Makindo Medical Notes

💊 Key Point: L-Dopa should always be given with a peripheral decarboxylase inhibitor such as benserazide (in Madopar) or carbidopa (in Sinemet) — never as L-Dopa alone. 🧠 Impulse control disorders may develop, leading to hypersexuality, binge eating, gambling or excessive spending — patients and carers must be warned and monitored for behavioural change. Always 🔗 check the BNF entry before prescribing or adjusting doses.

🧠 About

• Co-beneldopa (Madopar) is a combination of Levodopa and Benserazide, used for symptomatic treatment of idiopathic Parkinson’s disease (PD).
• Levodopa replenishes depleted dopamine in the basal ganglia, improving bradykinesia and rigidity, though tremor may respond less well.
• Benserazide inhibits peripheral decarboxylation of Levodopa, allowing more to reach the CNS while reducing nausea, vomiting and hypotension.
• Remains the most effective symptomatic therapy in PD, particularly in older patients.

⚙️ Mode of Action

• Levodopa (L-Dopa) is the metabolic precursor of dopamine.
• As dopamine itself does not cross the blood–brain barrier, Levodopa is administered and converted to dopamine within the CNS by dopa decarboxylase.
• Benserazide, a peripheral dopa-decarboxylase inhibitor (DDI), prevents premature peripheral conversion — enhancing CNS delivery and minimising peripheral side effects.
• The combination restores dopaminergic activity in the striatum, improving voluntary movement control.

💊 Indications & Dose

• Idiopathic Parkinson’s disease and parkinsonism of uncertain aetiology.
• Start with Madopar 62.5 mg (L-Dopa 50 mg + Benserazide 12.5 mg) 2–4 times daily, taken with food to minimise nausea.
• Titrate slowly at weekly intervals to the minimum effective dose; most patients stabilise on Madopar 125 mg 3–4 times daily.
• Maximum L-Dopa dose: around 800 mg/day (in divided doses).
• Try to smooth motor fluctuations by adjusting timing and frequency — smaller, more frequent doses may help "wearing-off".

📊 Typical Dosing Options

🧪 Pharmacology

• Class: Dopamine precursor + peripheral DOPA decarboxylase inhibitor.
• Onset: 20–60 minutes after oral dose; best absorbed on an empty stomach.
• Half-life: 1–2 hours; extended-release formulations available.
• Metabolism: Mainly hepatic; excreted in urine.

🤝 Interactions

• Antipsychotics and metoclopramide antagonise Levodopa and worsen Parkinsonism.
• Non-selective MAO inhibitors: contraindicated (risk of hypertensive crisis).
• Antihypertensives: additive postural hypotension — titrate cautiously.
• Iron supplements: reduce Levodopa absorption — separate by 2 hours.
• See BNF for full interaction list.

⚠️ Cautions

• Nausea and vomiting are common initially — use Domperidone (not metoclopramide) for symptomatic relief.
• Monitor for impulse control disorders — compulsive gambling, shopping, hypersexuality, or eating.
• Psychiatric illness: may exacerbate hallucinations or mania.
• Cardiac disease: risk of arrhythmias due to catecholamine metabolism.
• Renal or hepatic impairment: use cautiously and titrate slowly.

⛔ Contraindications

• Active malignant melanoma or history of melanoma (Levodopa may increase melanin synthesis).
• Severe psychosis or untreated narrow-angle glaucoma.

💢 Side Effects

• Neuropsychiatric: vivid dreams, hallucinations, anxiety, confusion, euphoria, depression.
• Motor: chorea, tremor, dyskinesia, dystonia, "on-off" fluctuations.
• Autonomic: orthostatic hypotension, sweating, salivation, palpitations.
• Gastrointestinal: nausea, vomiting, dyspepsia, constipation, diarrhoea, peptic ulceration.
• Other: sudden sleep attacks, leucopenia, Henoch–Schönlein purpura, neuroleptic malignant–like syndrome (if abruptly stopped).

🧠 Clinical Pearls

• Always co-prescribe a DDI (Benserazide or Carbidopa) — otherwise Levodopa is mostly metabolised before reaching the brain.
• Start low, go slow — titrate to balance motor benefit vs dyskinesia.
• Advise patients to take doses at consistent times daily; avoid abrupt withdrawal to prevent rigidity or NMS-like syndrome.
• Later motor complications include “wearing-off” and peak-dose dyskinesia — managed by dose fractionation or adjuncts like COMT or MAO-B inhibitors.
• Educate patients and carers about behavioural monitoring and the risks of sleep attacks or loss of impulse control.

📚 References

• BNF: Co-beneldopa (Madopar)
• NICE NG71: Parkinson’s Disease in Adults (2023 update).
• UpToDate: “Pharmacologic management of Parkinson disease.”
• Parkinson’s UK Professional Guide: “Levodopa safety and impulse control disorders.”