Makindo Medical Notes

⚠️ Important: Trihexyphenidyl (benzhexol) can worsen or precipitate acute confusion and delirium, especially in older adults and those with dementia. It should be avoided wherever possible in the elderly and used only under specialist guidance. Always 🔗 check the BNF entry for up-to-date prescribing advice.

🧠 About

• Trihexyphenidyl hydrochloride (also known as benzhexol) is a centrally acting antimuscarinic used in Parkinson’s disease and drug-induced extrapyramidal syndromes (EPS).
• It was once widely used in idiopathic Parkinson’s disease, but its use has declined due to poor cognitive tolerance in older patients.
• Its main benefit is reduction of resting tremor rather than rigidity or bradykinesia.

⚙️ Mode of Action

• Acts as a competitive antagonist at central muscarinic (M₁) receptors within the striatum.
• Restores balance between dopaminergic inhibition and cholinergic excitation in the basal ganglia.
• Reduces cholinergic overactivity secondary to dopaminergic loss (Parkinson’s) or dopamine blockade (antipsychotic use).
• Also has weak antihistaminic and local anaesthetic actions contributing to sedation.

💊 Indications & Dose

• Idiopathic Parkinson’s disease (as adjunct to levodopa or dopamine agonists):
  • Start with 1 mg twice daily, titrate gradually up to 6 mg/day if tolerated.
  • Particularly useful when tremor predominates.
• Drug-induced extrapyramidal syndromes (EPS):
  • Start 1 mg twice daily, increase cautiously to 5 mg three times daily (maximum 20 mg/day).
  • Half-dose in elderly or cognitively frail patients.
• Take with food to reduce gastric irritation.
• Do not stop abruptly — withdraw gradually to avoid rebound rigidity or dystonia.

🧪 Pharmacology

• Onset: 30–60 minutes (oral).
• Half-life: approximately 3–7 hours.
• Metabolism: hepatic.
• Excretion: renal.

🤝 Interactions

• Other anticholinergic drugs (e.g. tricyclics, antihistamines, orphenadrine, procyclidine) — ↑ risk of confusion, constipation, urinary retention.
• Antipsychotics: may mask tardive dyskinesia or worsen psychosis.
• Alcohol and sedatives: additive CNS depression.
• Antihypertensives: may potentiate orthostatic hypotension.

⚠️ Cautions

• Older adults: avoid due to risk of confusion, delirium, and cognitive decline.
• Cardiac disease or hypertension: may cause tachycardia and arrhythmia.
• Angle-closure glaucoma: may increase intraocular pressure.
• Benign prostatic hyperplasia: risk of urinary retention.
• Psychosis: may exacerbate hallucinations and paranoia.
• Use cautiously in renal or hepatic impairment.

⛔ Contraindications

• Myasthenia gravis (worsens muscle weakness).
• Mechanical bowel obstruction or paralytic ileus.
• Untreated narrow-angle glaucoma.

💢 Side Effects

• CNS: drowsiness, confusion, agitation, hallucinations, memory impairment, euphoria, worsening psychosis.
• Autonomic: dry mouth, blurred vision, constipation, urinary retention, tachycardia.
• Ocular: may precipitate angle-closure glaucoma.
• Gastrointestinal: nausea, vomiting.
• ⚠️ Delirium and worsening dementia are common reasons for discontinuation in older patients.

🧠 Clinical Pearls

• Most benefit is for resting tremor rather than rigidity or bradykinesia.
• In drug-induced Parkinsonism, consider stopping the causative agent first; if not possible, use short-term trihexyphenidyl.
• Avoid use in dementia or Lewy-body disease — may precipitate profound confusion or hallucinations.
• Re-evaluate need regularly; aim to discontinue once symptoms resolve.
• Educate patients on dry mouth, blurred vision, and constipation; encourage hydration and stool softeners if required.

📚 References

• BNF: Trihexyphenidyl (Benzhexol)
• NICE CKS: Parkinson’s disease – treatment principles.
• UpToDate: “Anticholinergic drugs in Parkinsonism.”
• MHRA Drug Safety Update (2023): Anticholinergic burden and cognitive risk.