Butyrophenones adverse effects

Additive effects can occur with both the main effects of the drugs as well as their adverse effects, thus an additive interaction can occur with an-timuscarinic antiparkinson drugs (main effect) or butyrophenones (adverse effect) that can result in serious antimuscarinic toxicity (see Antipsychotics + Antimuscarinics , p.708). 

Neuroleptic activity profiles. The marked differences in action spectra of the phenothiazines, their derivatives and analogues, which may partially resemble those of butyrophenones, are important in determining therapeutic uses of neuroleptics. Relevant parameters include antipsychotic efficacy (symbolized by the arrow) the extent of sedation and the ability to induce ex-trapyramidal adverse effects. The latter depends on relative differences in antagonism towards dopamine and acetylcholine, respectively (p. 188). Thus, the butyrophenones carry an increased risk of adverse motor reactions because Lullmann, Color Atlas of Pharmacology 2000 Thieme All rights reserved. Usage subject to terms and oonditlons of lloense. 

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. 

Antipsychotics. Phenothiazines, butyrophenones and thioxanthenes are best avoided unless the indications are compelling amounts in milk are small but animal studies suggest adverse effects on the developing nervous system. In particular. 

Antipsychotic butyrophenone blocks brain dopamine D, receptors. Tox marked EPS dysfiinction. hyperprolactinemia fewer ANS adverse effects than phenothiazines. 

Phenothiazines, butyrophenones, diphenylbutylpiperidines and thioxanthenes can oppose the effects of levodopa because of their dopamine antagonist properties, causing deterioration of motor function in Parkinson s disease. The antipsychotic effects and ex-trapyramidal adverse effects of these drugs can be opposed by levodopa. Of the atypical antipsychotics, risperidone and olanzapine cause deterioration in motor function in Parkinson s disease. Ziprasidone may act similarly, and there have been reports with quetiapine. Clozapine does not have this effect. 

The introduction of the phenothiazine derivative, chlorpromazine, has started a dramatic improvement in the clinical treatment of schizophrenia. During the past four decades, beside phenothiazines, various antipsychotics having different chemical structures have been identified and introduced into clinical practice (e.g., butyrophenones and benzamides). These drugs ( typical antipsychotics ) decreased the duration of hospitalizations and, with maintenance treatment, reduced the risk of relapse and re-hospitalization. However, they had significant adverse side effects such as tardive dyskinesia, orthostatic hypotension, prolactin increase, and QT prolongation. 

The butyrophenones (prototype haloper-idol) were introduced after the phenothiazines. With these agents, blockade of D2 receptors predominates entirely (p. 235B). Antimuscarinic and antiadrenergic effects are attenuated. The extrapyramidal motor disturbances that result from D2 receptor blockade are, however, preserved and constitute the clinically most important adverse reactions that often limit therapy. 

Adverse Neurological Effects Many neurological syndromes, particularly involving the extrapyramidal motor system, occur following the use of most antipsychotic drugs, especially with the high-potency D -receptor antagonists (tricyclic piperazines and butyrophenones). Acute adverse extrapyramidal effects are less likely with aripiprazole, clozapine, quetiapine, thioridazine, and ziprasidone, or low doses of olanzapine or risperidone. 

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