Antipsychotics pimozide

Two other randomly assigned placebo-controlled studies with the antipsychotics, pimozide (Vander-eycken and Pierloot, 1982) and sulpiride (Vander-eycken, 1984) failed to demonstrate any benefit for overall weight gain compared to placebo. 

APREPITANT ANTIPSYCHOTICS -PIMOZIDE t aprepitant levels Inhibition of metabolism Avoid co-administration (manufacturers recommendation)... 

ANTIPSYCHOTICS-PIMOZIDE GRAPEFRUIT JUICE Possibly t efficacy and t adverse effects Not evaluated Avoid concomitant use... 

GRAPEFRUIT JUICE ANTIPSYCHOTICS -PIMOZIDE Possibly t efficacy and t adverse effects. Interaction may occur rapidly, but clinical significance is uncertain Not evaluated in clinical trials Avoid concomitant use. No interaction was observed with haloperidol... 

High-potency antipsychotics include haloperidol, fluphenazine, thiothixine, and pimozide. 

The answer is b. (Katzung, p 4822) Haloperidol, a butyrophenone, is by far the most likely antipsychotic to produce extrapyramidal toxicides Other agents, such as piperazine (an aromatic phenothiazine), thiothixene (a thioxanthene), and pimozide (a diphenylbutyropiperidine) are comparitively less likely to produce extrapyramidal toxicity than haloperi-dol. The antagonism of dopamine in the nigrostriatal system might explain the Parkinson-like effects Both haloperidol and pimozide act mainly on D2 receptors, whereas thioridazine and piperazine act on ooadrenergie receptors, and have a less potent but definite effect on D2 receptors. 

The answer is d. (Hardman, p 420. Katzung, p 4852) Tourette s syndrome is effectively treated with haloperidol, a high-potency antipsychotic. If patients are unresponsive or do not tolerate haloperidol, they might be switched to pimozide. 

If a change in antipsychotic therapy is required, risperidone, molindone, thioridazine, haloperidol, pimozide, trifluoperazine, and fluphenazine may be considered. 

Dubitsky, G.M. (2000) Clinically important QT interval prolongation with three antipsychotics thioridazine, pimozide, sertindole, FDA. 

Other first generation (atypical) antipsychotics include thioxanthenes, haloperidol, pimozide, and loxapine. 

Pimozide (Orap). Pimozide is probably the most potent of all antipsychotics, but it is seldom used to treat schizophrenia. Instead, pimozide is most often used to treat Tourette s syndrome. There is actually no reason why pimozide can t be used to treat psychosis and no reason why other antipsychotics are not effective in Tourette s syndrome. Pimozide was simply used first in controlled clinical trials to treat Tourette s syndrome, and the physicians who routinely treat that illness became accustomed to using it. Pimozide is only available in an oral form. The lack of an injectable form to treat agitated patients as well as the lack of availability of data from controlled trials in schizophrenia patients likely explains why it has not been used very often in the treatment of schizophrenia. 

Antipsychotics. It was recognized some years ago that high potency typical anti-psychotics, that is, haloperidol (Haldol) and pimozide (Orap), were effective in treating OCD patients who had a comorbid tic disorder. The efficacy of these agents, however, is primarily in redncing the tics rather than the core symptoms of OCD. 

CypP450 3A3 /4 Antidepressants tricyclics, nefazodone, fluoxetine, fluvoxamine, citalopram, mirtazepine, venlafaxine Antipsychotics chlorpromazine, clozapine, pimozide, quetiapine, risperidone... 

Representatives of diphenylbutylpiperidines are pimozide, fluspirilene, and penfluridol, which belong to the powerful neuroleptic drugs with expressed antipsychotic properties similar to haloperidol. The principle distinctive feature of this series of drugs is their prolonged action. The mechanism of their action is not completely known however, it is clear that they block dopaminergic activity. 

Extrapyramidal symptoms (EPS) Dystonic reactions develop primarily with the use of traditional antipsychotics. EPS has occurred during the administration of haloperidol and pimozide frequently, often during the first few days of treatment. Neuroleptic malignant syndrome (NMS) A potentially fatal symptom complex sometimes referred to as NMS has been reported in association with administration of antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, rhabdomyolysis, and acute renal failure. 

Pimozide, penfluridol and fluspirilene are di-phenylbutylpiperidine derivatives. Pimozide and penfluridol are antipsychotics with high potency but they give relatively few extrapyramidal problems and exhibit minimal other adverse effects. Fluspirilene has similar pharmacological activity although the risk for extrapyramidal reactions seems to be somewhat higher. 

There are several antipsychotics that are substrates to CYP2D6 (von Bahr et ah, 1991 Jerling et ah, 1996 Ring et ah, 1996 (Fang and Gorrod, 1999 Flockhart and Oesterheld, 2000) (Table 26.3). Moreover, several antipsychotics may act as inhibitors of CYP2D6-mediated biotransformation. These include thioridazine, chlorpromazine, haloperidol, fluphenazine, and pimozide (Desta et ah, 1998 Shin et ah, 1999). Of particular salience is the fact that the serotonin selective reuptake inhibitors (SSRIs) fluoxetine and paroxetine are metabolized to a significant extent by this isoenzyme. 

The butyrophenones are chemically unrelated to the phenothiazines, but show a similar antipsychotic action. They were developed by P. A. Jansen and derived from fentanyl-type analgesics (see chapter 5). More than 4000 derivatives have been synthesized, of which the three most widely used antipsychotics are shown. Pimozide (4.91) is clearly derived from benperidol (4.92), even though it is no longer a butyrophenone. 

Area of assessment Clinically sedative antipsychotics, Less sedative antipsychotics, e.g. chlorpromazine, clozapine, e.g. haloperidol, perphenazine, olanzapine pimozide, sulpiride ... 

Antipsychotic drugs with strong sedative clinical effects (e.g. chlorpromazine. clozapine, olanzapine) produce subjective and objective sedation and impair most areas of performance in healthy volunteers, usually at doses far below those typically used in patients. Antipsychotic drugs with little sedative clinical action (e.g. pimozide, sulpiride, amisulpride) produce few subjective and objective effects in healthy... 

Alkylation of the basic amino group in (19-6) with butyrophenone (20-1), available from the acylation of fluorobenzene with 4-chlorobutyryl chloride, affords the antipsychotic drug droperidol (20-2) [21]. Alkylation of the fully reduced intermediate (19-7) with a side chain (20-3) yields pimozide (20-4) [22]. 

Pimozide and molindone are typical antipsychotic drugs. There is no significant difference in efficacy between these newer typical and the older typical... 

Neuroleptics are the drugs of choice in the treatment of tic disorders but they should only be considered in situations where the life of the child is seriously affected and when behavioural treatments have failed. Of the classical neuroleptics which have been used, haloperidol and pimozide have shown success but so far there have been no adequately controlled trials of any neuroleptic to objectively validate their efficacy. It would appear that only low doses of haloperidol are necessary (2-3mg/day) to obtain a significant reduction in tic frequency. It would seem reasonable to consider the use of the atypical antipsychotics for these disorders but, to date, there is no evidence of their efficacy in children. Recently there have been studies in which clonidine was used in the effective treatment of motor tics. The side effects are similar to those seen in the adult and include sedation, headache, irritability and sinus bradycardia. 

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