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Emergency physicians are familiar with the use of calcium channel blockers for
the treatment of hypertension and angina pectoris, and for control
of ventricular rate in supraventricular dysrhythmias. Less common
uses include prophylactic treatment of migraine headaches and treatment
of arterial vasospasm due to Raynaud disease, esophageal spasm,
and pulmonary hypertension.1 For the last 50 years,
calcium channel blockers have accounted for more poisoning deaths
than any other cardiovascular drug and are the second most common
cause of prescription drug poisoning death. In 2008, the American
Association of Poison Control Centers received reports of 10,398
toxic exposures to calcium channel blockers with 12 fatalities.2
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Intracellular calcium is the primary stimulus for smooth and
cardiac muscle contraction and for impulse formation in sinoatrial
pacemaker cells. At therapeutic concentrations, calcium channel
blockers bind to the subunit of the L-type calcium channel, causing
the channel to favor the closed state and thereby decreasing calcium
entry during the plateau phase (phase 2) of the transmembrane action
potential. At very high concentrations, some calcium channel blockers
(notably verapamil) may occupy the channel canal and completely
block calcium entry. The result is profound smooth muscle relaxation,
weakened cardiac contraction, blunted cardiac automaticity, and
intracardiac conduction delay.1 Clinically, these
effects produce hypotension and bradycardia. Animal data suggest
that verapamil overdose also impairs myocardial carbohydrate intake,
which contributes to the negative cardiac inotropy.3
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The three main pharmacologic classes of calcium channel blockers
are phenylalkylamines (verapamil and gallopamil), benzothiazepines (diltiazem),
and dihydropyridines (nifedipine and most newer agents—amlodipine, aranidipine, azelnidipine, barnidipine, benidipine, cilnidipine, clevidipine, efonidipine, felodipine, lacidipine, lercanidipine, manidipine, nicardipine, nilvadipine, nimodipine, nisoldipine, nitrendipine,
and pranidipine).
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All of these drugs relax vascular smooth muscle, reduce pacemaker
activity, and decrease cardiac contractility; however, these effects
occur at different dose ranges for each drug. In addition, all three
classes increase coronary blood flow in a dose-dependent fashion.4 Each
group binds a different region of the calcium channel and has different
affinities for calcium channels in various tissues. Verapamil is
the most potent negative inotrope of all calcium channel blockers,
causing at least equal depression of heart contraction and vascular
smooth muscle dilatation at any concentration.5 This
cardiotoxic effect may be one reason that verapamil overdose causes
more deaths than all other calcium channel blockers combined.
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Dihydropyridines bind more selectively to vascular smooth muscle
calcium channels than to cardiac calcium channels and therefore
relax smooth muscle at concentrations that produce almost no negative
inotropy. The differences in the effects of these agents warrants
preferential use of specific agents in particular clinical situations.6 For
example, verapamil and diltiazem are used to manage hypertension,
to achieve rate control in atrial flutter and atrial fibrillation,
and to abolish supraventricular reentrant tachycardias. Dihydropyridines
are typically used to treat diseases with increased peripheral vascular
tone such as hypertension, Prinzmetal angina, and vasospasm after
subarachnoid hemorrhage.1
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