 |
|
|
Trihexyphenidyl
|
|
| Systematic (IUPAC) name | |
| 1-cyclohexyl-1-phenyl-3-(1-piperidyl)propan-1-ol | |
| Identifiers | |
| CAS number | |
| ATC code | N04 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C20H31NO |
| Mol. mass | 301.466 g/mol |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | 3.3-4.1 hours |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
C US |
| Legal status |
Rx-Only (US) |
| Routes | Oral, as tablet or elixir |
Trihexyphenidyl, also known as Benzhexol, (sold under the brandnames Aparkan and Artane) is an antiparkinsonian drug of the antimuscarinic class. Chemically, it is a tertiary amine with alcohol, phenyl, and cyclohexyl moieties. It has been in clinical usage for decades. The drug is available as the hydrochloride salt.
Contents |
Pharmacology
The exact mechanism of action in parkinsonian syndromes is not precisely understood, but it is known that trihexyphenidyl blocks efferent impulses in parasympathetically innervated structures like smooth muscles (spasmolytic activity), salivary glands, and eyes (mydriasis). In higher doses direct central inhibition of cerebral motor centers may contribute. In very high doses central toxicity as seen in atropine overdose is noted.
It binds to the M1 muscarinic receptor.1
Pharmacokinetics
Trihexyphenidyl is rapidly absorbed from the GI-Tract. The onset of action is within 1 hour after oral dosing. The peak activity is noted after 2 to 3 hours. The duration of action of one single dose is 6 to 12 hours in a dose dependent manner. It is excreted in the urine, probably as unchanged drug. More precise data in animals and humans have so far not been determined.
Established uses
Trihexyphenidyl is used for the symptomatic treatment of Parkinson's disease in mono- and combination therapy. It is active in postencephalitic, arteriosclerotic, and idiopathic forms. The drug is also commonly used to treat extrapyramidal side effects occurring during antipsychotic treatment. It reduces the frequency and duration of oculogyric crises as well as of dyskinetic movements and spastic contractions. Excessive salivation may also respond. Trihexyphenidyl may improve psychotic depression and mental inertia frequently associated with Morbus Parkinson and symptomatic problems caused by antipsychotic treatment.
Therapeutic prospects
The drug hao is not able to cure Morbus Parkinson, but may provide substantial alleviation of symptoms. An estimated 50 to 75% of patients with Morbus Parkinson will react positively and experience a 20 to 30% symptomatic improvement. To increase therapeutic activity trihexyphenidyl is often given concomitantly with levodopa, other antimuscarinic or antihistaminic (e.g. diphenhydramine) agents. Combination treatment with dopaminergic agonists such as cabergoline is also possible. This is often termed a 'multidimensional approach'.
Investigational uses
Equivocal preleminary results from small studies exist for:
- Other Dyskinesias
- Huntington's Chorea
- Spasmodic Torticollis
- Dystonia2
Trihexyphenidyl does not improve cerebral palsy and hemiplegia.
Contraindications and cautions
- Hypersensitivity to trihexyphenidyl
- Narrow angle glaucoma
- Caution : Patients with obstructive diseases of the urogenital tract, patients with a known history of seizures and those with potentially dangerous tachycardia
- Patients under 18 yrs. of age should not be treated due to a lack of clinical experience.
- Trihexyphenidyl has been reported as a drug of abuse, and while this is uncommon it may be prudent to be cautious in prescribing this drug to patients with a history of drug addiction. The drug has euphoriant and aphrodisiac properties and is smoked, insufflated, swallowed, or dissolved under the tongue and has enhanced activity when injected. Some users report a rush in the genital area when used in such a way as to deliver the dose very quickly and for this and other reasons Artane® and similar drugs are referred to by some as Sexy Trihexy, Tri-Sexual, T. Hex, and Octane.citation needed
- Patients should allow a period to adjust to the dose when first adjusting to trihexyphenidyl and when the dose has been increased or added to a regimen with other drugs because acute somnolence and accumulated fatigue can make in particularly dangerous to opeate an automobile, heavy machinery or that containing hot liquids &c.
Pregnancy and lactation
The safe use of Trihexyphenidyl during pregnancy and lactation has so far not been assured.
Side-effects
Dose-dependent side effects are frequent. Particularly geriatric patients may react with confusional states or develop delirium.
- CNS : Drowsiness, vertigo, headache, and dizziness are frequent. With high doses nervousness, agitation, anxiety, delirium, and confusion are noted. Trihexyphenidyl may be abused due to a short acting mood-elevating and euphoriant effect. The normal sleep architecture may be altered (REM sleep depression). Trihexyphenidyl may lower the seizure-threshold.
- Peripheral side effects : Blurred vision, dry mouth, impaired sweating, abdominal discomfort, and obstipation are frequent. Tachycardia may be noted. Allergic skin reactions may occur. Parenteral use may cause orthostatic hypotension.
- Eyes : Trihexyphenidyl causes mydriasis with or without photophobia. It may precipitate narrow angle glaucoma.
- Tolerance may develop during therapy which requires dose adjustments.
Interactions
- Other anticholinergic drugs (e.g. spasmolytics, antihistamines, TCAs) : Side effects of trihexyphenidyl may be increased.
- Quinidine : Increased anticholinergic action (particular on AV conduction).
- Antipsychotics : Long term use of trihexyphenidyl may mask or increase the risk of tardive dyskinesia.
- Pethidine (meperidine) : Central effects and side effects of pethidine may be increased.
- Metoclopramide : Action of metoclopramide is decreased.
- Alcohol : Risk of serious intoxication.
Dosage
- Morbus Parkinson : One mg is given on the first day. Increments are usually 2mg every 3 days until 6 to 10mg are reached. In postencephalitic cases up to 15 mg might be necessary, but then excessive dryness of mouth or nausea could be a problem. To increase tolerability Trihexyphenidyl may be given in 3 divided doses.
- Extrapyramidal side effects : Usually, 5 to 15 mg daily are needed in 2 or 3 divided doses. Some patients, however, are successfully treated with as little as 1 mg daily.
Overdose
Trihexyphenidyl mimics an atropine intoxication with mydriasis, dryness of mucous membranes, red face, atonic states of bowels and bladder, and hyperthermia in high doses. Central consequences are agitation, confusion, and hallucinations. An untreated overdose may be fatal, particular in children. Premortal signs are respiratory depression and cardiac arrest. A specific antagonist is physostigmine which combines a peripheral and a central action. Carbachol can be used to treat atonic bowels and bladder. The vital functions should be monitored and stabilized. It may be necessary to treat hyperthermia with cooling blankets.
Abuse
According to a recent news report, trihexyphenidyl has become a drug of abuse among Iraqi soldiers and police3. The report states that the drug, taken in high doses, results in an increased sense of well-being and decreased anxiety. Although the drug is not considered physically addictive, the report suggests that the drug may become habit forming among some users due to its supposed psychological effects.
Brand names and dose forms
- Artane : elixir 2mg/5ml, tabletts 2mg and 5mg
- Generics (e.g. Cypress, URL, Watson, West-Ward) : elixir and/or tabletts
- Pacitane "http://www.wyethindia.com/products/pacitane.asp?prodid=7"
References
- ^ Giachetti A, Giraldo E, Ladinsky H, Montagna E (September 1986). "Binding and functional profiles of the selective M1 muscarinic receptor antagonists trihexyphenidyl and dicyclomine". Br. J. Pharmacol. 89 (1): 83–90. PMID 2432979.
- ^ Sanger TD, Bastian A, Brunstrom J, et al (May 2007). "Prospective open-label clinical trial of trihexyphenidyl in children with secondary dystonia due to cerebral palsy". J. Child Neurol. 22 (5): 530–7. doi:. PMID 17690057. http://jcn.sagepub.com/cgi/pmidlookup?view=long&pmid=17690057.
- ^ Mudhafer Al-Husaini and Erica Goode, New York Times, Dec. 20, 2008. "Abuse of Prescription Drugs Rises Among Stressed Iraqi Soldiers"
External links
- AHFS online database
- http://www.mentalhealth.com/drug/p30-t04.html
|
||||||||||||||||||||||||||
|
|||||||||||
Wikipedia content modification information:
- This page was last modified on 6 January 2009, at 03:27.
Wikipedia Authorship and Review
Wikipedia content provided here is not reviewed directly by PediaView.com. Wikipedia content is authored by an open community of volunteers and is not produced by or in any way affiliated with PediaView.com.
Wikipedia Usage Guidelines
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article on "Trihexyphenidyl".
The URL for this specific entry is:
All Wikipedia text is available under the terms of the GNU Free Documentation License. (See Copyrights for details). Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc.