Describe the chemistry of local anesthetics

Describe the chemistry of local anesthetics.

Local anesthetics are drugs that produce transient sensory, motor, and autonomic nervous system blockade following regional anesthesia. Local anesthetics are weak bases that consist of a lipophilic group (usually a benzene ring) and a hydrophilic group (usually a tertiary amine) separated by a connecting hydrocarbon chain. Most local anesthetics have an ester or an amide bond that links the hydrocarbon chain to the lipophilic group. The nature of this bond is the basis for classifying them as ester or amide local anesthetics. Examples of the ester group are cocaine, procaine (Novocain), chloroprocaine (Nesacaine), benzocaine (Americaine), and tetracaine (Pontocaine). Lidocaine (Xylocaine), mepiva-caine (Carbocaine), bupivacaine (Marcaine, Sensorcaine), etidocaine (Duranest), prilocaine (Citanest), and ropivacaine (Naropin) are examples of the amide local anesthetics. Mepivacaine, bupivacaine, and ropivacaine have an asymmet-ric carbon atom resulting in levoisomers and dextroisomers. Commercial preparations of mepivacaine and bupivacaine consist of racemic mixtures, whereas the recently developed ropivacaine and levo-bupivacaine consist of the pure levoisomers.

Local anesthetics in aqueous solution exist in dynamic equilibrium between the nonionized lipid-soluble form and the ionized water-soluble form. The pH at which there are equal amounts of nonionized and ionized molecules is known as the pKa of that drug. Local anesthetics have pKa values somewhat above physiologic pH and, as a result, less than 50% of the drug will exist in the lipid-soluble nonionized form.