Local Anesthetics:
Spinal Afferents and Local Anesthetic Mechanisms
of Action
Local anesthetics cause temporary loss of pain sensation without loss of consciousness by blocking conduction along sensory nerve fibers. Some selectivity for pain afferents is achieved partly by using the agent close to target neurons. All currently used drugs block voltagedependent Na+ channels in excitable cells, which decreases the likelihood of an action potential. The target site of the drugs is on the cytoplasmic side of the neuron membrane, so drug molecules must pass through the membrane.
They are both lipophilic and hydrophilic and
are weak bases (amides or
esters) that exist in equilibrium between ionized (hydrophilic) and nonionized
(lipophilic) forms. The latter diffuse more readily through the membrane; the
former diffuse more readily through cytoplasm. Esters are metabolized by plasma
cholinesterases; amides are hydrolyzed in the liver. Because they act on all
excitable cells, local anesthetics can cause toxicity, including fatal cardiovascular effects or seizures.
