DROPERIDOL EQUITY

Indications

• Prevention of postoperative nausea and vomiting
• Sedation in surgical procedures

Mechanism of action

Droperidol's exact mechanism of action is not fully understood, but it is known to cause central nervous system depression at subcortical levels, particularly in the midbrain and brainstem reticular formation. It antagonizes glutamic acid in the extrapyramidal system, inhibits catecholamine receptors, and has strong central antidopaminergic and weak central anticholinergic actions. Droperidol predominantly acts as a potent antagonist at dopamine D2 receptors while also exhibiting minor antagonistic effects on alpha-1 adrenergic receptors. The drug produces peripheral vasodilation and can decrease pulmonary arterial pressure, which may lead to hypotension.

Pharmacodynamics

Droperidol produces significant sedation and tranquilization, alleviating apprehension and inducing a mental state of detachment while preserving reflex alertness. It is effective against nausea and vomiting, particularly in surgical contexts, demonstrating antiemetic properties by antagonizing apomorphine-induced emesis. Droperidol enhances the effects of other central nervous system depressants and has mild alpha-adrenergic blocking effects, potentially leading to hypotension and reduced peripheral vascular resistance. It may also decrease the risk of epinephrine-induced cardiac arrhythmias without preventing other types of arrhythmias.

Pharmacokinetics

Droperidol is administered intravenously or transdermally, with a rapid onset of action. It is extensively metabolized in the liver, with caution advised in patients with hepatic impairment. The drug has a circulating half-life that varies based on individual patient factors, including age and organ function. Droperidol is excreted mainly in urine as metabolites. Dose adjustments may be necessary in renal impairment, as the drug's effects can be potentiated in such patients due to increased cerebral sensitivity.

Contra-indications

• Bradycardia
• CNS depression
• Comatose states
• Hypokalaemia
• Hypomagnesaemia
• Phaeochromocytoma
• Angle-closure glaucoma

Adverse effects

• Asthenia
• Heat stroke
• Delirium
• Gastrointestinal disorders
• Cardiac arrest
• Hepatic disorders
• Allergic dermatitis
• Confusion
• Hyperglycaemia
• Hyponatraemia
• Photosensitivity reaction
• Priapism
• SIADH
• Respiratory depression

Interactions

• Droperidol + dopaminereceptoragonists: Severe (decreases effects)
• Droperidol + levodopa: Unknown (decreases effects)
• Droperidol + alcohol: Enhanced effects

Precautions

• Patients receiving large initial doses should remain supine
• Caution in hepatic impairment
• Caution in renal impairment
• Elderly patients may require dose adjustments
• Consider starting with small doses in severe renal impairment

Pregnancy

Use only if potential benefit outweighs risk. Injection may depress neonatal respiration.

Breast-feeding

Amount too small to be harmful; however, avoid repeated administration.

Storage

Store below 25°C. Protect from light.

Formulations

• Injection solution
• Chewable tablet
• Oral suspension
• Oral solution

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. Within the CNS, droperidol acts principally at subcortical levels and exhibits a strong sedative effect. The drug also inhibits sympathetic postganglionic alpha-adrenergic receptor binding sites; however, therapeutic dosages of droperidol do not appear to completely block these receptors. Droperidol has antiemetic activity, but does not appear to exhibit analgesic activity. Because of its inhibitory effects on alpha-adrenergic receptor binding sites, droperidol attenuates the cardiovascular response to sympathomimetic amines. Droperidol also produces direct peripheral vasodilation, which alone or in conjunction with its alpha-adrenergic blocking activity may cause hypotension and decreased peripheral vascular resistance. Droperidol may decrease pulmonary arterial pressure (particularly in patients with preexisting elevations in pulmonary arterial pressure) and reduce the incidence of epinephrine-induced arrhythmias; however, droperidol's activity against other arrhythmias has not been observed. Droperidol produces the inhibition of K+ channels in cardiac myocytes. However, the effects of droperidol on K+ channels have not been studied in blood vessels. Therefore, /investigators/ designed the present study to determine whether droperidol modulates the activity of adenosine triphosphate (ATP)-sensitive K+ channels in vascular smooth muscle cells. Rat aortic rings without endothelium were suspended or used for isometric force and membrane potential recordings, respectively. Vasorelaxation and hyperpolarization induced by levcromakalim (10(-8) to 10(-5) M or 10(-5) M, respectively) were completely abolished by the ATP-sensitive K+ channel antagonist glibenclamide (10(-5) M). Droperidol (10(-7) M) and an alpha-adrenergic receptor antagonist phentolamine (3 x 10(-9) M) caused a similar vasodilator effect (approximately 20% of vasorelaxation compared with maximal vasorelaxation induced by papaverine 3 x 10(-4) M, whereas glibenclamide did not alter vasorelaxation induced by droperidol. Droperidol (3 x 10(-8) M to 10(-7) M) augmented vasorelaxation and hyperpolarization produced by levcromakalim, whereas phentolamine (3 x 10(-9) M) did not alter this vasorelaxation. Glibenclamide (10(-5) M) abolished the vasodilating and hyperpolarizing effects of levcromakalim in the aorta treated with droperidol (10(-7) M). These results suggest that droperidol augments vasodilator activity via ATP-sensitive K+ channels. However, it is unlikely that this augmentation is mediated by the inhibition of alpha-adrenergic receptors in vascular smooth muscles. ... An inhibitory dopaminergic receptor has been described that modulates catecholamine release from adrenal medulla. It has also been reported that low doses of droperidol increase arterial pressure in some patients with pheochromocytoma. The authors investigated whether an effect of droperidol on such a receptor could be one of the mechanisms involved in the hypertensive response. Isolated cat adrenal glands were perfused with Krebs-bicarbonate solution, and the catecholamine release was measured in the effluent. Then, the glands were stimulated by activation of the nicotinic receptor (nicotine, 5 uM), and the effect of low and high doses of droperidol and/or apomorphine on the catecholamine secretory responses evoked by nicotine was investigated. Low concentrations of d

Pharmacodynamics

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.