Propofol

Handb Exp Pharmacol. 2008:(182):227-52. doi: 10.1007/978-3-540-74806-9_11.

Abstract

The hypnotic agent propofol has pharmacokinetic characteristics that allow for rapid onset and offset of drug effect and fast elimination from the body. Elderly patients show a greater sensitivity to the hypnotic effect of propofol. The drug is extensively metabolized in the liver through the cytochrome P450 system and glucuronidation, with potential for drug interaction. Propofol does not cause significant inotropic depression at clinically relevant concentrations. But in vitro, propofol impairs isotonic relaxation of the heart and decreases free cytosolic Ca(2+) concentrations in myocardial cells. In animal models, the cardioprotective effects of propofol derive in part from its antioxidant and free radical scavenging properties. Propofol decreases cerebral blood flow and cerebral metabolic rate dose-dependently. The neuroprotective effect of propofol in animal models is attributed to its antioxidant property, the potentiation of gamma-aminobutyric acid type A (GABA(A))-mediated inhibition of synaptic transmission, and the inhibition of glutamate release. Subhypnotic doses of propofol induce sedative, amnestic, and anxiolytic effects in a dose-dependent fashion. Propofol impairs ventilation with a considerable effect on the control of ventilation and central chemoreceptor sensitivity. Propofol reduces the ventilatory response to hypercapnia and the ventilatory adaptation to hypoxia, even at subanesthetic doses. The drug potentiates hypoxic pulmonary vasoconstriction, an effect caused by inhibition of K(+) (ATP)-mediated pulmonary vasodilatation. Most of the pharmacological actions of propofol result from interaction with the GABA(A) receptor or with calcium channels. Propofol prolongs inhibitory postsynaptic currents mediated by GABA(A) receptors, indicating that its effects are associated with enhanced inhibitory synaptic transmission, but propofol also influences presynaptic mechanisms of GABAergic transmission. Propofol modulates various aspects of the host's inflammatory response. It decreases secretion of proinflammatory cytokines, alters the expression of nitric oxide, impairs monocyte and neutrophil functions, and has potent, dose-dependent radical scavenging activity similar to the endogenous antioxidant vitamin E.

Publication types

  • Review

MeSH terms

  • Anesthetics, Intravenous / pharmacokinetics
  • Anesthetics, Intravenous / pharmacology*
  • Anesthetics, Intravenous / therapeutic use
  • Animals
  • Anti-Inflammatory Agents / pharmacokinetics
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Central Nervous System / drug effects
  • Central Nervous System / metabolism
  • Central Nervous System Agents / pharmacokinetics
  • Central Nervous System Agents / pharmacology*
  • Central Nervous System Agents / therapeutic use
  • Humans
  • Inflammation / metabolism
  • Inflammation / prevention & control
  • Propofol / pharmacokinetics
  • Propofol / pharmacology*
  • Propofol / therapeutic use
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / metabolism

Substances

  • Anesthetics, Intravenous
  • Anti-Inflammatory Agents
  • Central Nervous System Agents
  • Receptors, GABA-A
  • Propofol