PARKIN TABLETS

Indications

• Parkinsonism
• Drug-induced extrapyramidal symptoms (excluding tardive dyskinesia)
• Acute dystonia

Dosage

Adults: Initially, 2.5 mg three times a day, increased by 2.5–5 mg daily as required, with usual maintenance 15–30 mg daily in 2–4 divided doses. Maximum daily dose of 60 mg should only be used in exceptional circumstances. For acute dystonia, the dosage is 5–10 mg via intramuscular or intravenous injection, with a maximum of 20 mg per day.

Mechanism of action

Trihexyphenidyl acts as a competitive antagonist of muscarinic acetylcholine receptors in the central nervous system. By inhibiting these receptors, it reduces cholinergic overactivity that results from a relative deficiency of dopamine, thereby helping to restore balance in neurotransmitter activity and alleviate symptoms of movement disorders.

Pharmacodynamics

The pharmacodynamic effects of Trihexyphenidyl include its ability to diminish the involuntary movements and muscle stiffness associated with Parkinson's disease and other movement disorders. By blocking cholinergic transmission, it alleviates symptoms such as tremors and rigidity, which are exacerbated by cholinergic excess in the context of dopamine deficiency. The onset of action can vary, with the effects typically seen within a few days of starting treatment.

Pharmacokinetics

Trihexyphenidyl is well absorbed from the gastrointestinal tract after oral administration. It is metabolized in the liver and has a half-life of approximately 3 to 6 hours, although this can vary. The drug is excreted primarily in the urine, with a portion being eliminated unchanged. Its pharmacokinetics may be affected by factors such as age, liver function, and renal impairment, necessitating caution in these populations.

Contra-indications

• Gastro-intestinal obstruction
• Myasthenia gravis

Adverse effects

• Memory loss
• Cognitive impairment
• Dizziness
• Dry mouth
• Constipation
• Urinary retention
• Blurred vision

Precautions

• Caution in patients with cardiovascular disease
• Caution in elderly patients
• Caution in patients with dementia
• Caution in patients with hepatic impairment
• Caution in patients with renal impairment

Pregnancy

Caution is advised as effects on the fetus are not fully understood.

Breast-feeding

Caution is advised due to potential effects on the infant.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Oral tablets
• Oral suspension
• Injection solution

Indications

• Parkinson's disease
• Drug-induced extrapyramidal symptoms
• Anticholinergic therapy adjunct

Dosage

Children: Refer to BNF for Children for appropriate dosing information.

Adults: Refer to BNF for appropriate dosing information.

Mechanism of action

Trihexyphenidyl is a non-selective muscarinic acetylcholine receptor antagonist with a higher affinity for the M1 subtype. It is suggested to enhance dopamine release in the striatum by modifying nicotinic acetylcholine receptor neurotransmission. This mechanism contributes to its efficacy in alleviating symptoms associated with Parkinson's disease and other movement disorders.

Pharmacodynamics

Benzhexol is effective as an adjunct treatment for parkinsonism and for alleviating drug-induced extrapyramidal symptoms. Its long duration of action allows for less frequent dosing. The drug has a wide therapeutic window, with non-fatal acute toxicity observed at doses up to 300 mg. Patients receiving benzhexol require monitoring of intraocular pressure and should be informed about the risks of anhidrosis and hyperthermia.

Pharmacokinetics

The pharmacokinetic profile of benzhexol includes absorption, distribution, metabolism, and excretion characteristics typical of antimuscarinic agents. Benzhexol is generally well-absorbed following oral administration, with a long half-life that supports its prolonged action. Specific details on its metabolic pathways and exact pharmacokinetic parameters are not provided, necessitating further investigation or reference to detailed pharmacokinetic studies.

Adverse effects

• Dry mouth
• Blurred vision
• Constipation
• Urinary retention
• Dizziness
• Sedation
• Confusion
• Anhidrosis
• Hyperthermia

Interactions

• Increased effects when used with other anticholinergic agents
• Potentially increased sedation when used with CNS depressants such as alcohol, benzodiazepines, or opioids

Precautions

• Caution in patients with glaucoma
• Caution in patients with urinary retention
• Caution in elderly patients due to increased sensitivity to anticholinergic effects
• Monitor intraocular pressure in patients with a history of glaucoma
• Assess iridocorneal angle before starting therapy

Pregnancy

Use in pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data on safety.

Breast-feeding

Not recommended during breastfeeding due to potential effects on the infant.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Tablets
• Oral solution

Indications

• Parkinson's disease
• Drug-induced extrapyramidal symptoms

Dosage

Children: Refer to the BNF for Children for appropriate dosing information for paediatric patients.

Adults: Refer to the BNF for specific dosing guidelines, as doses may vary based on the condition being treated and patient response.

Mechanism of action

Trihexyphenidyl is a non-selective muscarinic acetylcholine receptor antagonist, with a preference for the M1 subtype. It binds to central muscarinic receptors in the cerebral cortex more strongly than to peripheral receptors. This antagonism may indirectly enhance dopamine release in the striatum by modifying nicotinic acetylcholine receptor neurotransmission. Its exact mechanism of action in alleviating movement disorder symptoms remains partially understood.

Pharmacodynamics

Trihexyphenidyl is indicated for the treatment of parkinsonism and drug-induced extrapyramidal symptoms. It has a long duration of action, and acute toxicity is not fatal even at high doses (up to 300 mg). Patients undergoing therapy should have their iridocorneal angle examined and intraocular pressure monitored. There is a risk of anhidrosis and hyperthermia associated with its use.

Pharmacokinetics

The pharmacokinetics of trihexyphenidyl indicate that it has a long half-life, allowing for less frequent dosing. It is well-absorbed following oral administration, with peak plasma concentrations typically reached within a few hours. The drug undergoes hepatic metabolism and is excreted primarily in the urine. Due to its ability to cross the blood-brain barrier, it exhibits central nervous system effects.

Adverse effects

• dry mouth
• blurred vision
• constipation
• urinary retention
• dizziness
• confusion
• drowsiness
• anxiety
• tachycardia

Interactions

• clozapine+trihexyphenidyl: Unknown (additive effect)
• antipsychotics, second generation+trihexyphenidyl: Unknown (additive effect)

Precautions

• Monitor intraocular pressure during therapy
• Examine iridocorneal angle prior to treatment
• Counsel patients about risks of anhidrosis and hyperthermia

Pregnancy

Use in pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data on safety.

Breast-feeding

Caution is advised as it is not known whether trihexyphenidyl is excreted in human milk.

Storage

Store in a cool, dry place, away from direct sunlight and moisture.

Formulations

• tablets
• oral solution

Mechanism of action

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. Cerebral blood flow and oxygen metabolism were studied in six previously untreated patients with Parkinson's disease (PD) before and after anticholinergic treatment using positron emission tomography (PET) and compared with six controls. The PET study and an assessment of the disability and cognitive impairment were performed before and after administration of 6 mg trihexyphenidyl for 5 to 11 weeks. All PD patients showed improvements in motor symptoms after the trihexyphenidyl treatment. Cognitive function did not significantly differ between before and after trihexyphenidyl treatment. However, after trihexyphenidyl treatment, regional cerebral blood flow (rCBF) and regional oxygen metabolic rate (rCMRO2) decreased by 15% in the striatum and by 10% in all cortical areas contralateral to predominantly symptomatic limbs, and by 10% in the ipsilateral striatum and all cortical areas, significantly below the values of controls in most cerebral cortices and striatum. These findings suggest that trihexyphenidyl inhibits the cortical cholinergic system and significantly decreases rCBF and rCMRO2 in the cerebral cortices without cognitive impairment in untreated patients with PD. In common with other antimuscarinic agents, trihexyphenidyl produces an atropine-like blocking action on parasympathetic-innervated peripheral structures, including smooth muscle. In addition, trihexyphenidyl exhibits a direct spasmolytic action on smooth muscle and exhibits weak mydriatic, antisialagogue, and cardiovagal blocking effects. The exact mechanism of action of trihexyphenidyl in parkinsonian syndrome is not understood but may result from blockade of efferent impulses and from central inhibition of cerebral motor centers. In small doses, trihexyphenidyl depresses the CNS but larger doses cause cerebral excitement resembling the signs of atropine toxicity. In vivo microdialysis was used to study the effect of the non-selective muscarinic antagonist, trihexyphenidyl, on the decarboxylation of levodopa (L-dopa) in the striatum of hemi-Parkinson rats. In normal rats, continuous perfusion of trihexyphenidyl (1 mM) via the microdialysis probe induced a significant increase in striatal dopamine release, followed by a decrease to below baseline values. A similar effect was observed, though less pronounced, in denervated striatum of rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway. In these hemi-Parkinson rats, continuous striatal perfusion of trihexyphenidyl had no effect on the biotransformation of locally applied L-dopa (2 uM for 20 min) to dopamine in either intact or denervated striatum. However, systemic administration of trihexyphenidyl (1.5 mg/kg ip) produced an attenuation of the L- dopa-induced dopamine release in the intact striatum (contralateral to the lesion) of hemi-Parkinson rats. This effect was absent in the denervated striatum of these animals. We confirmed that L-dopa induces an increase in striatal dopamine output which is influenced by the severity of the dopaminergic denervation. The absence of an effect of trihexyphenidyl locally applied in the striatum, on biotransformation of L-dopa suggests that the site of action of antimuscarinic drugs may not be in the striatum and, therefore, remains unclear.

Pharmacodynamics

Trihexyphenidyl is an antimuscarinic indicated as an adjunct in the treatment of parkinsonism or as a treatment for drug-induced extrapyramidal symptoms. It has a long duration of action as it does not need to be given every day. It has a wide therapeutic window, with acute toxicity being non fatal in doses as high as 300 mg. Patients should have their iridocorneal angle examined before and intraocular pressure monitored during therapy. Patients should be counselled regarding the risk of anhidrosis and hyperthermia.

Mechanism of action

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. Cerebral blood flow and oxygen metabolism were studied in six previously untreated patients with Parkinson's disease (PD) before and after anticholinergic treatment using positron emission tomography (PET) and compared with six controls. The PET study and an assessment of the disability and cognitive impairment were performed before and after administration of 6 mg trihexyphenidyl for 5 to 11 weeks. All PD patients showed improvements in motor symptoms after the trihexyphenidyl treatment. Cognitive function did not significantly differ between before and after trihexyphenidyl treatment. However, after trihexyphenidyl treatment, regional cerebral blood flow (rCBF) and regional oxygen metabolic rate (rCMRO2) decreased by 15% in the striatum and by 10% in all cortical areas contralateral to predominantly symptomatic limbs, and by 10% in the ipsilateral striatum and all cortical areas, significantly below the values of controls in most cerebral cortices and striatum. These findings suggest that trihexyphenidyl inhibits the cortical cholinergic system and significantly decreases rCBF and rCMRO2 in the cerebral cortices without cognitive impairment in untreated patients with PD. In common with other antimuscarinic agents, trihexyphenidyl produces an atropine-like blocking action on parasympathetic-innervated peripheral structures, including smooth muscle. In addition, trihexyphenidyl exhibits a direct spasmolytic action on smooth muscle and exhibits weak mydriatic, antisialagogue, and cardiovagal blocking effects. The exact mechanism of action of trihexyphenidyl in parkinsonian syndrome is not understood but may result from blockade of efferent impulses and from central inhibition of cerebral motor centers. In small doses, trihexyphenidyl depresses the CNS but larger doses cause cerebral excitement resembling the signs of atropine toxicity. In vivo microdialysis was used to study the effect of the non-selective muscarinic antagonist, trihexyphenidyl, on the decarboxylation of levodopa (L-dopa) in the striatum of hemi-Parkinson rats. In normal rats, continuous perfusion of trihexyphenidyl (1 mM) via the microdialysis probe induced a significant increase in striatal dopamine release, followed by a decrease to below baseline values. A similar effect was observed, though less pronounced, in denervated striatum of rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway. In these hemi-Parkinson rats, continuous striatal perfusion of trihexyphenidyl had no effect on the biotransformation of locally applied L-dopa (2 uM for 20 min) to dopamine in either intact or denervated striatum. However, systemic administration of trihexyphenidyl (1.5 mg/kg ip) produced an attenuation of the L- dopa-induced dopamine release in the intact striatum (contralateral to the lesion) of hemi-Parkinson rats. This effect was absent in the denervated striatum of these animals. We confirmed that L-dopa induces an increase in striatal dopamine output which is influenced by the severity of the dopaminergic denervation. The absence of an effect of trihexyphenidyl locally applied in the striatum, on biotransformation of L-dopa suggests that the site of action of antimuscarinic drugs may not be in the striatum and, therefore, remains unclear.

Pharmacodynamics

Trihexyphenidyl is an antimuscarinic indicated as an adjunct in the treatment of parkinsonism or as a treatment for drug-induced extrapyramidal symptoms. It has a long duration of action as it does not need to be given every day. It has a wide therapeutic window, with acute toxicity being non fatal in doses as high as 300 mg. Patients should have their iridocorneal angle examined before and intraocular pressure monitored during therapy. Patients should be counselled regarding the risk of anhidrosis and hyperthermia.