- Regional nerve block anesthesia—injection of a small amount of local anesthetic into
the tissue immediately surrounding a nerve supplying the region to be anesthetized - Intravenous regional anesthesia—injection of local anesthetic into a suitable vein
supplying the limb to be anesthetized; the blood flow from this limb is then restricted
by a tourniquet - Epidural anesthesia—injection of local anesthetic into the space external to the dural
sac that encloses the spinal cord, enabling nerves to the pelvis to be selectively anes-
thetized during obstetrical labor and delivery
This multitude of applications has enabled local anesthetics to be used with ever-
increasing effectiveness and at times to replace the considerably more dangerous use of
general anesthetics.
Local anesthetics are frequently coadministered with vasoconstrictor molecules such
as epinephrine. Normally, they are applied or injected locally and then taken up by local
blood vessels into the systemic circulation, ultimately leading to their metabolic break-
down. The co-administration of a vasoconstrictor decreases the systemic absorption of
the local anesthetic, thereby increasing its effective half-life in the area of administra-
tion and decreasing the probability of systemic toxicity (i.e., cardiac toxicity) secondary
to systemic distribution.
Certain local anesthetic molecules are “dirty” or “not clean in terms of receptor inter-
actions.” This means that their molecular geometry enables them to bind to a variety of
other receptors, and not just specifically to the voltage-gated sodium channel. In this
regard, cocaine is a prototypic molecule. It is a local anesthetic molecule which, how-
ever, also inhibits neurotransmitter reuptake at noradrenergic synapses, thereby impart-
ing sympathomimetic properties. Cocaine also readily enters the CNS, producing a
short, intense amphetamine-like effect. In the CNS, cocaine inhibits dopamine reuptake
in the “pleasure centres.” Since it combines local anesthetic and sympathomimetic
pharmacophores in the same molecule, cocaine was once widely used for “packing
noses” during epistaxis(nosebleeds); the sympathomimetic vasoconstrictor properties
helped to decrease blood loss during the packing process. This vasoconstrictor property
accounts for the necrosis of the nasal septum seen in people who “snort” cocaine.
7.4.3 Targeting the Sodium Channel Protein:
Antiarrhythmic DrugsHistorically and romantically, the heartbeat is recognized as the quintessential hallmark
of life. Normally, the heart beats at 60–100 beats per minute (bpm), with each beat
yielding a ventricular contraction that ejects blood out to the body. Each heartbeat is an
electrical event that originates from a collection of electrically excitable cells within the
heart called the sinoatrial node(SA), anatomically located at the upper pole of the
heart. The sinoatrial node is the primary pacemaker of the heart. The electrical impulse
generated in the sinoatrial node spreads rapidly downward from the atria chambers of
the heart and reaches the atrioventricular node(AV), a collection of electrically excitable
cells that constitutes the electrical interface between the atria and ventricles of the heart.
From the AV node, the impulse propagates throughout the ventricles via an electrical
conduction system referred to as the His–Purkinje system. The electrical transmission
ENDOGENOUS CELLULAR STRUCTURES 419