indication

Used for induction and/or maintenance of anaesthesia and for management of refractory status epilepticus.

pharmacology

Propofol is a sedative-hypnotic agent for use in the induction and maintenance of anesthesia or sedation. Intravenous injection of a therapeutic dose of propofol produces hypnosis rapidly with minimal excitation, usually within 40 seconds from the start of an injection (the time for one arm-brain circulation).

mechanism of action

The action of propofol involves a positive modulation of the inhibitory function of the neurotransmitter gama-aminobutyric acid (GABA) through GABA-A receptors.

toxicity

Overdosage may increase pharmacologic and adverse effects or cause death.

IV LD₅₀=53 mg/kg (mice), 42 mg/kg (rats). Oral LD₅₀ (as a solution in soybean oil)=1230 mg/kg (mice), 600 mg/kg (rats)

biotransformation

Hepatically metabolized mainly by glucuronidation at the C1-hydroxyl. Hydroxylation of the benzene ring to 4-hydroxypropofol may also occur via CYP2B6 and 2C9 with subsequent conjugation to sulfuric and/or glucuronic acid. Hydroxypropofol has approximately 1/3 of hypnotic activity of propofol.

absorption

Rapid - time to onset of unconsciousness is 15-30 seconds, due to rapid distribution from plasma to the CNS. Distribution is so rapid that peak plasma concentrations cannot be readily measured. Duration of action is 5-10 minutes.

half life

Initial distribution phase t_1/2α=1.8-9.5 minutes. Second redistirubtion phase t_1/2β=21-70 minutes. Terminal elimination phase t_1/2γ=1.5-31 hours.

route of elimination

It is chiefly eliminated by hepatic conjugation to inactive metabolites which are excreted by the kidney.

drug interactions

Tacrine: The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by Propofol, a CYP1A2 inhibitors. Monitor the efficacy and toxicity of Tacrine if Propofol is initiated, discontinued or if the dose is changed.

Tizanidine: Propofol may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.