Pimozide , dosing

The administration of low doses of PCP to rodents induces hyperactivity and stereotypy (Chen et al. 1959 ). The observation that neuroleptics such as chlorpromazine, haloperidol, and pimozide, and adrenolytics such as alpha-methyl paratyrosine antagonize these behavioral effects of PCP suggests that they are mediated by facilitation of central dopaminergic neurotransmission (Murray and Horita 1979). The actions of PCP on central dopaminergic neurotransmission may be similar to amphetamine. A dose of PCP (2.5 mg/kg) in rats, which has no effects when given alone, enhances the behavioral effects of 1 and 3 mg/kg of d-amphetamine (Balster and Chait 1978). PCP, like dopamine, has also been shown to suppress plasma prolactin (Bayorh et al. 1983). However, the firm establishment of an excl usive relationship between dopamine neuro-transmission and PCP effects is difficult because of the prominent interactions of this drug with other neurotransmitter systems. 

Ziprasidone, pimozide, mesoridazine, and thioridazine have been shown to prolong the QT interval, and drugs with this potential have been associated with torsade de pointes-type arrhythmias and sudden death. Perform a baseline ECG and measure serum potassium and magnesium before initiation of treatment and periodically during treatment, especially during a period of dose adjustment. Patients with QT interval over 450 msec should not receive mesoridazine or thioridazine. Avoid ziprasidone in patients with histories of significant cardiovascular illness (eg. 

Aprepitant (Emend) [Centrally Acting Antiemetic] Uses Pre-vents N/V assoc w/ emetogenic CA chemo (eg, cisplatin) (use in combo w/ other antiemetics) Action Substance P/neurokinin l(NKi) receptor antagonist Dose 125 mg PO day 1, 1 h before chemo, then 80 mg PO qAM days 2 3 Caution [B, /-] Contra Use w/ pimozide, Disp Caps SE Fatigue, asthenia, hiccups Interactions T Effects W/ clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin T effects OF alprazolam, astem-izole, cisapride, dexamethasone, methylprednisolone, midazolam, pimozide, terfe-nadine, triazolam, chemo agents, eg, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, paclitaxel, vinblastine, vincristine, vinorelbine i effects W/ paroxetine,... 

WARNING Fatal Hep liver failure possible do not retreat closely monitor for worsening depression or emergence of suicidality, particularly in ped pts Uses Depression Action Neuronal uptake of serotonin norepinephrine Dose Initial 100 mg PO bid usual 300-600 mg/d in 2 doses Caution [C, ] Contra w/ MAOIs, pimozide, carbamazepine, alprazolam active liver Dz Disp Tabs SE Postural 4- BP allergic Rxns HA, drowsiness, xerostomia, constipation, GI upset, liver... 

WARNING Co administration w/ ritonavir assoc w/ Hep hepatic decomp w/ fatalities. D/C w/ S/Sxs of H Uses HIV 1 Infxn w/ highly Tx-experienced pts or HIV 1 strains resistant to multiple protease inhibitors. Must be used w/ ritonavir 200 mg Action Antiretroviral HIV-1 protease inhibitor Dose 500 mg PO bid w/ food, administer w/ ritonavir 200 mg PO bid Caution [C, -] Sulfa aU gy, Uvct Dz Contra Mod-severe hepatic insuff concomitant use w/ amiodarone, astemizole, bepridil, cisapride, ergots, flecainide, lovastatin, midazolam, pimozide, propafenone, quinidine, rifampin, simvastatin, terfenadine, triazolam, St. John s wort Disp Caps SE HA, GI distress, rash, fati e, fat redistribution, hyperglycemia, Hep, liver Dz, lipid elevations Interactions T Effects OF anticoagulants, antipits, azole antifun-... 

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. 

A child with Tourette s disorder is treated with a daily dose of 2 mg of pimozide for tics. A family doctor treats a streptococcal pharyngitis with clarithromycin, and 24 hours later the child develops palpitations. An electrocardiogram (ECG) reveals a QTc prolongation to 0.465 milliseconds. 

The work that has been done with chlorpromazine, haloperidol, and pimozide suggests that these drugs are metabolized more rapidly in children than in adults (Morselli et ah, 1982 Sallee et ah, 1987 Furlanut et ah, 1990). In addition, it appears that larger doses of chlorpromazine and haloperidol per body weight are needed in young people to achieve the same plasma concentrations as those in adults (Morselli et ah, 1979 Rivera-Calimlim et ah, 1979). 

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... 

The typical starting dose of pimozide is 0.5 mg in young children or 1 mg day in larger children. The dosage may be increased in 0.5 to 1 mg increments every 5 to 7 days over a 3 to 4-week period. The total dose in children typically ranges from 2-4 mg/day given in divided doses. 

Olanzapine has shown encouraging results, in doses ranging from 2.5 to 20 mg/day, in two open trials involving a total of 30 adults with TS (Budman et al., 2001 Stamenkovic et al., 2000). A 52-week doubleblind crossover study of olanzapine (5 or 10 mg) versus pimozide (2 or 4 mg) in four adult patients with TS conducted by Onofrj et al. (2000) found olanzapine superior to pimozide in terms of tic reduction, sedation, and patient preference. The small sample size limits the clinical import of these findings. 

Onofrj, M., Paci, C., D Andreamatteo, G., and Toma, L., (2000) Olanzapine in severe Gilles de la Tourette syndrome a 52-week double-blind cross-over study vs. low-dose pimozide. J Neurol. 247 443 46. 

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. 

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