Most older first-generation antipsychotic drugs, with the exception of thioridazine, have a strong antiemetic effect. This action is due to dopamine-receptor blockade, both centrally (in the chemoreceptor trigger zone of the medulla) and peripherally (on receptors in the stomach). Some drugs, such as prochlorperazine and benzquinamide, are promoted solely as antiemetics.
Phenothiazines with shorter side chains have considerable H1-receptor-blocking action and have been used for relief of pruritus or, in the case of promethazine, as preoperative sedatives. The butyrophenone droperidol is used in combination with the opioid fentanyl in neuroleptanesthesia. Droperidol has dose-associated risk of QT prolongation and has been removed from some markets. The use of these drugs in anesthesia practice is described in Chapter 25.
Choice among antipsychotic drugs is based mainly on differences in adverse effects and possible differences in efficacy. In addition, cost and the availability of a given agent on drug formularies also influence the choice of a specific antipsychotic. Because use of the older drugs is still widespread, especially for patients treated in the public sector, knowledge of such agents as chlorpromazine and haloperidol remains relevant. Thus, one should be familiar with one member of each of the three subfamilies of phenothiazines, a member of the thioxanthene and butyrophenone group, and all of the newer compounds—clozapine, risperidone, olanzapine, quetiapine, ziprasidone, lurasidone, iloperidone, asenapine, cariprazine, and aripiprazole. Each may have special advantages for selected patients. A representative group of antipsychotic drugs is presented in Table 29–3.
For approximately 70% of patients with schizophrenia, and probably for a similar proportion of patients with bipolar disorder with psychotic features, firstand second-generation antipsychotic drugs are of equal efficacy for treating positive symptoms.
TABLE 29–3 Some representative antipsychotic drugs.
1Other aliphatic phenothiazines: promazine, triflupromazine. 2Other piperidine phenothiazines: piperacetazine, mesoridazine. 3Other piperazine phenothiazines: acetophenazine, perphenazine, carphenazine, prochlorperazine, trifluoperazine.
However, the evidence favors second-generation drugs for benefit for negative symptoms and cognition, for diminished risk of tar-dive dyskinesia and other forms of EPS, and for lesser increases in prolactin levels.