腎機能障害患者における抗不整脈薬の使い方

Abstract

Antiarrhythmic drugs have a strong pharmacological effect as well as a significant toxicity. However, the therapeutic window of antiarrhythmic drugs is narrow. The pharmacokinetic and pharmacodynamic profiles of antiarrhythmic drugs show marked interpatient variations which are influenced by age and several diseases. Because removal of antiarrhythmic drugs from the systemic circulation depends on either renal elimination, hepatic metabolism, or both, especially patients with preexisting renal disease or impaired renal function may be at increased risk of treatment-related drug toxicity, including proarrhythmia. Having a much longer half-life than usual, the time to reach steady state is much longer in patients with impaired renal dysfunction than in those with normal renal function. To avoid excessive exposure, dosage must be reduced in patients with impaired renal function. The drug should be used with caution in elderly patients because both glomerular function and tubular function are reduced with aging. Moreover, nonrenal clearance usually varies widely within the population, making prediction of the optimal dosage difficult for an individual with impaired renal function. Knowledge of clinical pharmacology is helpful in both respects in order to obtain antiarrhythmic activity with minimal side-effects.