Alfaxolone/alfadolone

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Alfaxolone/alfadolone
Combination of
AlfaxaloneGeneral anaesthetic
AlfadoloneHypnotic
Clinical data
Trade namesAlthesin, Saffan
Other namesCT-1341, Alphadione, Alphathesin, Aurantex, Alfatesine
Routes of
administration		Intravenous
Identifiers
CAS Number
PubChem CID
UNII
CompTox Dashboard (EPA)
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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 It was withdrawn from the market due to severe drug reactions.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.[1] Anesthetic efficacy is achieved by allosteric potentiation of the GABAA chloride channel to produce 'fast' synaptic inhibition.[2]

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.[1]

Cremophor EL (aka. Polyoxyl 35 Castor Oil, a surfactant and derivative of castor oil) was the solubilizing agent (excipient / additive) of Althesin. [3]

A study 2001 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. [4] Alfaxolone/alfadolone has been re-branded as "Saffan" and is available for use in veterinary anaesthesia. [5] [6]

References

  1. ^ a b Dechêne JP (March 1976). "Alphathesin, a new steroid anaesthetic agent". Canadian Anaesthetists' Society Journal. 23 (2): 163–9. doi:10.1007/BF03005687. PMID 943212.
  2. ^ Belelli D, Lambert JJ (July 2005). "Neurosteroids: endogenous regulators of the GABA(A) receptor". Nature Reviews. Neuroscience. 6 (7): 565–75. doi:10.1038/nrn1703. PMID 15959466. S2CID 12596378.
  3. ^ Clarke RS, Dundee JW, Carson IW (October 1973). "Proceedings: A new steroid anaesthetic-althesin". Proceedings of the Royal Society of Medicine. 66 (10): 1027–30. doi:10.1177/003591577306601023. PMC 1645602. PMID 4148526.
  4. ^ MacPherson RD (October 2001). "Pharmaceutics for the anaesthetist". Anaesthesia. 56 (10): 965–79. doi:10.1111/j.1365-2044.2001.02216.x. PMID 11576099. S2CID 10768907.
  5. ^ Dyson DH, Allen DG, Ingwersen W, Pascoe PJ, O'Grady M (April 1987). "Effects of saffan on cardiopulmonary function in healthy cats". Canadian Journal of Veterinary Research. 51 (2): 236–9. PMC 1255310. PMID 3111675.
  6. ^ Nadeson R, Goodchild CS (May 2001). "Antinociceptive properties of neurosteroids III: experiments with alphadolone given intravenously, intraperitoneally, and intragastrically". British Journal of Anaesthesia. 86 (5): 704–8. doi:10.1093/bja/86.5.704. PMID 11575348.
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