Action And Clinical Pharmacology: The principal action of nitroglycerin is that of all nitrates, namely relaxation of vascular smooth muscle. Nitrates act primarily by reducing myocardial oxygen demand rather than increasing its oxygen supply. This effect is thought to be brought about predominantly by peripheral action. Although venous effects predominate, nitroglycerin produces, in a dose-related manner, dilation of both arterial and venous beds. Dilation of the post capillary vessels, including large veins, promotes peripheral pooling of blood and decreases venous return to the heart, reducing left ventricular end-diastolic pressure (pre-load). Arteriolar relaxation reduces systemic vascular resistance and arterial pressure (after-load). Left ventricular end-diastolic pressure and volume are decreased, resulting in reduction of ventricular size and wall tension. The reduction in ventricular wall tension results in a net decrease in myocardial oxygen consumption and a favorable net balance between myocardial oxygen supply and demand.
Pharmacokinetics: In one study of 13 healthy males, nitroglycerin was shown to have an apparent volume of distribution of approximately 250 L. No statistically significant differences were demonstrated between the mean values of maximum plasma concentration (Cmax) and time to achieve Cmax (Tmax) with equal doses (0.8 mg) of Nitrolingual Spray and sublingual nitroglycerin tablets.
Cmax after 0.8 mg of nitroglycerin by spray administration occurred on average within 5 minutes and the apparent plasma elimination half-life was approximately 5 minutes.
Nitroglycerin is rapidly metabolized in the liver by hepatic enzymes. The two active major metabolites are the hydrolysis products, 1,3- and 1,2-dinitroglycerols. There are also 2 inactive minor metabolites, the 1- and 2-mononitroglycerols which are considered biologically inactive. Nitroglycerin and its major metabolites are approximately 60% protein bound. Nitroglycerin is excreted by the renal route primarily as the 2 dinitrometabolites, which have an excretion half-life of approximately 3 to 4 hours.
Indications And Clinical Uses: For the management and treatment of acute attacks of angina pectoris.
Contra-Indications: Severe anemia, glaucoma, increased intracranial pressure, myocardial infarction, hypotension, known hypersensitivity to nitroglycerin or previous idiosyncratic reaction to organic nitrates.
Manufacturers’ Warnings In Clinical States: The use of nitroglycerin in patients with congestive heart failure or with acute myocardial infarction requires careful clinical and/or hemodynamic monitoring.
Precautions: Headaches or symptoms of hypotension, such as weakness or dizziness, particularly when arising suddenly from a recumbent position, may be due to overdosage. When they occur, the dose or frequency of application should be reduced.
Nitroglycerin is a potent vasodilator and causes a slight decrease in mean blood pressure (approximately 10 to 15 mmHg) in some patients when used in therapeutic dosages. Caution should be exercised in using the drug in patients who are prone to, or who might be affected by hypotension. Alcohol may enhance sensitivity to the hypotensive effects of nitrates.
Tolerance to this drug and cross tolerance to other nitrates or nitrites may occur. Physical dependence has also been described. With the chronic use of nitrates, there have been reports of anginal attacks being more easily provoked as well as reports of rebound in hemodynamic effects, occurring soon after nitrate withdrawal.
Pregnancy: Animal reproduction studies have not been done with nitroglycerin sublingual spray. As with all medication, nitroglycerin should only be given to a pregnant woman if clearly indicated.
Lactation: Because it is not known if nitroglycerin is excreted in human milk, caution should be exercised when this spray is administered to a nursing mother.
Children: The safety and effectiveness of nitroglycerin in children has not been established.
Adverse Reactions: The use of nitroglycerin has been associated with headache, faintness, giddiness, lightheadedness, pallor, feeling cold, numbness of the legs. Nitroglycerin may also cause flushing, tachycardia, nausea, vomiting, restlessness, retrosternal discomfort, postural hypotension or dermatitis. An occasional individual may exhibit marked sensitivity to the hypotensive effects of nitrates. Clinically significant methemoglobinemia is rare at conventional doses, but may occur especially in patients with genetic hemoglobin abnormalities.
Symptoms And Treatment Of Overdose: Symptoms: Symptoms of overdosage are primarily related to vasodilation, and include cutaneous flushing, headache, nausea, dizziness, and hypotension. Methemoglobinemia is also possible.
Treatment: No specific antidote is available. Treatment should be symptomatic and supportive.
Dosage And Administration: Do not shake canister. Not for inhalation.
Upon initiating therapy with Nitrolingual Spray, especially when changing from another form of nitroglycerin administration, patients should be followed closely by their physicians in order to determine the minimal effective dose for each patient.
With the onset of an acute attack of angina pectoris, 1 or 2 metered doses (0.4 or 0.8 mg) of nitroglycerin, as determined by experience, may be administered onto or under the tongue, without inhaling. The optimal dose may be repeated twice at 5 to 10 minute intervals. Dosage must be individualized and should be sufficient to provide relief without producing untoward reactions.
During administration, the patient should be at rest, ideally in the sitting position, and the canister kept vertical with the nozzle head up. The opening in the nozzle head should be kept as close to the mouth as possible. Patients should familiarize themselves with the position of the spray orifice, identified by the finger rest on top of the valve, in order to facilitate administration at night.
Availability And Storage: Each metered dose contains: nitroglycerin 0.4 mg in an aromatized oily solution. Nonmedicinal ingredients: dichlorodifluoromethane, dichlorotetrafluoroethane, ether, menthol, peppermint oil and vegetable oil. Nonflammable nontoxic propellant. Aerosol bottles delivering 200 metered doses. Do not expose the aerosol unit to temperatures above 50°C and do not open. (Shown in Product Recognition Section)
NITROLINGUAL® Spray Rhône-Poulenc Rorer Nitroglycerin Antianginal