💊 COMT Inhibitors

COMT inhibitors are a class of drugs used in the management of Parkinson's disease. They are typically used as an adjunct to levodopa therapy.

Catechol-O-methyltransferase (COMT) is an enzyme that metabolises levodopa in the periphery and in the brain. By inhibiting COMT, these drugs reduce the peripheral breakdown of levodopa, allowing more levodopa to cross the blood-brain barrier. This prolongs the half-life of levodopa and increases its availability in the brain, leading to more sustained dopaminergic stimulation.

COMT inhibitors are indicated for the treatment of Parkinson's disease as an adjunct to levodopa and a DOPA decarboxylase inhibitor (e.g., carbidopa or benserazide). They are used in patients experiencing 'wearing-off' phenomena or motor fluctuations, where the effect of levodopa starts to diminish before the next dose. They help to smooth out motor fluctuations and improve 'on' time.

Absolute contraindications include phaeochromocytoma due to the theoretical risk of hypertensive crisis. They should also be avoided in patients with a history of neuroleptic malignant syndrome (NMS) or rhabdomyolysis unrelated to trauma. Caution is advised in patients with severe hepatic impairment due to potential for liver toxicity.

Common side effects include dyskinesia, which may require a reduction in levodopa dose. Nausea, vomiting, and diarrhoea are also frequent, with diarrhoea sometimes being severe and persistent. Urine discolouration (reddish-brown) is a harmless but common side effect. Rarely, hepatotoxicity can occur, particularly with older agents like tolcapone.

Liver function tests (LFTs) should be monitored, especially during the initial months of treatment, due to the risk of hepatotoxicity. Patients should be monitored for the development or worsening of dyskinesia, which may necessitate levodopa dose adjustment. Regular assessment of motor fluctuations and 'on'/'off' times is also important.

When prescribing, always check for allergies, especially to other Parkinson's medications. Counsel patients about the potential for urine discolouration and the importance of reporting persistent diarrhoea or jaundice. Emphasise that this medication must be taken with levodopa and not on its own.

COMT inhibitors (e.g., entacapone, opicapone) are used to extend the action of levodopa in Parkinson's disease. They are particularly useful for motor fluctuations. Key side effects include dyskinesia, gastrointestinal upset, and harmless urine discolouration. Tolcapone is rarely used due to liver toxicity concerns.

SBAs often test the understanding of COMT inhibitors' role as an adjunct to levodopa, not as monotherapy. Questions may focus on their mechanism in reducing 'wearing-off' or their common side effects like dyskinesia and urine discolouration. Another common theme is distinguishing between the different classes of drugs used in Parkinson's disease.