Nitrates Amlodipine

Systemic and coronary arteries are influenced by movement of calcium across cell membranes of vascular smooth muscle. The contractions of cardiac and vascular smooth muscle depend on movement of extracellular calcium ions into these walls through specific ion channels. Calcium channel blockers, such as amlodipine (Norvasc), diltiazem (Cardizem), nicardipine (Cardene), nifedipine (Procardia), and verapamil (Calan), inhibit die movement of calcium ions across cell membranes. This results in less calcium available for the transmission of nerve impulses (Fig. 41-1). This drug action of the calcium channel blockers (also known as slow channel blockers) has several effects on die heart, including an effect on die smooth muscle of arteries and arterioles. These drug dilate coronary arteries and arterioles, which in turn deliver more oxygen to cardiac muscle. Dilation of peripheral arteries reduces die workload of die heart. The end effect of these drug is the same as that of die nitrates. 

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... 

STE ACS class lla recommendation and NSTE ACS class I recommendation for patients with ongoing ischemia who are already taking adequate doses of nitrates and P-blockers or in patients with contraindications to or intolerance to P-blockers (diltiazem or verapamil for STE ACS and diltiazem, verapamil, or amlodipine for NSTE ACS). 

As described in the previous section, calcium channel blockers should not be administered to most patients with ACS. Their role is a second-line treatment for patients with certain contraindications to P-blockers and those with continued ischemia despite P-blocker and nitrate therapy. Administration of either amlodipine, diltiazem, or verapamil is preferred.2 Agent selection is based on heart rate and left ventricular dysfunction (diltiazem and verapamil are contraindicated in patients with bradycardia, heart block, or systolic heart failure). Dosing and contraindications are described in Table 5-2. 

Because it prolongs the QT interval, ranolazine should be reserved for patients who have not achieved an adequate response to other antianginal drugs. It should be used in combination with amlodipine, /3-blockers, or nitrates. 

Drugs that may be affected by PDE5 inhibitors include alpha-blockers, amlodipine, angiotensin II receptor blockers, bendroflumethiazide, enalaphl, metoprolol, nifedipine, nitrates, protease inhibitors. 

Dilation of venous blood vessels leads to a decrease in cardiac preload by increasing venous capacitance arterial dilators reduce systemic arteriolar resistance and decrease afterload. Nitrates (see p. 175) are commonly employed venous dilators for patients with congestive heart failure. If the patient is intolerant of ACE inhibitors, the combination of hydralazine and isosorbide dinitrate is most commonly used. Amlodipine and felodipine (see p. 188) have less negative inotropic effect than other calcium channel blockers, and seem to decrease sympathetic nervous activity. 

Ranolazine is indicated for the treatment of chronic angina. Based on controlled trials, the improvement in exercise time is a modest increase of 15 to about 45 seconds compared with placebo. In a large ACS trial, ranolazine reduced recurrent ischemia but did not improve the primary efficacy composite end point of cardiovascular death, MI, or recurrent ischemia. Because it prolongs the QT interval, ranolazine should be reserved for patients who have not achieved an adequate response to other antianginal drugs. It should be used in combination with amlodipine, )3-blockers, or nitrates. 

The effects of amlodipine and isosorbide-5-mono-nitrate for 3 weeks on exercise-induced myocardial stunning have been compared in a randomized, double-blind, crossover study in 24 patients with chronic stable angina and normal left ventricular function (4). Amlodipine attenuated stunning, evaluated by echocardiography, significantly more than isosorbide, without difference in anti-ischemic action or hemodynamics. Amlodipine was better tolerated than isosorbide, mainly because of a lower incidence of headache (4). 

Adrenergic receptor antagonists Amlodipine or felodipine (nitrates)... 

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