Trihexyphenidyl is indicated as an adjunct in the treatment of all forms of parkinsonism (postencephalitic, arteriosclerotic, and idiopathic). It is often useful as adjuvant therapy when treating these forms of parkinsonism with levodopa.
Trihexyphenidyl is a non-selective muscarinic acetylcholine receptor antagonist but binds with higher affinity to the M1 subtype. In vivo studies have shown that trihexyphenidyl demonstrates higher affinity for central muscarinic receptors located in the cerebral cortex and lower affinity for those located peripherally. Other studies suggest that trihexyphenidyl may modify nicotinic acetylcholine receptor neurotransmission, leading indirectly to enhanced dopamine release in the striatum. Although the anticholinergic has proven to be useful in the treatment of symptoms associated with Parkinson’s disease or other movement disorders, its mechanism of action has yet to be fully elucidated.
Parkinson’s disease (if used in combination with cocareldopa or co-beneldopa) Adult: Maintenance 2-6 mg daily in divided doses, use not recommended because of toxicity in the elderly and the risk of aggravating dementia Parkinsonism | Drug-induced extrapyramidal symptoms (but not tardive dyskinesia) BY MOUTH Adult: 1 mg daily, then increased in steps of 2 mg every 3-5 days, adjusted according to response; maintenance 5-15 mg daily in 3-4 divided doses, not recommended for use in Parkinson’s disease because of toxicity in the elderly and the risk of aggravating dementia; maximum 20 mg per day Elderly: Lower end of range preferable, not recommended for use in Parkinson’s disease because of toxicity in the elderly and the risk of aggravating dementia
Cannabinoids, barbiturates, opiates, and alcohol may have additive effects with, and thus, an abuse potential exists. Concurrent use of alcohol or other CNS depressants with may cause increased sedative effects. Monoamine oxidase inhibitors and tricyclic antidepressants possessing significant anticholinergic activity may intensify the anticholinergic effects of antidyskinetic agents because of the secondary anticholinergic activities of these medications. Prophylactic administration of anticholinergic agents, such as , as a prevention of drug-induced parkinsonism during neuroleptic therapy is not recommended. There may be an increased risk for the development of tardive dyskinesia during concomitant administration of anticholinergics and neuroleptics. The usual dose of either or levodopa may need to be reduced during concomitant therapy, since concomitant administration may increase drug-induced involuntary movements.
Gastro-intestinal obstruction . myasthenia gravis Cardiovascular disease . elderly . hypertension . liable to abuse . prostatic hypertrophy . psychotic disorders . pyrexia . those susceptible to angle-closure glaucoma
Very rare Angle-closure glaucoma Frequency not known Anxiety . blurred vision . confusion . constipation . dizziness . dry mouth . euphoria . hallucinations . impaired memory . nausea . rash . restlessness . tachycardia . urinary retention . Vomiting
PREGNANCY Use only if potential benefit outweighs risk. BREAST FEEDING Avoid.
In humans, doses up to 300 mg (5 mg/kg) have been ingested without fatalities or sequelae. However, rare cases of death associated with Trihexyphenidyl over dosages taken in conjunction with other CNS-depressant agents have been reported or in patients with a compromised respiratory condition. Trihexyphenidyl blood concentrations associated with the fatalities ranged from 0.03 to 0.80 mg/I.
Signs and Symptoms: Over dosage with Trihexyphenidyl produces typical central symptoms of atropine intoxication (the central anticholinergic syndrome). Correct diagnosis depends upon recognition of the peripheral signs of parasympathetic blockade, including dilated and sluggish pupils; warm, dry skin; facial flushing; decreased secretions of the mouth, pharynx, nose, and bronchi; foul-smelling breath; elevated temperature; tachycardia, cardiac arrhythmias; decreased bowel sounds; and urinary retention. Neuropsychiatric signs such as delirium, disorientation, anxiety, hallucinations, illusions, confusion, incoherence, agitation, hyperactivity, ataxia, lip smacking and tasting movements, loss of memory, paranoia, combativeness, and seizures may be present. The condition can progress to stupor, coma, paralysis, cardiac and respiratory arrest, and death.
Treatment: Treatment of acute overdose involves symptomatic and supportive therapy. Gastric lavage or other methods to limit absorption should be instituted. A small dose of diazepam or a short-acting barbiturate may be administered if CNS excitation is observed. Phenothiazines are contra-indicated because the toxicity may be intensified due to their antimuscarinic action, causing coma. Respiratory support, artificial respiration or vasopressor agents may be necessary. Hyperpyrexia must be reversed, fluid volume replaced and acid-balance maintained. Urinary catheterization may be necessary. It is not known if Trihexyphenidyl is dialyzable.
Store at temperature not exceeding 30ºC in a dry place. Protect from light.
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