Talk:Flumazenil

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Summary sheet: Flumazenil
Flumazenil
Flumazenil.svg
Chemical Nomenclature
Common names Anexate, Flumazepil, Romazicon, Ro 15-1788
Substitutive name Flumazenil
Systematic name ethyl 8-fluoro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate
Class Membership
Chemical class Benzodiazepine
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.











Intravenous
Dosage
Common 0.2 - 1 mg
Duration

DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.


Flumazenil (sold as Anexate, Romazicon, and known by its developmental code Ro 15-1788) is an antisedative substance of the imidazobenzodiazepine chemical class that produces antisedative effects when administered, especially when reversing benzodiazepines.

It is a highly selective benzodiazepine receptor antagonist[1] that is primarily used in the treatment of benzodiazepine overdoses via competitive inhibition at the benzodiazepine binding site on the GABAA receptor,[2] although it has also been used to treat overdoses of non-benzodiazepine hypnotics such as zolpidem and zopiclone (see Z-drug). However, it is ineffective for reversing overdoses of barbiturates, opioids, or alcohol. Due to its short half-life, multiple doses and careful patient monitoring are required to prevent recurrence of overdose symptoms.(<-- is this sentence necessary here?) [citation needed] (1. I think it should be elsewhere? 2. The cite flag isn't really too needed. Although it's definitely preferred, it's obvious that if flumazenil lasts short, some benzodiazepines last longer.)

It is also used medically to reverse the effects of benzodiazepines following surgery, in a way similar to naloxone being used for surgeries involving opioids.[citation needed] <--(Is a cite flag needed much here? That's kind of a "common sense"/inferrable thing) Outside of an acute care setting, flumanezil may also be effective in reducing excessive daytime sleepiness while improving vigilance in primary hypersomnias, such as idiopathic hypersomnia.[citation needed] (this def needs a cite flag)

Flumazenil was first introduced in 1987 by Hoffmann-La Roche under the trade name"Anexate, but only approved by the FDA on December 20, 1991. Flumazenil went off patent in 2008, so, at present, generic formulations of this drug are available.[citation needed](this def needs a cite flag)


Whether flumazenil produces any psychoactive effects on its own is currently subject to debate. Although the body produces no known benzodiazepine receptor agonists, some studies suggest that flumazenil does produce effects on its own.[3]

History and culture

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Chemistry

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Flumazenil is an organic heterocyclic compound that is 5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepine which is substituted at positions 3, 5, 6, and 8 by ethoxycarbonyl, methyl, oxo, and fluoro groups, respectively. It is used as an antidote to benzodiazepine overdose. It has a role as a GABA antagonist and an antidote to benzodiazepine poisoning. It is an ethyl ester, an organofluorine compound and an imidazobenzodiazepine.[4]

Pharmacology

Flumazenil, an imidazobenzodiazepine derivative, antagonizes the actions of benzodiazepines on the central nervous system. Flumazenil competitively inhibits the activity at the benzodiazepine recognition site on the GABA/benzodiazepine receptor complex.[5] It also exhibits weak partial agonism of GABAA receptor complexes that contain α6-type monomers; the clinical relevance of this is unknown.[6]

Flumazenil does not antagonize all of the central nervous system effects of drugs affecting GABA-ergic neurons by means other than the benzodiazepine receptor (including ethanol, barbiturates, and most anesthetics) and does not reverse the effects of opioids. It will however antagonize the action of non-benzodiazepine z-drugs, such as zolpidem and zopiclone, because they act via the benzodiazepine site of the GABA receptor[7] - it has been used to successfully treat z-drug overdose.[8]

Intravenous flumazenil has been shown to antagonize sedation, impairment of recall, psychomotor impairment and ventilatory depression produced by benzodiazepines in healthy human volunteers. The duration and degree of reversal of sedative benzodiazepine effects are related to the dose and plasma concentrations of flumazenil.

Flumazenil is sold under a wide variety of brand names worldwide like Anexate, Lanexat, Mazicon, Romazicon. In India it is manufactured by Roche Bangladesh Pharmaceuticals and USAN Pharmaceuticals.

Low-dose, slow subcutaneous flumazenil administration is a safe procedure for patients withdrawing from long-term, high-dose benzodiazepine dependence.[9] It has a low risk of seizures even amongst those who have experienced convulsions when previously attempting benzodiazepine withdrawal.[10]

Subjective effects

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Flumazenil producing any effects in the body on its own is questionable. A study has suggested that it produces performance-declining effects that appear to be dose-dependent.[11] Flumazenil often produces effects by means of immediate withdrawal, similar to naloxone. As such, a patient may wake up agitated, extremely wakeful, or could experience seizures.


Physical effects
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Toxicity and harm potential

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As a result, it may contain incomplete or even dangerously wrong information. You can help by expanding upon or correcting it.
Note: Always conduct independent research and use harm reduction practices if using this substance.

It is strongly recommended that one use harm reduction practices when using this substance.

Lethal dosage

Tolerance and addiction potential

Dangerous interactions

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Although many psychoactive substances are reasonably safe to use on their own, they can suddenly become dangerous or even life-threatening when combined with other substances. The following list includes some known dangerous combinations (although it is not guaranteed to include all of them). Independent research (e.g. Google, DuckDuckGo) should always be conducted to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.

Legal status

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  • Sweden: Flumazenil is a prescription only medication.[12]

See also

External links

Literature

References

  1. Whitwam, J. G., & Amrein, R. (1995). Pharmacology of flumazenil. Acta Anaesthesiologica Scandinavica, 39(s108), 3-14.
  2. Whyte, IM (2004). "Benzodiazepines". Medical toxicology. Philadelphia: Williams & Wilkins. pp. 811–22. ISBN 0-7817-2845-2.
  3. Neave, N., Reid, C., Scholey, A., Thompson, J., Moss, M., Ayre, G., ... & Girdler, N. (2000). Dose-dependent effects of flumazenil on cognition, mood, and cardio-respiratory physiology in healthy volunteers. British dental journal, 189(12), 668.
  4. Sivilotti ML (2016) Flumazenil, naloxone and the 'coma cocktail'. British journal of clinical pharmacology 81, 428-436 [PubMed:26469689]
  5. Hood, Sean David; Norman, Amanda; Hince, Dana Adelle; Melichar, Jan Krzysztof; Hulse, Gary Kenneth (February 2014). "Benzodiazepine dependence and its treatment with low dose flumazenil". British Journal of Clinical Pharmacology. 77 (2): 285–294. doi:10.1111/bcp.12023. ISSN 1365-2125. PMC 4014019. PMID 23126253.
  6. Hadingham, K. L.; Garrett, E. M.; Wafford, K. A.; Bain, C.; Heavens, R. P.; Sirinathsinghji, D. J.; Whiting, P. J. (February 1996). "Cloning of cDNAs encoding the human gamma-aminobutyric acid type A receptor alpha 6 subunit and characterization of the pharmacology of alpha 6-containing receptors". Molecular Pharmacology. 49 (2): 253–259. ISSN 0026-895X. PMID 8632757.
  7. Gunja, Naren (June 2013). "The clinical and forensic toxicology of Z-drugs". Journal of Medical Toxicology. 9 (2): 155–162. doi:10.1007/s13181-013-0292-0. ISSN 1937-6995. PMC 3657020. PMID 23404347.
  8. Gunja, Naren (June 2013). "The clinical and forensic toxicology of Z-drugs". Journal of Medical Toxicology. 9 (2): 155–162. doi:10.1007/s13181-013-0292-0. ISSN 1937-6995. PMC 3657020. PMID 23404347.
  9. Faccini, Marco; Leone, Roberto; Opri, Sibilla; Casari, Rebecca; Resentera, Chiara; Morbioli, Laura; Conforti, Anita; Lugoboni, Fabio (October 2016). "Slow subcutaneous infusion of flumazenil for the treatment of long-term, high-dose benzodiazepine users: a review of 214 cases". Journal of Psychopharmacology (Oxford, England). 30 (10): 1047–1053. doi:10.1177/0269881116647505. ISSN 1461-7285. PMID 27166362. S2CID 27167585.
  10. Tamburin, Stefano; Faccini, Marco; Casari, Rebecca; Federico, Angela; Morbioli, Laura; Franchini, Enrica; Bongiovanni, Luigi Giuseppe; Lugoboni, Fabio (October 2017). "Low risk of seizures with slow flumazenil infusion and routine anticonvulsant prophylaxis for high-dose benzodiazepine dependence". Journal of Psychopharmacology (Oxford, England). 31 (10): 1369–1373. doi:10.1177/0269881117714050. ISSN 1461-7285. PMID 28613124. S2CID 42432213.
  11. Neave, N., Reid, C., Scholey, A., Thompson, J., Moss, M., Ayre, G., ... & Girdler, N. (2000). Dose-dependent effects of flumazenil on cognition, mood, and cardio-respiratory physiology in healthy volunteers. British dental journal, 189(12), 668.
  12. http://rkrattsbaser.gov.se/sfst?fritext=1992%3A1554&upph=false&post_id=3