What will the nurse assess for before administering isosorbide dinitrate a nitrate?

Isosorbide Dinitrate.

This drug is available in tablets for SL use, in chewable form, in tablets for oral use, and in sustained-release (SR) capsules. Partial or complete nitrate tolerance (see later) develops with regimens of isosorbide dinitrate administered as 30 mg three or four times daily. A dosage schedule should be adopted that allows a 12-hour or longer nitrate-free interval. If the drug is administered on a three-times-daily schedule (e.g., at 8am, 1pm, and 6pm), the antianginal benefit lasts for approximately 6 hours, and the magnitude of the antianginal benefit decreases with each successive dose.

The Hospitalized Patient

G. Michael Felker and John R. Teerlink

The most significant addition to the 2009 American College of Cardiology and American Hospital Association (ACC/AHA) updated guidelines was inclusion of specific new recommendations regarding the hospitalized patient (Table 24G.1). Although there were a number of new class I indications involving the diagnosis of heart failure, the use of B-type natriuretic peptide and N-terminal pro-B natriuretic peptide (NT-proBNP), recognition of acute coronary syndromes, recognition of potential precipitating factors, use of supplemental oxygen, use of intravenous inotropic or pressure agents in patients with clinical evidence of hypotension with hypoperfusion, use of pulmonary artery catheters, and transition of intravenous to oral diuretics, the level of evidence supporting each of these recommendations was based on consensus opinion or standard use of care (i.e., level of evidence, C). Stronger class I recommendations (level of evidence, B) were provided for the use of intravenous diuretics to decongest patients, initiation of ACE inhibitors/ARBs, and beta blockers before hospital discharge, as well as the importance of postdischarge systems of care.

The updated guidelines offer qualified support (class IIa) for the use of urgent catheterization and revascularization, the use of vasodilators (intravenous nitroglycerin, nitroprusside, nesiritide), invasive hemodynamic monitoring, and ultrafiltration. More muted support (class IIb) was given for the use of inotropic agents (dopamine, dobutamine, or milrinone) in patients with severe left ventricular dysfunction, low blood pressure, and evidence of low cardiac output. In contrast, the use of inotropic agents in patients without evidence of decreased organ perfusion, as well as the routine use of invasive hemodynamic monitoring, was not recommended (class III indication).

Therapeutic Agents to Reduce Angina and Ischemia

The goal of antianginal therapy is to reduce symptoms of cardiac ischemia and to improve quality of life.12,13 β-Blockers, which prevent the binding of catecholamines to the β-adrenergic receptor, lower heart rate and myocardial contractility, thereby reducing myocardial workload, myocardial oxygen demand, and ischemia and anginal symptoms. β-Blockers raise the ischemic threshold and delay or prevent the onset of angina with exercise. β-Blockers also reduce the rate of secondary cardiac events and sudden cardiac death in post-MI patients, but to date there have been no placebo-controlled outcome trials in angina patients. All β-blockers appear to be equally effective in patients with chronic stable angina (Table 62-12). The β-blocker dose should be titrated to a target resting heart rate of 50 to 60 beats per minute as tolerated by the patient.

Calcium-channel blockers (Table 62-13) reduce afterload by their peripheral vasodilatory effects and thus lower myocardial workload and myocardial oxygen demand. Calcium-channel blockers also reduce coronary vascular resistance and inhibit coronary vasospasm by preventing coronary arterial smooth muscle contraction. This favorable reduction in myocardial oxygen demand, coupled with an increase in myocardial oxygen supply, results in a reduction in angina and ischemia. Non-dihydropyridine calcium-channel blockers, such as verapamil and diltiazem, also reduce heart rate. Conversely, dihydropyridine calcium-channel antagonists, such as amlodipine, have greater effect on vascular smooth muscle, are better peripheral and coronary vasodilators, and hence may have advantages for use in the hypertensive patient with angina. In randomized clinical trials, calcium-channel blockers and β-blockers are generally equally effective in relieving angina, improving time to onset of angina, and improving time to ischemic ST depression during exercise. Because calcium-channel blockers have not been shown to reduce death or MI in patients with stable or previously unstable ischemic heart disease, these agents are usually used in patients who cannot tolerate β-blockers or who require additional pharmacotherapy to control their symptoms. When calcium-channel blockers are used withβ-blockers, care must be taken not to cause symptomatic bradycardia with verapamil and diltiazem. When calcium-channel blockers are used alone, diltiazem is often preferred because dihydropyridine calcium-channel blockers can increase the heart rate.

Nitrates (Table 62-14) continue to be widely prescribed for antianginal treatment and are effective when they are administered sublingually, orally, or topically.14 They act as vasodilators by entering vascular smooth muscle, where they are metabolized to nitric oxide, which relaxes vascular smooth muscle, including in coronary arteries. These effects reduce angina by improving coronary blood flow. Nitrates also lower preload because of their venodilatory effects, with a resulting reduction in LV end-diastolic pressure and wall tension, which in turn lowers subendocardial oxygen demand. When nitrates are used in patients with stable angina, they improve exercise tolerance, time to onset of angina, and ST segment depression during treadmill exercise testing. Long-acting nitrates, which are frequently combined with β-blockers and calcium-channel blockers, have additive antianginal and anti-ischemic effects in patients with stable ischemic heart disease. Sublingual nitroglycerin or oral spray can terminate an angina attack and can be used as prophylaxis to prevent exertional angina. Long-acting nitrates administered orally or transdermally are used to prevent angina and to improve exercise tolerance. For avoidance of nitrate tolerance or tachyphylaxis, an 8- to 12-hour nitrate-free interval daily is recommended. Nitroglycerin and nitrates can cause vasodilation-induced headache, a decrease in blood pressure, and, more rarely, severe hypotension with bradycardia due to activation of the vagal Bezold-Jarisch reflex. Because the vasodilation by nitroglycerin is markedlyexaggerated and prolonged in the presence of the phosphodiesterase inhibitors sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis), these agents and nitrates should not be used concurrently.

Isosorbide dinitrate—(Cardio; Cedocarb; Dilatrate-Sr; Dinisor; Insucar; Isd; Iso-Bid; Isobid; Isocard; Isonate; Iso-Par; Isorbid; Isordil; Isorem; Isotrate; Rigedal; Sorbitrate)

Long-acting Organic Nitrates.

Isosorbide dinitrate and its major active metabolite, isosorbide mononitrate, are orally administered organic nitrates that are available as extended-release preparations for the prevention of angina. As with nitroglycerin, tolerance rapidly develops, and a daily drug-free interval is recommended. With once-daily dosing (in the morning) of isosorbide dinitrate or isosorbide mononitrate, a 12-hour duration of effect is achieved. Nicorandil is a newer long-acting nitrate-like drug that also has potassium-channel-activating properties. It functions as a balanced venous and arteriolar vasodilator, reducing preload and afterload and improving angina. Nicorandil does not appear to be associated with significant tolerance.

Practical Tips

H-ISDN should not be used in patients who have no prior use of ACE inhibitors/ARBs or β-blockers and should not be substituted for ACE inhibitors/ARBs in patients who are tolerating therapy without difficulty. Adherence to this combination has generally been poor because of the number of daily doses and tablets required, and the side-effect profile including headache and dizziness. However, the benefit of these drugs can be substantial in specific patient populations who have been studied in randomized trials. Therefore, slower titration of the drugs should be performed to enhance tolerance of the therapy. If the fixed-dose combination is available, the initial dose should be one tablet containing 37.5 mg of hydralazine hydrochloride and 20 mg of isosorbide dinitrate three times daily. The dose can be increased to two tablets three times daily for a total daily dose of 225 mg of hydralazine hydrochloride and 120 mg of isosorbide dinitrate. When the two drugs are used separately, both pills should be administered at least three times daily. Initial low doses of the drugs given separately may be progressively increased to a goal similar to that achieved in the fixed-dose combination trial.

Isosorbide mononitrate and dinitrate

Other Therapies

Isosorbide dinitrate spray: Nitric oxide causes vasodilation and improves microvascular blood flow. Several placebo-control trials support that this may be efficacious in reducing pain from DPN.

Acetyl-l-carnitine has shown some pain relief but needs further trials to prove its efficacy.

Spinal cord stimulation is used in refractory painful diabetic neuropathy. Electrodes are used to stimulate the dorsal columns of the spinal cord. In a small multicenter RCT involving 60 patients conducted over 6 months, spinal cord stimulation in refractory painful diabetic neuropathy resulted in a significant improvement in pain and quality of life.42

Electric nerve stimulation has been reported to have some benefit in a few clinical trials but is not widely available in clinical practice.43

Surgical decompression of peripheral nerves (Dellon procedure) is a controversial method that is no longer recommended because of the lack of well-designed trials proving its efficacy.44