Usage
Trihexyphenidyl is prescribed for the treatment of Parkinson’s disease symptoms (tremor, rigidity, and bradykinesia) and for drug-induced extrapyramidal symptoms (EPS), such as dystonia, akathisia, and parkinsonism, caused by antipsychotic medications. It belongs to the anticholinergic class of drugs. Trihexyphenidyl works by blocking the activity of acetylcholine, a neurotransmitter in the brain, which helps to rebalance the levels of dopamine and acetylcholine, thus reducing the motor symptoms of Parkinson’s disease and EPS.
Alternate Names
Trihexyphenidyl hydrochloride is also known as benzhexol hydrochloride internationally. Brand names include Artane and Pacitane.
How It Works
Pharmacodynamics: Trihexyphenidyl primarily acts as an anticholinergic agent, meaning it blocks the effects of acetylcholine at muscarinic receptors within the central nervous system. This leads to a reduction in cholinergic activity, which helps to alleviate some of the symptoms associated with Parkinson’s disease and drug-induced parkinsonism.
Pharmacokinetics:
- Absorption: Trihexyphenidyl is well-absorbed from the gastrointestinal tract.
- Metabolism: It is metabolized in the liver.
- Elimination: It is primarily excreted in the urine. Specific information on CYP enzyme involvement is limited.
Mode of Action: At the cellular level, trihexyphenidyl competitively inhibits the binding of acetylcholine to muscarinic receptors, primarily M1 receptors in the central nervous system. This reduces the effects of excessive cholinergic activity, which contributes to the motor symptoms observed in Parkinson’s disease and drug-induced extrapyramidal reactions. The precise mechanism of action in alleviating symptoms is complex and involves interactions within the basal ganglia circuitry.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Trihexyphenidyl’s main action is the competitive antagonism of muscarinic M1 receptors.
Dosage
Standard Dosage
Adults:
Initial dosage is typically 1 mg per day, taken orally. This can be gradually increased by 2 mg increments every 3-5 days until optimal symptom control is achieved. The usual maintenance dosage ranges from 6-10 mg per day, divided into three or four doses, taken with meals. The maximum recommended dose generally does not exceed 15 mg per day.
Children:
Use in children is not recommended due to limited clinical experience and potential for serious side effects. However, if necessary, dosage must be determined by the child’s physician based on weight and clinical condition. Start with a very low dose and titrate cautiously, monitoring carefully for adverse effects.
Special Cases:
- Elderly Patients: Start with a lower dose (1 mg per day) and titrate cautiously, as elderly patients are more susceptible to adverse effects.
- Patients with Renal Impairment: Dose adjustment may be necessary. Monitor renal function and adjust the dose accordingly.
- Patients with Hepatic Dysfunction: Dose adjustment may be necessary. Monitor liver function and adjust the dose accordingly.
- Patients with Comorbid Conditions: Exercise caution in patients with glaucoma, cardiovascular disease, gastrointestinal or urinary tract obstruction, and prostatic hypertrophy.
Clinical Use Cases
Trihexyphenidyl is not indicated for intubation, surgical procedures, mechanical ventilation, or emergency situations like status epilepticus or cardiac arrest.
Dosage Adjustments
Dose adjustments are based on patient response and tolerance. Careful titration is necessary, especially in elderly patients and those with renal or hepatic impairment.
Side Effects
Common Side Effects
Dry mouth, blurred vision, dizziness, nausea, nervousness, constipation, drowsiness, urinary retention.
Rare but Serious Side Effects
Glaucoma, cardiac arrhythmias, hallucinations, delirium, paralytic ileus, heat stroke, neuroleptic malignant syndrome (NMS).
Long-Term Effects
Cognitive impairment, memory problems, and dependence.
Adverse Drug Reactions (ADR)
Any signs of NMS (fever, muscle rigidity, altered mental status, autonomic instability), angle-closure glaucoma, or cardiac arrhythmias should prompt immediate discontinuation of trihexyphenidyl and supportive medical care.
Contraindications
- Narrow-angle glaucoma
- Hypersensitivity to trihexyphenidyl
- Gastrointestinal obstruction
- Urinary retention
- Prostatic hypertrophy
Drug Interactions
Trihexyphenidyl may interact with other anticholinergic medications (e.g., antihistamines, tricyclic antidepressants), enhancing anticholinergic effects. It can also interact with certain antipsychotics, levodopa, and medications that prolong the QT interval. Alcohol, barbiturates, and opioids can have additive sedative effects when combined with trihexyphenidyl.
Pregnancy and Breastfeeding
Pregnancy Safety Category: C. Trihexyphenidyl should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult with a specialist.
While it is unknown if trihexyphenidyl is excreted in human milk, caution should be exercised when administering it to nursing mothers. Monitor infants for potential anticholinergic effects.
Drug Profile Summary
- Mechanism of Action: Anticholinergic agent, blocks muscarinic M1 receptors in the CNS.
- Side Effects: Dry mouth, blurred vision, dizziness, constipation, nausea, urinary retention, cognitive impairment, hallucinations (rare).
- Contraindications: Narrow-angle glaucoma, urinary retention, GI obstruction.
- Drug Interactions: Other anticholinergics, antipsychotics, levodopa, QT prolonging drugs.
- Pregnancy & Breastfeeding: Use with caution. Category C.
- Dosage: 1-15 mg/day; individualize, titrate cautiously.
- Monitoring Parameters: Monitor for adverse effects, including cognitive changes, glaucoma, and cardiac arrhythmias.
Popular Combinations
Trihexyphenidyl may be used in combination with levodopa in the treatment of Parkinson’s disease. Dose adjustments of both drugs are often necessary to optimize efficacy and minimize adverse effects.
Precautions
Screen for glaucoma, prostatic hypertrophy, and urinary retention. Avoid in patients with narrow-angle glaucoma. Use with caution in elderly patients. Monitor for cognitive changes, particularly in the elderly.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Trihexyphenidyl?
A: Start with 1 mg daily and titrate by 2 mg increments every 3-5 days until optimal benefit is achieved. The usual maintenance dose is 6-10 mg/day divided TID-QID, with a maximum of 15 mg/day. Elderly patients should start with a lower dose.
Q2: What are the common side effects of Trihexyphenidyl?
A: Dry mouth, blurred vision, constipation, nausea, dizziness, and urinary retention are common side effects.
Q3: Is Trihexyphenidyl safe during pregnancy?
A: Trihexyphenidyl is Pregnancy Category C. Its use during pregnancy should be carefully considered and only if the potential benefit outweighs the potential risk to the fetus.
Q4: How does Trihexyphenidyl work?
A: It is an anticholinergic agent that blocks muscarinic M1 receptors in the CNS, helping to rebalance acetylcholine and dopamine levels.
Q5: What are the serious side effects of Trihexyphenidyl to watch for?
A: Angle-closure glaucoma, cardiac arrhythmias, neuroleptic malignant syndrome, hallucinations, and delirium are rare but serious side effects.
Q6: Can Trihexyphenidyl be used in children?
A: It is generally not recommended due to a lack of sufficient data on safety and efficacy in the pediatric population. If use is deemed necessary, dosing should be individualized with careful monitoring by a physician.
Q7: Does Trihexyphenidyl interact with other medications?
A: Yes, it can interact with other anticholinergic medications, antipsychotics, levodopa, and QT-prolonging agents.
Q8: What should patients avoid while taking Trihexyphenidyl?
A: Patients should avoid alcohol and other CNS depressants, as they can potentiate the sedative effects of Trihexyphenidyl. Caution should also be exercised in hot weather or during strenuous exercise due to the risk of hyperthermia.
Q9: What should I monitor in patients taking Trihexyphenidyl?
A: Monitor for cognitive changes (especially in the elderly), signs of angle-closure glaucoma (eye pain, blurred vision), and cardiac arrhythmias (palpitations, irregular heartbeat). Regular assessment of bowel and bladder function is also recommended.
Q10: What should I do if a patient experiences a severe side effect?
A: Discontinue trihexyphenidyl immediately and provide supportive care. Contact a toxicologist or specialist for appropriate management.
