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| Clinical data | |
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| Trade names | Isordil, others[1] |
| Other names | ISDN; (3R,3aS,6S,6aS)-hexahydrofuro[3,2-b]furan-3,6-diyl dinitrate |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682348 |
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| Routes of administration | By mouth |
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| Pharmacokinetic data | |
| Bioavailability | 10–90%, average 25% |
| Metabolism | Liver |
| Eliminationhalf-life | 1 hour |
| Excretion | Kidney |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.001.583 |
| Chemical and physical data | |
| Formula | C6H8N2O8 |
| Molar mass | 236.136 g·mol−1 |
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Isosorbide dinitrate is a medication used forheart failure,esophageal spasms, and to treat and preventangina pectoris.[1] It has been found to be particularly useful in heart failure due tosystolic dysfunction together withhydralazine.[2][1] It is takenby mouth or under the tongue.[1]
Common side effects includeheadache,lightheadedness with standing, andblurred vision.[1] Severe side effects includelow blood pressure.[1] It is unclear if use inpregnancy is safe for the baby.[1] It should not be used together withPDE5 Inhibitors.[1] Isosorbide dinitrate is in thenitrate family of medications and works bydilating blood vessels.[1]
Isosorbide dinitrate was first written about in 1939.[3] It is on theWorld Health Organization's List of Essential Medicines.[4] Isosorbide dinitrate is available as ageneric medication.[1][5] A long-acting form exists.[1] In 2023, isosorbide was the 125th most commonly prescribed medication in the United States, with more than 5 million prescriptions.[6][7]
It is used for angina, in addition to other medications for congestive heart failure, and for esophageal spasms.[1] It is available as an oral tablet both in extended release and slow release. The onset of action for Isosorbide Dinitrate is thirty minutes and the onset of action for oral extended release is 12–24 hours.
Long-acting nitrates can be more useful as they are generally more effective and stable in the short term.
After long-term use for treating chronic conditions, tolerance may develop in patients, reducing its effectiveness. The mechanisms ofnitrate tolerance have been thoroughly investigated in the last 30 years and several hypotheses have been proposed. These include:
The last hypothesis might represent a unifying hypothesis, and an isosorbide dinitrate-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:[9] these include endothelial and autonomic dysfunction.[10]
Similar to other nitrites and organic nitrates, isosorbide dinitrate is converted tonitric oxide (NO), an active intermediate compound which activates the enzymeguanylate cyclase (atrial natriuretic peptide receptor A). This stimulates the synthesis ofcyclic guanosine 3',5'-monophosphate (cGMP) 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.[11]
Isosorbide dinitrate is sold in the US under the brand names Dilatrate-SR bySchwarz and Isordil byValeant, according toFDA Orange Book. It is sold under the trade name Isoket in the United Kingdom, Argentina, and Hong Kong. It is also a component ofBiDil.
