8.1:
Local Anesthetics: Chemistry and Structure-Activity Relationship
Local anesthetics, or LAs, are drugs that induce a temporary loss of sensation in a limited body area, preventing pain during a medical procedure.
Injectable LAs are administered subcutaneously or into the subarachnoid spaces. Surface anesthetics are applied superficially on scraped skin or mucous membranes on different sites like the nose and mouth.
Chemically, LAs are amphiphilic molecules, consisting of a hydrophilic amine and a lipophilic aromatic ring joined by ester or amide linkage.
Ester-linked-LAs, like procaine, are readily hydrolyzed by plasma esterases. So, their numbing effect is short and less intense.
In contrast, amide-linked LAs like lidocaine are more stable and have a prolonged anesthetic effect.
LAs work by reversibly blocking sodium ion channels in nerves, transiently inhibiting the transmission of sensory and motor impulses.
As weak bases, they are mostly unionized at the physiological pH and can cross the lipid bilayer.
Once inside the axon, they ionize and block the receptors of the sodium ion channels to stop impulse transmission.
The hydrophobic binding sites shield the LAs from metabolism while enhancing their potency and anesthesia duration.
8.1:
Local Anesthetics: Chemistry and Structure-Activity Relationship
Local anesthetics (LAs) are drugs that induce a temporary loss of sensation in a limited body area, preventing pain. Cocaine was the first local anesthetic discovered in the late 19th century. Cocaine is a benzoic acid ester obtained from the leaves of coca shrubs and was often used for its psychotropic effects. Cocaine was first isolated in 1860 by Albert Niemann. Sigmund Freud studied the physiological actions of cocaine. Carl Koller later introduced it into clinical practice in 1884 as a topical anesthetic for ophthalmological surgery. Soon after, infiltration and conduction block anesthesia in dentistry and general surgery extensively used cocaine. However, cocaine severely affects the central nervous system and causes cardiotoxicity, which led to the search for an alternative. Later in 1905, procaine, a synthetic substitute for cocaine, was discovered. Lidocaine, benzocaine, and tetracaine are other LAs used in clinical practice.
Usually, LAs act on peripheral nerves blocking sensory and motor impulses in a restricted area. In contrast, general anesthetics act on the central nervous system and affect the whole body. As a result, patients administered local anesthetics do not lose consciousness. This makes local anesthetics safer than general anesthetics for patients with poor health undergoing minor surgeries.