DRUGS



“Therapeutic” serum concentrations of antiar­rhythmic drugs are those that usually exert ther­apeutic effects without adverse effects in most pa­tients. However, dosage and blood concentrations must be adjusted for any particular patient, and the measured serum concentration is of secondary importance if the response to the drug is appro­priate and side effects absent. The therapeutic-to-toxic ratio of most antiarrhythmic drugs is rela­tively narrow, and knowledge of drug pharma­cokinetics is important to avoid toxic peak and subtherapeutic trough concentrations. Most antiarrhythmic drugs can be administered at inter­vals equal to the elimination half-life of the drug after an initial loading dose. At a constant dosing interval without a loading dose, the time required to reach steady state is a function of the elimi­nation half-life of the drug. Ninety-four per cent of steadystate level is achieved after four half-lives and 99 per cent after seven half-lives. The same principle applies to the decrease in drug lev­els after discontinuation of the drug. Therefore, a drug with a longer half-life takes longer to reach steady state and longer to be eliminated than does one with a shorter half-life. Drugs with shorter half-lives are inconvenient to administer orally because of more frequent dosing requirements. Some medications with relatively short half-lives can be given in long-acting forms that release the drug gradually and result in adequate blood con­centrations for a longer period of time without a high peak level immediately upon administration of the drug. The pharmacokinetics of drug distri­bution and elimination are often important; for example, lidocaine blood concentrations may be high after an intravenous bolus but drop very quickly as the drug is redistributed throughout the body. Once this early redistribution phase occurs, blood concentrations fall much less precipitously during the elimination phase, at which time the lidocaine is metabolized by the liver. Therefore, to avoid very high serum concentrations within the first 10 minutes and a subtherapeutic nadir after redistribution has occurred, lidocaine ther­apy may be initiated in two or more boluses, 5 to 10 minutes apart instead of as one larger bolus.