allowing more levodopa to reach the brain.

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    Dopamine Agonists

    Drugs that directly stimulate dopamine receptors in the brain, providing an alternative way to increase dopamine signaling.

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    Dyskinesias

    A side effect of levodopa therapy that involves involuntary movements like grimacing, tongue thrusting, and limb movements.

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    When do dyskinesias appear?

    These movements develop within a few months of starting levodopa therapy at the optimal dose.

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    How do dyskinesias progress over time?

    Dyskinesias worsen over time and most patients experience them after a few years.

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    What influences the intensity of dyskinesias?

    The intensity of dyskinesias is directly related to the level of levodopa in the body.

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    What medications can interfere with levodopa's effects?

    Medications like phenothiazines, butyrophenones, and metoclopramide can block dopamine receptors, counteracting the positive effects of levodopa.

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    How does levodopa reach the brain?

    Levodopa is absorbed into the brain through specialized carriers that transport amino acids, but only a small percentage of the administered dose reaches the brain.

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    Postural Hypotension

    A state of low blood pressure upon standing, often seen in patients taking levodopa.

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    What are the symptoms of postural hypotension?

    Postural hypotension is common in levodopa patients, but usually asymptomatic. Dizziness and fainting are less common.

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    Levodopa Fluctuation

    A side effect of long-term levodopa treatment where the effectiveness of the medication fluctuates significantly, leading to periods of good motor control followed by periods of severe disability.

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    On-Off effect

    A type of levodopa fluctuation marked by abrupt transitions between periods of good and poor motor control. This can make daily activities unpredictable and difficult.

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    End of Dose Deterioration

    This refers to the period of time when a patient with Parkinson's Disease experiences the most intense symptoms and has limited movement. It typically occurs at the end of the levodopa dosage cycle.

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    Wearing off

    A type of levodopa fluctuation characterized by a reduction in motor control that occurs toward the end of the dosage interval, before the next dose is taken.

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    Abnormal Movements

    Abnormal involuntary movements are an adverse effect of levodopa treatment that can significantly limit a patient's quality of life. These movements are often severe and unpredictable.

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    Domperidone (Motilium)

    This antipsychotic drug is used to block the effects of levodopa-induced nausea and vomiting. It works by antagonizing dopamine receptors in the chemoreceptor trigger zone (CTZ), a brain area involved in triggering nausea.

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    Reserpine

    This drug prevents the storage of dopamine in synaptic vesicles, effectively blocking the action of levodopa. It is a potent antipsychotic but can cause serious side effects.

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    Non-Selective MAO Inhibitor (MAOI)

    These drugs prevent the breakdown of dopamine and norepinephrine, potentially causing a hypertensive crisis when combined with levodopa. They are used to treat depression.

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    What is Levodopa?

    A drug that converts to dopamine (a neurotransmitter) in the brain. It helps treat Parkinson's disease by increasing dopamine levels.

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    What are Levodopa Potentiators?

    Drugs like carbidopa and benserazide that prevent levodopa from breaking down in the body before it reaches the brain. This makes levodopa more effective.

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    What is the 'on-off' effect?

    A side effect of levodopa treatment for Parkinson's disease where the body experiences alternating periods of good and bad motor control.

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    What is peripheral decarboxylase?

    An enzyme that breaks down levodopa before it can reach the brain. It's the reason why pyridoxine (vitamin B6) can decrease levodopa's effectiveness.

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    What is Carbidopa used for?

    A drug that inhibits peripheral decarboxylase, preventing levodopa from being broken down in the periphery. This allows more levodopa to reach the brain and be converted to dopamine.

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    What is dopamine?

    A neurotransmitter that plays a vital role in movement, mood, and rewards. Its deficiency in the brain is a major cause of Parkinson's disease.

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    What is the Striatum?

    A brain region responsible for planning, executing, and controlling movements. It's heavily involved in Parkinson's disease.

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    What is dopamine oxidation?

    A process that occurs in the brain where dopamine, after being released, is broken down. This can lead to a decrease in dopamine levels and contribute to Parkinson's symptoms.

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    Anticholinergics in Parkinson's

    Anticholinergics can improve Parkinson's symptoms, especially tremor, for a few hours after a single dose. However, their overall effectiveness is lower than levodopa, and they have less severe side effects.

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    Anticholinergics for Drug-Induced Parkinsonism

    Anticholinergics are the only drugs that effectively treat Parkinsonism induced by medications like phenothiazines.

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    Anticholinergics and Side Effects in Elderly

    Older patients, especially males, often experience side effects like memory impairment, confusion, blurred vision, and urinary retention when using anticholinergics.

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    Most Common Anticholinergic

    Trihexyphenidyl is the most commonly used anticholinergic drug in treating Parkinson's disease.

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    Initial Treatment for Mild Parkinson's

    When Parkinson's disease is mild, anticholinergics or selegiline might be sufficient to manage symptoms.

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    Newer DA Agonists for Early Parkinson's

    Monotherapy with newer DA agonists like ropinirole or pramipexole is increasingly used for early Parkinson's, especially in younger patients, due to fewer motor complications.

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    Standard Parkinson's Therapy

    Levodopa combined with a decarboxylase inhibitor is considered the standard therapy for Parkinson's disease, and has replaced levodopa alone.

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    Selegiline for 'Wearing Off' Effect

    Selegiline can be combined with levodopa during the deterioration phase of Parkinson's therapy to help overcome the 'wearing off' effect of levodopa.

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    What is Restless Leg Syndrome (RLS)?

    Restless Legs Syndrome (RLS) is a condition that causes an irresistible urge to move the legs, often accompanied by unpleasant sensations like tingling, itching, or aching. It typically worsens during periods of rest, especially at night.

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    What are the types of Restless Legs Syndrome?

    RLS can be primary (idiopathic), meaning its cause is unknown, or secondary, meaning it is caused by other conditions like iron deficiency, pregnancy, or nerve damage.

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    What are the main medications for Restless Legs Syndrome?

    Non-ergot dopamine agonists, such as ropinirole and pramipexole, are considered the most effective drugs for treating RLS. Low doses taken before bedtime can often provide significant relief.

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    Are MAO-B inhibitors effective for Restless Legs Syndrome?

    MAO-B inhibitors, like selegiline, are medications that block the enzyme responsible for breaking down dopamine. However, their effectiveness in treating RLS is controversial, and they are not typically used for this purpose.

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    What side effect can selegiline have?

    Selegiline can sometimes cause insomnia and agitation because it's metabolized into amphetamine, a stimulant. This side effect is more common at higher doses.

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    Does rasagiline have any potential benefits for RLS?

    Although selegiline isn't typically used for RLS, there's some evidence that rasagiline, another MAO-B inhibitor, might have neuroprotective effects in Parkinson's disease.

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    What are the main side effects of selegiline?

    Common side effects of selegiline include postural hypotension (low blood pressure upon standing), nausea, confusion, and worsening of levodopa-induced involuntary movements. It can also worsen psychosis in some cases.

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    What are some potential uses for selegiline in Parkinson's disease?

    Selegiline might be used to reduce the 'wearing-off' effect of levodopa and to increase its effectiveness. However, it's important to note that selegiline is not typically used for RLS.

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    Study Notes

    Parkinsonism

    • Parkinsonism is an extrapyramidal motor disorder
    • Characterized by rigidity, tremor, and hypokinesia
    • Secondary symptoms include posture, gait, facial expression, and drooling
    • Dementia can occur
    • Untreated, symptoms worsen over time, leading to rigidity, immobility, and difficulty breathing
    • Parkinson's disease (PD) is a common type
    • Mostly idiopathic, but some cases are arteriosclerotic or post-encephalitic
    • Wilson's disease (hepatolenticular degeneration) is a rare cause
    • Degeneration of substantia nigra pars compacta (SN-PC) and nigrostriatal (dopaminergic) tract is a key lesion in PD
    • Dopamine deficiency in the striatum causes an imbalance between dopaminergic (inhibitory) and cholinergic (excitatory) systems, leading to motor dysfunction.
    • Oxidative damage to neurons is a contributing factor (e.g., by byproducts of dopamine metabolism)
    • Free radicals damage lipid membranes and DNA, leading to neuronal death
    • Ageing and environmental toxins contribute to this
    • Synthetic toxin (MPTP) accelerates degeneration
    • Glutamate excitotoxicity may play a role in neuronal death
    • Drugs like neuroleptics and metoclopramide can induce parkinsonism

    Classification of Antiparkinsonian Drugs

    • Drugs affecting brain dopaminergic system
      • Dopamine precursor (Levodopa)
      • Peripheral decarboxylase inhibitors (Carbidopa, Benserazide)
      • Dopaminergic agonists (Bromocriptine, Ropinirole, Pramipexole)
      • MAO-B inhibitor (Selegiline, Rasagiline)
      • COMT inhibitors (Entacapone, Tolcapone)
    • Drugs affecting brain cholinergic system
      • Central anticholinergics (Trihexyphenidyl, Procyclidine, Biperiden)
      • Antihistaminics (Orphenadrine, Promethazine)
    • Glutamate antagonist (Amantadine)

    Levodopa

    • Effective treatment for PD
    • Immediate precursor of dopamine
    • Decarboxylated in peripheral tissues to dopamine
    • Minimal dopamine crosses the blood-brain barrier
    • Dopamine is stored, and released
    • Brain dopamine levels increase in patients treated with levodopa
    • Patients who respond well have higher levels

    Levodopa Actions

    • Minimal effects in healthy individuals

    • Marked symptomatic improvement in patients with PD

    • Resolves hypokinesia and rigidity, then tremor

    • Improves secondary symptoms (posture, gait, speech, etc.)

    • The effect is almost complete in early-stage disease. Improvement diminishes with disease progression

    CNS effects of Levodopa

    • Possible excitement, psychosis in some patients
    • Elevated sexual activity in some patients
    • Dementia isn't improved by levodopa
    • Used to awaken patients in hepatic coma

    Cardiovascular Effects

    • Tachycardia can result from peripheral dopamine
    • Postural hypotension is fairly common

    Dopaminergic Receptors

    • Two main subtypes (D1 and D2) exist
    • Each with additional subtypes (D3, D4, and D5)
    • D1-like receptors are excitatory
    • D2-like receptors are inhibitory
    • Receptors located differentially in the brain and play distinct roles
    • Both D1 and D2 present in the striatum (important for treatment response)

    Adverse Effects of Levodopa Therapy

    • Common and frequently troubling
    • Dose-related, but usually reversible
    • Symptoms like nausea, vomiting, postural hypotension, cardiac arrhythmias, exacerbation of angina, taste changes, and alteration in taste can occur
    • Serious side effects include dyskinesias
    • Abnormal movements (facial tics, grimacing, etc.)
    • These may become as debilitating as the original Parkinson's disease (PD) itself
    • Dose-limited side effects may persist

    Levodopa Interactions

    • Pyridoxine interferes with levodopa therapy
    • Antagonists to dopamine may reverse effects
    • Monoamine oxidase (MAO) inhibitors prevent dopamine degradation; could cause a hypertensive crisis

    Peripheral Decarboxylase Inhibitors

    • Carbidopa and benserazide block peripheral dopamine production
    • Increases the amount of levodopa that crosses the blood-brain barrier.
    • Reduces peripheral side effects of levodopa
    • Allows lower doses and more rapid onset of treatment.

    Pharmacokinetics of Levodopa

    • Rapidly absorbed by small intestine (aromatic amino acid transport system)
    • Bioavailability is affected by gastric emptying, competing amino acids, and high first-pass metabolism in the gut and liver.
    • Half-life (t1/2) is 1-2 hours
    • Mostly excreted in urine as metabolites after conjugation

    Dopamine Agonists (Bromocriptine, Ropinirole, Pramipexole)

    • Useful in later stages of PD where levodopa may not be effective
    • Useful as monotherapy
    • Act on dopamine receptors in the striatum
    • Effective for symptom relief and may reduce fluctuation in motor performance (“on–off” effect)
    • Fewer motor complications than levodopa
    • Side effects similar to levodopa, but possibly better tolerated
    • Lower risk of neuronal degeneration

    MAO-B Inhibitors

    • Selective MAO-B inhibitors, selegiline, rasalagiline
    • Slow progression of PD
    • Reduce levodopa dose needed
    • Reduced fluctuation in motor performance (“on–off” effect)
    • Possible side effects: postural hypotension, nausea, confusion, dyskinesia, psychosis

    COMT Inhibitors

    • Entacapone and tolcapone
    • Improve levodopa efficacy
    • Useful to increase "on" time and reduce "off" time (fluctuations in motor performance)
    • Side effects: diarrhoea, discoloration of urine (tolcapone), potentially liver toxicity (tolcapone)

    Centrally Acting Anticholinergics (Trihexyphenidyl, Benztropine)

    • Primarily useful in mild PD and those receiving levodopa for a longer duration
    • Less effective than dopamine-related therapies in more advanced stages of PD
    • Primarily focus on reducing cholinergic activity, thus reducing motor symptoms.

    General Considerations

    • PD drugs predominantly address symptoms, not the underlying neurodegenerative process
    • Symptom management may improve quality of life
    • Levodopa is still the most effective therapy
    • Gradual dose titration and frequent monitoring are paramount

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    Description

    Test your knowledge on the symptoms, effects, and treatments related to levodopa therapy and Restless Legs Syndrome. This quiz covers key concepts including postural hypotension, medication side effects, and the characteristics of RLS. Perfect for students and professionals in neurology and pharmacology.

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