Haloperidol antiemetic effects

Tourette s syndrome, a heterogeneous behavioral disorder associated with motor and vocal tics of variable form and severity, can be effectively treated with haloperidol. Antipsychotics can also be employed to control disturbed behavior in senile dementia or Alzheimer s disease, since they decrease confusion, agitation, and hyperactivity. Most of these drugs also exhibit a strong antiemetic effect and can sometimes be used clinically for this purpose. 

Haloperidol was introduced for the treatment of psychoses in Europe in 1958 and in the United States in 1967 (Fig. 22.7). it is an effective aiternative to more famiiiar antipsychotic phenothiazine drugs and also is used for the manic phase of bipolar (manic-depressive) disorder. Haloperidol decanoate has been introduced as depot maintenance therapy. When injected every 4 to 6 weeks, the drug appears to be as effective as daily orally administered haloperidol. Other currently available (mostly in Europe) butyrophenones include the very potent spiperone (spiroperidol) as well as trifluperidol and droperidol. Droperidol, a short-acting, sedating butyrophenone, is used in anesthesia for its sedating and antiemetic effects and, sometimes, in psychiatric emergencies as a sedative-neuroleptic. Droperidol often is administered in combination with the potent narcotic analgesic fentanyl for preanesthetic sedation and anesthesia. 

Metoclopramide, administered at doses higher than those required to inhibit apomorphine-induced emesis, was more effective than haloperidol in antagonizing cisplatin-induced emesis in dogs [80]. This was observed despite the fact that metoclopramide was considerably weaker than haloperidol as a D2-dopamine antagonist [43]. Subsequently, antiemetic efficacy of metoclopramide administered at high doses has been reported in cancer patients... 

Metoclopramide may be considered as a prototype 5-HT3 antagonist because its antiemetic efficacy both in animals and man could not be adequately explained by D2-dopamine blockade. In fact, metoclopramide was considerably weaker as a D2-antagonist than haloperidol or domperidone and yet it was effective against emesis induced by anticancer agents both in animals [43, 80] and cancer patients [135]. 

Butyrophenones Haloperidol, droperidol and domperidone act by blocking dopamine receptors. The butyrophenones are moderately effective antiemetics, but high-dose haloperidol was found to... 

Antiemetics that act on the vomiting centre have antimuscarinic (their principal mode) and anti-histaminic action (hyoscine, promethazine) they alleviate vomiting from any cause. In contrast, drugs that act on the CTZ (haloperidol, ondansetron) are effective only for vomiting mediated by stimulation of the chemoreceptors (by morphine, digoxin, cytotoxics, uraemia). The most efficacious drugs act at more than one site (Table 31.1). 

Thirty randomized, controlled trials from 1975 to 1996 were analyzed to quantify the antiemetic efficacy and adverse effects of cannabis when given to 1366 patients receiving chemotherapy. Oral nabUone, oral dronabinol, and intramuscular levonantradol were compared with conventional antiemetics (prochlorperazine, metoclopramide, chlor-promazine, thiethylperazine, haloperidol, domperidone, and aliza-pride) or placebo. Across all trials, cannabinoids were slightly more effective than active comparators and placebo when the chemotherapy regimen was of moderate emetogenic potential, and patients preferred them. No dose-response relationships were evident to the authors. The cannabinoids were also more toxic side effects included euphoria, drowsiness, sedation, somnolence, dysphoria, depression, hallucinations, and paranoia. The efficacy of cannabinoids as compared to SSRls has not been studied. Use of these agents should be considered when other regimens do not provide desired efficacy. 

Haloperidol blocks dopamine receptors in the brain and hence produces a very high incidence of movement disorders such as parkinsonism (see phenothiazine derivatives). Its mechanism of action in Gilles de la Tourette s syndrome is unknown. In addition to blocking dopamine receptors, haloperidol has many other central and peripheral effects it has weak peripheral anticholinergic and antiemetic... 

The documentation is limited. The manufacturers of flupentixoP and haloperidol warn that, in common with other antipsychotic drugs, the effects of alcohol maybe enhanced. Warn patients that if they drink alcohol while taking chlorpromazine, and to a lesser extent flupenthixol, sulpiride or thioridazine (probably other related drugs as well), they may become very drowsy, and should not drive or handle other potentially dangerous machinery. Some risk is possible with any antipsychotic that causes drowsiness, including those used as antiemetics, such as prochlorperazine. 

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