Steroid Anaesthetics

Less serious reactions to barbiturates, mainly affecting the skin, occur far more frequently than the previously mentioned acute reactions. 

A case of allergy to propanidid reported by Dundee et al. (1974) showed typical manifestations of contact dermatitis and a typical delayed hypersensitivity reaction to skin testing. Propanidid has not been much in use in the United Kingdom since 1973, when Althesin, the steroid i.v. anaesthetic, replaced it. 

The detailed account of acute reactions to steroid anaesthetics given here does not reflect their frequency. These reactions (anaphylactic or anaphylactic-like) are not 

What is special about these steroids (alphaxalone and alphadolone) is their novel effect as anaesthetics and their chemical similarity to progesterone (Fig. 2). It was Seyle (1941) who first noted the general anaesthetic effect of progesterone, when injected in large amounts intravenously in rats. The background for the introduction of steroid anaesthetics has been reviewed by Sutton (1972). The review by Phillips (1974) of the structure-activity relationships of steroidal anaesthetics is recommended for further reference. 

There have been many reports of reactions to Althesin, a mixture of two steroids, alphaxalone und alphadolone, dissolved in sodium chloride solution containing 20% polyoxyethylated castor oil (Cremophor EL). Apart from their anaesthetic effects, these steroids are weak oestrogen antagonists, but possess no other steroid properties. This preparation is a rapid and short-acting anaesthetic induction agent, it produces less cardiovascular and respiratory depression than barbiturates, and has no hang-over effect. 

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Intracellular steroid receptors, which alter gene expression, exist for corticosteroids, oestrogens and progesterone in the brain, as in the periphery but they cannot account for the relatively rapid depression of CNS function induced by some steroids. This was explained when Harrison and Simmonds (1984) discovered that alphaxalone (the steroid anaesthetic) potentiated the duration of GABA-induced currents at the GABAa receptor in slices of rat cuneate nucleus just like the barbiturates (Fig. 13.6). Of the... 

Harrison, NL and Simmonds, MA (1984) Modulation of the GABA receptor complex by a steroid anaesthetic. Brain Res. 323 287-292. 

It is a slower acting steroid anaesthetic which is a combination of two preganedione derivatives, alphaxolone and alphadolone acetate. It produces analgesia and sleep lasting 20-30 minutes. It is less irritant, blood pressure and respiration are not much affected. It has been used as an inducing agent in place of thiopentone but due to hypersensitivity reactions its use is very limited. 

Chen G, Ensor CR, Bohner B (1966) The neuropharmacology of 2-(o-chlorophenyl)-2-methylaminocyclohexanone hydrochloride. J Pharm Exp Ther 152 332-339 Child KJ, Currie JP, Davis B et al. (1971) The pharmacological properties in animals of CT1341 - a new steroid anaesthetic agent. Br J Anaesth 43 2-24 Christensen HD, Lee IS (1973) Anesthetic potency and acute toxicity of optically active di-substituted barbituric acids. Toxicol Appl Pharmacol 26 495-503 Domenjoz R (1959) Anaesthesist 8 16... 

Alfadolone-Alfaxalone Steroid anaesthetic (contraindicated in dogs) Anesthesia... 

Fig. 2. Chemical structure of progesterone and the two structurally related intravenous steroid anaesthetics, alphaxalone and alphadolone...

Fig. 3. Histamine release (means standard errors) from the leucocytes of a patient with allergy to Althesin, the steroid anaesthetic preparation, and its various components...

Peters RL, Edmondson HA, Reynolds TB, Meister JC, Curphey TJ (1969) Hepatic necrosis associated with halothane anesthesia. Am J Med 47 748-764 Phillips GH (1974) Structure-activity relationship in steroidal anaesthetics. In Halsy MJ, Millar RA, Sutton JA (eds) Molecular mechanisms in general anaesthesia. Churchill-Livingstone, Edinburgh London, pp 32-46... 

Assem ESK (1977) Examples of the correlation between the structure of certain groups of drugs and adverse effects mediated by immune and non-immune mechanisms (with particular reference to muscle relaxants and steroid anaesthetics). In Bundgaard H, Juul P, Kofod H (eds) Drug design and adverse reactions. Munksgaard, Copenhagen, pp 209-226... 

Steroidal Anaesthetics A Correlation with Anaesthetic Activity, J. Pharm, Pharmacol. 26, 120P (1974). 

Table 10.14 Skin and leukocyte tests with the various components of the intravenous steroid anaesthetic, Althesin, in a patient who developed an anaphylactic reaction to this preparation...

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