Nitrates Calcium-channel blockers

Many studies have demonstrated that nitrates, calcium channel blockers, and blockers increase time to onset of angina and ST depression during treadmill tests in patients with angina of effort (Figure 12-5). Although exercise tolerance increases, there is usually no change in the angina threshold, ie, the rate-pressure product at which symptoms occur. 

All three of the drug groups currently approved for use in angina (organic nitrates, calcium channel blockers, and 3-blockers) decrease myocardial oxygen requirement by decreasing the determinants of oxygen demand (heart rate, ventricular volume, blood pressure, and contractility). In some... 

The hypotensive adverse effects of apomorphine may possibly be increased by nitrates, calcium-channel blockers and alpha blockers. There is some evidence that ACE inhibitors, beta blockers and diuretics do not increase the risk of hypotension. Nevertheless, caution is advised with all antihypertensives, and patients should be told about the symptoms of orthostatic hypotension and what to do should they occur. 

Nitrates Calcium-channel blockers Calcium-channel blockers Nifedipine Sodium nitroprusside + Miscellaneous... 

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. 

If die nitrates are administered witii the antihypertensives, alcohol, calcium channel blockers, or the phe-notiiiazines, there may be an increased hypotensive effect. When nitroglycerin is administered intravenously (IV), die effects of heparin may be decreased. Increased nitrate serum concentrations may occur when the nitrates are administered witii aspirin. 

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... 

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. 

Beta-Blockers, Nitrates, and Calcium Channel Blockers... 

Discontinue, if possible, drugs that may promote reflux (calcium channel blockers, /3-blockers, nitrates, theophylline). 

Drugs that may interact with nitrates include alcohol, alteplase, aspirin, beta-blockers, calcium channel blockers, dihydroergotamine, heparin, nondepolarizing muscle relaxants, phenothiazines, phosphodiesterase inhibitors (eg, sildenafil, tadalafil, vardenafil), and vasodilators. 

Nitrates are required for symptomatic relief of chest pain they are not proven to improve hard outcomes such as MI or death. Nitrates should be given initially sublingually or by spray, followed by oral or transdermal routes if pain is relieved. Lack of pain relief mandates i.v. administration. Beta-blockers such as metoprolol are used and may reduce the risk of subsequent MI. Calcium channel blockers such as dilfiazem, verapamil, or long-acting di-hydropyridines can be added for symptom control if nitrates and beta-blockers do not suffice they do not improve outcomes. In fact, they may worsen outcomes in the presence of left ventricular dysfunction or CHF in acute coronary syndrome. 

L A. Verapamil is an L-type calcium channel blocker. Nitroglycerin and isosorbide are both organic nitrates and have no direct effect on L-type calcium channels at the SA node, while propranolol and metoprolol are (3-adrenoceptor blockers and will slow heart rate by blocking the actions of norepinephrine and epinephrine on (3-receptors at the SA node. 

This class of drugs includes the oral vasodilators, hydralazine and minoxidil, which are used for long-term outpatient therapy of hypertension the parenteral vasodilators, nitroprusside, diazoxide, and fenoldopam, which are used to treat hypertensive emergencies the calcium channel blockers, which are used in both circumstances and the nitrates, which are used mainly in angina (Table 11-3). 

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