History - Whenever possible, determine the time of ingestion as well as the type, amount, and preparation (immediate or sustained release) of drug ingested. In overdose, this property makes absorption unpredictable and prolongs the duration of toxicity. Extended-release preparations slowly release the drug from a matrix to facilitate once-daily dosing. As the dose is increased, the rate of CCB clearance decreases, prolonging the half-life. PHARMACOKINETICS - Most calcium channel blockers (CCBs) are highly protein bound, have a large volume of distribution, and are metabolized in the liver. However, as the dose is increased, this selectivity can be lost, and dihydropyridine CCBs (including nifedipine and amlodipine) may affect the myocardium and conducting system, resulting in decreased inotropy and bradycardia. ĭihydropyridine intoxication generally results in arterial vasodilation and reflex tachycardia, whereas diltiazem and verapamil toxicity cause peripheral vasodilation, decreased cardiac inotropy, and bradycardia. In contrast, verapamil and diltiazem are relatively weak vasodilators but have a depressive effect on cardiac conduction and contractility. Dihydropyridines (including nifedipine, amlodipine, felodipine, nicardipine, nisoldipine, isradipine, and lacidipine) are potent vasodilators that have little negative effect upon cardiac contractility or conduction at standard doses. L-type calcium channels are responsible for myocardial contractility and vascular smooth muscle contractility they also affect conducting and pacemaker cells.
PATHOPHYSIOLOGY - Calcium channel blockers (CCBs) can be divided into two major categories based upon their predominant physiologic effects: dihydropyridines, which preferentially block the L-type calcium channels in the vasculature and non-dihydropyridines, such as verapamil and diltiazem, which selectively block L-type calcium channels in the myocardium.
(See "Major side effects and safety of calcium channel blockers".) An overview of the major side effects of CCBs is presented separately. A summary table to facilitate emergency management is provided ( table 1).
The management of CCB intoxication will be reviewed here.
Although only 16 percent of all cardiovascular drug exposures were due to CCBs, this class accounted for 38 percent of deaths. As an example, over 9500 cases of CCB intoxication, caused by intentional or unintentional overdose, were reported to poison centers in the United States during 2002. The potential toxicity of these agents is substantial and is often underappreciated by the public. These medications are available in both immediate-release and extended-release preparations the latter are in wide clinical use ( figure 1). INTRODUCTION - Calcium channel blockers (CCBs) are used in the treatment of hypertension, angina pectoris, cardiac arrhythmias, and other disorders.
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