Sufentanil

Structural formula
General
Non-proprietary name	Sufentanil
other names	N - [4- (methoxymethyl) -1- (2-thiophen-2-ylethyl) -4-piperidyl] - N -phenyl-propanamide Sufentanil citras
Molecular formula	C 22 H 30 N 2 O 2 S
External identifiers / databases
CAS number 56030-54-7 60561-17-3 ( citrate ) PubChem 41693 DrugBank DB00708 Wikidata Q417915
Drug information
ATC code	N01 AH03
Drug class	Opioid analgesic
properties
Molar mass	386.55 g · mol -1
Melting point	97 ° C 136.5 ° C (citrate)
solubility	76 mg l −1 in water (at 25 ° C)
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances danger H and P phrases H: 300 + 310 + 330 P: 260-264-280-284-301 + 310-302 + 350
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Sufentanil is a synthetic opioid , which is the strongest pain reliever approved in Germany in human medicine, is used primarily in anesthesia and is structurally related to fentanyl .

effect

Sufentanil mediates its effects via opioid receptors , which are mainly found in the central nervous system . As an opioid with a purely agonistic effect, sufentanil binds with high affinity to µ-opioid receptors, but also to κ-receptors, and thus leads to typical opioid effects such as analgesia , respiratory depression, euphoria and miosis . It has 7–10 times the relative analgesic potency of fentanyl and 700–1000 times that of morphine (reference opioid). This makes it the most potent of all clinically used opioids. After intravenous administration, sufentanil is rapidly distributed in fatty tissues due to its lipophilicity . The duration of action is approx. 30 minutes. The breakdown takes place predominantly in the liver , a small proportion is excreted unchanged via the kidneys .

In healthy volunteers, compared to fentanyl, sufentanil led to stronger and longer lasting analgesia with less and less lasting respiratory depression. The cause could be based on a higher affinity of sufentanil for the µ ₁ subreceptor and a comparatively lower affinity for the µ ₂ subreceptor, since analgesia is primarily induced via µ ₁ subreceptors, whereas respiratory depression is primarily induced via µ ₂ subreceptors. A different involvement of the two µ-opioid subreceptors in the analgesic and respiratory depressive effects could be shown by experiments with the selective µ ₁ -antagonist naloxonazine, which can neutralize the analgesic effects of morphine but not the respiratory depressive effects.

Compared to fentanyl, sufentanil is characterized by a much stronger hypnosedative effect. While the hypnotic dose of sufentanil is given as 3.5 µg / kg, the comparable dose of fentanyl is 20–50 µg / kg.

application

Sufentanil is mainly used in anesthesia and intensive care medicine as a pain reliever. It can be delivered repetitively or continuously by means of a syringe pump . A transdermal form of application has also been developed. Due to its high analgesic potency, it should only be administered under supervision so as not to overlook possible respiratory depression. In intensive care medicine, sufentanil is preferably used for continuous analgesic sedation because it is more controllable and has a greater therapeutic range than fentanyl, but at the same time also has a stronger sedating effect and less often leads to respiratory depression.

Interactions

The effect of sufentanil can be influenced by certain calcium antagonists . The combined administration of nimodipine with sufentanil is said to increase its analgesic potency - depending on the exact experimental conditions - by 3.25–50 times. In comparison, the respiratory depression potency of sufentanil is increased to a lesser extent by nimodipine. At the same time, the development of tolerance is suppressed. Further investigations showed that the development of tolerance is based, among other things, on an up-regulation of the protein kinases GRK2, GRK3, GRK6 and beta-arrestin 2, which is prevented by nimodipine. Associated with the development of tolerance is a down-regulation of the µ-opioid receptors with a concentration decrease of 55–67%, which is prevented by the simultaneous administration of nimodipine. In contrast to calcium antagonists, the calcium agonist Bay K 8644 increased the development of tolerance to the analgesic effects of sufentanil.

unwanted effects

Like all opioids , sufentanil can produce the typical opioid side effects. These include respiratory depression up to apnea , euphoria , constipation as well as nausea and vomiting .

Legal status in Germany

Sufentanil is a marketable and prescription narcotic drug in the Federal Republic of Germany due to its listing in Appendix 3 BtMG. Handling without permission or prescription is generally punishable. Further information can be found in the main article Narcotics Law in Germany .

Research history

Sufentanil was first published in 1976 by Paul Janssen , who had already synthesized the widely used opioid derivative fentanyl . The active ingredient became a common tool in surgical anesthesia at the end of the 1980s .

Trade names

Monopreparations sufenta (D, A, CH), various generic (D, A, CH)

Web links

Commons : Sufentanil  - Collection of images, videos and audio files

Individual evidence

1. ↑ ^{a b} Entry on sufentanil in the ChemIDplus database of the United States National Library of Medicine (NLM), accessed on November 3, 2011.
2. ^ Royal Pharmaceutical Society (Ed.): Clarke's Analysis of Drugs and Poisons FOURTH EDITION . Pharmaceutical Press, London / Chicago 2011, ISBN 978-0-85369-711-4 .
3. ↑ ^{a b} Sufentanil citrate data sheet from Sigma-Aldrich , accessed on January 27, 2016 ( PDF ).
4. ↑ Karow, Lang-Roth: general and special pharmacology and toxicology (2005).
5. ↑ PL Bailey et al .: Differences in Magnitude and Duration of Opioid-Induced Respiratory Depression and Analgesia with Fentanyl and Sufentanil , Anesth. Analg. 1990, 70, 8.
6. ↑ GSF Ling et al .: Separation of opioid analgesia from respiratory depression: evidence for different receptor mechanisms. J. Pharmacol. Exp. Ther. 1985, 232, 149.
7. ↑ M. Dierssen, K. Flórez, MA Hurlé: Calcium channel modulation by dihydropyridines modifies sufentanil-induced antinociception in acute and tolerant conditions. Naunyn Schmiedeberg's Arch. Pharmacol. 1990, 342, 559.
8. ↑ F. Ruiz, M. Dierssen, J. Flórez, MA Hurlé: Potentiation of acute opioid-induced respiratory depression and reversal of tolerance by the calcium antagonist nimodipine in awake rats. , Naunyn Schmiedebergs Arch. Pharm. 1993, 348, 633.
9. ↑ MA Hurlé: Changes in the expression of G protein-coupled receptor kinases and beta-arrestin 2 in rat brain during opioid tolerance and supersensitivity. J. Neurochem. 2001, 77, 486.
10. ↑ A. Diaz, F. Ruiz, J. Flórez, MA Hurlé, A. Pazos: Mu-opioid receptor regulation during opioid tolerance and supersensitivity in rat central nervous system. , J. Pharmacol. Exp. Ther. 1995, 274, 1545.
11. ^ A. Díaz, A. Pazos, J. Flórez, MA Hurlé: Autoradiographic mapping of mu-opioid receptors during opiate tolerance and supersensitivity in the rat central nervous system. Naunyn Schmiedebergs Arch Pharmacol. 2000, 362, 101.
12. ↑ JV Garaulet, MLLaorden, MV Milanes: Effect of chronic administration of dihydropyridine Ca ²⁺ channel ligands on sufentanil-induced tolerance to µ- and κ-opioid agonists in the guinea pig ileum myenteric plexus , Reg. Peptides 1996, 63, 1.
13. ↑ Niemegeers CJ, Schellekens KH, Van Bever WF, Janssen PA: Sufentanil, a very potent and extremely safe intravenous morphine-like compound in mice, rats and dogs. Drug research . 1976; 26 (8): 1551-1556.
14. ^ Dariusz Maciejewski: Sufentanil in anaesthesiology and intensive therapy. Anaesthesiology Intensive Therapy 2012; 44: 35-41.

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