Makindo Medical Notes

💊 Key Point: L-Dopa must always be prescribed with a peripheral dopa-decarboxylase inhibitor (Carbidopa in Sinemet or Benserazide in Madopar) to prevent premature dopamine breakdown. 🚫 Never prescribe L-Dopa alone. 🧠 Impulse control disorders such as gambling, hypersexuality or binge eating can occur — warn and monitor patients and carers. Always 🔗 check the BNF entry for the latest dosing and cautions.

🧠 About

• Co-careldopa (Sinemet) combines Levodopa with Carbidopa, a peripheral DOPA-decarboxylase inhibitor (DDI).
• It is the cornerstone of symptomatic treatment in idiopathic Parkinson’s disease.
• Levodopa replenishes depleted dopamine within the basal ganglia, improving bradykinesia and rigidity.
• Carbidopa prevents peripheral conversion of Levodopa to dopamine, reducing nausea, vomiting and hypotension while increasing CNS availability.
• Preferred in older adults and frail patients as it remains the most potent and cost-effective motor therapy.

⚙️ Mode of Action

• Levodopa is a dopamine precursor that crosses the blood–brain barrier and is decarboxylated to dopamine in the CNS.
• Carbidopa inhibits peripheral dopa-decarboxylase, preventing systemic dopamine formation and its unwanted side effects.
• This dual mechanism ensures greater bioavailability of Levodopa for CNS conversion, allowing lower dosing and fewer peripheral adverse effects.
• Improves voluntary movement by restoring dopaminergic–cholinergic balance within the basal ganglia circuitry.

💊 Indications & Dosing

• Idiopathic Parkinson’s disease and parkinsonism of uncertain aetiology.
• Start with Sinemet 62.5 mg (L-Dopa 50 mg + Carbidopa 12.5 mg) two to four times daily, taken with food to minimise nausea.
• Titrate gradually to achieve symptomatic benefit while avoiding dyskinesia or confusion.
• Usual maintenance: 100–200 mg L-Dopa per dose, 3–4 times per day.
• Maximum: ~800 mg Levodopa per day (BNF guidance).
• Doses may be divided through the day to smooth motor fluctuations (“wearing-off”).

📊 Common Preparations

🧪 Pharmacology

• Class: Dopamine precursor + peripheral decarboxylase inhibitor.
• Half-life: 1–2 hours (CR forms: ~3–4 hours).
• Metabolism: hepatic (COMT, MAO); renal excretion.
• Onset: 20–60 min; food can delay absorption slightly.

🤝 Interactions

• Antipsychotics, metoclopramide: antagonise dopamine; worsen Parkinsonism.
• Non-selective MAO inhibitors: contraindicated → risk of hypertensive crisis.
• Antihypertensives: additive postural hypotension — monitor carefully.
• Iron supplements: reduce absorption — separate by 2 hours.
• Protein-rich meals can impair absorption → encourage consistent meal timing.

⚠️ Cautions

• Impulse control disorders: monitor for gambling, hypersexuality, binge eating.
• Psychiatric illness: may worsen hallucinations or mania.
• Cardiac disease: arrhythmogenic risk via catecholamine metabolism.
• Renal or hepatic impairment: titrate slowly.
• Do not stop abruptly — risk of neuroleptic malignant–like syndrome.

⛔ Contraindications

• Active or past malignant melanoma (Levodopa may increase melanin synthesis).
• Untreated narrow-angle glaucoma.
• Severe psychosis.

💢 Side Effects

• Neuropsychiatric: confusion, vivid dreams, euphoria, depression, psychosis.
• Motor complications: dyskinesia, dystonia, “on–off” fluctuations.
• Autonomic: postural hypotension, palpitations, sweating, salivation.
• Gastrointestinal: nausea, vomiting, dyspepsia, constipation, ulcer disease.
• Haematologic/immune: leucopenia, Henoch–Schönlein purpura (rare).
• Other: sudden sleep attacks, orthostatic hypotension, fatigue.

🧠 Clinical Pearls

• Levodopa remains the gold standard for symptomatic control in Parkinson’s disease.
• Start low, titrate gradually, and review regularly for dyskinesia or hallucinations.
• Advise on safe driving and operating machinery — sudden sleep episodes can occur.
• Domperidone (not metoclopramide) can be used to relieve nausea.
• Educate patients and carers on recognising behavioural change early — it is often reversible with dose adjustment.
• Adjust Levodopa dosing if adding COMT inhibitors (Entacapone) or MAO-B inhibitors (Selegiline/Rasagiline).

📚 References

• BNF: Co-careldopa (Sinemet)
• NICE NG71: Parkinson’s disease in adults (2023 update).
• UpToDate: “Pharmacologic management of Parkinson disease.”
• Parkinson’s UK: Levodopa and impulse-control disorders guidance.