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Chlorprothixene

Chlorprothixene is a typical antipsychotic drug of the thioxanthine class. It has a low antipsychotic potency (half to 2/3 of chlorpromazine). Its principal indications are the treatment of psychotic disorders (e.g. schizophrenia) and of acute mania occurring as part of bipolar disorders. more...

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The drug was introduced 1959 to the market on a global scale and is hence a first generation antipsychotic with 45+ years of clinical experience. It is still today of clinical and also some research interest.

Mechanisms of Action

Chlorprothixene exerts strong blocking effects at the following postsynaptic receptors:

  • 5-HT2 : anxiolysis, antipsychotic effects
  • D1, D2, D3 : antipsychotic effects
  • H1 : sedation, weight gain
  • muscarinic : anticholinergic side-effects, extrapyramidal side-effects attenuated
  • Alpha1 : hypotension, tachycardia

Uses

Other uses are pre- and postoperative states with anxiety and insomnia, severe nausea / emesis (in hospitalized patients), the amelioration of anxiety and agitation linked due to use of selective serotonin reuptake inhibitors for depression and, off-label, the amelioration of alcohol and opioid withdrawal. It may also be used cautiously to treat nonpsychotic irritability, aggression, and insomnia in pediatric patients.

An intrinsic antidepressant effect of chlorprothixene has been discussed, but not proven yet. Likewise, it is unclear, if chlorprothixene has genuine (intrinsic) analgesic effects. However, Chlorprothixene can be used as comedication in severe chronic pain. An antiemetic effect, as with most antipsychotics, exists.

Side-effects

Chlorprothixene has a strong sedative activity with a high incidence of anticholinergic side-effects. The types of side effects encountered (dry mouth, massive hypotension and tachycardia, hyperhidrosis, substantial weight gain etc.) normally do not allow a full effective dose for the remission of psychotic disorders to be given. So cotreatment with another, more potent, antipsychotic agent is needed.

Chlorprothixene is structurally related to chlorpromazine, with which it shares in principal all side effects. Allergic side-effects and liver damage seem to appear with an appreciable lower frequency. The elderly are particularly sensitive to anticholinergic side-effects of chlorprothixene (precipitation of narrow angle glaucoma, severe obstipation, difficulities in urinating, confusional and delirant states). In patients >60 years the doses should be particularly low.

Early and late extrapyramidal side-effects may occur but have been noted with a low frequency (one study with a great number of participants has delivered a total number of only 1%).

Dosage

In any case, the initial doses of chlorprothixene should be as low as possible (e.g. 30mg at bedtime, 15mg morning dose) and be increased gradually. Patients receiving 90mg daily (and more) of the drug should be hospitalized, particularly during the initial phase of treatment. The theoretical maximum is 800mg daily which can usually not been given due to side-effects as stated above. Elderly and pediatric patients should be treated with particular low initial doses. Dose increments should be done slowly.

Read more at Wikipedia.org


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Treatment of postherpetic neuralgia
From American Family Physician, 2/15/05 by Carrie Morantz

The Quality Standards Subcommittee of the American Academy of Neurology has released a report on postherpetic neuralgia treatment. "Practice Parameter: Treatment of Postherpetic Neuralgia" appears in the September 2004 issue of Neurology and is available online at http://www.aan.org.

Acute herpetic neuralgia is characterized as burning, aching, electric-shock--like pain, or unbearable itching in association with the outbreak of a herpes zoster rash. The pain is associated with dysesthesias, paresthesias, hyperalgesia, hyperesthesia, and allodynia (production of pain by innocuous stimuli). The pain may precede the onset of the herpetic rash and, rarely, herpetic neuralgia can occur without the development of a rash.

Postherpetic neuralgia, persistence of the pain of herpes zoster more than three months after resolution of the rash, is relatively common, affecting 10 to 15 percent of those with herpes zoster. Zoster-associated pain is used to describe the continuum of pain from acute herpes zoster to the development of postherpetic neuralgia. The time interval used in the clinical case definition of postherpetic neuralgia varies in the literature from one to six months after resolution of the rash. The incidence of postherpetic neuralgia increases with age. The duration of postherpetic neuralgia is highly variable.

Administration of antiviral agents within 72 hours of the onset of herpes zoster can reduce the intensity and duration of acute illness, and can prevent postherpetic neuralgia, as may the use of amitriptyline. Efforts at prevention of herpes zoster and postherpetic neuralgia are important in that 40 to 50 percent of those with postherpetic neuralgia do not respond to any treatment. The practice parameter focused on which treatments provide benefit in terms of decreased pain and improved quality of life. Among the findings and key recommendations are the following:

* Tricyclic antidepressants (amitriptyline, nortriptyline, desipramine, and maprotiline), gabapentin, pregabalin, opioids, and topical lidocaine patches are effective and should be used in the treatment of postherpetic neuralgia. There is limited evidence to support the use of nortriptyline over amitriptyline and the data are insufficient to recommend one opioid over another. Amitriptyline has significant cardiac effects in elderly patients when compared with nortriptyline and desipramine.

* Aspirin in cream may be effective in the relief of pain in patients with postherpetic neuralgia but the magnitude of benefit is low, as with capsaicin.

* In countries where preservative-free intrathecal methylprednisolone is available, it may be considered in the treatment of postherpetic neuralgia.

* Acupuncture, benzydamine cream, dextromethorphan, indomethacin, epidural methylprednisolone, epidural morphine sulfate, iontophoresis of vincristine, lorazepam, vitamin E, and zimelidine are not of benefit.

* The efficacies of carbamazepine, nicardipine, biperiden, chlorprothixene, ketamine, He:Ne laser irradiation, intralesional triamcinolone, cryocautery, topical piroxicam, extract of Ganoderma lucidum, dorsal root entry zone lesions, and stellate ganglion block are unproven in the treatment of postherpetic neuralgia.

* There is insufficient evidence at this time to make any recommendations on the long-term effects of these treatments.

COPYRIGHT 2005 American Academy of Family Physicians
COPYRIGHT 2005 Gale Group

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