Vanlersberghe C, Camu F
Department of Anesthesiology, V.U.B. Medical Center, University of Brussels, Laarbeeklaan 101, B-1090, Brussels, Belgium.
Handb Exp Pharmacol. 2008(182):227-52. doi: 10.1007/978-3-540-74806-9_11.
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.
催眠药丙泊酚具有药代动力学特性，可使药物作用迅速起效和消退，并能快速从体内清除。老年患者对丙泊酚的催眠作用更为敏感。该药物在肝脏中通过细胞色素P450系统和葡萄糖醛酸化作用进行广泛代谢，存在药物相互作用的可能性。在临床相关浓度下，丙泊酚不会引起明显的心肌收缩力抑制。但在体外，丙泊酚会损害心脏的等张舒张，并降低心肌细胞中游离胞质Ca(2+)浓度。在动物模型中，丙泊酚的心脏保护作用部分源于其抗氧化和自由基清除特性。丙泊酚剂量依赖性地降低脑血流量和脑代谢率。丙泊酚在动物模型中的神经保护作用归因于其抗氧化特性、增强γ-氨基丁酸A型（GABA(A)）介导的突触传递抑制作用以及抑制谷氨酸释放。亚催眠剂量的丙泊酚以剂量依赖性方式诱导镇静、遗忘和抗焦虑作用。丙泊酚会损害通气功能，对通气控制和中枢化学感受器敏感性有相当大的影响。即使在亚麻醉剂量下，丙泊酚也会降低对高碳酸血症的通气反应和对低氧的通气适应能力。该药物会增强低氧性肺血管收缩，这是由抑制K(+)（ATP）介导的肺血管舒张引起的。丙泊酚的大多数药理作用是通过与GABA(A)受体或钙通道相互作用产生的。丙泊酚可延长由GABA(A)受体介导的抑制性突触后电流，表明其作用与增强抑制性突触传递有关，但丙泊酚也会影响GABA能传递的突触前机制。丙泊酚可调节宿主炎症反应的各个方面。它可减少促炎细胞因子的分泌，改变一氧化氮的表达，损害单核细胞和中性粒细胞功能，并具有与内源性抗氧化剂维生素E相似的强大剂量依赖性自由基清除活性。
