{{Short description|Pharmaceutical combination}} {{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 446334829 | type = combo | component1 = Alfaxalone | class1 = General anaesthetic | component2 = Alfadolone | class2 = Hypnotic
<!-- Clinical data --> | tradename = Althesin, Saffan | Drugs.com = | MedlinePlus = | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_US = <!-- A / B / C / D / X --> | pregnancy_category= | legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled--> | legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> | legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM --> | legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> | legal_status = | routes_of_administration = Intravenous
<!-- Identifiers --> | CAS_number_Ref = {{cascite|correct|CAS}} | CAS_number = 23930-19-0 | CAS_number2 = 14107-37-0 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = BD07M97B2A | UNII2_Ref = {{fdacite|correct|FDA}} | UNII2 = OE1C96974E | ATCvet = | ATC_prefix = <!-- 'none' if uncategorised --> | ATC_suffix = | PubChem = 24732 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = | synonyms = CT-1341, Alphadione, Alphathesin, Aurantex, Alfatesine }}
'''Alfaxolone/alfadolone''' (brand names '''Althesin''' (human), '''Saffan''' (veterinary)) is a short acting intravenous anesthetic agent. It was withdrawn from the market due to severe drug reactions. It is composed of a 3:1 mixture of alfaxalone and alfadolone, two neurosteroids.
==Mechanism== Alfaxolone/alfadolone is short-duration, intravenous anesthetic made from a combination of two steroidal compounds, alfaxalone and alfadolone, of which the former is the primary anesthetic agent. Alfadolone acts to increase the solubility of the mixture in which it is dissolved, a polyethylated castor oil adjuvant.<ref name=Althesin>{{cite journal | vauthors = Dechêne JP | title = Alphathesin, a new steroid anaesthetic agent | journal = Canadian Anaesthetists' Society Journal | volume = 23 | issue = 2 | pages = 163–9 | date = March 1976 | pmid = 943212 | doi = 10.1007/BF03005687 | doi-access = free }}</ref> Anesthetic efficacy is achieved by allosteric potentiation of the GABA<sub>A</sub> chloride channel to produce 'fast' synaptic inhibition.<ref name=Neurosteroids>{{cite journal | vauthors = Belelli D, Lambert JJ | s2cid = 12596378 | title = Neurosteroids: endogenous regulators of the GABA(A) receptor | journal = Nature Reviews. Neuroscience | volume = 6 | issue = 7 | pages = 565–75 | date = July 2005 | pmid = 15959466 | doi = 10.1038/nrn1703 }}</ref>
==Clinical use==
Alfaxolone/alfadolone is short-acting, rapid onset anesthetic which has been used for out-patient surgery. It does not have significant analgesic properties and anesthesia has often been maintained with inhalational anesthetics such as halothane. These have also been accompanied by neuromuscular blockers. Procedures carried out under this drug are greatly varied and have included orthopedic, gynecological, dental and urological surgery. Notable effects include a drop in arterial and venous pressure in a quarter of patients; this is accompanied by a compensatory mild tachycardia in around 35% of those observed in a population skewed towards geriatrics.<ref name=Althesin />
Cremophor EL (aka. Polyoxyl 35 Castor Oil, a surfactant and derivative of castor oil) was the solubilizing agent (excipient / additive) of Althesin. <ref>{{cite journal | vauthors = Clarke RS, Dundee JW, Carson IW | title = Proceedings: A new steroid anaesthetic-althesin | journal = Proceedings of the Royal Society of Medicine | volume = 66 | issue = 10 | pages = 1027–30 | date = October 1973 | doi = 10.1177/003591577306601023 | pmid = 4148526 | pmc = 1645602 }}</ref>
A 2001 study found that Cremophor EL, when previously used as a solubilizing agent in lipid emulsions, was responsible for severe anaphylactoid reactions. Drugs using it were reformulated to use other emulsifiers. <ref>{{cite journal | vauthors = MacPherson RD | title = Pharmaceutics for the anaesthetist | journal = Anaesthesia | volume = 56 | issue = 10 | pages = 965–79 | date = October 2001 | pmid = 11576099 | doi = 10.1111/j.1365-2044.2001.02216.x | s2cid = 10768907 | doi-access = free }}</ref> Alfaxolone/alfadolone has been re-branded as "Saffan" and is available for use in veterinary anaesthesia. <ref>{{cite journal | vauthors = Dyson DH, Allen DG, Ingwersen W, Pascoe PJ, O'Grady M | title = Effects of saffan on cardiopulmonary function in healthy cats | journal = Canadian Journal of Veterinary Research | volume = 51 | issue = 2 | pages = 236–9 | date = April 1987 | pmid = 3111675 | pmc = 1255310 }}</ref> <ref>{{cite journal | vauthors = Nadeson R, Goodchild CS | title = Antinociceptive properties of neurosteroids III: experiments with alphadolone given intravenously, intraperitoneally, and intragastrically | journal = British Journal of Anaesthesia | volume = 86 | issue = 5 | pages = 704–8 | date = May 2001 | pmid = 11575348 | doi = 10.1093/bja/86.5.704 | url = http://www.anesthesia-analgesia.org/content/97/3/798.full | doi-access = free }}</ref>
== References == {{Reflist|2}}
{{Anesthetics}} {{GABAAR PAMs}}
{{DEFAULTSORT:Alfaxolone alfadolone}} Category:General anesthetics Category:Neurosteroids Category:Combination drugs Category:GABAA receptor positive allosteric modulators Category:Pregnanes