Dinitrate

Isosorbide dinitrate (ISDN) is a medication used for heart failure, esophageal spasms, and to treat and prevent chest pain from not enough blood flow to the heart. It belongs to a group of medicines called nitrates which work by relaxing blood vessels and increasing the supply of blood and oxygen to the heart while reducing its workload.

Medical uses

Isosorbide dinitrate is used primarily for the treatment and prevention of angina pectoris and as a secondary treatment for heart failure. It is also beneficial in managing esophageal spasms.

Mechanism of action

The primary mechanism by which isosorbide dinitrate acts is through the relaxation of vascular smooth muscle, leading to vasodilation. This process is mediated by the release of nitric oxide (NO) which activates guanylate cyclase, resulting in an increase of cyclic guanosine monophosphate (cGMP). The increase in cGMP leads to the dephosphorylation of myosin light chains within the smooth muscle cells, causing relaxation. Vasodilation of the veins decreases venous return to the heart, thereby reducing left ventricular end-diastolic pressure (preload). Vasodilation of the arteries also reduces systemic vascular resistance and arterial pressure (afterload). The overall effect is a reduction in myocardial oxygen demand and an increase in oxygen supply.

Side effects

Common side effects of isosorbide dinitrate include headache, dizziness, and orthostatic hypotension. Less common side effects may include tachycardia, nausea, and flushing. Tolerance to the medication can develop over time, which may reduce its effectiveness.

Contraindications

Isosorbide dinitrate should not be used in patients with hypersensitivity to nitrates, severe anemia, closed-angle glaucoma, and hypotension. It is also contraindicated in patients who are using sildenafil (Viagra), tadalafil (Cialis), or vardenafil (Levitra) due to the risk of severe hypotension.

Pharmacokinetics

Isosorbide dinitrate is well absorbed after oral administration, with peak plasma concentrations occurring within 1 hour. It undergoes extensive first-pass metabolism in the liver, which results in a bioavailability of about 25%. The metabolites of isosorbide dinitrate, including isosorbide mononitrate, are also active. The elimination half-life of isosorbide dinitrate is about 1 hour, while its metabolites have longer half-lives.

Interactions

Isosorbide dinitrate can interact with other medications, including phosphodiesterase inhibitors (such as sildenafil), antihypertensive drugs, and alcohol, all of which can enhance its hypotensive effects. Patients should be advised to report all concurrent medication use to their healthcare provider.

See also

• Nitroglycerin
• Heart failure
• Angina pectoris
• Vasodilator
• Pharmacology of cardiovascular drugs