Local Anesthetics

• benzene ring • quaternary amine • intermediate chain w ester or amide linkage

Ester - readily hydrolyzed Amide - not hydrolyzed LA with ester will be shorter acting

ionization is an equilibrium process that is reversible

The predominating form is dependent on the pKa of the amine and pH of the medium as described by the Henderson-Hasselbach equation:

• amide anesthetic. • Metabolized by cytochrome P450 enzymes. • The N- dealkylated metabolite retains activity. • antiarrhythmic agent. • pKa 7.6

Primary amines are difficult to ionize. The most difficult form of an amine to ionize is a tertiary amine.

• unique from other LA because it inhibits catacholamine uptake, particularly dopamine, at CNS synapses. • hydrolyzed at both esters • pKa 8.7

• chiral carbon (As a consequence of a chiral center, optical isomeric forms of this local anesthetic are possible.) • Marketed as a racemic mixture and as the levo isomer, levobupivacaine. • long-acting amide • pKa 8.1

Bupivacaine is racemic - 50% of one isomer, 50% of another. Levobupivacaine is an isomer

• an exception to the basic quarternary amine local anesthetic structure. • very short acting • topical preparation

Benzocaine

Bupivacaine

Cocaine

Lidocaine