Nondihydropyridine calcium-channel blockers

Treatment with nondihydropyridine calcium channel blockers (diltiazem and verapamil) may worsen HF and increase the risk of death in patients with advanced LV dysfunction due to their negative inotropic effects. Conversely, dihydropyridine calcium channel blockers, although negative inotropes in vitro, do not appear to decrease contractility in vivo. Amlodipine and felodipine are the two most extensively studied dihydropyridine calcium channel blockers for systolic H F.39 4() These two agents have not been shown to affect patient survival, either positively or negatively. As such, they are not routinely recommended as part of a standard HF regimen however, amlodipine and felodipine can safely be used... 

The nondihydropyridine calcium channel blockers have been shown to also decrease protein excretion in patients with diabetes,20 but the reduction in proteinuria appears to be related to the reductions in blood pressure. The maximal effect of nondihydropyridine calcium channel blockers on proteinuria is seen with a blood pressure reduction to less than 130/80 mm Hg and no additional benefit is seen with increased doses. Dihydropyridine calcium channel blockers, however, do not have the same effects on protein excretion, and may actually worsen protein excretion.17... 

Antihypertensive therapy should be initiated in diabetic or nondiabetic CKD patients with an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker. Nondihydropyridine calcium channel blockers are generally used as second-line antiproteinuric drugs when ACEIs or angiotensin II receptor blockers are not tolerated. 

The nondihydropyridine calcium channel blockers, such as verapamil and diltiazem, have efficacy rates similar to that of adenosine, but are considered second line. Intravenous calcium channel blockers have a few disadvantages. In contrast to adenosine, caution should be taken in hypotensive patients. Adenosine may cause hypotension, but appears to be safe in patients who present with hypotension due to the short half-life. In addition, calcium channel blockers also should be used with caution in patients with systolic heart failure, patients receiving concurrent beta-blocker therapy, and in those with accessory pathways. 

Patients with asymptomatic left ventricular systolic dysfunction and hypertension should be treated with P-blockers and ACE inhibitors. Those with heart failure secondary to left ventricular dysfunction and hypertension should be treated with drugs proven to also reduce the morbidity and mortality of heart failure, including P-blockers, ACE inhibitors, ARBs, aldosterone antagonists, and diuretics for symptom control as well as antihypertensive effect. In African-Americans with heart failure and left ventricular systolic dysfunction, combination therapy with nitrates and hydralazine not only affords a morbidity and mortality benefit, but may also be useful as antihypertensive therapy if needed.66 The dihydropyridine calcium channel blockers amlodipine or felodipine may also be used in patients with heart failure and left ventricular systolic dysfunction for uncontrolled blood pressure, although they have no effect on heart failure morbidity and mortality in these patients.49 For patients with heart failure and preserved ejection fraction, antihypertensive therapies that should be considered include P-blockers, ACE inhibitors, ARBs, calcium channel blockers (including nondihydropyridine agents), diuretics, and others as needed to control blood pressure.2,49... 

Calcium channel blockers (CCBs) prevent the flow of calcium ions through channels in heart tissue. Inhibiting calcium flow decreases the strength of contraction of the heart and decreases blood pressure. Most CCBs fall into the dihydropyridine structural class, with nifedipine (Adalat, A.132) being the prototypical example (Figure A.38). Nondihydropyridine CCBs include diltiazem (Cardizem, A.135) and verapamil (Calan, A.136). 

Calcium channel blockers Group toxicity dihydropyridines can cause headache, ankle edema, gingival hyperplasia and flushing nondihydropyridine can cause bradycardia, constipation, gingival hyperplasia, and AV block ... 

The calcium channel blockers also effective treatments for hypertension in patients with CKD but without diabetes. However, as was mentioned previously, only the nondihydropyridine CCBs have data suggesting a reduction in the rate of decline of renal function. There are currently no data to suggest that higher doses of nondihydropyridine CCBs are needed to elicit a reduction in proteinuria as compared to a reduction in blood pressure. 

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