Local Anesthetics
A review of the Mechanism of Action, Properties, Additives, and Toxicity.
The use of local anesthetics (LA) dates back to the time of Incas who would use the pulp of chewed coca leaves to aid with injuries and pain. In the 1860, Albert Niemann of Vienna isolated pure cocaine hydrochloride, which was then distributed to physicians for investigational purposes. It was initially used as a topical anesthetic on the conjunctiva of eyes. Overtime, physicians discovered its pain blocking effect when injected directly into surgically exposed nerves. The first epidural was performed on a dog in 1885. In 1898, the first spinal with cocaine was used to treat cancer pain. In 1911, the first percutaneous brachial plexus blocks were reported. Cocaine was regularly added to other products, such as wine tonics and Coca-Cola, to alleviate pain. The FDA ended this in the early 1900s.
Cocaine is the only naturally producke LA. LAs can be categorized base on their chemical side chain: Ester vs. Amide. Esters contain 1 “i” (ie. Procaine, benzocaine, etc.). Amides contain 2 “i’s” (ie. Lidocaine, Bupivacaine, etc.).
The mechanism of action of LAs is to block voltage-gated Na channels on nerve fibers. Na channels are involved in initiating and propagating action potentials in axons, dendrites, and muscle tissue. By blocking the influx of Na into the cell, you restrict the cell’s ability to depolarize, ultimately disrupting transmission of the nerve’s signal. The non-ionized form of the LA travels through the cellular membrane to bind the alpha-subunit of the Na channel intracellularly.
LAs are usually described by their speed of onset, duration of action, and potency.
Speed of onset is related to increases in lipid solubility and decreasing pKA. As pKA decreases and gets closer to physiologic pH (7.40), there are more non-ionized LA molecules that cross into the intracellular space. Increased lipid solubility increases duration of action as it is less likely to be taken up by blood. Potency of LAs increase with increasing molecular weight and lipid solubility - penetrates nerve fibers easier, binds Na channels with greater affinity.
Some providers will use additives to their LA solution to increase the onset of action (Bicarb), increase duration of block (epinephrine, clonidine/dexmedetomidine, dexamethasone), and increase the density of the block (opiates).
Toxicity of LAs are related to its serum concentration (affected by dose and site of injection) and by specific medication used (ie. Bupivicaine is most cardiotoxic of all LAs). The sites of injections most commonly leading to high serum levels are intercostal blocks, casuals, epidurals, and brachial plexus blocks. These are areas of high vascularity. The progression of signs and symptoms during toxic serum levels is vertigo > tinnitus > perioral numbness > tremors > myoclonic jerks > convulsions > coma > cardiac arrest.
