Antipsychotics autonomic effects

Most antipsychotic drugs cause unpleasant subjective effects in nonpsychotic individuals. The mild to severe EPS, including akathisia, sleepiness, restlessness, and autonomic effects are unlike any associated with more familiar sedatives or hypnotics. Nevertheless, low doses of some of these drugs, particularly quetiapine, are used to promote sleep onset and maintenance, although there is no approved indication for such usage. 

Other side effects characteristic of most neuroleptic-antipsychotic drugs include autonomic effects such as postural hypotension and impaired sexual function. Increased plasma prolactin represents an endocrine effect. 

Haloperidol is a member of the butyrophenone class of drugs. It thus has greater potency and less autonomic effects than thiothixene, a member of the thioxanthene class of antipsychotics. 

Other autonomic effects of antipsychotic drugs are probably mediated by the hypothalamus, such as an impairment of the body s abihty to regulate temperature. Clozapine can induce moderate elevations of body temperature that can be confusing clinically central effects on temperatme regulation and cardiovascular and respiratory function probably contribute to the featmes of neuroleptic malignant syndrome (see Table 18-1). 

HT2, and receptors and possesses very little extrapyramidal toxicity but significant sedative and autonomic side effects. Flumazenil is a benzodiazepine antagonist, and carbamazepine is an anticonvulsant neither possesses significant antipsychotic properties. 

A rare, but potentially fatal idiosyncratic adverse effect is neuroleptic malignant syndrome. This can occur with any antipsychotic drug. The symptoms are rigidity, hyperthermia, autonomic lability, and reduced level of consciousness. Massively elevated levels of creatinine kinase are usually found. Prior to 1984, the mortality rate was around 25% but improved early recognition has considerably reduced this. Management is cessation of antipsychotics, appropriate conservative measures and dantrolene if necessary for muscle rigidity. 

The first phenothiazine antipsychotic drugs, with chlorpromazine as the prototype, proved to have a wide variety of central nervous system, autonomic, and endocrine effects. Although efficacy of these drugs is primarily driven by D2-receptor blockade, their adverse actions were traced to blocking effects at a wide range of receptors including a adrenoceptors and muscarinic, Hi histaminic, and 5-HT2 receptors. 

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. 

Unlike antipsychotic or antidepressant drugs, which exert several actions on the central or autonomic nervous system, lithium ion at therapeutic concentrations is devoid of autonomic blocking effects and of activating or sedating effects, though it can produce nausea and tremor. 

Pioneers in the field recognized and wrote about the lobotomy-like effects of the neuroleptic drugs when they first came into use, but in recent years drug advocates have promoted the false impression that these medications have a specific antipsychotic or antischizophrenic effect. In reality, the overriding clinical effect of these highly toxic chemical agents is to render patients and inmates more emotionally flat and indifferent, more apathetic and docile, and less autonomous and self-directed. 

Some of the effects of antipsychotic drugs on sexual function have been attributed by Aizenberg et al. to increased prolactin secretion by the anterior pituitary (74, 76), other effects may result from their specific autonomic actions (75). Prolactin secretion by the anterior pituitary is tonically inhibited by the hypothalamus, with dopamine acting as the prolactin release-inhibiting factor (PIF). Thus, conventional neuroleptics cause dose-related increases in serum prolactin levels (hy-... 

Because of the lack of dependency and tolerable adverse effect profile, antidepressants have emerged as the treatment of choice for the long-term management of chronic anxiety, especially in the presence of comorbid depressive symptoms. Buspirone is an additional anxiolytic option (Table 69-7) in patients without comorbid depression or other anxiety disorders (e.g., panic disorder and SAD). Because of the high risk of adverse effects and toxicity, barbiturates, antipsychotics, antipsychotic-antidepressant combinations, and antihistamines generally are not indicated in the treatment of GAD. The benzodiazepines are more effective in treating the somatic and autonomic symptoms of GAD as opposed to the psychic symptoms (e.g., apprehension and worry), which are reduced by antidepressants. ... 

The pharmacology of benzodiazepine derivatives differs significantly from that of the neuroleptics, in that the benzodiazepines have no psychoplegic (antipsychotic) activity and cause no extrapyramidal, autonomic, or endocrine side effects. In addition, unlike the neuroleptics, which lower the seizure threshold, these substances are anticonvulsants. In addition, they are anxiolytics, muscle relaxants, and mild sedatives. Although the benzodiazepine derivatives do not produce pronounced autonomic or CV side effects, they can reduce or block the emotionally induced changes in cardiovascular functions, probably through actions on the limbic system. 

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