Nitrate therapy

Each of the transdermal nitroglycerin systems is effective in treating angina pectoris when worn for 12—16 h followed by an off period. The FDA recommends the period without dmg (8—12 h) to mitigate the possibiUty of the patient acquiring a tolerance to the antianginal effects of nitrate therapy. Thus, a noncontinuous dosing schedule of nitrates is recommended even with the transdermal deflvery system (81). 

The major limitation of nitrate therapy is the development of tolerance with continuous use. The loss of anti-anginal effects may occur within the first 24 hours of continuous nitrate therapy. While the cause of tolerance is unclear, several mechanisms have been proposed. These include depletion of the sulfhydryl groups necessary for the conversion of nitrates to nitric oxide, activation of neurohormonal systems, increased intravascular volume, and generation of free radicals that degrade nitric oxide. The most effective method to avoid tolerance and maintain the anti-anginal efficacy of nitrates is to allow a daily nitrate-free interval of at least 8 to 12 hours. Nitrates do not provide protection from ischemia during the nitrate-free period. Therefore, the nitrate-free... 

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. 

Oral nitrates play a limited role in ACS because clinical trials have failed to show a mortality benefit for IV followed by oral nitrate therapy in acute MI. Therefore, other life-saving therapy, such as ACE inhibitors and /T-blockers, should not be withheld. 

Ca2+ channel blocker, long-acting nitrate therapy... 

Is Nitrate Therapy Associated with Adverse Vascular Effects 295... 

Elderly Clinical experience for organic nitrates reported in the literature identified a potential for severe hypotension and increased sensitivity to nitrates in the elderly. Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy. 

Angina Nitrate therapy may aggravate angina caused by hypertrophic cardiomyopathy. 

Vascular headache, postural hypotension, and reflex tachycardia are common side effects of organic nitrate therapy. Fortunately, tolerance to nitrate-induced headache develops after a few days of therapy. Postural hypotension and tachycardia can be minimized by proper dosage adjustment and by instructing the patient to sit... 

Parker JD and Parker JO. Drug therapy Nitrate therapy for stable angina pectoris. N Engl J Med... 

Carvedilol may be used in patients unable to tolerate an ACE inhibitor. Carvedilol may be used in patients who are not receiving digitalis, hydralazine and nitrate therapy. 

Angina pectoris, hypertension, congestive heart failure, acute myocardial ischaemia, acute pulmonary oedema, unstable coronary syndromes especially when associated with elevated filling pressures. Nitrate therapy may exaggerate outflow obstruction in hypertrophic obstructive cardiomyopathy. 

Bader KF. 1966. Organ deposition of silver following silver nitrate therapy of burns. Plast Reconstr Surg 37 550-551. 

Strauch B, Buch W, Grey W, et al. 1969. Methemoglobinemia A complication of silver nitrate therapy used in burns. AORN Journal 10 54-56. 

Nitrate therapy may be used to terminate an acute anginal attack, to prevent effort- or stress-induced attacks, or for long-term prophylaxis, usually in combination with j3-blockers or calcium channel antagonists. Suhhngual, huccal, or spray nitroglycerin products are preferred for alleviation of anginal attacks because of rapid absorption (Table 11-1). Symptoms may be prevented by prophylactic oral or transdermal products (usually in combination with j3-blockers or calcirun channel antagonists), but development of tolerance may be problematic. 

Nitrate therapy should be the first step in managing acute attacks of chronic stable angina if the episodes are infrequent (e.g., a few times per month). If angina occurs no more often than once every few days, then sublingual nitroglycerin tablets or spray or buccal products may be sufficient. 

Aspirin in low dosages (under 300 mg/day) is widely used in cardiovascular prophylaxis, but its use is accompanied by an increased risk of gastrointestinal bleeding (SEDA-21, 100). Of particular interest therefore are data from a retrospective case-control study showing that nitrate therapy may reduce the risk of aspirin-induced gastrointestinal bleeding (111). As nitrates are often used in the same population of patients, such data merit further confirmation from larger prospective studies. 

In an assessment of how nitrate tolerance might be avoided, the efficacy of thrice-daily buccal glyceryl trinitrate and that of four times a day oral isosorbide dinitrate were compared (71) over 2 weeks, prolonged antianginal efficacy was maintained only with thrice-daily buccal administration. Nevertheless, in another study, transdermal glyceryl trinitrate seemed to offer a prolonged effect, sufficient to wean patients with unstable angina from intravenous nitrate therapy (71). 

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