Do calcium entry blockers act on circulating ionized calcium?

Abstract

Dear Sir,We should like to draw your attention to the previously unknown ability of calcium entry blockers to decrease the concentration of physiologically active ionized calcium (Ca 2÷) in serum.First we studied the action of a single administration of verapamil 5 mg intravenously and nifedipine 20 mg orally on the fractional composition of serum calcium. Both drugs produced qualitatively similar and quantitatively close shifts in this variable: 5-15 minutes after administration of verapamil and nifedipine the serum level of Ca 2+ determined by ion-selective electrodes was reduced. The maximal shift in this variable was usually found 30-45 minutes after the administration of verapamil and nifedipine [1,2]. Sixty minutes after verapamil infusion or nifedipine intake the serum level of Ca 2÷ tended to normalize, though it was still lower than the initial value (p < 0.05}. The mean maximal fall in the serum level of Ca 2÷ was 0.21 mM/1 (19.8% of the initial value) after the infusion of verapamil and 0.18 mM/ 1 (16.8% of the initial value) after intake of nifedipine. It should be emphasized that the reduced serum level of Ca 2+ was noted in every patient receiving calcium entry blockers during the acute drug test. The total level of the serum calcium assessed by atomic absorption spectrophotometry was not affected by calcium entry blockers. There were no changes in the plasma levels of sodium and potassium. A single oral dose of 60 mg diltiazem, 20 mg nicardipine, 10 mg nisoldipine, or 2.5 mg isradipine was accompanied by a decrease in the serum level of Ca 2÷ of 0.08-0.11 mM/l, 0.07-0.18 mM/1, 0.11-0.20 raM/l, and 0.06-0.17 mM/1, respectively (p < 0.05 in all groups) without any shifts in the serum level of total calcium. Hence, the ability to decrease the serum level of Ca 2÷ should be considered to be a feature common to all calcium entry blockers. Administration of calcium entry blockers diminished the so-called degree of ionization of serum calcium, i.e., the percentage ratio between Ca 2+ and the total calcium.These findings enabled us to call this previously unknown action of calcium entry blockers calcium binding. The influence of calcium entry blockers upon serum calcium is short term.Having studied the serum level of Ca 2÷ in 10 patients with angina pectoris receiving verapamil 240-320 mg daily, or nifedipine 80 mg daily for 8-12 months, we did not find any deviations in this variable. Such a transient effect of the calcium-binding action of calcium entry blockers seems to explain the failure of other authors [3] who studied the effect of calcium entry blockers only after the course of treatment, but not within the first hours, to find any shifts in the level of Ca 2÷.Our in vitro studies demonstrated that verapamil added to sera markedly and significantly increased the calcium-binding capacity of serum buffers, expressed as the negative decimal logarithm of the so-called threshold concentration. Moreover, a single oral dose of nifedipine and nisoldipine also enhanced the calcium-binding capacity of serum ...