Diprivan Mechanism of Action

Pharmacotherapeutic group: Anaesthetics, general. ATC Code: N01A X10.
Pharmacology: Pharmacodynamics: Propofol (2,6-diisopropylphenol) is a short-acting general anaesthetic agent with a rapid onset of action of approximately 30 seconds.
Recovery from anaesthesia is usually rapid. The mechanism of action, like all general anaesthetics, is poorly understood. However, propofol is thought to produce its sedative/anaesthetic effects by the positive modulation of the inhibitory function of the neurotransmitter GABA through the ligand-gated GABA_A receptors.
In general, falls in mean arterial blood pressure and slight changes in heart rate are observed when DIPRIVAN is administered for induction and maintenance of anaesthesia. However, the haemodynamic parameters normally remain relatively stable during maintenance and the incidence of untoward haemodynamic changes is low.
Although ventilatory depression can occur following administration of DIPRIVAN, any effects are qualitatively similar to those of other intravenous anaesthetic agents and are readily manageable in clinical practice.
DIPRIVAN reduces cerebral blood flow, intracranial pressure and cerebral metabolism. The reduction in intracranial pressure is greater in patients with an elevated baseline intracranial pressure.
Recovery from anaesthesia is usually rapid and clear headed with a low incidence of headache and post-operative nausea and vomiting.
In general, there is less post-operative nausea and vomiting following anaesthesia with DIPRIVAN than following anaesthesia with inhalational agents. There is evidence that this may be related to a reduced emetic potential of propofol.
DIPRIVAN, at the concentrations likely to occur clinically, does not inhibit the synthesis of adrenocortical hormones.
Pharmacokinetics: The decline in propofol concentrations following a bolus dose or following the termination of an infusion can be described by a three compartment open model with very rapid distribution (half-life 2 to 4 minutes), rapid elimination (half-life 30 to 60 minutes), and a slower final phase, representative of redistribution of propofol from poorly perfused tissue.
Propofol is extensively distributed and rapidly cleared from the body (total body clearance 1.5-2 litres/minute). Clearance occurs by metabolic processes, mainly in the liver, to form inactive conjugates of propofol and its corresponding quinol, which are excreted in urine.
When DIPRIVAN is used to maintain anaesthesia, blood concentrations of propofol asymptotically approach the steady-state value for the given administration rate. The pharmacokinetics are linear over the recommended range of infusion rates of DIPRIVAN.
Toxicology: Pre-clinical Safety Data: Published studies in animals (including primates) at doses resulting in light to moderate anaesthesia demonstrate that the use of anaesthetic agents during the period of rapid brain growth or synaptogenesis results in cell loss in the developing brain that can be associated with prolonged cognitive deficiencies. The clinical significance of these non-clinical findings is not known.