Since calcium channel blockers (CCBs) were first introduced experimentally in the 1960s, their use has steadily risen to make them among the most frequently prescribed cardiovascular medications. Mirroring this widespread use, poisonings involving CCBs have also risen. The combination of sustained-release formulations to improve compliance and the potent hemodynamic effects complicates the management of patients poisoned with CCBs. The hallmarks of CCB toxicity include hypotension and bradydysrhythmias. Unfortunately, in severely poisoned patients, no therapeutic intervention is demonstrated to be consistently effective. Management decisions must be made on an individual patient basis with careful assessment of the physiologic response to each treatment.
CCBs were first introduced commercially in the United States in the late 1970s. Currently, there are 10 individual CCBs available in either immediate or sustained-release formulations (Table 60–1), plus several combination products. They are used for a variety of medical conditions, including hypertension, stable angina, dysrhythmias, migraine headache, Raynaud phenomenon, and subarachnoid hemorrhage.
Table 60–1. Classification of Calcium Channel Blockers Available in the United States |Favorite Table|Download (.pdf)
Table 60–1. Classification of Calcium Channel Blockers Available in the United States
|Verapamil (Calan, Isoptin, Verelan)|
|Diltiazem (Cardizem, Dilacor, Tiazac)|
|Nifedipine (Adalat, Procardia)|
In 1986, more than 1200 exposures and seven deaths related to CCBs were reported to the American Association of Poison Control Centers. In 2007, those figures increased to 10,084 exposures with 435 of moderate to major toxicity, including 17 deaths (Chap. 135). This reported rise in fatalities is most likely the result of the increased use and access to these drugs, along with the introduction of sustained-release preparations in 1988.
There are many types of calcium channels, including L, N, P, T, Q, and R types, that can be found either intracellularly on the sarcoplasmic reticulum or on cell plasma membranes, particularly in neuronal and secretory tissue.91
All CCBs commercially available in the United States exert their physiologic effects by antagonizing L-type voltage-sensitive calcium channels and are classified into three structural groups (see Table 60–1).50,107 Each group binds a slightly different region of the alpha1c subunit of the calcium channel and thus has different affinities for the various L-type calcium channels, both in the myocardium and the vascular smooth muscle.1,28 Verapamil and diltiazem have profound inhibitory effects on the sinoatrial (SA) and atrioventricular (AV) nodal tissue, whereas the dihydropyridines as a class have little, if any, direct myocardial effects at therapeutic doses.51,107 A fourth class of CCBs, sometimes referred to as "nonselective," includes mibefradil and bepridil, which are no longer available in the United States because of adverse drug events.
These receptor-binding differences among the CCB classes determine their potential therapeutic role. Verapamil and diltiazem are used in ...