💊 Levodopa

Levodopa is a dopamine precursor and the most effective symptomatic treatment for Parkinson's disease. It is always co-administered with a peripheral decarboxylase inhibitor.

Levodopa is a prodrug that crosses the blood-brain barrier, where it is converted to dopamine by the enzyme DOPA decarboxylase. Dopamine then replenishes the depleted stores in the striatum, improving motor symptoms. Peripheral decarboxylase inhibitors (e.g., carbidopa, benserazide) prevent levodopa's conversion to dopamine outside the brain, reducing peripheral side effects and increasing central availability.

Levodopa is the primary treatment for motor symptoms in Parkinson's disease, particularly bradykinesia and rigidity. It is also used for post-encephalitic parkinsonism and symptomatic parkinsonism following carbon monoxide or manganese intoxication. It is generally reserved for patients whose symptoms significantly impact their quality of life.

Absolute contraindications include narrow-angle glaucoma, severe psychoses, and malignant melanoma. It should be used with extreme caution in patients with severe cardiovascular or pulmonary disease, bronchial asthma, or endocrine disorders. It is also contraindicated with non-selective MAO inhibitors due to the risk of hypertensive crisis.

Common adverse effects include nausea, vomiting, orthostatic hypotension, and cardiac arrhythmias, especially early in treatment. Long-term use often leads to motor complications such as dyskinesias (involuntary movements) and 'wearing-off' phenomena (fluctuations in motor response). Psychiatric effects like hallucinations and confusion can also occur.

Blood pressure should be monitored regularly, especially during initial titration, due to the risk of orthostatic hypotension. Patients should be monitored for the development of dyskinesias and 'wearing-off' phenomena. Psychiatric status should also be assessed periodically. Liver and renal function tests may be considered.

Always check for a history of narrow-angle glaucoma or severe psychoses. Be vigilant for drug interactions, especially with non-selective MAO inhibitors (contraindicated) and iron salts (reduce absorption). Counselling should include advice on taking the medication with food to reduce nausea, the potential for orthostatic hypotension, and the development of motor fluctuations over time.

Levodopa is the most effective drug for Parkinson's motor symptoms but its long-term use is associated with motor fluctuations and dyskinesias. It is always given with a peripheral decarboxylase inhibitor (e.g., carbidopa/benserazide) to reduce peripheral side effects and increase central bioavailability. The 'wearing-off' phenomenon refers to the return of symptoms before the next dose is due.

SBAs frequently test the concept of 'wearing-off' and dyskinesias as long-term complications of levodopa therapy. Questions might also focus on the importance of co-administration with a peripheral decarboxylase inhibitor and why this is done. The drug interactions, particularly with MAO inhibitors, are another common theme.