Nitrates -- Nitroglycerine in Heart Attack

Sublingual nitroglycerin very rarely opens occluded coronary arteries. However, in patients with Acute Myocardial Infarction the potential for reductions in ventricular filling pressures, wall tension, and cardiac work coupled with improvement in coronary blood flow, especially in ischemic zones, and antiplatelet effects make nitrates a logical and attractive pharmacological intervention in Acute Myocardial Infarction.

In patients with Heart Attack, the administration of nitrates reduces the pulmonary capillary wedge pressure and systemic arterial pressure, left ventricular chamber volume, infarct size and the incidence of mechanical complications. As with other interventions to spare ischemic myocardium in Acute Myocardial Infarction, intravenous nitroglycerin appears to be of the greatest benefit in patients treated earliest after the onset of symptoms.

How nitrates are administered?

Intravenous nitroglycerin can be administered safely to patients with evolving Myocardial Infarction as long as the dose is titrated carefully to avoid induction of reflex tachycardia or systemic arterial hypotension.
Patients with inferior wall infarction are particularly sensitive to an excessive fall in preload, particularly if concurrent right ventricular infarction is present. In such cases nitrate-induced venodilatation could impair cardiac output and reduce coronary blood flow, thus worsening myocardial oxygenation rather than improving it.

Doses of nitroglycerin administered

A useful regimen employs an initial infusion of 5 to 10 micrograms/minute with increases of 5 to 20 micrograms/minute until the mean arterial blood pressure is reduced by 10 percent if its baseline level in normotensive patients and by 30 percent in hypertensive patients, but in no case below a systolic blood pressure of 90 mm/Hg.
Alternatively, nitroglycerin may be administered as a sustained-release oral preparation (30 to 60 mg/d) or as ointment (1 to 3 inches every 6 to 8 hours for patients with a systolic pressure greater than 120 mm/Hg). Nitroglycerin can also be given sublingually at doses of 0.3 to 0.6 mg. This route may be more hazardous because the rate of absorption is difficult to control and arterial pressure may decline precipitously.

What adverse effects may nitroglycerin have?

Clinically significant methemoglobinemia has been reported to occur during the administration of intravenous nitroglycerin. Although uncommon, this problem is seen when unusually large doses of nitrates are administered.
It is important not only for its potential to cause symptoms of lethargy and headache but also because elevated methemoglobin levels can impair the oxygen-carrying capacity of the blood, potentially exacerbating ischemia. Dilatation of the pulmonary vasculature supplying poorly ventilated lung segments may produce a ventilation-perfusion mismatch.
Tolerance to intravenous nitroglycerin (as manifested by increasing nitrate requirements) develops in many patients often as soon as 12 hours after the infusion is started. Despite the theoretical and demonstrated benefit of sulfhydryl agents in diminishing tolerance, their use has not become widespread.

Updated: March, 13 2008 23:12:00

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