Cocaine appeared in the first published reports of an effective
local anesthetic agent in 1884 and 1885.1 Halstead’s
experiments with cocaine demonstrated its effectiveness in more
than 1000 minor surgical cases.1 Modern local anesthetic
agents have supplanted cocaine as the agent of choice as they are
more efficacious and safer to use.2 They are all synthetic
derivatives of cocaine. The Emergency Physician will routinely be
confronted with acute wounds, abscesses, and other injuries requiring
local anesthesia. An expert knowledge of local anesthesia is a required
piece of our armamentarium. One must know the agents available,
the techniques for optimum pain relief, and the methods to avoid
and treat adverse reactions.
The molecule that comprises the structure of any commercially
available local anesthetic agent has three major components. They
consist of a lipophilic aromatic chain joined by either an amide or
an ester linkage to a hydrophilic tertiary amide.3 Local
anesthetics are classified according to their intermediate chain
as either esters or amides. Procaine was the first available injectable
ester local anesthetic agent and was synthesized in 1905.4 Lidocaine
was the first amide anesthetic agent and was first produced in 1945.4 Researchers
have produced agents with varied anesthetic properties based upon
potency, onset, and duration of action by making substitutions at
different sites on the basic molecule.4 An appreciation
of these different properties permits the Emergency Physician to
make logical choices regarding the optimal use of these agents.
Neural depolarization results from a rapid influx of sodium ions
through special sodium channels within the nerve cell membrane.3,5,6 Local
anesthetic agents function by reversibly binding to specific protein
receptors within these sodium channels.3,5,6 The local
anesthetic agent impedes sodium influx and blocks depolarization.4,5,7,8 Local
anesthetic agents with longer protein binding to the sodium channel
results in a longer duration of blockade and anesthesia. Small diameter
nerve fibers responsible for pain and temperature sensation are
blocked preferentially before fibers that propagate touch, motor
function, and proprioception.3,6,9
Local anesthetic potency is determined by the lipid solubility
of the agent.8,10 Highly lipid-soluble agents more readily
traverse the lipoprotein nerve cell membrane and are more effective
at inducing blockade.
The primary determinant of a local anesthetic’s onset
of action is its pKa.11 The pKa is the pH at which a given
drug exists in equal proportions as ionized and unionized molecules.
The unionized molecules more readily cross the nerve cell membrane.
A portion of the molecule becomes charged once inside the neuron.
It is this ionized portion that binds most completely to receptor
proteins within the sodium channels.3,10 Commercially available
local anesthetic agents are weak bases with pKa’s of 7.6
to 8.9.3 Agents with a lower pKa at physiologic pH (7.4)