Clozapine autonomic effects

Clozapine has more affinity for the D4 receptor than the D, or D2 receptors. This drug also has a higher affinity for non-dopaminergic receptors (e.g., 5HT2, H, a,) than for dopaminergic receptors. This accounts for the marked sedation and autonomic effects seen with the drug. 

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). 

Autonomic effects Autonomic effects result from blockade of peripheral muscarinic receptors and alpha adrenoceptors and are more difficult to manage in elderly patients. Tolerance to some of the autonomic effects occurs with continued therapy. As shown in Figure 29-1, thioridazine has the strongest autonomic effects and haloperidol the weakest. Clozapine and most of the atypical drugs have intermediate autonomic effects. 

In CONCLUSION, the use of the "classical" neuroleptics, as exemplified by the phenothiazines, thioxanthines, butyrophenones and diphenylbutyl-piperidines, has been a landmark in the pharmacotherapy of schizophrenia and psychotic disorders. The efficacy of such drugs in the alleviation of the symptoms of schizophrenia is universally accepted. However, it is also evident that they have a spectrum of adverse effects that frequently renders their long-term use problematic. Side effects such as akathisia, Parkinsonism, tardive dyskinesia and the all too frequent changes in peripheral autonomic activity are largely predictable from the structure of the molecules and the basic animal pharmacology data. Such adverse effects, and the difficulties encountered when attempting to reduce their frequency and severity by concurrent medication, has stimulated the development of "atypical" neuroleptics such as clozapine and risperidone which, hopefully, will combine efficacy with a reduction in side effects. 

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