Makindo Medical Notes

⚠️ Important: Levodopa is always co-administered with a peripheral decarboxylase inhibitor (benserazide or carbidopa) to reduce peripheral side effects (e.g., nausea, vomiting, hypotension).

📖 About

• 💊 Introduced in the 1960s, Levodopa revolutionised Parkinson’s disease (PD) treatment.
• 🧠 PD pathophysiology: progressive loss of nigrostriatal dopaminergic neurons → dopamine depletion in the striatum.
• ⏳ Effectiveness often wanes with years of therapy; motor fluctuations and dyskinesias emerge.

⚙️ Mode of Action

• 🚪 Crosses the blood–brain barrier (dopamine itself cannot).
• 🔄 Decarboxylated in CNS to dopamine → restores striatal dopamine.
• 🛡️ Peripheral inhibitor (benserazide or carbidopa) prevents premature breakdown → less nausea, vomiting, hypotension.

🎯 Indications

• Idiopathic Parkinson’s disease (first-line for motor symptom control in most patients).
• Post-encephalitic parkinsonism (famously described in Oliver Sacks’ Awakenings).
• Other parkinsonian syndromes (e.g., CO or manganese toxicity) — but usually less effective in atypical parkinsonism (e.g., MSA, PSP).

💊 Formulations & Typical Doses

Doses are individualised. Start low, titrate slowly. Typical total daily dose: 400–800 mg Levodopa in divided doses.

• Co-Beneldopa (Madopar®)
  • 62.5 mg (50/12.5), 125 mg (100/25), CR forms, and dispersible forms available.
  • Common start: 62.5 mg TDS → titrate to effect.
• Co-Careldopa (Sinemet®)
  • 62.5 mg, 110 mg, 125 mg, and CR versions.
  • Common start: 62.5 mg TDS → titrate gradually.

⛔ Contraindications

• Drug-induced parkinsonism (little benefit).
• Severe psychosis, narrow-angle glaucoma (relative contraindications).

⚠️ Side Effects

• 🤢 GI: nausea, vomiting.
• 💔 CVS: orthostatic hypotension, palpitations.
• 🧠 CNS: hallucinations, confusion, delirium (esp. in elderly).
• 🌀 Motor: dyskinesias, dystonia, “on–off” and “wearing-off” phenomena with long-term use.
• 🚨 Abrupt withdrawal → neuroleptic malignant syndrome-like reaction (rigidity, hyperthermia, autonomic instability).

🔄 Interactions

• 🍗 Protein-rich meals: reduce absorption/competition at gut and BBB transporters.
• 💊 Pyridoxine (Vit B₆): increases peripheral metabolism if given without inhibitor (rarely an issue now).
• 🚫 Dopamine antagonists (e.g., antipsychotics, metoclopramide): reduce efficacy.

💡 Levodopa Pearls

Levodopa is the most effective treatment for Parkinson’s disease, but long-term use is limited by motor and psychiatric complications. These pearls highlight practical and exam-relevant points.

• 🌟 “Honeymoon Period” — initial dramatic benefit for motor symptoms, but after 5–10 years fluctuations and dyskinesias become common.
• ⏱️ “On–Off” phenomena — unpredictable swings between mobility (often with dyskinesias) and immobility (“off” state).
• ⌛ “Wearing off” — each dose lasts a shorter time; may need smaller, more frequent doses or adjuncts (COMT/MAO-B inhibitors).
• ➕ Adjuncts — COMT inhibitors (entacapone), MAO-B inhibitors (rasagiline), and dopamine agonists (ropinirole, pramipexole) can reduce fluctuations.
• 🎰 Impulse Control Disorders — especially with dopamine agonists, but also possible with Levodopa (gambling, hypersexuality, compulsive spending/eating).
• 🧠 Neuropsychiatric effects — hallucinations and psychosis (especially in elderly); manage by simplifying meds first, then consider quetiapine/clozapine if needed.
• 🩸 Postural Hypotension — common; worsens falls. Encourage slow postural changes; may require fludrocortisone or midodrine.
• ✍️ Prescribing safety — always write “micrograms (mcg)” clearly; avoid confusion between 125 mcg and 125 mg.
• 🏥 Perioperative care — never omit doses; if NBM, give via NG or dispersible preparations. Omission risks a malignant-like crisis.
• 🚩 Red Flags — early falls, dysphagia, poor Levodopa response → consider atypical parkinsonism (e.g., MSA, PSP).

📚 References

• BNF: Co-beneldopa
• BNF: Co-careldopa
• BTS/SIGN Parkinson’s Guidelines