Antipsychotic Drugs (Haloperidol, Droperidol, Olanzapine, and Ziprasidone)
Pharmacology
Haloperidol and droperidol are butyrophenone neuroleptic drugs, often referred to as “first-generation” or “typical” antipsychotics, that are useful for the management of acutely agitated psychotic patients and as antiemetics. They have strong central antidopaminergic activity and weak anticholinergic and anti–alpha-adrenergic effects.
Olanzapine and ziprasidone are second-generation or “atypical” antipsychotic agents. They have weaker and more selective antidopaminergic activity, and a higher ratio of serotonin-to-dopamine antagonism. This provides less risk for extrapyramidal side effects. However, olanzapine has greater anticholinergic effects, and both have greater antihistaminic and anti–alpha-adrenergic effects. Therefore, they have a greater propensity to cause sedation and orthostatic hypotension.
Pharmacokinetics. Haloperidol is well absorbed from the GI tract and by the intramuscular route. Droperidol is available only for parenteral use and is also well absorbed by the intramuscular route. Droperidol has a more predictable and rapid onset of 3–10 minutes, and both have peak pharmacologic effects that occur within 30–40 minutes of an intramuscular injection. Both drugs are metabolized principally by the liver. The serum half-life for haloperidol is 12–24 hours. Olanzapine and ziprasidone are well absorbed from the GI tract and by the intramuscular route. Olanzapine IM results in rapid absorption, with peak levels occurring within 15 to 45 minutes, whereas ziprasidone IM has peak levels occurring at approximately 60 minutes. Both drugs are metabolized principally by the liver. The serum half-life for olanzapine is 20–54 hours, and for ziprasidone it is 2–5 hours.
Indications
Haloperidol is used for the management of acute agitated functional psychosis or extreme agitation induced by stimulants or hallucinogenic drugs, especially when drug-induced agitation has not responded to a benzodiazepine.
Droperidol has a more rapid onset and greater efficacy for agitation and is also useful for drug- or toxin-induced nausea and vomiting, but its role in routine therapy is uncertain because of reports of deaths and a “black box” warning about QT prolongation (see Item IV.D below). Therefore, other antiemetic drugs (eg, metoclopramide [See Metoclopramide] and ondansetron [See Ondansetron]) should be considered as first-line drugs to control persistent nausea and vomiting.
Olanzapine and ziprasidone by the IM route are approved for the management of acute agitation associated with schizophrenia, in addition to bipolar mania for olanzapine. Both have been used for the management of acute undifferentiated agitation of either psychiatric or organic (eg, drug-induced) origin. Their role in therapy remains to be determined, and superiority over haloperidol is not established. Ziprasidone may have a more delayed onset. Their use in elderly, hemodynamically unstable, or diabetic patients may be disadvantageous.
Note: Benzodiazepines are the usual first-line therapy for stimulant (eg, cocaine or amphetamine) intoxications and alcohol withdrawal syndromes. Physostigmine may be preferred for anticholinergic-induced agitated delirium.
Contraindications
Severe CNS depression in the absence of airway and ventilatory control.
Related posts:
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
