Changes

==Introduction==

==Introduction==

The only available steroid anaesthetic for use in veterinary patients is '''alfaxalone'''. It is a progesterone derived ''neurosteroid''.  

The only available steroid anaesthetic for use in veterinary patients is '''alfaxalone''' (3-α-hydroxy-5-α-pregnane-11,20-dione). It is a progesterone derived ''neurosteroid''.

==Mechanism of Action==

==Mechanism of Action==

==Pharmacological Considerations==

==Pharmacological Considerations==

Alfaxalone is available as either a single agent solution at 10mg/ml, or in combination with alfadolone with polyoxyethylated castor oil as a solvent. Alfaxalone can be administered intravenously and intramuscularly, though the efficacy of intramuscular injection is species dependant - '''do not''' rely on intramuscular injection of alfaxalone to sedate or induce anaesthesia in dogs. It has a rapid onset of action, inducing anaesthesia with 30-60 seconds when given intravenously. Its duration of action is dose dependent.  If given intramuscularly, onset of anaesthesia is within 7-10 minutes.  Recovery occurs due to a combination of metabolism via and redistribution.  

Alfaxalone is water-insoluble, and was first available in combination with the similar molecule alfadolone solubilised in polyoxyethylated castor oil (Cremophor EL) for use in humans, cats and dogs. A newer formulation of alfaxalone (without alfadolone) solubilised in cyclodextrin is available for dogs and cats.

 

Alfaxalone can be administered intravenously in cats and dogs and intramuscularly in cats, though the efficacy of intramuscular injection is species dependent - '''do not''' rely on intramuscular injection of alfaxalone to sedate or induce anaesthesia in dogs. It has a rapid onset of action, inducing anaesthesia with 30-60 seconds when given intravenously. Its duration of action is dose dependent.  If given intramuscularly, onset of anaesthesia is within 7-10 minutes.  Recovery occurs due to a combination of metabolism via and redistribution.  

The formulation of alfaxalone in cyclodextrin has a volume of distribution after a single injection of a clinical dose in dogs and cats of 2.4 L/kg and 1.8 L/kg, respectively. In cats, the mean terminal plasma elimination half-life (t1/2) for alfaxalone is approximately 45 minutes for a 5 mg/kg dose. Mean plasma clearance for a 5 mg/kg dose is 25.1 ± 7.6 mL/kg/min. In dogs, the mean terminal plasma elimination half-life (t1/2) for alfaxalone is approximately 25 minutes for a 2 mg/kg dose. Plasma clearance for a 2 mg/kg dose is 59.4 ± 12.9 mL/kg/min. (Product literature)

The formulation of alfaxalone in cyclodextrin has a volume of distribution after a single injection of a clinical dose in dogs and cats of 2.4 L/kg and 1.8 L/kg, respectively. In cats, the mean terminal plasma elimination half-life (t1/2) for alfaxalone is approximately 45 minutes for a 5 mg/kg dose. Mean plasma clearance for a 5 mg/kg dose is 25.1 ± 7.6 mL/kg/min. In dogs, the mean terminal plasma elimination half-life (t1/2) for alfaxalone is approximately 25 minutes for a 2 mg/kg dose. Plasma clearance for a 2 mg/kg dose is 59.4 ± 12.9 mL/kg/min. (Product literature)

===Drug Interactions===

===Drug Interactions===

Alfaxalone in cyclodextrin has been used safely after administration of an extremely wide range of premedication and peri-operative drugs.  Dose dependant CNS depression can be accentuated by administration of sedatives and analgesics.  Alfaxalone should not be administered concurrently with other intravenous anaesthetic induction drugs, but has been used safely as an induction agent prior to maintenance with halothane, isoflurane, sevoflurane and desflurane. It should not be mixed in the same syringe as other medications, as the cyclodextrin has a propensity to bind other chemicals.  If a need exists to dilute the alfaxalone in cyclodextrin solution, it has been shown to be stable in 0.9% Saline for up to 7 days.  Slight absorbtion to plastic of giving sets has been recognised, though this appears to be of no clinical significance.

Alfaxalone in cyclodextrin has been used safely after administration of an extremely wide range of premedication and peri-operative drugs.  Dose dependent CNS depression can be accentuated by administration of sedatives and analgesics.  Alfaxalone should not be administered concurrently with other intravenous anaesthetic induction drugs, but has been used safely as an induction agent prior to maintenance with halothane, isoflurane, sevoflurane and desflurane. It should not be mixed in the same syringe as other medications, as the cyclodextrin has a propensity to bind other molecules.  If a need exists to dilute the alfaxalone in cyclodextrin solution, it has been shown to be stable in 0.9% Saline for up to 7 days.  Slight adsorption to plastic of giving sets has been recognised, though this appears to be of no clinical significance.

==Contraindications and Side Effects==

==Contraindications and Side Effects==

===Cardiovascular Effects===

===Cardiovascular Effects===

*At clinical doses, and employing the concepts of balanced anaesthesia, alfaxalone in cyclodextrin causes little cardiovascular effect, however a dose dependent decrease in arterial blood pressure thought to be due to myocardial contractility and stroke volume can be recognised at supra-clinical doses.

*At clinical doses, and employing the concepts of balanced anaesthesia, alfaxalone in cyclodextrin causes little cardiovascular effect, however a dose dependent decrease in arterial blood pressure thought to be due to decreased myocardial contractility and stroke volume can be recognised at supra-clinical doses.

===Respiratory Effects===

===Respiratory Effects===