Pharmacology of Local Anaesthetic Agents

Abstract

The most important clinical properties of local anaesthetic agents are potency, onset, duration of action and relative blockade of sensory and motor fibres. These qualities are related primarily to the physicochemical properties of the various compounds. In general, lipid solubility determines the relative intrinsic potency of the various agents, while protein binding influences the duration of anaesthesia and pKa is correlated with the onset of action. In general, the local anaesthetics for infiltration, peripheral nerve blockade, and extradural anaesthesia can be classified into three groups: agents of low potency and short duration, for example procaine and chloroprocaine; agents of moderate potency and duration, for example lignocaine, mepivacaine and prilocaine; and agents of high potency and long duration, for example amethocaine, bupivacaine and etidocaine. These local anaesthetics also vary in terms of onset: chloroprocaine, lignocaine, mepivacaine, prilocaine and etidocaine have a rapid onset, while procaine, amethocaine and bupivacaine are characterized by a longer latency period.

Evaluation of intrathecal neostigmine in different doses added to bupivacaine for postoperative analgesia

“…2,3 Bupivacaine was the first local anaesthetic that produced adequate pain relief, without a major effect on motor fibres. 4 Neostigmine has been shown to counteract haemodynamic effects of clonidine and bupivacaine. 5,6 Considering the above facts, we designed the present study to evaluate efficacy and safety of intrathecal bupivacaine alone and in combination with neostigmine for postoperative analgesia.…”

Encapsulation of mepivacaine prolongs the analgesia provided by sciatic nerve blockade in mice

“…1 BVC is the drug of choice in surgery due to its moderate onset and long duration of action, as well as its significant differentiation between motor and sensory blockade. Although chemically related to BVC, MVC has lower systemic and cardiotoxicity, induces rapid onset of anesthesia but has a restrained duration of action.…”

“…Despite being chemically related, they exhibit differences in physicochemical properties such as partition coefficients, 13 ionization and solubility, [4][5][6][7] features that are determinant in their anesthetic potency. 1 Sciatic nerve blockade was used as an experimental model, providing information about the intensity and duration of blockade induced by LA agents. 10 Many studies have utilized motor or sensory blockade to assess LA activity in rats [14][15][16][17] and mice.…”

Lack of effect of cimetidine on the pharmacokinetics of bupivacaine in healthy subjects.

“…When given in excessive doses or when injected inadvertently into a vein local anaesthetic agents produce central nervous system and cardiovascular toxicity in relation to their plasma concentrations (Covino, 1984). Because of this the pharmacokinetics of local anaesthetics have been studied extensively.…”

“…However, cimetidine has also been shown to inhibit the elimination of many other drugs (Somogyi & Muirhead, 1987), including lignocaine, which is structurally related to bupivacaine (Kim & Tasch, 1986;Feely et al, 1982;Knapp et al, 1983;Bauer et al, 1984). All of the amide local anaesthetic agents are metabolized primarily in the liver (Covino, 1984) and cimetidine is capable of impairing drug oxidation at this site.…”