Isosorbide dinitrate


Isosorbide dinitrate 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 has been found to be particularly useful in heart failure due to systolic dysfunction together with hydralazine in black people. It is taken by mouth or under the tongue.
Common side effects include headache, lightheadedness with standing, and blurred vision. Severe side effects include low blood pressure. It is unclear if use in pregnancy is safe for the baby. It should not be used together with medications within the sildenafil family. ISDN is in the nitrate family of medications and works by dilating blood vessels.
Isosorbide dinitrate was first written about in 1939. It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system. ISDN is available as a generic medication. A long-acting form exists.

Medical uses

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.

Side effects

After long-term use for treating chronic conditions, tolerance may develop in patients, reducing its effectiveness. The mechanisms of nitrate tolerance have been thoroughly investigated in the last 30 years and several hypotheses have been proposed. These include:
  1. Severe allergic reactions ; fainting; fast or slow heartbeat; nausea; new or worsening chest pain; vomiting.
  2. Impaired biotransformation of ISDN to its active principle NO
  3. Neurohormonal activation, causing sympathetic activation and release of vasoconstrictors such as endothelin and angiotensin II which counteract the vasodilation induced by ISDN
  4. Plasma volume expansion
  5. The oxidative stress hypothesis
The last hypothesis might represent a unifying hypothesis, and an ISDN-induced inappropriate production of oxygen free radicals might induce a number of abnormalities which include the ones described above.
Furthermore, nitrate tolerance is shown to be associated with vascular abnormalities which have the potential to worsen patients prognosis: these include endothelial and autonomic dysfunction.
In the short run, ISDN can cause severe headaches, necessitating analgesic administration for relief of pain, as well as severe hypotension, and, in certain cases, bradycardia. This makes some physicians nervous and should prompt caution when starting nitrate administration.

Mechanism of action

Similar to other nitrites and organic nitrates, isosorbide dinitrate is converted to nitric oxide, an active intermediate compound which activates the enzyme guanylate cyclase. This stimulates the synthesis of cyclic guanosine 3',5'-monophosphate which then activates a series of protein kinase-dependent phosphorylations in the smooth muscle cells, eventually resulting in the dephosphorylation of the myosin light chain of the smooth muscle fiber. The subsequent sequestration of calcium ions results in the relaxation of the smooth muscle cells and vasodilation.

Society and culture

Isosorbide dinitrate is sold in the US under the brand names Dilatrate-SR by Schwarz and Isordil by Valeant, according to FDA Orange Book. In the United Kingdom, Argentina, and Hong Kong, a trade name of it is Isoket. It is also a component of BiDil.