Pimozide effects

Kjellberg, B., and Randrup, A. The effects of amphetamine and pimozide, a neuroleptie, on the social behaviour of vervet monkeys (Cercopithecus sp.). In Vinar, 0. Votaya. Z. and Bradley, P.B., eds. Advances in Neuropsychopharmacology. Amsterdam-London North Holland Publishing Co., 1971. pp. 305-310. 

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. 

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. 

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. 

The dopamine agonist bromocriptine produces the male-odor induced effects, while they are prevented by pimozide, which blocks dopaminergic transmission (Kaba etal, 1992). 

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. 

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 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-... 

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. 

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. 

In this example, clarithromycin, a potent CYP3A inhibitor blocks the principal pathway of pimozide metabolism (CYP3A), and plasma concentrations of pimozide increase. A higher pimozide concentration (a pharmacokinetic effect) is associated with prolongation of QT c in EKG readings and potentially fatal torsades de pointes (via potassium channel blockade, a pharmacodynamic effect see Flockhart et al., 2000, May-hew et ah, 2000). As exemplified by this vignette, the... 

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