Pimozide side effects

In terms of pharmacological action, pimozide is similar to haloperidol. It is used in hospitals as well as in outpatient settings for supportive therapy of patients suffering from schizophrenia, paranoid conditions, and mental and neurotic disorders with paranoid characteristics. It is unfit for use in severe psychoses because it does not possess psychomotor-sedative action. It is used for treating patients who suffer from Turretts s syndrome. Pimozide has a number of side effects, many of which are similar to those of phe-nothiazine and a number of others. A synonym of this drug is orap. 

Lopinavir is available in the United States only as a fixed-dose combination with ritonavir (Kaletra). In this regimen, a low dose of ritonavir is used to inhibit the rapid inactivation of lopinavir by CYP3A4. Side effects, which are generally mild, include diarrhea, nausea, asthenia, and headache. Pancreatitis occurs rarely. Ritonavir is a potent inhibitor of CYP3A4 and also inhibits CYP2D6. In addition to the drugs contraindicated for all protease inhibitors, fiecainide, propafenone, pimozide, and rifampin should not be given with lopinavir-ritonavir combination therapy. 

Fluphenazine, a typical neuroleptic of the phenothi-azine class, has been less widely used for treatment of tics than haloperidol or pimozide. A controlled trial of haloperidol, fluphenazine, and trifluoperazine found comparable tic-reducing efficacy, but greater sedation and extrapyramidal side effects for haloperidol fluphenazine was the best tolerated (Borison et al., 1982). In an open-label trial with 21 subjects who had an unsatisfactory response to haloperidol, fluphenazine had a superior side effect profile to that of haloperidol in the dose range employed (mean dose of fluphenazine, 7 mg/day, range 2-15 mg/day) (Goetz et al., 1984). In this group selected for an unsatisfactory response to haloperidol, 11 of the 21 subjects (52%) had a better response to fluphenazine than haloperidol, 6 subjects had a comparable response, and 2 subjects preferred haloperidol. 

The side effects of typical neuroleptics are extensively discussed in Chapters 26 and 41 in this volume. Given its potent calcium channel blocking properties, additional considerations apply to the use of pimozide. The use of pimozide requires caution regarding the possibility of QT prolongation, and we typically obtain an electrocardiogram (EKG) to measure the QTc interval at baseline, and obtain a repeat EKG during the dose... 

Tourette s syndrome is a well-studied condition, characterized by motor and phonic tics and by behavioral and psychological problems. While many neurotransmitters were implicated in the etiology of this disorder, it is now believed that the dopaminergic system and noradrenergic systems are involved. Two major clinical trials (Shapiro et ah, 1989 Sallee et al, 1997) indicated that haloperidol and pimozide reduced the severity of tics by 65%. However, these medications are associated with side effects (including possible cognitive impairment, sedation, dysphoria, and tardive dyskinesia) that may limit their effectiveness in children with MR. 

Several double-blind studies have demonstrated that typical agents are effective in decreasing problematic behaviors in children with DD. For example, haloperidol reduced anger, hyperactivity, and stereotypies (Campbell et al., 1979) in the dose range of 0.25-4 mg/day. Pimozide reduced problematic behaviors in children with PDD (Naruse et al., 1982). However, the possible long-term side effect of tardive dyskinesia remains a concern when using these agents. 

Pimozide is FDA-labeled for Tourette s disorder and is particularly interesting in that it is a highly specific DA antagonist that may produce fewer adverse effects than haloperidol. In open studies with adequate doses, this agent has demonstrated efficacy for acute schizophrenia. Several double-blind trials comparing pimozide with other neuroleptics also found it to be an equally effective maintenance therapy ( 34, 35, 36, 37 and 38). We consider this agent to be as effective as the other standard agents, with the same, but perhaps less severe, side effects. 

Finally, the specific DA antagonist pimozide may have merit as a maintenance medication because of its long half-life and minimal side effect profile ( 209, 210). 

The neuroleptics that are widely available may be divided into two general categories, those with low potency (such as chlorpromazine and thioridazine) and those with high potency (exemplified by haloperidol, trifluoperazine and pimozide). The former groups have a lower propensity to cause extrapyramidal side effects but are more sedative and likely to cause postural hypotension and have anticholinergic side effects. In vitro studies have shown that chlorpromazine has an affinity for all five types of dopamine receptor and has some preference for D2 and D3 receptors. By contrast, haloperidol is more potent than chlorpromazine for the D2, D3 and D4 receptors with a low affinity for the D and D5 receptors. 

The serum concentrations of "classical neuroleptics and their metabolites vary considerably in patients, even when the dose of drug administered has been standardized. Such interindividual variation may account for the differences in the therapeutic and side effects. High interindividual variations in the steady-state plasma levels have been reported for pimozide, fluphenazine, flupenthixol and haloperidol, some of these differences being attributed to differences in absorption and metabolism between patients. 

The diphenylbutylpiperidines are structurally related to the butyrophenones and have essentially similar properties. Pimozide is the most well-established member of this series and is a potent neuroleptic that, like other potent neuroleptics, is likely to cause extrapyramidal side effects. 

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. 

NITRATES 1. ANALGESICS-nefopam 2. ANTIARRHYTHMICS -disopyramide, propafenone 3. ANTIDEPRESSANTS-TCAs 4. ANTI EMETICS-cydizine 5. ANTIHISTAMINES -chlorphenamine, cyproheptadine, hydroxyzine 6. ANTIMUSCARINICS -atropine, benzatropine, cydopentolate, dicydover-ine, flavoxate, homat-ropine, hyoscine, orphenadrine, oxybutynin, procyclidine, propantheline, tolterodine, trihexyphenidyl, tropicamide. 7. ANTI-PARKINSON S DRUGS-dopaminergics 8. ANTI-PSYCHOTICS - pheno-thiazines, clozapine, pimozide 9. MUSCLE RELAXANTS-baclofen 1. t risk of antimuscarinic side-effects when isosorbide dinitrate is co-administered with these drugs 2. 1 efficacy of sublingual nitrate tablets... 

ARIPIPRAZOLE, HALOPERIDOL, CLOZAPINE, PIMOZIDE, RISPERIDONE, SERTINDOLE PROTEASE INHIBITORS Possibly T levels of antipsychotic Inhibition of CYP3A4- and/or CYP2D6-mediated metabolism Avoid co-administration of clozapine with ritonavir, and pimozide or sertindole with protease inhibitors. Use other antipsychotics with caution as 1 dose may be required with risperidone, watch closely for extrapyramidal side-effects and neuroepileptic malignant syndrome... 

ANTIPSYCHOTICS-PHENOTHIAZINE, CLOZAPINE, PIMOZIDE NITRATES 1. T risk of antimuscarinic side-effects when isosorbide dinitrate is co administered with these drugs. 2.1 efficacy of sublingual nitrate tablets 1. Additive effect both of these drugs cause antimuscarinic side-effects 2. Antimuscarinic effects i saliva production, which i dissolution of the tablet 1. Warn patient of these effects 2. Consider changing the formulation to a sublingual nitrate spray... 

Other, chemically distinct dopamine blockers were then developed, such as thiothixene, haloperidol, loxapine, molindone, and pimozide. All of these antipsychotics are potent dopamine blockers and collectively were called neuroleptics because they inadvertently cause certain neurological side effects (discussed below). More recently, atypical antipsychotic medications have been developed (clozapine and risperidone), which are effective antipsychotics yet are weak dopamine blockers and cause minimal neurological side effects. This group is discussed separately below. 

The diphenylbutylpiperidine class can Itc considered a modification of the fluorohulyrophenonc class. Because of their high hydrophobic character, the compounds are inherently long acting. Penfluridol has undergone clinical trials in the United Slates, and pimozide has been approved for antipsychotic use. Overall, side effects for the two compounds resemble tho.se pmduced by the lluorobutyrophc-nones. 

Antipsychotics can be divided by chemical class phenothiazines, e.g. chlorpromazine. fluphazine and thioridazine butyrophenones, e.g. haioperidol thioxanthines, e.g. nupenthixol benzamides, e.g. sulpiride diphenylbutyl-piperazines, e.g. pimozide dibenzazepines, e.g. clozapine. None is entirely selective, but in schizophrenia they act mainly at dopamine D2 receptors, though clozapine has important actions at D4 receptors. Those antipsychotics with markedly depressant side-effects are also, somewhat misleadingly, known as major tranquillizers. 

Whenever symptoms are severe enough to impair the child s ability to function, drug therapy should be initiated. Haloperi-dol and pimozide (dopamine [D2] receptor antagonists) are approved by the FDA and are highly effective with a relatively rapid onset. Clonidine is significantly less effective but has no risk of extrapyra-midal side effects. Psychotherapy and behavioral treatment are useful adjuncts. " ... 

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