Pharmacology: Pharmacodynamics: Propofol (2,6-Diisopropyl phenol) is a short acting general anaesthetic agent with a rapid onset of action of approximately 30 to 40 seconds. Recovery from anaesthesia is usually rapid. The mechanism of action, like all general anaesthetics, is poorly understood.
In general, fall in blood pressure and slight changes in the heart rate are observed when propofol is administered for induction and maintenance of anaesthesia. However, the hemodynamic parameters normally remain relatively stable during maintenance and the incidence of untoward hemodynamic changes is low.
Although ventilatory depression can occur following administration of propofol, any effects are qualitatively similar to those of other intravenous agents and are readily manageable in clinical practice.
Propofol reduces cerebral blood flow, intracranial pressure and cerebral metabolic requirement of oxygen. The reduction in the 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 (PONV).
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. The first phase is characterised by a very rapid distribution (half life 2-4 minutes) followed by rapid elimination (half life 30-60 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 propofol is used to maintain anaesthesia, the blood concentrations asymptotically approach the steady state value for the given administration rate. The pharmacokinetics are linear over the recommended range of infusion rates of propofol.