|Trade names||Inapsine, Droleptan, Dridol, others|
|Main uses||Nausea, agitation, migraines|
|Onset of action||< 10 min|
|Duration of action||Up to 12 hrs|
|Elimination half-life||2.3 hours|
|Chemical and physical data|
|Molar mass||379.435 g·mol−1|
|3D model (JSmol)|
Droperidol is a medication used to prevent and treat nausea and vomiting including that due to chemotherapy. It has also been used for sedative in those who are agitated and during anesthesia and for migraines. It is given by injection into a vein or muscle. Onset is within 10 minutes with a maximum effect up to 30 minutes. Effects may last up to 12 hours.
Common side effects include low blood pressure, movement disorders, fast heart rate, and sleepiness. Other concerns include QT prolongation, and neuroleptic malignant syndrome. Safety during pregnancy and breastfeeding is unclear. It is in the butyrophenone family of medication and works by blocking dopamine receptors.
Droperidol came into medical use in 1967. It is available as a generic medication. In 2001 the company making it stopped doing so. It historically has been inexpensive. Availability improved in 2019 as a new manufacturer entered the market. In the United Kingdom 2.5 mg of injectable solution costs the NHS about 4 pounds as of 2020.
Droperidol is used to prevent postoperative nausea and vomiting in adults. For treatment of nausea and vomiting, droperidol and ondansetron are equally effective; droperidol is more effective than metoclopramide.
Some practitioners recommend the use of 0.5 mg to 1 mg intravenously for the treatment of vertigo in an otherwise healthy elderly who have not responded to Epley maneuvers.
Evidence supports the use of droperidol for psychosis of recent onset. For agitation benefits begin within 5 to 10 minutes when used intravenously. It has the benefit over haloperidol and lorazapam of being faster in onset.
Droperidol is probably useful in migraine headaches.
The typical dose is 0.625 to 1.25 mg every 6 hours as needed for nausea. In the elderly the lower range of doses is recommended. For agitation 5 mg may be used. For migraines it may be used at a dose of 2.5 mg.
Dysphoria, sedation, hypotension resulting from peripheral alpha adrenoceptor blockade, prolongation of QT interval which can lead to torsades de pointes, and extrapyramidal side effects such as dystonic reactions/neuroleptic malignant syndrome.
In 2001, the FDA added a Black Box Warning, citing concerns of QT prolongation and torsades de pointes. The evidence for this is disputed, with 9 reported cases of torsades in 30 years and all of those having received doses in excess of 5 mg. QT prolongation is a dose-related effect, and it appears that droperidol is not a significant risk in low doses.
Many consider the risks to be over stated at typical doses. A review of the cases submitted to the FDA found that most cases were not related to droperidol and ondansetron has similar QT prolonging effects. Doses that have resulted in concerns have been greater than 300 mg. As of 2019 there does not appear to be a need to routinely get an ECG before giving the medication or for continuous QT monitoring afterwards.
A study in 2015 showed that droperidol is relatively safe and effective for the management of violent and aggressive adults in hospital emergency departments in doses of 10mg and above and that there was no increased risk of QT prolongation and torsades de pointes.
Droperidol is synthesized from 1-benzyl-3-carbethoxypiperidin-4-one, which is reacted with o-phenylenediamine. Evidently, the first derivative that is formed under the reaction conditions, 1,5-benzodiazepine, rearranges into 1-(1-benzyl-1,2,3,6-tetrahydro-4-piridyl)-2-benzymidazolone. Debenzylation of the resulting product with hydrogen over a palladium catalyst, and subsequent alkylation of this using 4-chloro-4'-fluorobutyrophenone yields droperidol.
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