Parkinson's Disease Overview
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Questions and Answers

What is primarily affected in Parkinson's disease as described in the summary?

  • Movement and cognitive function
  • Motor function primarily (correct)
  • Cognitive function only
  • Only motor skills
  • What symptom is often recognized as 'pill-rolling' in Parkinson's disease?

  • Cognitive impairment
  • Difficulty in walking
  • Tremor at rest (correct)
  • Bradykinesia
  • Which of the following is associated with Parkinson's disease in its later stages?

  • Dementia and depression (correct)
  • Severe tremors exclusively
  • Only motor symptoms
  • Non-motor symptoms only
  • What percent decrease in striatal dopamine content is typically needed for Parkinson's symptoms to appear?

    <p>20-40%</p> Signup and view all the answers

    Which of the following is NOT typically involved in the diagnosis of Parkinson's disease?

    <p>Definitive laboratory tests</p> Signup and view all the answers

    What is a common psychological side effect associated with Levodopa treatment in Parkinson's disease patients?

    <p>Schizophrenia-like syndrome</p> Signup and view all the answers

    Which intervention can help manage the 'off effect' in Parkinson's disease patients receiving Levodopa?

    <p>Co-administration of COMT inhibitors</p> Signup and view all the answers

    What distinguishes Pramipexole and Ropinirole from other dopamine agonists?

    <p>They are D1,2 selective and better tolerated.</p> Signup and view all the answers

    Which of the following is NOT a side effect associated with MAO-B inhibitors like Selegiline?

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

    What is the primary action of Amantadine in the treatment of Parkinson's disease?

    <p>Stimulates dopamine release</p> Signup and view all the answers

    What is the primary mechanism by which levodopa acts in treating Parkinson's disease?

    <p>It is converted to dopamine in the brain after reaching the CNS.</p> Signup and view all the answers

    Which of the following statements about levodopa pharmacokinetics is true?

    <p>Levodopa is rapidly decarboxylated in extracerebral tissues.</p> Signup and view all the answers

    What is the purpose of using a DOPA-decarboxylase inhibitor alongside levodopa?

    <p>To prevent the degradation of levodopa before it reaches the CNS.</p> Signup and view all the answers

    What percentage of patients typically experience initial improvement in rigidity and bradykinesia when using levodopa?

    <p>About 80%</p> Signup and view all the answers

    Which combination is often used to improve the effectiveness of levodopa in patients experiencing motor fluctuations?

    <p>Levodopa + DOPA-decarboxylase inhibitor + COMT inhibitor.</p> Signup and view all the answers

    Which of the following antiepileptic drugs primarily enhances GABA action?

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

    What is a common clinical use for Carbamazepine?

    <p>Treatment of focal seizures</p> Signup and view all the answers

    Which mechanism of action is NOT associated with the function of common antiepileptic drugs?

    <p>Enhancement of dopamine release</p> Signup and view all the answers

    Which statement about the pharmacokinetics of Carbamazepine is correct?

    <p>It is given orally and has a plasma half-life of about 30 hours.</p> Signup and view all the answers

    What is a notable side effect of Phenobarbital that limits its use?

    <p>Excessive sedation</p> Signup and view all the answers

    What is a characteristic feature of Jacksonian epilepsy?

    <p>Repetitive jerking starting from a local muscle group</p> Signup and view all the answers

    Which type of seizure is characterized by a sudden cessation of activity followed by a brief stare?

    <p>Absence seizure</p> Signup and view all the answers

    What is a defining aspect of status epilepticus?

    <p>Seizures lasting several minutes without interruption</p> Signup and view all the answers

    In what condition is Lennox-Gastaut syndrome primarily seen?

    <p>Children with progressive mental retardation</p> Signup and view all the answers

    Which best describes partial seizures?

    <p>Seizures originating locally but can become generalized</p> Signup and view all the answers

    Which drug primarily acts as a positive allosteric modulator of GABA-A receptors?

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

    What is the approximate half-life of valproate in the plasma?

    <p>15 hours</p> Signup and view all the answers

    Which of the following statements about gabapentin is true?

    <p>It is also used as an analgesic for neuropathic pain.</p> Signup and view all the answers

    What type of seizures is valproate NOT particularly useful for?

    <p>Partial seizures</p> Signup and view all the answers

    Which of the following characteristics is associated with pregabalin compared to gabapentin?

    <p>Similar mechanism of action.</p> Signup and view all the answers

    Study Notes

    Parkinson's Disease

    • Progressive neurodegenerative disorder affecting movement
    • Non-motor symptoms often precede motor symptoms
    • Motor symptoms:
      • Suppression of voluntary movements (bradykinesia)
      • Tremor at rest, starts in hands ('pill-rolling' tremor)
      • Cognitive impairment (variable)
      • "Shop window disease": difficulty initiating walking, stopping, or changing direction
    • Etiology:
      • Usually no obvious underlying cause
      • Can occur after cerebral ischemia, viral encephalitis, or other brain damage
      • Rare cases of early onset familial PD with genetic mutations
    • Pathophysiology:
      • Characterized by Lewy bodies, accumulations of α-synuclein in neurons
      • Degeneration of dopaminergic neurons in substantia nigra
      • Dopamine deficiency disrupts motor control
    • Diagnosis:
      • Primarily clinical, based on history and neurological exam
      • No definitive lab tests
      • Imaging studies, like dopamine transporter (DAT) scans, support diagnosis
    • Striatal dopamine content drops to 20-40% of normal before symptoms appear

    Drug Treatment

    • Levodopa:
      • First-line treatment, precursor of dopamine
      • Rapidly decarboxylated to dopamine by DOPA-decarboxylase
      • Only a small amount reaches the CNS
      • Often administered with a DOPA-decarboxylase inhibitor (carbidopa or benserazide)
      • Well absorbed from small intestine, short plasma half-life (2 hrs)
      • Slow release preparations available
      • Combination with DOPA-decarboxylase inhibitor and COMT inhibitor (entacapone or tolcapone) used for 'end of dose' motor fluctuations
      • Therapeutic effectiveness: about 80% see initial improvement, 20% see near-normal motor function
      • Effectiveness declines over time
      • Increases life expectancy, potentially due to improved motor function
      • ADRs:
        • Involuntary movements (dyskinesia), more prevalent with short-acting levodopa
        • Nausea and anorexia
        • Postural hypotension
        • Psychological effects:
          • Schizophrenia-like syndrome with hallucinations
          • Confusion, disorientation, insomnia, or nightmares
      • Rapid fluctuations in clinical state: "off effect" is a sudden worsening of motor symptoms, treated with sustained-release preparations or COMT inhibitors
    • Dopamine Agonists:
      • Pramipexole, ropinirole, rotigotine, apomorphine
      • Pramipexole and ropinirole are D1/D2 selective, better tolerated, fewer fluctuations
      • Can cause somnolence, hallucinations, compulsive behaviors
      • Short plasma half-life (6-8 hrs), 3 times daily dosing
      • Slow-release once-daily formulations now available
      • Rotigotine: newer agent, transdermal patch delivery
      • Apomorphine (injection): for 'off effect' control with levodopa, must be combined with antiemetics, last choice if other drugs fail
    • MAO-B Inhibitors:
      • Selegiline, rasagiline, safinamide (under clinical trials)
      • Selegiline:
        • Selective and irreversible
        • Adjunct to levodopa
        • ADRs: excitement, anxiety, insomnia
      • Rasagiline:
        • Selective and irreversible
        • May retard disease progression
    • Other Drugs:
      • Amantadine:
        • Mechanism unknown, believed to release dopamine, inhibit amine uptake, or act directly on dopamine receptors
        • Newer research suggests NMDA receptor blockade as a possible target
        • Less effective than levodopa, but reduces dyskinesia
      • Acetylcholine Antagonists (Benztropine):
        • Muscarinic antagonists compensate for dopamine deficiency
        • Rarely used except to treat parkinsonian symptoms in patients on antipsychotics
        • ADRs: dry mouth, constipation, vision impairment, urinary retention

    Summary of Drug Treatment:

    - For motor complications of dopaminergic therapy (motor fluctuations and dyskinesia): use adjuvant dopamine agonists, MAO-B inhibitors (rasagiline or selegiline), entacapone, intermittent apomorphine injections
    - Delayed-release levodopa can reduce motor complications in later-stage Parkinson's but shouldn't be first-line treatment
    - Amantadine can be used to decrease dyskinesia
    

    Annex (Disimpairment Parkinson Treatment)

    • Low frequency repetitive transcranial magnetic stimulation (rTMS) improves motor system function
    • Deep brain stimulation
    • Physical therapy may be helpful, modest benefit
    • Exercise:
      • Modest benefit
      • Home-based balance and strengthening exercise programs less severe cases (reduce fall risk)
      • Tai chi better than stretching or resistance training at reducing falls in Parkinson's disease
      • Exercise benefits less pronounced in patients with high disease severity

    Epilepsy

    • Epilepsy is a common disorder that affects 0.5-1% of the population.
    • Characterized by seizures, which result from episodic neuronal discharges.
    • Often there is no identifiable cause.

    Types of Seizures

    • Partial Seizures:
      • Begin locally and can become generalised.
      • Jacksonian epilepsy: Repetitive jerking of a muscle group beginning on one side of the body, spreading to much of the body before dying out. Patient may not lose consciousness.
      • Psychomotor epilepsy: Stereotyped purposive movements or complex behaviour (dressing, walking, combing hair)
    • Generalised Seizures:
      • Involve the whole brain.
      • Tonic-clonic Seizures (Grand mal): Tonic phase with strong contraction of the whole musculature, involuntary cry, loss of respiration, synchronous jerks, unconsciousness.
      • Absence Seizures (Petit mal): Patient stops what they are doing, stares for a few seconds, with little or no movement.
      • Lennox-Gastaut Syndrome: Occurs in children and is associated with progressive mental retardation.
      • Status epilepticus: Continuous uninterrupted seizures, requiring emergency medical treatment.

    Antiepileptic drugs (AEDs)

    • Aim to inhibit abnormal neuronal discharge, not the underlying cause.
    • Often need to be taken continuously for many years, so minimizing side effects is vital.
    • Mechanisms of action:
      • Enhancement of GABA action.
      • Inhibition of sodium channel function.
      • Inhibition of calcium channel function.
    • Newer AEDs with novel mechanisms are being developed.

    Enhancement of GABA Action

    • Phenobarbital:
      • Clinical uses are similar to phenytoin.
      • Not often used due to sedation.
      • Widely used in veterinary practice.
    • Benzodiazepines:
      • Used for acute seizures, especially in children (diazepam), often administered rectally.
      • Used for status epilepticus (lorazepam, diazepam, clonazepam IV), acting rapidly.
    • Vigabatrin:
      • Used for refractory complex partial seizures.
    • Tiagabine:
      • Reduces seizure frequency in patients with partial seizures.

    Inhibition of Sodium Channel Function

    • Carbamazepine:
      • One of the most widely used AEDs.
      • Chemically related to tricyclic antidepressants.
      • Used for certain partial seizures (psychomotor epilepsy), neuropathic pain, and manic-depressive illness.
      • Oral administration, plasma half-life of about 30 hours.
      • Strong inducer of hepatic enzymes.
      • Slow release preparation available for patients with transient side effects.
    • Phenytoin:
      • Used for tonic-clonic seizures and some types of partial seizures.
      • Not typically first-line due to potential for adverse effects.
    • Lamotrigine:
      • Used for various seizure types including partial and generalised seizures.
    • Lacosamide:
      • Used for partial-onset seizures, with a good safety profile.

    Inhibition of Calcium Channel Function

    • Ethosuximide:
      • Used for absence seizures.
      • May be ineffective for other types of seizures.
    • Valproate:
      • Useful for certain types of infantile epilepsy, with low toxicity and lack of sedative action.
      • Used in adolescents with tonic-clonic, myoclonic, and absence seizures.
      • Well absorbed orally and excreted.
      • Plasma half-life of about 15 hours.

    Newer AEDs

    • Gabapentin and Pregabalin:
      • Effective against partial seizures with less severe side effects.
      • Gabapentin is relatively safe due to its absorption profile.
      • Plasma half-life of about 6 hours requiring dosing two to three times daily.
      • Free of interactions with other drugs.
      • Used as an analgesic for neuropathic pain.
      • Pregabalin is more potent but similar to gabapentin.
    • Ganaxolone:
      • Positive allosteric modulator of GABA-A receptors containing delta subunits.
    • Tonabersat:
      • Neuronal gap junction inhibitor.

    Other Uses of AEDs

    • Bipolar disorder:
      • Valproate, carbamazepine, oxcarbazepine, lamotrigine, topiramate.
    • Migraine prophylaxis:
      • Valproate, gabapentin, topiramate.
    • Anxiety disorders:
      • Gabapentin.
    • Neuropathic pain:
      • Gabapentin, pregabalin, carbamazepine, lamotrigine.

    AEDs and Women

    • AEDs can increase oral contraceptive metabolism, reducing their effectiveness.
    • AEDs can induce hepatic CYP3A4 enzymes.
    • AEDs may produce teratogenic effects.
    • AEDs can result in vitamin K deficiency in newborns.

    Clinical Uses of AEDs

    • Generalised tonic-clonic seizures:
      • Carbamazepine (preferred due to favorable effectiveness/risk ratio), phenytoin, valproate.
      • Newer agents include vigabatrin, lamotrigine, topiramate, levetiracetam.
      • Single drug therapy is preferred to avoid pharmacokinetic interactions.
    • Partial (focal) seizures:
      • Carbamazepine, valproate.
      • Alternatives include clonazepam, phenytoin, gabapentin, pregabalin, lamotrigine, topiramate, levetiracetam, zonisamide.
    • Absence seizures:
      • Ethosuximide, valproate, lamotrigine.
      • Valproate is useful when absence seizures coexist with tonic-clonic seizures.
    • Neuropathic pain:
      • Carbamazepine, gabapentin.
    • Stabilise mood in mono- or bipolar affective disorder:
      • As an alternative to lithium: carbamazepine, valproate.

    When to Start AED Therapy

    • Start AED therapy only after diagnosis of epilepsy is confirmed, unless exceptions.
    • Consider AED therapy after the second epileptic seizure.
    • Consider AED therapy after a first unprovoked seizure if:
      • Electroencephalogram shows definite epileptic activity.
      • Patient has a neurological deficit.
      • Brain imaging demonstrates a structural abnormality.
    • Patients may choose not to take AEDs after full discussion of risks and benefits.

    Choosing AED Therapy

    • Individualize AED treatment based on:
      • Epilepsy syndrome.
      • Seizure type.
      • Other medications and comorbidities.
      • Patient lifestyle.
      • Patient, family, and caregiver preferences.
    • Choose AEDs based on the presenting epilepsy syndrome.
    • Treat patients with monotherapy wherever possible.
    • If initial treatment is unsuccessful, switch to monotherapy with a different drug.
      • Caution is needed during the changeover period.

    Specific Drug Recommendations

    • Carbamazepine:
      • Use with caution due to the possibility of causing syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia.
      • Monitor sodium levels in older adults due to increased risk of SIADH.
      • Offer controlled-release carbamazepine preparations to reduce adverse effects.
    • Valproate:
      • First-line treatment for newly diagnosed generalized tonic-clonic seizures, newly diagnosed myoclonic seizures, tonic or atonic seizures, and newly diagnosed idiopathic generalized epilepsy.

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    Description

    Explore the key features of Parkinson's Disease, a progressive neurodegenerative disorder that primarily affects movement. This quiz covers its symptoms, etiology, pathophysiology, and diagnostic criteria, providing a comprehensive overview of the condition.

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