Antipsychotics sedative effects

The short-acting clomethia2ole [533-45-9] (1), sometimes used as therapy for sleep disorders ia older patients, shares with barbiturates a risk of overdose and dependence. Antihistamines, such as hydroxy2iae [68-88-2] (2), are also sometimes used as mild sedatives (see HiSTAMlNES AND HISTAMINE antagonists). Antidepressants and antipsychotics which have sedative effects are used to treat insomnia when the sleep disorder is a symptom of some underlyiag psychiatric disorder. 

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). 

Most antipsychotic drug interactions are relatively minor and often involve additive CNS, ACh, or sedative effects. 

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. 

Antipsychotics are drugs that have a specific sedative effect, and which improve the attitude and calm the behavior of psychotic patients. They do not cause dependence, and have been proposed for treating psychotic disorders (elimination of psychotic symptomatology— delirium, hallucinations) and schizophrenic patients. Drugs of this group are also frequently referred to as neuroleptics. The term major tranquilizer was used previously to distinguish them from minor tranquilizers/anxiolytics. 

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. 

Molindone is a more active antipsychotic than chloropromzine. Its sedative effect is less expressed. Side effects are also expressed less than with powerful neuroleptics. It facilitates the reduction of spontaneous movements and aggressiveness, and is used for treatment of psychotic disturbances, particularly in cases of chronic and severe schizophrenia. A synonym of this drug is moban. 

Loxapine is a more expressed, active antipsychotic than chlorpromazine. Its sedative effect is inferior to that of chlorpromazine. Indications for its use and side effects correspond with those of phenothiazine derivatives. Loxapine is used for treating psychotic disturbances, in particular cases of chronic and severe schizophrenia. Synonyms of this drug are loxapac and loxitane. 

Sertindole is one of the newer antipsychotic medications available. It is classified chemically as a phenylindole derivative and has activity at dopamine and serotonin receptors. It is not associated with sedative effects. Sertindole was voluntarily withdrawn from the market late 1998 due to concerns over the risk of cardiac arrhythmia s. The European Commission recommended lifting the marketing restrictions on sertindole in 2005 with a regulatory requirement of ECG monitoring. 

Mechanism of Action An antipsychotic, antiemetic, and antidyskinetic agent that competitiveiy biocks postsynaptic dopamine receptors, interrupts nerve impulse movement, and increases turnover of dopamine in the brain. Has strong extrapyrami-dai and antiemetic effects weak antichoiinergic and sedative effects. Therapeutic Effect Produces tranquiiizing effect. 

Second phase (duration about one week) the sedative effect recedes while the antipsychotic effect is retained during this phase, despite a pronounced reduction in emotional tension, there is still a danger of unexpected emotional outbreaks and over-reactions. 

Taken with alcohol they potentiate the sedative effects and impairment of psychomotor performance. Hepatic enzyme induction by barbiturates or nicotine may reduce plasma levels. Cimetidine may increase levels by enzyme inhi bition. Some antipsychotic drugs may compete for similar metabolic pathways. 

Antipsychotics produce more important pharmacodynamic than pharmacokinetic interactions because of their multiple effects. Additive effects may occur when these drugs are combined with others that have sedative effects, a-adrenoceptor-blocking action, anticholinergic effects, and—for thioridazine and ziprasidone—quinidine-like action. 

Other classes of drugs not included in Figure 22-3 that may exert sedative effects include most antipsychotic and many antidepressant drugs and certain antihistaminic agents (eg, hydroxyzine, promethazine). As discussed in other chapters, these agents differ from conventional sedative-hypnotics in both their effects and their major therapeutic uses. Since they commonly exert marked effects on the peripheral autonomic nervous system, they are sometimes referred to as "sedative-autonomic" drugs. Certain antihistaminics with sedative effects are available in over-the-counter sleep aids. Their autonomic properties and their long durations of action can result in adverse effects. 

Barbiturate overdose may be treated with gastric lavage and oral administration of activated charcoal. Supportive therapy of cardiovascular, respiratory, and renal function also should be provided. Coadministration of alcohol and barbiturates may increase the sedative effect of chloral hydrate. Long-term use of barbiturates leads to dependence. Sudden discontinuation of an antipsychotic drug may cause withdrawal symptoms such as nausea, vomiting, anorexia, diarrhea, rhinorrhea, sweating, insomnia, restlessness, and vertigo.151... 

It is not clear that so-called antipsychotic drugs are superior to other types of drugs with sedative effects but different mechanisms of action. Lithium, benzodiazepines and opium have been shown to be comparable to neuroleptics in the treatment of psychotic states in some studies. The ability of the neuroleptic drugs to reduce the most characteristic symptoms of psychosis such as hallucinations, delusions and thought disorder have often been interpreted as evidence of their specifically antipsychotic or antischizophrenic action (The National Institute of Mental Health Psychopharmacology Service Center Collaborative Study... 

Clozapine and olanzapine are the most likely of the atypical agents to cause anticholinergic (anti-muscarinic) effects. They are more likely than other atypicals to cause weight gain (glucose tolerance may be impaired and should be monitored in susceptible individuals) and are second only to quetiapine in their sedative effects. Sexual dysfunction and skin problems are rare with atypical antipsychotics. Risperidone and amisulpride are as likely as classical antipsychotics to raise prolactin concentrations and cause galactorrhoea. 

In general, low-potency antipsychotics have fewer EP side effects, a greater sedative effect, a greater hypotensive effect and more anticholinergic side effects. 

Chlorpromazine produces a tranquihty characterized by a detached serenity without depression of mental faculties or clouding of consciousness. It depresses the CNS selectively by reducing input directed to the reticular formation through collaterals arriving from the sensory pathways. Chlorpromazine-induced sedation differs from that caused by barbiturates in that the patient can be easily aroused. In practice, the more sedative neuroleptics are often prescribed for agitated, overactive patients, and the less sedative agents are used for apathetic, withdrawn patients. However, sedation is not necessary for its antipsychotic property for two reasons (1) tolerance develops to the sedative effects, and (2) fluphenazine, prochlorperazine, and trifluoperazine are excellent neuroleptics that lack pronounced sedative effects. 

Concomitant use of phensuximide and other CNS depressants (alcohol, narcotics, anxiolytics, antidepressants, antipsychotics, and other anticonvulsants) may increase sedative effects. 

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. 

Central nervous system (CNS) depressants such e alcohol, narcotic analgeie, tricyclic antidepresants (see Cliap. 31), and the antipsychotic dru (see (Dli i. 32), increase the sedative effects of the antianxiety dru. Combination of any of th se dru with the antianxiely dni is dangerous and can cause serious respiratory depression and profound sedation. Ingestion of alcohol with the antianxiely dru can cause convulsions and coma... 

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