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Can be higher in some cases 2 Average wholesale price (AWP, for AB-rated generic when available) for quantity listed Source: Red Book Update, Vol 26, No 3, March 2007 AWP may not accurately represent the actual pharmacy cost because wide contractual variations exist among institutions 3 Indicates piperazine structure 4 For risperidone, daily doses above 6 mg increase the risk of extrapyramidal syndrome Risperidone 6 mg is approximately equivalent to haloperidol 20 mg
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Risperidone is an antipsychotic that blocks some serotonin receptors (5-HT2) and dopamine receptors (D2) Risperidone causes fewer extrapyramidal side effects than the typical antipsychotics at doses less than 6 mg It appears to be as effective as haloperidol and possibly as effective as clozapine in treatment-resistant patients without requiring weekly white cell counts Risperidone-induced hyperprolactinemia, even on low doses, has been reported, and that effect is thought to be more common with risperidone than with other atypical antipsychotics Risperidone is available in a long-acting injectable preparation Olanzapine is a potent blocker of muscarinic, anticholinergic, 5-HT2, and dopamine D1, D2, and D4 receptors
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High doses of olanzapine (125 175 mg daily) appear to be more effective than lower doses The drug appears to be more effective than haloperidol in the treatment of negative symptoms It is available in an orally disintegrating form for patients who are unable to tolerate standard oral dosing and in an injectable form for the management of acute agitation associated with schizophrenia and bipolar disorder Serum alanine aminotransferase is more elevated in patients taking olanzapine than in those taking haloperidol Olanzapine is associated with a much lower incidence of dystonic reaction than haloperidol and is perhaps less likely to induce tardive dyskinesia Its most common side effects include somnolence, agitation, nervousness, headache, insomnia, dizzi-
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Table 25 5 Relative potency and side effects of antipsychotics
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Drug Phenothiazines Chlorpromazine Thioridazine Mesoridazine Perphenazine Trifluoperazine Fluphenazine Thioxanthene Thiothixene Dihydroindolone Molindone Dibenzoxazepine Loxapine Butyrophenone Haloperidol Dibenzodiazepine Clozapine Benzisoxazole Risperidone Thienobenzodiazepine Olanzapine Dibenzothiazepine Quetiapine Benzisothiazolyl piperazine Ziprasidone Dipiperazine Aripiprazole
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Chlorpromazine: Drug Potency Ratio 1:1 1:1 1:2 1:10 1:20 1:50 1:20 1:10 1:10 1:50 1:1 1:50 1:20 1:1 1:1 1:20
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Anticholinergic Effects1 4 4 3 2 1 1 1 2 2 1 4 1 1 1 1 1
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Extrapyramidal Effect1 1 1 2 3 4 4 4 3 3 4 1 1 1 0
4, strong effect; 1, weak effect
ness, and significant weight gain Multiple case reports have linked olanzapine and clozapine to new-onset type 2 diabetes Further investigation is ongoing to clarify the risk, risk factors, and pathophysiology The manufacturer has alerted physicians to an association between olanzapine and a significantly higher risk of stroke and death in elderly patients Quetiapine is a neuroleptic with greater 5-HT2 relative to D2 receptor blockade as well as a relatively high affinity for 1and 2-adrenergic receptors It appears to be as efficacious as haloperidol in treating positive and negative symptoms of schizophrenia, with less extrapyramidal side effects even at high doses More common side effects include somnolence, dizziness, and postural hypotension Because of an association with lens changes seen in patients on long-term treatment, an eye examination to detect cataract formation is recommended at initiation of treatment and then at 6-month intervals during treatment
Ziprasidone has both anti-dopamine receptor and antiserotonin receptor effects, with good efficacy for both positive and negative symptoms of schizophrenia Ziprasidone is not associated with significant weight gain, hyperlipidemia, or new-onset diabetes and offers a good alternative for some patients It has been implicated in QTc interval delay of > 500 ms in some patients, although in several cases of overdose there were no incidents of torsades de pointes or sudden death Patients taking ziprasidone should be screened for cardiac risk factors A pretreatment ECG is indicated for patients at risk for cardiac sequelae (including patients taking other medications that might prolong the QTc interval) Aripiprazole is the first neuroleptic that is a dopamine stabilizer A partial agonist at the dopamine D2 and serotonin 5-HT1 receptors and an antagonist at 5-HT2 receptors, it is effective against positive and negative symptoms of schizophrenia It functions as an antagonist or agonist, depending on the dopaminergic activity at the dopamine receptors This
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