Movement disorders

Question 1

Amantadine

Answer 1

Enhances dopaminergic transmission, has mild antimuscarinic properties, is an antagonist at NMDA receptors

Used in tremor dominant disease to reduce levodopa induced dyskinesias.

Renally cleared - need dose reduction in renal impairment

Adverse effects - mostly dose related.
Antimuscarinic effects - dry mouth, constipation, blurred vision, urinary retention
Hallucinations, confusion, delirium (rare)
50% develop livedo reticularis (skin mottling); 5-10% develop ankle oedema

Question 2

Benztropine, Biperiden, Benzhexol

Answer 2

Anticholinergic.
Decrease cholinergic influences in the basal ganglia, thus maintain a balance in the face of diminished dopaminergic influences.

Rarely used in PD because of limited efficacy and high adverse effects. Can be used to reduce extrapyramidal effects of antipsychotic drugs.

Drug induced parkinsonism, dystonias and akinesia respond reasonably well. May aggravate tardive dyskinesia

Adverse effects due to anticholinergic actions

Question 3

Bromocriptine, cabergoline, pergolide

Answer 3

Ergot derived dopamine agonists that act directly on dopamine receptors.

Question 4

Apomorphine, pramipexole, ropinirole, rotigotine

Answer 4

Non-ergot derived dopamine agonists that act directly on dopamine receptors.

Question 5

Entacapone

Answer 5

Peripherally acting, reversible, COMT inhibitor (catechol-O-methyltransferase). It inhibits the peripheral breakdown of levodopa, resulting in increased levodopa across the BBB.

Useful in the treatment of motor flucturations associated with long term levodopa use.

May potentiate the adverse effects of levodopa. May require reduction in levodopa dose by 10%-30%

Do not cease abruptly (can have withdrawal syndrome that resembles neuroleptic malignant syndrome)
Interactions- tricyclic antidepressants, venlafaxine, and drugs metabolised y COMT. Do not use in conjunction with irreversible nonselective monoamine oxidase inhibitors (phenelzine, tranylcypromine)

Question 6

Levodopa

Answer 6

Metabolic precursor of dopamine, Levodopa crosses the BBB, dopamine does not. Formulated with a decarboxylase inhibitor (benserazide or carbidopa) to inhibit peripheral conversion.

Peripheral effects of dopamine (hypotension, cardiac arrhythmias, nausea, vomiting).

Available in various formulations: IR, CR, dispersible, enteral gel,

CR have lower availability so so increase in total dose (up to 50%) required when switching.

Combined with benserazide or carbidopa = equivalent.

Commencing treatment: SE nausea and vomiting
Avoid rapid ceasation as can give withdrawal syndrome that resembles NMS

Phenytoin, metoclopramide, prochloperazine and antipsychotics all reduce effects

Question 7

Selegiline

Answer 7

Selective irreversible inhibitor of MAO-B enzyme that catabolises dopamine in the brain. Selegiline is metabolised to desmethylselegiline, methylamphetamine, and amphetamine.

Selegiline can cause dyskinesias, mood elevation, hallucinations, bruxism and confusion. Commonly causes insomnia.

Question 8

Chlorpromazine and haloperidol

Answer 8

First generation antipsychotics with dopamine blocking actions. Used for short term treatment of chorea,

Question 9

Piracetam

Answer 9

Piracetam is a derivative of GABA. Used to treat myoclonus, particularly that of cortical origin. Thought to modulate the neurotransmitter system, including glutaminergic and cholinergic systems, and facilitate microcirculation.

Question 10

Tetrabenazine

Answer 10

Reversibly inhibits the uptake of monoamines into striatal neurones, depleting dopamine, noradrenaline and serotonin. Used to treat chorea, tics and tardive syndromes.

Dose dependent adverse effects: drowsiness, insomnia, akathisia, parkinosonism - titrate dose gradually. Serious adverse effects - depression, suicidal ideation, neuroleptic malignant syndrome, extrapyramidal disorders, QTc prolongation, dysphagia.

Can cease without tapering. If on hold more than 5 days, gradual dose reintroduction required.