Therapeutic Management of PD - Motor Complications

Flashcards covering the pharmacological management and motor complications of Parkinson's Disease (PD) according to the lecture notes.

Motor fluctuations

End-of-dose deterioration and on-off phenomena resulting from intermittent, non-physiologic restoration of striatal dopamine.

Dyskinesia

Involuntary motor movements caused by exposure to peak plasma levels of Levodopa and pulsatile stimulation of D2-like receptors.

Levodopa-Induced Dyskinesia Risk Factors

Specific patient and treatment characteristics including young age, low body weight, and a Levodopa dose of $>600\,mg/day$.

Controlled-Released (CR) Levodopa

A preparation with limited benefit in delaying motor fluctuations compared to immediate-release, primarily used for night-time akinesia and simplifying complex regimens.

COMT Inhibitors

Drugs that inhibit Catechol-o-methyl transferase in the brain and periphery to prevent the metabolism of dopamine and Levodopa.

3-O-methyldopa (3-OMD)

An inert metabolite formed by the conversion of levodopa; COMT inhibitors act peripherally to inhibit this conversion.

COMTi

Increases plasma half-life of levodopa, which is valuable for decreasing ‘off’ time associated with end-of-dose deterioration and improving overall motor function in patients with Parkinson's disease.

COMT Inhibitor Side Effects

Common adverse reactions include diarrhoea, abdominal pain, and urine discolouration.

Entacapone

The most commonly used COMT inhibitor, administered up to $200\,mg$ with each dose of levodopa, and available in combination with Co-careldopa.

Tolcapone

A potent COMT inhibitor with both central and peripheral actions, though not routinely used due to the risk of hepatotoxicity requiring intensive monitoring.

Opicapone

A newer COMT inhibitor with a favorable side effect profile and the benefit of once daily (OD) dosing, though it may increase dyskinesia risk.

Amantadine

A dopaminergic stimulant used to treat severe dyskinesia, typically administered at $100-200\,mg$ BD (twice daily).

Amantadine Side Effects

Potential adverse effects including confusion, oedema, and visual disturbances.

STOP: AE overcome benefits

NICE Guidelines for PD Motor Complications

Offer a choice of DA (dopamine agonist), MAO-B inhibitor, or COMT inhibitor as supplementation to Levodopa for patients with dyskinesia or motor fluctuations.