Podcast
Questions and Answers
What is primarily affected in Parkinson's disease as described in the summary?
What is primarily affected in Parkinson's disease as described in the summary?
What symptom is often recognized as 'pill-rolling' in Parkinson's disease?
What symptom is often recognized as 'pill-rolling' in Parkinson's disease?
Which of the following is associated with Parkinson's disease in its later stages?
Which of the following is associated with Parkinson's disease in its later stages?
What percent decrease in striatal dopamine content is typically needed for Parkinson's symptoms to appear?
What percent decrease in striatal dopamine content is typically needed for Parkinson's symptoms to appear?
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Which of the following is NOT typically involved in the diagnosis of Parkinson's disease?
Which of the following is NOT typically involved in the diagnosis of Parkinson's disease?
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What is a common psychological side effect associated with Levodopa treatment in Parkinson's disease patients?
What is a common psychological side effect associated with Levodopa treatment in Parkinson's disease patients?
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Which intervention can help manage the 'off effect' in Parkinson's disease patients receiving Levodopa?
Which intervention can help manage the 'off effect' in Parkinson's disease patients receiving Levodopa?
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What distinguishes Pramipexole and Ropinirole from other dopamine agonists?
What distinguishes Pramipexole and Ropinirole from other dopamine agonists?
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Which of the following is NOT a side effect associated with MAO-B inhibitors like Selegiline?
Which of the following is NOT a side effect associated with MAO-B inhibitors like Selegiline?
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What is the primary action of Amantadine in the treatment of Parkinson's disease?
What is the primary action of Amantadine in the treatment of Parkinson's disease?
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What is the primary mechanism by which levodopa acts in treating Parkinson's disease?
What is the primary mechanism by which levodopa acts in treating Parkinson's disease?
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Which of the following statements about levodopa pharmacokinetics is true?
Which of the following statements about levodopa pharmacokinetics is true?
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What is the purpose of using a DOPA-decarboxylase inhibitor alongside levodopa?
What is the purpose of using a DOPA-decarboxylase inhibitor alongside levodopa?
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What percentage of patients typically experience initial improvement in rigidity and bradykinesia when using levodopa?
What percentage of patients typically experience initial improvement in rigidity and bradykinesia when using levodopa?
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Which combination is often used to improve the effectiveness of levodopa in patients experiencing motor fluctuations?
Which combination is often used to improve the effectiveness of levodopa in patients experiencing motor fluctuations?
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Which of the following antiepileptic drugs primarily enhances GABA action?
Which of the following antiepileptic drugs primarily enhances GABA action?
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What is a common clinical use for Carbamazepine?
What is a common clinical use for Carbamazepine?
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Which mechanism of action is NOT associated with the function of common antiepileptic drugs?
Which mechanism of action is NOT associated with the function of common antiepileptic drugs?
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Which statement about the pharmacokinetics of Carbamazepine is correct?
Which statement about the pharmacokinetics of Carbamazepine is correct?
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What is a notable side effect of Phenobarbital that limits its use?
What is a notable side effect of Phenobarbital that limits its use?
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What is a characteristic feature of Jacksonian epilepsy?
What is a characteristic feature of Jacksonian epilepsy?
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Which type of seizure is characterized by a sudden cessation of activity followed by a brief stare?
Which type of seizure is characterized by a sudden cessation of activity followed by a brief stare?
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What is a defining aspect of status epilepticus?
What is a defining aspect of status epilepticus?
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In what condition is Lennox-Gastaut syndrome primarily seen?
In what condition is Lennox-Gastaut syndrome primarily seen?
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Which best describes partial seizures?
Which best describes partial seizures?
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Which drug primarily acts as a positive allosteric modulator of GABA-A receptors?
Which drug primarily acts as a positive allosteric modulator of GABA-A receptors?
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What is the approximate half-life of valproate in the plasma?
What is the approximate half-life of valproate in the plasma?
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Which of the following statements about gabapentin is true?
Which of the following statements about gabapentin is true?
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What type of seizures is valproate NOT particularly useful for?
What type of seizures is valproate NOT particularly useful for?
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Which of the following characteristics is associated with pregabalin compared to gabapentin?
Which of the following characteristics is associated with pregabalin compared to gabapentin?
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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
-
Amantadine:
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.
