Droperidol

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Structural formula
Structure of droperidol
General
Non-proprietary name Droperidol
other names
  • 1- {1- [4- (4-fluorophenyl) -4-oxobutyl] -1,2,5,6-tetrahydropyridin-4-yl} -2,3-dihydro-1 H -benzimidazole-2-one ( IUPAC )
  • Droperidolum ( Latin )
Molecular formula C 22 H 22 FN 3 O 2
Brief description

white to almost white, polymorphic powder

External identifiers / databases
CAS number 548-73-2
EC number 208-957-8
ECHA InfoCard 100.008.144
PubChem 3168
DrugBank DB00450
Wikidata Q174259
Drug information
ATC code
Drug class

Antipsychotics , antiemetics

Mechanism of action

Inhibition of dopaminergic receptors in the area postrema

properties
Molar mass 379.44 g · mol -1
Physical state

firmly

Melting point

145.75 ° C

Vapor pressure

2.69 n Pa (25 ° C)

pK s value

7.46

solubility
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
07 - Warning

Caution

H and P phrases H: 302
P: no P-phrases
Toxicological data

750 mg kg −1 ( LD 50ratoral )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Droperidol ( Dehydrobenzperidol, DHB, DHBP ) is a neuroleptic that is used to prevent and treat nausea and vomiting after operations .

Mechanism of action

Droperidol has a strong affinity for the D 2 receptor (see dopamine receptor ) in the area postrema, a part of the vomiting center where the substance has an inhibitory effect, and a lower affinity for D 3 , 5-HT 2 and α 1 receptors .

Contraindications

Droperidol must not be used in patients with:

  • Hypersensitivity / allergy to droperidol or any of the other ingredients;
  • Hypersensitivity / allergy to butyrophenones ;
  • known or suspected prolonged QT time (QTc> 450 ms in women and> 440 ms in men). This also applies to patients with congenitally prolonged QT, patients with a family history of congenital prolonged QT, and patients on treatment with drugs known to prolong QT;
  • Hypokalemia or hypomagnesaemia ;
  • Bradycardia (less than 55 heartbeats per minute);
  • Known concomitant medication that can lead to bradycardia;
  • Pheochromocytoma ;
  • Comatose states;
  • Parkinson's Disease;
  • Severe depression .

Side effect / interaction

Until the 1980s, the drug Thalamonal was given as a premedication before surgery. It is a combination of the two active ingredients fentanyl and droperidol. The aim was to relieve the patient of the fear of the surgical procedure and at the same time to sedate them. However, after the operation, many patients expressed their wish not to have this drug administered again in the future. Many of them complained of inner turmoil, depressive episodes, even panic under the influence of the two active ingredients, all of which was accompanied by external fatigue. Several of them even withdrew or refused to give permission for the procedure at the last minute because of the short-term and drastic deterioration in their mental health. Since then, anesthetists have only used the active ingredient combination in exceptional cases. It has now become standard to use benzodiazepines for premedication , which most patients find pleasant and anxiety-relieving. They also cause anterograde amnesia , so that the unpleasant aspects before the operation are no longer remembered by the patient.

History of the withdrawal and re-registration

The peroral dosage forms were withdrawn from the market by the manufacturer (Janssen) in 2001 because cardiac side effects ( QT syndrome ) had occurred during high-dose oral long-term therapy . The parenteral form of administration, where this side effect was not a problem, was discontinued for commercial and tactical reasons. Droperidol was still approved for use in Germany and was available from foreign manufacturers or distributors (e.g. Abbott, USA).

After Janssen-Cilag announced that it would stop selling Droperidol worldwide at the end of June 2001, the then Swiss Agency for Medicinal Products (IKS) banned the sale of the substance at the end of September 2001. Droperidol is being produced again in Switzerland by the Sintetica company and is also legally available again in Swiss stores.

After the announced cessation of production, the license of the company Arzneimittel ProStrakan was bought by the former license holder Janssen-Cilag , which after a new approval procedure in 2007 led to approvals in various European countries (including on March 27, 2008 in Germany).

Significance and areas of application

Old registration

Droperidol was never used in psychiatry, instead it is used in anesthesia . Together with a highly potent analgesic (mostly fentanyl ), it is a component of neuroleptanalgesia , the use and importance of which in clinical anesthesiology has lost importance since around 1980 (increasing availability of alternative methods such as TIVA ). On the other hand, droperidol is an important and one of the best-studied drugs for postoperative nausea and vomiting (PONV). For PONV, 0.5 mg - 1 mg droperidol is slowly administered intravenously. For neuroleptanalgesia, mostly higher dosages are used.

New approval

After the new approval, the finished drug Xomolix is available for anesthesia:

Trade names

Monopreparations

Xomolix (D, A), Dehydrobenzperidol (A), Droperidol (CH)

See also

Web links

Individual evidence

  1. a b European Pharmacopoeia Commission (ed.): EUROPEAN PHARMACOPOE 5TH EDITION . tape 5.0-5.8 , 2006.
  2. a b c d e Entry on Droperidol in the ChemIDplus database of the United States National Library of Medicine (NLM)
  3. a b data sheet Droperidol from Sigma-Aldrich , accessed on March 29, 2011 ( PDF ).
  4. a b Pharmazeutische Zeitung No. 27, p. 25 f.
  5. a b Product information for Xomolix 2.5 mg / ml solution for injection (ProStrakan Limited). Status: October 2009, accessed January 24, 2016.
  6. (Höfling S, Dworzak H, Butollo W, Neeef W,: The fear process under different high doses of thalamonal for premedication, Anesthesiologist 1983; 32; 512-518).
  7. Xomolix Receives Additional Key European Approvals , ProStakan press release of April 2, 2008 on the website www.cmocro.com.
  8. Specialist information Droperidol ® Sintetica of the Medicinal Compendium ® of Switzerland.
  9. Rote Liste Service GmbH (Ed.): Rote Liste 2017 - drug directory for Germany (including EU approvals and certain medical devices) , Rote Liste Service GmbH, Frankfurt / Main, 2017, edition 57, ISBN 978-3-946057-10 -9 , p. 397.
  • Larsen Anesthesia (5th Edition)
  • E. Burgius, intensive course in general and special pharmacology