These drugs are applied locally and block nerve conduction. Nerve fibers are not affected equally. Loss of sympathetic function occurs first, followed by loss of pinprick sensation and temperature, and finally, motor function. The effect of local anesthetics is reversible: their use is followed by complete recovery of nerve function with no evidence of structural damage.
All the local anesthetics consist of a hydrophilic amino group linked through a connecting group of variable length to a lipophilic aromatic portion (benzene ring, Figure 26–1). In the intermediate chain, there is either an ester linkage or an amide linkage.
Main structures of the ester and amide local anesthetics.
The commonly used local anesthetics can be classified as esters or amides based on the linkage in this intermediate chain. It is not as important to know which drugs are esters and which are amides, as it is to know that there is a difference. The amide local anesthetics are chemically stable in vivo, whereas the esters are rapidly hydrolyzed by plasma cholinesterase. One interesting, but trivial, fact is that metabolism of the ester local anesthetics leads to formation of para-aminobenzoic acid (PABA), which is thought to be allergenic.
|ESTERS ||AMIDES |
The “-caine” ending on each of these drug names tells you that they are local anesthetics.
Adverse effects of the local anesthetics result from systemic absorption of toxic amounts of the drugs.
Death can occur from respiratory failure secondary to medullary depression or from hypotension and cardiovascular collapse.
Local anesthetics block the sodium channel in the nerve membrane.
Application of a local anesthetic inhibits the inward movement of Na+ ions. This results in elevation of the threshold for electrical excitation, reduction in the rate of rise of the action potential and slowing of the propagation of the impulse. At high enough concentrations, the local anesthetics completely block conduction of impulses down the nerve.
For those of you interested in this area, there is a fascinating story relating pH to ionization of the local anesthetics to drug action. For details, see your textbook.
Some local anesthetics have a vasodilator effect resulting in termination of their action. For these anesthetics, a small amount of a vasoconstrictor can be added to the injection. This leads to increased duration of action, reduction in risk of systemic toxicity, and lessens bleeding locally. Epinephrine is the most common vasoconstrictor. Epinephrine-containing solutions are not injected into tissues supplied by end arteries, such as the fingers, toes, ears, nose, or penis.