Alfaxolone/alfadolone

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. Anesthetic efficacy is achieved by allosteric potentiation of the GABAA chloride channel to produce 'fast' synaptic inhibition.

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.

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

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. Alfaxolone/alfadolone has been re-branded as "Saffan" and is available for use in veterinary anaesthesia.

References

References

1. (March 1976). "Alphathesin, a new steroid anaesthetic agent". Canadian Anaesthetists' Society Journal.
2. (July 2005). "Neurosteroids: endogenous regulators of the GABA(A) receptor". Nature Reviews. Neuroscience.
3. (October 1973). "Proceedings: A new steroid anaesthetic-althesin". Proceedings of the Royal Society of Medicine.
4. (October 2001). "Pharmaceutics for the anaesthetist". Anaesthesia.
5. (April 1987). "Effects of saffan on cardiopulmonary function in healthy cats". Canadian Journal of Veterinary Research.
6. (May 2001). "Antinociceptive properties of neurosteroids III: experiments with alphadolone given intravenously, intraperitoneally, and intragastrically". British Journal of Anaesthesia.