You are on page 1of 1

General Anesthesia Mechanism of Action Numerous theories have been proposed to explain the action of general anesthetics.

Many of the recent investigations have involved inhalation anesthetics. (The terms volatile anesthetic, potent agent, and inhaled anesthetic are synonymous with inhalation anesthetic.) Most evidence indicates that the synaptic transmission of nerve impulses is reversibly inhibited in several areas of the central nervous system. The extent of inhibition and consequently the progressive depression of function are correlated with the partial pressure of the inhaled anesthetic at various sites. The inhibition is believed to occur at a lipophilic site on the biologic membrane of synapses and possibly on small, unmyelinated nerve fibers. Suppression of spinal reflex activity is thought to produce some relaxation of skeletal muscles. Although no single concept explains all the phenomena, a few theories explain many of the actions that have been observed. The following are some of the more widely accepted theories: 1. The protein receptor theory proposes that hydrophobic areas of specific proteins in the central nervous system act as receptor sites. The steep dose-response curve of inhaled anesthetics seems to support this theory by indicating that a critical number of receptor sites must be occupied before patient movement in response to noxious stimuli is obtunded. 2. The Meyer-Overton Theory is also called the critical volume hypothesis to explain the correlation between lipid solubility (oil/gas partition coefficient) and the anesthetic potency. This theory proposes that when enough anesthetic molecules dissolve (that is, a critical volume is reached) at a crucial hydrophobic site such as the lipid cellular membrane, anesthesia is achieved. As the cell membrane expands in response to the dissolved anesthetic molecules, changes in the ionic channels occur and alter the sodium flux involved in in cellular depolarization. Because some lipid-soluble compounds are not anesthetics, this theory does not give a complete explanation of anesthetic action. 3. Endogenous endorphins or opiate-like substances suppress various pain pathways. Several classes of endorphins is antagonized by naloxone (a specific narcotic antagonist), but the relative potency of inhaled anesthetics is not altered. Although some degree of analgesia may be explained by this mechanism, it does not correlate well with the level of anesthesia achieved by inhaled anesthetics. In summary, no single theory for the mechanism of action can explain all the effects observed with anesthetic agents. The spectrum of anesthetic activity varies with the different anesthetics; the effects on the central nervous system and skeletal muscles are similar but not identical; structural and spatial differences exist among agents; changes at both the membrane and cellular levels occur; and optical isomers produce different responses. Although similar in many respects and, anesthetic agents are individually unique and probably work through numerous mechanisms and at multiple sites to produce their effects. Meeker, M. H. & Rothrock, J.C. (1995). Alexaders Care of the Patient in Surgery. (10th ed.) Mosby. Inc. pg. 152