Local Anesthetics circulation would lead to unwanted systemic reactions such as: ¼ blockade of inhibitory CNS neurons, manifested by restlessness and seizures (countermeasure: injection of a benzodiazepine, p. 226); general paralysis with respiratory arrest after higher concentrations. ¼ blockade of cardiac impulse conduction, as evidenced by impaired AV conduction or cardiac arrest (countermeasure: injection of epinephrine). Depression of excitatory processes in the heart, while undesired during local anesthesia, can be put to therapeutic use in cardiac arrhythmias (p. 134). Forms of local anesthesia. . | 204 Local Anesthetics Local Anesthetics Local anesthetics reversibly inhibit impulse generation and propagation in nerves. In sensory nerves such an effect is desired when painful procedures must be performed . surgical or dental operations. Mechanism of action. Nerve impulse conduction occurs in the form of an action potential a sudden reversal in resting transmembrane potential lasting less than 1 ms. The change in potential is triggered by an appropriate stimulus and involves a rapid influx of Na into the interior of the nerve axon A . This inward flow proceeds through a channel a membrane pore protein that upon being opened activated permits rapid movement of Na down a chemical gradient Na ext 150 mM Na int 7 mM . Local anesthetics are capable of inhibiting this rapid inward flux of Na initiation and propagation of excitation are therefore blocked A . Most local anesthetics exist in part in the cationic amphiphilic form cf. p. 208 . This physicochemical property favors incorporation into membrane interphases boundary regions between polar and apolar domains. These are found in phospholipid membranes and also in ion-channel proteins. Some evidence suggests that Na -channel blockade results from binding of local anesthetics to the channel protein. It appears certain that the site of action is reached from the cytosol implying that the drug must first penetrate the cell membrane p. 206 . Local anesthetic activity is also shown by uncharged substances suggesting a binding site in apolar regions of the channel protein or the surrounding lipid membrane. Mechanism-specific adverse effects. Since local anesthetics block Na influx not only in sensory nerves but also in other excitable tissues they are applied locally and measures are taken p. 206 to impede their distribution into the body. Too rapid entry into the circulation would lead to unwanted systemic reactions such as blockade of inhibitory CNS neurons manifested by restlessness and seizures countermeasure .
