Haloperidol sedative effects

Sleep and sedative effects of the atypical antipsychotics could be related to different mechanisms antagonism of 5-HT2 receptors, antihistaminic and antimus-carinic effects, and probably an a-1 noradrenergic effect. The difference in the effect on sleep between risperidone and haloperidol may be due to their differential actions on serotoninergic receptors (Trampus and Ongini 1990 Trampus et al. 1993). 

Typical Antipsychotics. Low doses of high potency typical antipsychotics such as haloperidol or fluphenazine (0.5-2mg given once or twice daily) are generally quite effective for psychotic symptoms after TBI. Unfortunately, as noted earlier, many post-TBl patients are susceptible to the extrapyramidal side effects of these medicines, especially if there was any injury to brain regions such as the basal ganglia. Low potency antipsychotics are not a viable alternative, because their anticholinergic and sedative effects are equally, if not more, problematic for patients who have suffered TBI. We recommend using typical antipsychotics, even for psychotic symptoms, as briefly as possible and in the lowest effective dose, if at all. Fortunately, there are now alternatives. 

Haloperidol is one of the most actively used modem neuroleptics. Its high antipsychotic activity is combined with a moderate sedative effect. It effectively stops various types of psychomotor excitement. It is used for schizophrenic psychoses, manic, paranoid, and delirious conditions, depression, psychomotor excitement of various origins, and for delirium and hallucinations of different origin. The most common synonyms are haldol, vezadol, linton, and others. 

Therapy with haloperidol or pimozide should be initiated at very low doses of 0.25 to 0.5 mg/day given at bedtime and then increased gradually. Gradual titration over 2 to 3 weeks helps minimize ex-trapyramidal and sedative effects while permitting careful assessment of response. Symptoms may regress within 48 to 72 hours after an effective dose is reached. Doses less than 5 mg/day are effective in controlling tics for most patients, but occasionally up to 10 mg/day or even 20 mg/day are required. Pimozide is considered comparable or possibly superior to haloperidol in efficacy when equivalent doses are used. ... 

Procyclidine may reduce the antipsychotic effectiveness of haloperidol and phenothiazines, possibly by direct CNS antagonism related to its anticholinergic properties. Haloperidol and phenothiazine exert their effects in part by blocking the hyperactivity of dopaminergic transmission in the mesocortical and mesolimbic systems. Concomitant use with phenothiazine derivatives, especially thioridazine having pronounced anticholinergic effects, also increases the risk of anticholinergic adverse effects. Paralytic ileus may result from concomitant use with phenothiazines or tricyclic antidepressants. Concomitant use with alcohol and other CNS depressants increases procyclidine s sedative effects. 

The psycholeptic action, characteristic of these phenothiazines, was later found in other series, notably among the thioxanthenes [e.g. chlor-prothixine (75.74), Taractan ], and the phenylbutyrophenones introduced by Janssen in Belgium about 1958 [e.g. haloperidol (75.75)]. To-day a distinction is made between the high-dose psycholeptics, such as chloro-promazine and chlorprothixen, which have an additional sedative effect, and the low-dose psycholeptics, such as perphenazine, trifluoperazine, fluphenazine, haloperidol, and thiothixene, which have a strong, but purely psycholeptic, action. 

There is an increased central nervous system (CNS) depressant effect when the skeletal muscle relaxants are administered with other CNS depressants, such as alcohol, antihistamines, opiates, and sedatives. There is an additive anticholinergic effect when cyclobenzaprine is administered with other drugs with anticholinergic effects (eg, antihistamines, antidepressants, atropine, haloperidol). See Chapter 30 for information on diazepam. 

There is, however, a unique risk in the bipolar form that antidepressant treatment may trigger a switch into mania. This may occur either as the natural outcome of recovery from depression or as a pharmacological effect of the drug. Particular antidepressants (the selective serotonin reuptake inhibitors) seem less liable to induce the switch into mania than other antidepressants or electroconvulsive therapy. Treatment for mania consists initially of antipsychotic medication, for instance the widely used haloperidol, often combined with other less specific sedative medication such as the benzodiazepines (lorazepam intramuscularly or diazepam orally). The manic state will usually begin to subside within hours and this improvement develops further over the next 2 weeks. If the patient remains disturbed with manic symptoms, additional treatment with a mood stabilizer may help. 

In terms of pharmacological action, pimozide is similar to haloperidol. It is used in hospitals as well as in outpatient settings for supportive therapy of patients suffering from schizophrenia, paranoid conditions, and mental and neurotic disorders with paranoid characteristics. It is unfit for use in severe psychoses because it does not possess psychomotor-sedative action. It is used for treating patients who suffer from Turretts s syndrome. Pimozide has a number of side effects, many of which are similar to those of phe-nothiazine and a number of others. A synonym of this drug is orap. 

Temazepam (Restoril) [C-IV] [Sedative/Hypnotic/ Benzodiazepine] Uses Insomnia, anxiety, depression, panic attacks Action Benzodiaz ine Dose 15-30 mg PO hs PRN X in elderly Caution [X, /-] Potentiates CNS dqjressive effects of opioids, barbs, EtOH, antihistamines, MAOIs, TCAs Contra NAG Disp Caps SE Confusion, dizziness, drowsiness, hangover Interactions T Effects W/ cimetidine, disulfiram, kava kava, valerian T CNS depression W/ anticonvulsants, CNS depressants, EtOH t effects OF haloperidol, phenytoin X effects W/ aminophylline, dyphylline, OCPs, oxtriphylline, rifampin, theophylline, tobacco X effects OF levodopa EMS Use caution w/ other benzodiazepines, antihistamines, opioids and verapamil, can T CNS depression concurrent EtOH can T CNS depression abruptly D/C after >10 d use may cause withdrawal OD May cause profound CNS depression, confusion, bradycardia, hypotension, and altered reflexes flumazenil can be used as antidote, activated charcoal may be effective... 

Because of multiple receptor actions, which occur at different concentrations, different neuroleptics have different action profiles. There are many classifications for neuroleptic drugs, the least useful of which is probably based on their chemical structure. Other classifications include linear classifications based on the propensity to cause EPS, or multidimensional ones such as the Liege star which combines information on three positive effects (anti-autistic, antiproductive, antipsychotic), and three negative (hypotensive, extrapyramidal, sedative). In a general way, the more sedative neuroleptics such as levomepromazine, used more to treat acute agitation states, cause more hypotension related to alpha blockade, whereas those that act best on delirium (productive states) such as haloperidol tend to cause more EPS. 

The neuroleptics that are widely available may be divided into two general categories, those with low potency (such as chlorpromazine and thioridazine) and those with high potency (exemplified by haloperidol, trifluoperazine and pimozide). The former groups have a lower propensity to cause extrapyramidal side effects but are more sedative and likely to cause postural hypotension and have anticholinergic side effects. In vitro studies have shown that chlorpromazine has an affinity for all five types of dopamine receptor and has some preference for D2 and D3 receptors. By contrast, haloperidol is more potent than chlorpromazine for the D2, D3 and D4 receptors with a low affinity for the D and D5 receptors. 

The butyrophenones and diphenylbutylpiperidines differ from the phenothia-zines and thioxanthines in that they are not tricyclic structures. The first butyrophenone to be developed was haloperidol, and this is the most widely used, potent neuroleptic. Unlike many of the phenothiazines, these neuroleptics largely lack antihistaminic, anticholinergic and adrenolytic activity they are also non-sedative in therapeutic doses. Their potent antidopaminergic activity renders them likely to cause extrapyramidal side effects. Of the various butyrophenones shown in Figure 11.10, benperidol has been selectively used to suppress asocial sexual behaviour. 

Three cases of radial nerve palsy were reported in demented elderly patients confined to wheelchairs who were treated with haloperidol. The combination of extrapyra-midal and sedative adverse effects, added to wheelchair confinement, may have resulted in pressure on the upper arm with subsequent neuropathy (18). 

The interaction of the dopamine antagonist haloperidol 5 mg orally with subanesthetic doses of ketamine has been studied in a placebo-controlled study in 20 healthy volunteers over 4 days (53). Haloperidol pretreatment reduced impairment of executive cognitive functions produced by ketamine and reduced the anxiogenic effects of ketamine. However, it failed to block the ability of ketamine to produce psychosis, perceptual changes, negative symptoms, or euphoria, and it increased the sedative and prolactin responses to ketamine. These results imply that ketamine may impair executive cognitive functions via dopamine receptor activation in the frontal cortex, but that the psychoactive effects of ketamine are not mediated via dopamine receptors, but rather via NMDA receptor antagonism. 

---