Droperidol

From WikiProjectMed
Jump to navigation Jump to search
Droperidol
Skeletal formula of droperidol
Ball-and-stick model of droperidol
Names
Pronunciation/droʊˈpɛrIdɔːl/
Trade namesInapsine, Droleptan, Dridol, others
Clinical data
Main usesNausea, agitation, migraines[1][2]
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out)
Routes of
use
Intravenous, intramuscular[1]
Onset of action< 10 min[1]
Duration of actionUp to 12 hrs[1]
External links
AHFS/Drugs.comMonograph
Legal
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
Pharmacokinetics
MetabolismLiver
Elimination half-life2.3 hours
Chemical and physical data
FormulaC22H22FN3O2
Molar mass379.435 g·mol−1
3D model (JSmol)

Droperidol is a medication used to prevent and treat nausea and vomiting including that due to chemotherapy.[1] It has also been used for sedative in those who are agitated and during anesthesia and for migraines.[1][2] It is given by injection into a vein or muscle.[1] Onset is within 10 minutes with a maximum effect up to 30 minutes.[1] Effects may last up to 12 hours.[1]

Common side effects include low blood pressure, movement disorders, fast heart rate, and sleepiness.[1] Other concerns include QT prolongation, and neuroleptic malignant syndrome.[1] Safety during pregnancy and breastfeeding is unclear.[3] It is in the butyrophenone family of medication and works by blocking dopamine receptors.[4]

Droperidol came into medical use in 1967.[5] It is available as a generic medication.[4] In 2001 the company making it stopped doing so.[5] It historically has been inexpensive.[5] Availability improved in 2019 as a new manufacturer entered the market.[6] In the United Kingdom 2.5 mg of injectable solution costs the NHS about 4 pounds as of 2020.[4]

Medical use

Nausea

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.[7]

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.

Agitation

Evidence supports the use of droperidol for psychosis of recent onset.[8] For agitation benefits begin within 5 to 10 minutes when used intravenously.[9] It has the benefit over haloperidol and lorazapam of being faster in onset.[10]

Migraines

Droperidol is probably useful in migraine headaches.[11]

Dosage

The typical dose is 0.625 to 1.25 mg every 6 hours as needed for nausea.[4] In the elderly the lower range of doses is recommended.[4] For agitation 5 mg may be used.[1] For migraines it may be used at a dose of 2.5 mg.[2]

Side effects

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.[12]

Black box

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.[13] QT prolongation is a dose-related effect,[14] and it appears that droperidol is not a significant risk in low doses.

Many consider the risks to be over stated at typical doses.[11] 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.[15] Doses that have resulted in concerns have been greater than 300 mg.[6] 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.[16][17]

A study in 2015 showed that droperidol is relatively safe and effective for the management of violent and aggressive adults[18] in hospital emergency departments in doses of 10mg and above and that there was no increased risk of QT prolongation and torsades de pointes.

Chemistry

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. Droperidol synth.png

History

Discovered at Janssen Pharmaceutica in 1961, droperidol is a butyrophenone which acts as a potent D2 (dopamine receptor) antagonist with some histamine and serotonin antagonist activity.[19]

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 "Droperidol Monograph for Professionals". Drugs.com. Retrieved 13 October 2020.
  2. 2.0 2.1 2.2 Thomas, MC; Musselman, ME; Shewmaker, J (February 2015). "Droperidol for the treatment of acute migraine headaches". The Annals of pharmacotherapy. 49 (2): 233–40. doi:10.1177/1060028014554445. PMID 25416184.
  3. "Droperidol (Inapsine) Use During Pregnancy". Drugs.com. Retrieved 13 October 2020.
  4. 4.0 4.1 4.2 4.3 4.4 BNF 79 : March 2020. London: Royal Pharmaceutical Society. 2020. p. 452. ISBN 9780857113658.
  5. 5.0 5.1 5.2 Richards, JR; Schneir, AB (May 2003). "Droperidol in the emergency department: is it safe?". The Journal of emergency medicine. 24 (4): 441–7. doi:10.1016/s0736-4679(03)00044-1. PMID 12745049.
  6. 6.0 6.1 "Droperidol Is Back (and Here's What You Need to Know)". ACEP Now. Retrieved 13 October 2020.
  7. Domino KB, Anderson EA, Polissar NL, Posner KL (June 1999). "Comparative efficacy and safety of ondansetron, droperidol, and metoclopramide for preventing postoperative nausea and vomiting: a meta-analysis". Anesthesia and Analgesia. 88 (6): 1370–9. doi:10.1213/00000539-199906000-00032. PMID 10357347.
  8. Khokhar, MA; Rathbone, J (15 December 2016). "Droperidol for psychosis-induced aggression or agitation". The Cochrane database of systematic reviews. 12: CD002830. doi:10.1002/14651858.CD002830.pub3. PMID 27976370.
  9. Zun, LS (March 2018). "Evidence-Based Review of Pharmacotherapy for Acute Agitation. Part 1: Onset of Efficacy". The Journal of emergency medicine. 54 (3): 364–374. doi:10.1016/j.jemermed.2017.10.011. PMID 29361326.
  10. "Droperidol Is Back (and Here's What You Need to Know) - Page 3 of 3". ACEP Now. Retrieved 13 October 2020.
  11. 11.0 11.1 Lai, PC; Huang, YT (January 2018). "Evidence-based review and appraisal of the use of droperidol in the emergency department". Ci ji yi xue za zhi = Tzu-chi medical journal. 30 (1): 1–4. doi:10.4103/tcmj.tcmj_195_17. PMID 29643708.
  12. Park CK, Choi HY, Oh IY, Kim MS (2002). "Acute dystonia by droperidol during intravenous patient-controlled analgesia in young patients". J. Korean Med. Sci. 17 (5): 715–7. doi:10.3346/jkms.2002.17.5.715. PMC 3054934. PMID 12378031.
  13. Kao LW, Kirk MA, Evers SJ, Rosenfeld SH (April 2003). "Droperidol, QT prolongation, and sudden death: what is the evidence?". Annals of Emergency Medicine. 41 (4): 546–58. doi:10.1067/mem.2003.110. PMID 12658255.
  14. Lischke V, Behne M, Doelken P, Schledt U, Probst S, Vettermann J (November 1994). "Droperidol causes a dose-dependent prolongation of the QT interval". Anesthesia and Analgesia. 79 (5): 983–6. doi:10.1213/00000539-199411000-00028. PMID 7978420.
  15. Wilson, William C.; Grande, Christopher M.; Hoyt, David B. (2007). Trauma: Critical Care. CRC Press. p. 373. ISBN 978-1-4200-1684-0.
  16. "Droperidol Is Back (and Here's What You Need to Know) - Page 2 of 3". ACEP Now. Retrieved 13 October 2020.
  17. Perkins, Jack; Ho, Jeffrey D.; Vilke, Gary M.; DeMers, Gerard (July 2015). "American Academy of Emergency Medicine Position Statement: Safety of Droperidol Use in the Emergency Department". The Journal of Emergency Medicine. 49 (1): 91–97. doi:10.1016/j.jemermed.2014.12.024.
  18. Calver, Leonie; Page, Colin; Downes, Michael; Chan, Betty; Kinnear, Frances; Wheatley, Luke; Spain, David; Ibister, Geoffrey (September 2015). "The safety and effectiveness of droperidol for sedation of acute behavioral disturbance in the emergency department". Annals of Emergency Medicine. 66 (3): 231–238. doi:10.1016/j.annemergmed.2015.03.016. PMID 25890395. Retrieved 18 July 2018.
  19. Peroutka SJ, Synder SH (December 1980). "Relationship of neuroleptic drug effects at brain dopamine, serotonin, alpha-adrenergic, and histamine receptors to clinical potency". The American Journal of Psychiatry. 137 (12): 1518–22. doi:10.1176/ajp.137.12.1518. PMID 6108081. Retrieved 2009-06-21.

Further reading

Identifiers: