Allergic reactions to local anesthetics

The majority of adverse reactions to local anesthetics are due to high plasma levels from excessive quantities of a drug. These are often blamed on idiosyncrasy, sensitivity, or allergy. The incidence of reactions due to allergy to local anesthetics is low compared to that with other drugs. Allergic reactions may be systemic or local. More than 80% of reactions are cell mediated, resulting in contact dermatitis. The remainder are caused by circulating antibodies that give rise to systemic anaphylaxis. Acute anaphylactic reactions are rare but invariably fatal unless promptly treated. Localized systemic anaphylactic reactions manifested by urticaria, laryngeal edema, and extrinsic asthma are less serious and amenable to treatment. There is no foolproof test for screening of susceptible persons. The intradermal test is of no value for detecting possible systemic sensitivity. The patch test is useful for detecting contact allergy. Systemic reactions are treated with epinephrine, antihistamines, and steroids. Contact dermatitis responds to topical steroids.     

Stereoselective activity of local anesthetics

Most local anesthetic molecules contain an asymmetric carbon atom in their structure.Therefore, they provide excellent examples of chiral drugs that exist as two enantiomers, where each form may exhibit striking differences in its pharmacologic profile. Bupivacaine is currently marketed as a racemic mixture of both its S-(-)- and R-(+)-enantiomers. Fuelled by concerns about the cardiovascular toxicity of this preparation, research has focused on the pharmacology of the single enantiomers.The R-(+)-enantiomer has a higher potency as a sodium channel blocker than its “chiral twin” but correspondingly, also causes higher cardiovascular and central nervous system toxicity at lower doses.This work on bupivacaine has in turn driven the development and release of ropivacaine, an optically pure S-(-)-propyl homologue of bupivacaine.When compared with racemic bupivacaine, it demonstrates a significantly improved toxicity profile.This paper reviews some of the more recent literature on this subject in order to provide an account of current thinking on this important group of drugs.     

Systemic local anesthetics in pain control

Analgesia has been reported as a potential effect of systemically administered local anesthetics for over four decades. Interest in the use of these drugs as analgesics has been stimulated by the advent of oral formulations and the findings of several controlled studies that suggest efficacy of these preparations in neuropathic pain syndromes. We review the pharmacology of local anesthetics and critically evaluate the medical literature describing the analgesic consequences of systemic administration. The data extant support their analgesic effect in selected pain syndromes.     

Tricyclic antidepressants as long-acting local anesthetics

Amitriptyline, nortriptyline, imipramine, doxepin, desipramine, protriptyline, trimipramine, and maprotiline are tricyclic antidepressants (TCAs) used orally in treating major depressive disorders. Recent studies showed that amitriptyline is more potent in blocking the sciatic nerve functions in vivo by local injection than bupivacaine, a long-acting local anesthetic. We therefore tested whether various TCAs could likewise act as local anesthetics in vivo after single injection via the rat sciatic notch. The duration of complete sciatic nerve blockade by TCAs and the time to reach full recovery were measured with neurobehavioral assays and compared with results from bupivacaine. Amitriptyline, doxepin, and imipramine at 5mM elicited a longer complete sciatic nerve blockade than did bupivacaine at 15.4mM (0.5%), whereas trimipramine and desipramine at 5mM produced a shorter blockade. In contrast, nortriptyline, protriptyline, and maprotiline failed to elicit complete sciatic nerve blockade. Thus, TCAs have very different efficacy as local anesthetics in vivo. The duration of rat sciatic nerve blockade in vivo by TCAs is not well correlated with the 50% inhibitory concentration (IC(50)) of TCAs in blocking human cardiac Nav1.5 Na(+) channels expressed in human embryonic kidney cells. With this in vitro expression system, TCAs appear more potent than bupivacaine as Na(+) channel blockers in Nav1.5 Na(+) channels. We suggest that the ability of TCAs to pass through various membrane barriers within peripheral nerve trunks is crucial to their local anesthetic efficacy in vivo. TCAs with a tertiary amine appear more effective in penetrating these membrane barriers than TCAs with a secondary amine.     

Synthesis and biological activities of local anesthetics

Local anesthetics are mainly used in stomatology, ophthalmology, gynecology and surgery to temporarily relieve pain. Local anesthetics act on nerve endings or around nerve trunks, and are combined with specific sodium ion (Na⁺) channel sites on the nerve membrane. They can affect the membrane potential by reducing Na⁺ passage through sodium ion channels, thus blocking the generation and conduction of nerve impulses, reversibly blocking the generation and conduction of sensory nerve impulses. Local anesthetics are used for convenience in local surgical operations and treatments. Herein, we mainly review the research progress on local anesthetics and discuss the important aspects of design, synthesis and biological activity of various new compounds.

Local anesthetics are mainly used in stomatology, ophthalmology, gynecology and surgery to temporarily relieve pain.     

手术室局麻药中毒的风险管理及护理

目的 分析手术室局麻药中毒的风险管理及护理.方法 选取2010年6月至2012年6月收治的行局麻手术治疗的患者46例.根据其使用的管理模式及护理方式不同,分为对照组及观察组各23例,比较两组患者的局麻药物中毒率、麻醉医师及患者对护理人员的综合护理质量评分.结果 观察组局麻药物中毒率明显低于对照组(P＜0.01),观察组患者对护理人员综合护理质量评分明显高于对照组(P＜0.01).结论 针对性的局麻药物中毒风险管理及护理干预可以有效降低中毒事件的发生率,提高护理质量.