Cardiovascular agents calcium channel blockers

The so-called calcium channel blockers constitute a class of cardiovascular agents that have gained prominence in the past few years. These drugs, which obtund contraction of arterial vessels by preventing the movement of calcium ions needed for those contractions, have proved especially useful in the treatment of angina and hypertension. Dihydropyridines such as nifedipine (30) are par-... 

ACE inhibitors and angiotensin-receptor blockers (ARB) have definite benefits in patients with nephropathy and are believed to have renoprotective effects in most patients. Due to their ability to cause an initial bump in serum creatinine, these agents should be used cautiously when employed in combination with the calcineurin inhibitors. The dihydropyridine calcium channel blockers have demonstrated an ability to reverse the nephrotoxicity associated with cyclosporine and tacrolimus (Table 52-8). In general, antihypertensive therapy should focus on agents with proven benefit in reducing the progression of cardiovascular disease and should be chosen on a patient-specific basis.55 See Chapter 2 for further recommendations for treating HTN. 

The effects of the prototypical calcium channel blockers are seen most prominently in the cardiovascular system (Table 19.1), although calcium channels are widely distributed among excitable cells. The following calcium channel-blocking drugs are clinically the most widely used compounds in this very extensive class of pharmacological agents amlodipine, diltiazem, isradipine, nifedipine, nicardipine, nimodipine, and verapamil. 

Antihypertensive Agents. Hypertension (high blood pressure) is a significant risk factor for cardiovascular diseases such as angina heart attacks, and strokes. /(-Adrenoceptor (adrenergic nervous system receptors of the /(-type) antagonists (/(-blockers), calcium channel blockers, angiotensinconverting enzyme (ACE) inhibitors, and potassium channel activators... 

The calcium channel blockers currently used to treat angina pectoris are listed in Table 22-3. Although the chemistry and exact mechanism of action of each drug are somewhat distinct, all of these agents exert their effects by limiting calcium entry into specific cardiovascular tissues. Certain calcium channel blockers are said to be selective if they affect vascular smooth muscle, but have little or no affect on the heart. Nonselective calcium channel blockers affect the vasculature and inhibit calcium entry into cardiac muscle cells. Individual agents are discussed below. 

Dunn NR, Freemantle SN, Mann RD. Cohort study on calcium channel blockers, other cardiovascular agents, and the prevalence of depression. Br J Clin Pharmacol 1999 48(2) 230-3. 

Three landmark placebo-controlled clinical trials have established the benefits of both hypertension treatment and diuretic therapy. The Systolic Hypertension in the Elderly Program (SHEP), the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension), and the Medical Research Council (MRC) trial " showed significant reductions in stroke, myocardial infarction, and aU-cause cardiovascular disease and mortality with thiazide diuretic-based therapy versus placebo. These trials allowed for /3-blockers as add-on therapy for BP control. Newer agents (i.e., ACE inhibitors, angiotensin II receptor blockers [ARBs], and calcium channel blockers [CCBs]) were not available at the time of these studies. However, subsequent clinical trials have compared these newer antihypertensive agents (ACE inhibitors, ARBs, and CCBs) to diuretics." These data show similar effects, but most trials used a prospective, open-label, blinded end point (PROBE) study methodology that is... 

When calcium channel blockers are used clinically it is assumed that the major effects are limited to the cardiovascular system, and indeed, few side effects have been reported for these agents. However, calcium channels in the cardiovascular system... 

CCAs (channel blockers influx inhibitors) have been used primarily for the treatment of cardiovascular disorders (e.g., supraventricular arrhythmias, angina, and hypertension). Agents such as verapamil exert their effects by modulating the influx of Ca across the cell membrane, thus interfering with calcium-dependent functions. Based partly on the common effects of lithium and this class of drugs (e.g., effects on Ca "" activity), the CCAs have been studied as a potential treatment for mania. Janicak et al. (251) reported the results of a 3-week, double-blind comparison of verapamil versus placebo, which did not demonstrate a beneficial effect for verapamil (up to 480 mg/day) in 33 acutely manic hospitalized patients. 

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