Alfaxolone/alfadolone

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Alfaxolone/alfadolone
Combination of
Alfaxalone general anaesthetic
Alfadolone hypnotic
Clinical data
Trade names Saffan
Legal status
?
Routes Intravenous
Identifiers
CAS number 8067-82-1 N
ATC code ?
PubChem CID 24732
 N (what is this?)  (verify)

Alfaxolone/alfadolone (Althesin) is a short acting intravenous anaesthetic 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 It was withdrawn from the market due to severe drug reactions.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[edit]

Alfaxolone/alfadolone is short-duration, intravenous anaesthetic made from a combination of two steroidial compounds, alfaxalone and alfadolone of which the former is the primary anasethetic agent. Alfadolone acts to increase the solubility of the mixture in which it is dissolved, a polyethylated castor oil adjuvant.[1] Anaesthetic efficacy is achieved by allosteric potentiation of the GABAA chloride channel to produce 'fast' synaptic inhibition.[2]

Clinical use[edit]

Alfaxolone/alfadolone is short-acting, rapid onset anaesthetic which has been used for out-patient surgery. It does not have significant analgesic properties and anaesthesia has often been maintained with inhalational anaesthetics such as halothane. These have also been accompanied by neuromuscular blockers. Procedures carried out under this drug are greatly varied and have included orthopaedic, gynaecological, 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[edit]

  1. ^ a b Dechêne, JP (March 1976). "Alphathesin, a new steroid anaesthetic agent.". Canadian Anaesthetists' Society journal 23 (2): 163–9. 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. 
  3. ^ Clarke, R. S.; Dundee, J. W.; Carson, I. W. (1973). "A new steroid anaesthetic-Althesin". Proceedings of the Royal Society of Medicine 66 (10): 1027–1030. PMC 1645602. PMID 4148526.  edit
  4. ^ MacPherson, R. D. (2001). "Pharmaceutics for the anaesthetist". Anaesthesia 56 (10): 965–979. doi:10.1111/j.1365-2044.2001.02216.x. PMID 11576099.  edit
  5. ^ Dyson, D. H.; Allen, D. G.; Ingwersen, W.; Pascoe, P. J.; O'Grady, M. (1987). "Effects of Saffan on cardiopulmonary function in healthy cats". Canadian journal of veterinary research 51 (2): 236–239. PMC 1255310. PMID 3111675.  edit
  6. ^ Nadeson, R.; Goodchild, C. S. (2001). "Antinociceptive properties of neurosteroids III: Experiments with alphadolone given intravenously, intraperitoneally, and intragastrically". British journal of anaesthesia 86 (5): 704–708. doi:10.1093/bja/86.5.704. PMID 11575348.  edit