indication

Droperidol is ssed to produce tranquilization and to reduce the incidence of nausea and vomiting in surgical and diagnostic procedures.

pharmacology

Droperidol produces marked tranquilization and sedation. It allays apprehension and provides a state of mental detachment and indifference while maintaining a state of reflex alertness. Droperidol produces an antiemetic effect as evidenced by the antagonism of apomorphine in dogs. It lowers the incidence of nausea and vomiting during surgical procedures and provides antiemetic protection in the postoperative period. Droperidol potentiates other CNS depressants. It produces mild alpha-adrenergic blockade, peripheral vascular dilatation and reduction of the pressor effect of epinephrine. It can produce hypotension and decreased peripheral vascular resistance and may decrease pulmonary arterial pressure (particularly if it is abnormally high). It may reduce the incidence of epinephrine-induced arrhythmias, but it does not prevent other cardiac arrhythmias.

mechanism of action

The exact mechanism of action is unknown, however, droperidol causes a CNS depression at subcortical levels of the brain, midbrain, and brainstem reticular formation. It may antagonize the actions of glutamic acid within the extrapyramidal system. It may also inhibit cathecolamine receptors and the reuptake of neurotransmiters and has strong central antidopaminergic action and weak central anticholinergic action. It can also produce ganglionic blockade and reduced affective response. The main actions seem to stem from its potent Dopamine(2) receptor antagonism with minor antagonistic effects on alpha-1 adrenergic receptors as well.

toxicity

The intravenous LD₅₀ of droperidol is 20-43 mg/kg in mice; 30 mg/kg in rats; 25 mg/kg in dogs and 11-13 mg/kg in rabbits. The intramuscular LD₅₀ of droperidol is 195 mg/kg in mice, 104-110 mg/kg in rats; 97 mg/kg in rabbits and 200 mg/kg in guinea pigs. The manifestations of droperidol overdosage are an extension of its pharmacologic actions.

biotransformation

Extensively metabolized.

absorption

Completely absorbed following intramuscular administration.

half life

Biphasic distribution. The rapid distribution phase is 1.4 ± 0.5 minutes and the slower distribution phase is 14.3 ± 6.5 minutes. Elimination half-life in adults is 134 ± 13 minutes and may be increased in geriatric patients. In children, it is 101.5 ± 26.4 minutes.

drug interactions

Artemether: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Brimonidine: Droperidol may enhance the CNS depressant effect of brimonidine. Consider therapy modification.

Buprenorphine: Droperidol may enhance the CNS depressant effect of CNS Depressants like buprenorphine. Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use.

Butabarbital: Droperidol may enhance the CNS depressant effect of CNS Depressants like butabarbital. Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use.

Butalbital: Droperidol may enhance the CNS depressant effect of CNS depressants such as butalbital. Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use.

Butorphanol: Droperidol may enhance the CNS depressant effect of butorphanol. Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use.

Carisoprodol: Droperidol may enhance the CNS depressant effect of carisoprodol. Consider dose reductions of droperidol or of other CNS agents with concomitant use.

Lumefantrine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Quinupristin: This combination presents an increased risk of toxicity

Tacrine: The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Droperidol, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents.

Tacrolimus: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Tetrabenazine: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Thiothixene: May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.

Toremifene: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.

Trimethobenzamide: Trimethobenzamide and Droperidol, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Trimipramine: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Triprolidine: Triprolidine and Droperidol, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.

Trospium: Trospium and Droperidol, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.

Voriconazole: Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Vorinostat: Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Ziprasidone: Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

Zuclopenthixol: Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).