Makindo Medical Notes

Orphenadrine hydrochloride is a centrally acting anticholinergic used as an adjunct in the management of Parkinson’s disease and drug-induced extrapyramidal syndromes (EPS). It provides modest symptomatic benefit by reducing cholinergic overactivity within the basal ganglia. It should only be used under specialist advice, and its use has declined with the advent of better-tolerated dopaminergic therapies. Always 🔗 check the BNF entry here for up-to-date dosing and cautions.

⚙️ Mode of Action

• Acts as a centrally acting antimuscarinic agent.
• Reduces cholinergic activity in the striatum, restoring the dopamine–acetylcholine balance that is disrupted in Parkinsonism.
• Also exhibits weak antihistaminic and skeletal muscle relaxant effects, contributing to mild sedation and relaxation.
• In drug-induced EPS (e.g. from antipsychotics), it helps relieve dystonia, rigidity, and akathisia by countering central cholinergic excess.

💊 Indications & Dose

• Parkinson’s disease or drug-induced extrapyramidal symptoms (EPS):
  • Start Orphenadrine 50 mg three times daily, increasing gradually to 100 mg three times daily (max 400 mg/day).
  • In older adults, use half the usual dose due to increased susceptibility to anticholinergic effects and confusion.
• Administer with food to minimise gastrointestinal discomfort.
• Avoid abrupt discontinuation to prevent rebound rigidity or dystonia.

🧪 Pharmacology

• Onset: 30–60 minutes after oral administration.
• Half-life: approximately 14 hours.
• Metabolism: hepatic (extensive first-pass metabolism).
• Excretion: primarily renal.

🤝 Interactions

• Other anticholinergics or antihistamines: additive dry mouth, constipation, urinary retention, blurred vision.
• Antipsychotics (phenothiazines, butyrophenones): may worsen tardive dyskinesia or cognitive blunting.
• Alcohol, benzodiazepines, opioids: additive CNS depression.
• Antihypertensives: risk of postural hypotension and confusion in elderly.

⚠️ Cautions

• Cardiac disease / hypertension: may cause tachycardia and palpitations.
• Angle-closure glaucoma: risk of raised intraocular pressure.
• Prostatic hypertrophy / urinary retention: may worsen symptoms.
• Renal or hepatic impairment: use lower doses and titrate slowly.
• Do not stop abruptly — taper to avoid cholinergic rebound.

⛔ Contraindications

• Myasthenia gravis — worsens muscle weakness.
• Mechanical GI obstruction or paralytic ileus.
• Angle-closure glaucoma (absolute contraindication).

💢 Side Effects

• Central: drowsiness, dizziness, confusion, agitation, hallucinations (particularly in elderly).
• Autonomic: dry mouth, blurred vision, constipation, urinary retention, tachycardia.
• Ocular: risk of angle-closure glaucoma; advise on eye pain or vision changes.
• Rare: euphoria, ataxia, vomiting, hypersensitivity rash.

🧠 Clinical Pearls

• Most effective for acute dystonic reactions and drug-induced parkinsonism rather than idiopathic Parkinson’s disease.
• In idiopathic Parkinson’s, anticholinergics are now reserved for younger patients with predominant tremor who cannot tolerate dopaminergic therapy.
• Older patients are prone to delirium and memory impairment; avoid unless absolutely necessary.
• Educate patients to maintain hydration and monitor for urinary difficulty or blurred vision.

📚 References

• BNF: Orphenadrine Hydrochloride
• NICE CKS: Parkinson’s disease management.
• British National Formulary, Edition 87 (2024).
• UpToDate: “Anticholinergic drugs in Parkinsonism.”