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Local Anesthetic Overview
Class I A-C
Local anesthetics are medications used to reversibly block pain sensation in a specific part of the body in order to perform small surgical procedures.
The common suffix for local anesthetics is -caine, like procaine, tetracaine, lidocaine, Michael Caine - no wait, that’s the actor.
Anyway, so there are two classes of local anesthetics - called esters and amides.
Both classes inhibit conduction of action potentials across nerve fibers by blocking sodium (Na+) channels - and thus the perception of pain by the brain.
Pain is sensed by receptors called free nerve endings which are the 1st order neurons in the pain pathway. These neurons send their axons to synapse with 2nd order neurons in the spinal cord which carries the sensory information to the brain, and you feel pain.
Free nerve endings can be triggered in several ways; by mechanical stimulation, like getting punched; by thermal stimulation like heat and cold; or by chemical stimulation from molecules like bradykinin and histamine.
These noxious stimuli trigger the opening of cation channels on the membrane called transient receptor potential channels. This allows Na+ and other positive ions to flow into the cell. The extra positive charge that flows in makes the cell less negative, - which is called depolarization.
This depolarization causes nearby voltage-gated sodium channels to open up as well, setting off this chain reaction that continues down the entire length of the axon.
Now, voltage-gated Na+ channels are unique because they have inactivation gates on the intracellular side.
At resting membrane potential, the channel is closed. When the membrane depolarizes, the channel opens and sodium ions rush into the cell. A few milliseconds later, the inactivation gate closes and blocks Na+ from entering the cell even though the channel is still open. This ends the depolarization process.
Finally, when the cell repolarizes, the inactivation gate opens, the activation gate closes, and the channel enters the closed state again - ready to start another action potential.
Now, local anesthetics are used to inhibit the conduction of action potentials in free nerve endings. These medications are molecules that have an aromatic part, and an amine chain that are linked by either an ester or an amide bond.
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