Antipsychotics endocrine effects

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 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. 

CJ-Receptors are localized ia the brain stem and limbic stmcture, regions associated with endocrine function (76). In the periphery, CJ-receptors are found in the Hver, heart, ileum, vas deferens, and on lymphocytes and thymocytes. Although there is insufficient evidence to clearly define the functional role of CNS CJ-sites, based on the effects of PCP and the interaction of haloperidol with CJ-sites, CJ-receptor ligands may be antipsychotics or used for the treatment of substance abuse. Several CJ-receptor ligands have shown neuroprotective effects in vivo. Ifenprodil (315) and CNS 1102 (316) are being developed for treatment of stroke (Table 18). 

Knegtering H, van der Moolen AEGM, Castelein S, et al. What are the effects of antipsychotics on sexual dysfunctions and endocrine functioning Psychoneuroendocrinology 2003 28(Suppl 2) 109—123. 

Laita P, Cifuentes A, Doll A, Llorente C, Cortes I, PareUada M, Moreno D, Ruiz-Sancho A, GraeU M, Arango C (2007) Antipsychotic-related abnormal involuntary movements and metabolic and endocrine side effects in children and adolescents. J Child Adolesc Psychopharmacol 17 487-502. 

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. 

Hypothalamus and Endocrine Systems Endocrine changes occur because of effects of antipsychotic drugs on the hypothalamus or pituitary, including their antidopaminergic actions. Most older antipsychotics and risperidone increase prolactin secretion, probably due to a blockade of the pituitary actions of the tuberoinfundibular dopaminergic neurons. These neurons project from the arcuate nucleus of the hypothalamus to the median eminence, where they deliver DA to the anterior pituitary via the hypophyseoportal blood vessels. Dj receptors on lactotropes in the anterior pituitary mediate the tonic prolactin-inhibiting action of DA (see Chapter 55). 

Endocrine A raised prolactin concentration occurs not uncommonly as an adverse effect of antipsychotic drugs but is less often associated with antidepressants. In a comprehensive review of case reports and prospective and retrospective studies, it was documented that all antidepressant classes, except mirtazapine, have been reported to cause hyperprolactinemia [2 ]. However, the findings were mostly derived from case reports and were inconsistent for individual agents within each antidepressant class. 

Endocrine A cross-sectional study investigated the effect of antipsychotic-induced hyperprolactinemia on testosterone, luteinising hormone, follicle-stimulating hormone, inhibin B and puberty in 104 boys with mainly autism spectrum disorders [SI -]. Patients with antipsychotic-induced hyperprolactinemia had significantly lower testosterone levels with adjustment for age compared to patients without hyperprolactinemia and without antipsychotic treatment. 

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