Local anaesthetic agents

Abstract 

Local anaesthetics are weak bases and consist of a lipophilic aromatic ring, a link and a hydrophilic amine. The chemistry of the link classifies them as amides or esters. They act by blocking the sodium ionophore, especially in the activated state of the channel, and frequency dependence can be shown. The speed of onset is related to dose and proportion of drug in the unionized lipid-soluble form, which in turn is determined by the pK_a and the ambient pH. Local anaesthetic agents, being weak bases, are bound in the plasma to α₁-acid glycoproteins, influencing duration of action. Esters undergo hydrolysis by esterases in the plasma. Amides are subject to phase I and II hepatic cytochrome P450 metabolism. The development of the S-enantiomers, levobupivacaine and ropivacaine, has not been without some controversy with regards to therapeutic benefits when assessed by clinical potency models such as the minimum local analgesic concentration (MLAC). Drugs derived from biological toxins that target and bind to the sodium ionophore are gaining acceptance for use as analgesics in chronic pain.

Keywords: Articaine, bupivacaine, chloroprocaine, levobupivacaine, lidocaine, local anaesthetics, pharmacology, ropivacaine, saxitoxin, tetrodotoxin