Benztropine
Benztropine
Generic Name
Benztropine
Mechanism
- Competitive blockade of central and peripheral muscarinic acetylcholine receptors (primarily M1/M2), reducing the activity of acetylcholine which is pathologically increased in Parkinsonian disorders and antipsychotic‑induced dystonia.
- Antidystonic and anti‑nausea effects stem from decreased cholinergic tone in the vestibular nuclei and cerebellum.
- By restoring the dopaminergic‑acetylcholinergic balance in the basal ganglia, benztropine improves bradykinesia, rigidity, and tremor.
Pharmacokinetics
| Parameter | Details |
| Absorption | Oral bioavailability ~70 % (rapid, peak ~1 h); intramuscular injection gives faster onset. |
| Distribution | Extensive CNS penetration; plasma protein binding 75–85 %. |
| Metabolism | Hepatic via oxidative N‑dealkylation (CYP2D6, CYP3A4). Metabolites inactive. |
| Elimination | Renal excretion; 80 % in urine as unchanged drug. |
| Half‑life | 10–12 h (oral); 1–2 h (IM). Dose adjustments for renal impairment. |
| Special Populations | Caution in elderly/renal disease: longer half‑life → accumulation, anticholinergic load. |
Indications
- Antipsychotic‑induced extrapyramidal symptoms (acute dystonia, akathisia, parkinsonism).
- Parkinson’s disease (motor fluctuation, rigidity, bradykinesia).
- Benign essential tremor (adjunct).
- Pre‑operative anti‑emetic prophylaxis in selected cases.
Contraindications
- Absolute Contraindications:
- Acute angle‑closure glaucoma.
- Intestinal obstruction or paralytic ileus.
- Blindness of lenses or severe mydriasis.
- Warnings:
- Severe hepatic dysfunction: monitor liver enzymes.
- Renal impairment: dose adjustment.
- Elderly patients: increased risk of delirium, cognitive decline, falls.
- Precautions:
- Ocular: may worsen myopia or cause uveitis.
- Psychiatric: can exacerbate psychosis; avoid in uncontrolled psychiatric illness.
Dosing
| Situation | Route | Dose | Frequency | Titration |
| Acute dystonia | IM | 3.5–7 mg | Single | Repeat every 30 min until symptom resolution (max 3 doses). |
| Parkinsonism | Oral | 2 mg daily | Once | Increase to 4 mg/day after 24 h if inadequate. |
| Parkinson’s adjunct | Oral | 2–4 mg daily | BID/PO | Start low; titrate to effect/side‑effects. |
| Benign tremor | Oral | 2–4 mg daily | BID | Same titration approach. |
• Loading/maintenance: If starting oral therapy, consider 4 mg once on day 1 then 2 mg daily.
• Tapering: Gradual reduction over 1–2 weeks to avoid rebound dystonia.
Adverse Effects
Common (≥10 % incidence)
• Dry mouth, blurred vision, constipation, urinary retention.
• Increased heart rate, tachycardia.
Serious (≤1 %)
• Neuroleptic malignant syndrome (rare with benztropine alone).
• Severe hallucinations or delirium, especially in the elderly.
• Anticholinergic crisis: hyperpyrexia, seizures.
Monitoring
- Clinical: Frequency of dystonic movements, tremor severity, bowel and bladder function.
- Vital signs: Heart rate, blood pressure, ocular pupil size (especially before/after dosing).
- Laboratory: Renal function (CrCl or eGFR) for dose adjustment; liver panel if hepatic impairment.
- Cognitive/psychomotor: Assess for confusion or falls in elderly patients, especially after dose escalation.
Clinical Pearls
- “Dystonia first” rule: In patients on first‑generation antipsychotics, give 3.5–7 mg IM benztropine *before* initiating oral dose to avert early dystonia.
- Dual‑mode dosing: Combine oral basal dose (2 mg daily) with short‑acting IM or intranasal doses for breakthrough acutely‑exacerbated symptoms.
- Elderly dosing caution: A single 1–2 mg dose often suffices; avoid >4 mg/day.
- Drug interactions: CYP2D6 inhibitors (e.g., fluoxetine) can prolong half‑life; CYP3A4 inhibitors (e.g., ketoconazole) may increase serum concentration.
- Parental guidance: Emphasize that benztropine is not an antipsychotic; its anticholinergic side‑effects may mimic sedation or confusion—monitor closely.
- Tapering strategy: Abrupt cessation in chronic Parkinson’s patients can precipitate rebound dystonia—taper over 1–2 weeks.
- Use in Parkinson’s dementia: Low doses (≤1 mg) have shown benefit in gait but may worsen cognition; weigh risks/benefits.
*Benztropine* remains a cornerstone anticholinergic therapy for motor disorders in a rapidly evolving pharmacotherapy landscape.