Antiarrhythmics administration routes

Local anesthetic action, also known as "membrane-stabilizing" action, is a prominent effect of several 3 blockers (Table 10-2). This action is the result of typical local anesthetic blockade of sodium channels (see Chapter 26) and can be demonstrated experimentally in isolated neurons, heart muscle, and skeletal muscle membrane. However, it is unlikely that this effect is important after systemic administration of these drugs, since the concentration in plasma usually achieved by these routes is too low for the anesthetic effects to be evident. These membrane-stabilizing 3 blockers are not used topically on the eye, where local anesthesia of the cornea would be highly undesirable. Sotalol is a nonselective 3-receptor antagonist that lacks local anesthetic action but has marked class III antiarrhythmic effects, reflecting potassium channel blockade (see Chapter 14). 

Lidocaine, similar to procaine, is an effective, clinically used local anesthetic (Fig. 26.11) (see Chapter 16). Its cardiac effects, however, are distinctly different from those of procainamide or quinidine. Lidocaine normally is reserved for the treatment of ventricular arrhythmias and, in fact, usually is the drug of choice for emergency treatment of ventricular arrhythmias. Its utility in these situations results from the rapid onset of antiarrhythmic effects on intravenous infusion. In addition, these effects cease soon after the infusion is terminated. Thus, lidocaine therapy may be rapidly modified in response to changes in the patient s status. Lidocaine is effective as an antiarrhythmic only when given parenterally, and the intravenous route is the most common. Antiarrhythmic activity is not observed after oral administration because of the rapid and efficient first-pass metabolism by the liver. Parenterally administered lidocaine is approximately 60 to 70% plasma protein bound. Flepatic metabolism is rapid (plasma half-life, -15-30 minutes) and primarily involves N-deethylation to yield monoethylglycinexylide, followed by amidase-catalyzed hydrolysis into N-ethylglycine and 2,6-dimethylaniline (2,6-xylidine) (Fig. 26.12). 

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