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The symptoms of Parkinson’s disease are specific to each patient, which means each patient also requires an individual treatment plan. The main goal of any treatment plan is to maintain the patient’s functional ability, but there must be a balance between adequate treatment and minimisation of medication side effects.

Dopamine is a neurotransmitter that is partly responsible for controlling normal voluntary movement and coordination, and most medicines used for Parkinson’s act either by making more dopamine available or by stimulating postsynaptic receptors, which are normally activated by dopamine.

Levodopa

Levodopa is the gold standard of Parkinson’s treatment. It works by replenishing depleted dopamine. It is given with an extracerebral dopadecarboxylase inhibitor to limit side effects and ensure effective brain dopamine concentrations are achieved with a lower dose of levodopa.

There are two oral levodopa preparations available: co-beneldopa and cocareldopa. Both are typically taken three times daily at the start of treatment, but may be taken more frequently as the condition advances. Levodopa is started at low doses and increased as tolerated. This is particularly important for elderly patients.

Modified-release preparations of levodopa are also available. These are usually taken by patients just before going to bed in order to control nocturnal immobility and rigidity.

Side effects include:

• Nausea and vomiting (likely to be worse when starting treatment)
• Postural hypotension
• Drowsiness
• Dizziness
• Confusion
• Hallucinations.

Long-term use of levodopa can result in motor complications, such as response fluctuations (on/off phenomena, end-of-dose deterioration) and dyskinesia (involuntary movement).

Catechol-O-methyltransferase inhibitors

Catechol-O-methyltransferase (COMT) inhibitors can be used with levodopa to prevent its breakdown and allow more of the drug to reach the brain. There are two different COMT inhibitors available: entacapone and tolcapone.

Entacapone doses should be taken at the same time as doses of levodopa. Because of its potency, only the first morning dose of tolcapone must be taken with levodopa and subsequent doses taken approximately six and 12 hours later. A combination product of co-careldopa and entacapone can be taken, which can reduce tablet burden for patients.

COMT inhibitors have the same side effects as levodopa as they act by making more levodopa available. Entacapone colours urine reddish brown and products containing iron should not be taken at the same time of day as they affect absorption. Entacapone also enhances the anticoagulant effect of warfarin.

Tolcapone is only used when patients fail to respond to or are intolerant of entacapone, and it should only be continued when there is clinical benefit. This is because it can cause potentially life-threatening hepatotoxicity and should only be used under specialist supervision.

Patients must have regular liver function tests whilst prescribed tolcapone and must be advised to report any symptoms of liver toxicity, which may include nausea, fatigue, lethargy, anorexia, jaundice, dark urine, pruritus (severe itching) or right upper quadrant tenderness.