Biperiden

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Biperiden
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Clinical data
Pregnancy
category
  • AU: B2
  • US: C (Risk not ruled out)
Routes of
administration
Oral, IM, IV
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability33 ± 5% (oral)
Protein binding60%
MetabolismHepatic hydroxylation
Elimination half-life18 to 24 hours
ExcretionRenal
Identifiers
CAS Number
PubChem CID
DrugBank
E number{{#property:P628}}
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Chemical and physical data
FormulaC21H29NO
Molar mass311.461 g/mol

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Biperiden is an antiparkinsonian agent of the anticholinergic type. The original brand name - still existing - is Akineton®, manufactured by BASF/Knoll Pharma. Generics are available worldwide.

Pharmacokinetics

The oral bioavailability is only 33 +/- 5% due to extensive first-pass metabolization. In young, healthy volunteers peak plasma concentrations following an oral single dose of 4mg in immediate release form are reached after 1.5 hours. The elimination half-life has been determined as 18.4 hours, and may be prolonged in geriatric patients. After IV dosing of 4mg the elimination half-life is approximately 24 hours.

Pharmacology

Biperiden has an atropine-like blocking effect on all peripheral structures which are parasympathetic-innervated (e.g. cardiovascular and visceral organs). It also has a prominent central blocking effect on M1 receptors.

Uses

Biperiden is used for the adjunctive treatment of all forms of Parkinson's disease (postencephalitic, idiopathic, and arteriosclerotic). It seems to exert better effects in the postencephalitic and idiopathic than in the arteriosclerotic type. Biperiden is also commonly used to improve parkinsonian signs and symptoms related to antipsychotic drug therapy. It relieves muscle rigidity, reduces abnormal sweating and salivation, improves abnormal gait, and to lesser extend, tremor.

Contraindications and cautions

  • Hypersensitivity to biperiden
  • Narrow angle glaucoma
  • Ileus
  • Caution : Patients with obstructive diseases of the urogenital tract, patients with a known history of seizures and those with potentially dangerous tachycardia

Special patient groups

Pregnancy and lactation

  • Pregnancy : In animal studies biperiden had no embryo- or fetotoxic effects. There is no sufficient clinical data on pregnant women. The drug should therefore be used cautiously during pregnancy.
  • Lactation : Biperiden is found in the milk of lactating women. No sufficient clinical data exists regarding effects for the newborns. Additionally, biperiden may decrease maternal milk production. It is therefore recommended that biperiden is not used during lactation.

Pediatric patients

Children and adolescents aged 1 year and older may be treated. The clinical experience is mainly on the shortterm treatment of acute drug induced dystonic reactions. Doses should be reduced according to the weight of the patients.

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. Biperiden may be abused due to a short acting mood-elevating and euphoriant effect. The normal sleep architecture may be altered (REM sleep depression). Biperiden may lower the seizure-threshold. Some instances of dementia have been noted to correllate with chronic administration of anticholinergic medications such as Biperiden for Parkinson's disease.[1]
  • 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 : Biperiden causes mydriasis with or without photophobia. It may precipitate narrow angle glaucoma.

Interactions

  • Other anticholinergic drugs (e.g. spasmolytics, antihistamines, TCAs) : Side effects of biperiden may be increased.
  • Quinidine : Increased anticholinergic action (particular on AV conduction).
  • Antipsychotics : Long term use of biperiden 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

Strictly individual. Oral, and in some countries, IV and IM use is possible. The usual oral daily doses are between 2 and 16mg. If possible, patients should be started with a low initial dose which is increased slowly.

Overdose

Biperiden 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.

History

Biperiden was synthesized by the German chemist W. Klavehn from Knoll AG, Germany. In March 1953 a patent was applied for in Germany and subsequently in many other countries.

Notes

  1. Nishiyama K, Mizuno T, Sakuta M, Kurisaki H (1993). "Chronic dementia in Parkinson's disease treated by anticholinergic agents. Neuropsychological and neuroradiological examination". Adv Neurol. 60: 479–83. PMID 8420174.

References

  • AHFS database online
  • Scientific Information on Akineton (Swiss)
  • Arnd Barocka, Psychopharmakotherapie in Klinik und Praxis, Schattauer-Verlag , 1998 (German language)
  • Albers, Lawrence (2001–2002). Handbook of Psychiatric Drugs. Laguna Hills, California: Current Clinical Strageties. Unknown parameter |coauthors= ignored (help)

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