局麻药

局麻药 要点: 1.局麻药能通过作用于神经轴突内冲动的产生和传导,阻断电压-门控性钠通道,它们具有多种有益或有害的生物学效应. 2.目前常用的局麻药分两类:酯类和酰胺类. 3.局麻药的效能低,特异性差,部分与其结构限制有关.它们必须具有较高的溶解度,而且能够迅速在水性环境中及生物膜的脂质中弥散. 4.叔胺基团的可逆性质子化使局水星环境麻药在生理性PH值条件下携带电荷; 局麻药的碱性形式在脂质环境中更具可溶性,但其酸性形式更易在水性环境中溶解. 5.酯类局麻药主要经血浆假性胆碱酯酶代谢;酰胺类则主要在肝脏由于与细胞色素P450相连接的酶类进行代谢. 6.局麻药的主要全身性毒性可累及心脏和脑.缺氧和酸中毒可加重这些中毒反应.布比卡因过量后复苏十分困难.因此,防止误注入血管或过量应用十分重要.进行大神经阻滞时应逐渐增加药物剂量,并分次给药. 7.市售浓度的局麻药溶液对神经具有直接毒性.区域麻醉过程中, 局麻药的神经内浓度通常低于中毒浓度阈值,这是因为局麻药溶液需要经过组织进行扩散以及由注射部位弥散梯度才能达到神经.向组织间隙受限的部位注射可增加局部毒性反应的危险性. 8.区域麻醉中局麻药的适宜使用,需要了解病人的临床情况,区域麻醉的部位,强度和持续时间,以及镇痛需要.需要了解局麻药在神经附近沉积的解剖学影响因素,适当的药物选择和剂量,以及应用局麻药后临床效果的评估. 9.近来致力于面麻醉新配方的研发.开发单一立体异构体以减少全身性毒性反应,提高感觉选择性. 10.局麻药正逐渐运用于术后长期输注,局部和全身用药可用于慢性疼痛治疗.进一步研究和发展,将会促使更安全,选择性更高的药物问世,有助于在急性疼痛和慢性疼痛治疗中的长期应用. Local Anesthetics KEY POINT 1. Local anesthetics block voltage-gated sodium channels by interrupting the initiation and propagation of impulses in axons,but they have a wide variety of other biologic actions,both desirable and undesirable. 2 The currently available local anesthetics are of two chemical classes:aminoesters and aminoamides. 3 The low potency and lack of specificity of the available local anesthetics are due in part to the bility and diffuse rapidly in both aqueous environments and the lipid phases of biologic membranes. 4 Reversible protonation of the tertiary amine group makes local anesthetics uncharged at basic pH and charged at acid pH;the base forms are more soluble in lipid environments,whereas the acid forms are more soluble in aqueous environments 5 Aminoesters are primarily metabolized by plasma esterases;cytochrome P450-linked enzymes. 6 The principal systemic toxicities of local anesthetics involve the heart and the brain .Hypoxemia and acidosis exacerbate these toxicities.Resuscitation after bupivacaine overdose is particularly difficult.Therefore,prevention of intravascular injection or overdose is crucial,and major nerve blockade should involve incremental,fractionated dosing. 7 Local anesthetics are directly toxic to nerve at the concentrations supplied in commercial solutions.Intraneural concentrations during regional anesthesia are generally below the threshold for toxicity because of spread of solutions through tissues and diffusions gradients form injection sites into never.Injection into a constrained tissues space increase the risk of local toxicity. 8 Optimal use of local anesthetics in regional anesthesia requires an understanding of the individual patient’s of regional anesthesia and analgesia required;anatomic factors affecting the deposition of drug near nerves;proper drug selection and dosing;and ongoing assessment of clinical effects after administration of local anesthetics. 9 Recent efforts have led to the development of several new formulations for topical anesthesia.Single-stereoisomer formulations have been developed in an effort to reduce systemic toxicity and improve sensory selectivity. 10 Local anesthetics are increasingly being used for postoperative infusion and local and systemic administration in the management of chronic pain.Futher research and development may lead to safe,more selective agents that can facilitate more prolonged administration in the setting of acute of chronic pain.