The principal pharmacological action of isosorbide dinitrate is relaxation of vascular smooth muscle and consequent dilatation of peripheral arteries and veins, especially the latter. ... Arteriolar relaxation reduces systemic vascular resistance, systolic arterial pressure, and mean arterial pressure (afterload).
It is used for angina, in addition to other medications for congestive heart failure, and for esophageal spasms.
Long-acting nitrates can be more useful as they are generally more effective and stable in the short term.
Adverse reactions to isosorbide dinitrate are generally dose-related, and almost all of these reactions are the result of isosorbide dinitrate’s activity as a vasodilator. Headache, which may be severe, is the most commonly reported side effect. Headache may be recurrent with each daily dose, especially at higher doses. Transient episodes of lightheadedness, occasionally related to blood pressure changes, may also occur. Hypotension occurs infrequently, but in some patients it may be severe enough to warrant discontinuation of therapy. Syncope, crescendo angina, and rebound hypertension have been reported but are uncommon.
Extremely rarely, ordinary doses of organic nitrates have caused methemoglobinemia in normalseeming patients. Methemoglobinemia is so infrequent at these doses that further discussion of its diagnosis and treatment is deferred.
Multiple-dose studies with ISDN and other nitrates have shown that maintenance of continuous 24-hour plasma levels results in refractory tolerance. Every dosing regimen for Isordil Titradose tablets must provide a daily dose-free interval to minimize the development of this tolerance. With immediate-release ISDN, it appears that one daily dose-free interval must be at least 14 hours long.
The effects of the second and later doses have been smaller and shorter-lasting than the effects of the first.
Large controlled studies with other nitrates suggest that no dosing regimen with Isordil Titradose tablets should be expected to provide more than about 12 hours of continuous anti-anginal efficacy per day.
As with all titratable drugs, it is important to administer the minimum dose which produces the desired clinical effect. The usual starting dose of Isordil Titradose is 5 mg to 20 mg, two or three times daily. For maintenance therapy, 10 mg to 40 mg, two or three times daily is recommended. Some patients may require higher doses. A daily dose-free interval of at least 14 hours is advisable to minimize tolerance. The optimal interval will vary with the individual patient, dose and regimen.
The vasodilating effects of isosorbide dinitrate may be additive with those of other vasodilators. Alcohol, in particular, has been found to exhibit additive effects of this variety.
Concomitant use of Isordil Titradose with phosphodiesterase
inhibitors in any form is contraindicated.
Amplification of the vasodilatory effects of Isordil by sildenafil can result in severe hypotension. The time course and dose dependence of this interaction have not been studied. Appropriates upportive care has not been studied, but it seems reasonable to treat this as a nitrate overdose, with elevation of the extremities and with central volume expansion.
Severe hypotension, particularly with upright posture, may occur with even small doses of isosorbide dinitrate. This drug should therefore be used with caution in patients who may be volume depleted or who, for whatever reason, are already hypotensive. Hypotension induced by isosorbide dinitrate may be accompanied by paradoxical bradycardia and increased angina pectoris.
Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy.
As tolerance to isosorbide dinitrate develops, the effect of sublingual nitroglycerin on exercise tolerance, although still observable, is somewhat blunted.
Some clinical trials in angina patients have provided nitroglycerin for about 12 continuous hours of every 24-hour day. During the daily dose-free interval in some of these trials, anginal attacks have been more easily provoked than before treatment, and patients have demonstrated hemodynamic rebound and decreased exercise tolerance. The importance of these observations to the routine, clinical use of immediate-release oral isosorbide dinitrate is not known.