Isosorbide dinitrate

Template:Short description Template:Use dmy dates Template:Drugbox Isosorbide dinitrate is a medication used for heart failure, esophageal spasms, and to treat and prevent angina pectoris.<ref name=AHFS2016/> It has been found to be particularly useful in heart failure due to systolic dysfunction together with hydralazine.<ref>Template:Cite journal</ref><ref name=AHFS2016/> It is taken by mouth or under the tongue.<ref name=AHFS2016>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Common side effects include headache, lightheadedness with standing, and blurred vision.<ref name=AHFS2016/> Severe side effects include low blood pressure.<ref name=AHFS2016/> It is unclear if use in pregnancy is safe for the baby.<ref name=AHFS2016/> It should not be used together with PDE5 Inhibitors.<ref name=AHFS2016/> Isosorbide dinitrate is in the nitrate family of medications and works by dilating blood vessels.<ref name=AHFS2016/>

Isosorbide dinitrate was first written about in 1939.<ref name=Fis2006>Template:Cite book</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO21st">Template:Cite book</ref> Isosorbide dinitrate is available as a generic medication.<ref name=AHFS2016/><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> A long-acting form exists.<ref name=AHFS2016/> In 2022, isosorbide was the 119th most commonly prescribed medication in the United States, with more than 5Template:Nbspmillion prescriptions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Medical uses

It is used for angina, in addition to other medications for congestive heart failure, and for esophageal spasms.<ref name="AHFS2016"/> 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.

Side effects

Tolerance

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. Impaired biotransformation of isosorbide dinitrate to its active principle NO (or a NO-related species)
2. Neurohormonal activation, causing sympathetic activation and release of vasoconstrictors such as endothelin and angiotensin II which counteract the vasodilation induced by isosorbide dinitrate
3. Plasma volume expansion
4. The oxidative stress hypothesis<ref name="pmid7814613">Template:Cite journal</ref>

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:<ref name="pmid10467211">Template:Cite journal</ref> these include endothelial and autonomic dysfunction.<ref name="pmid18634978">Template:Cite journal</ref>

Mechanism of action

Similar to other nitrites and organic nitrates, isosorbide dinitrate is converted to nitric oxide (NO), an active intermediate compound which activates the enzyme guanylate cyclase (atrial natriuretic peptide receptor A). This stimulates the synthesis of cyclic 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.<ref>Template:Cite book</ref>

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. It is sold under the trade name Isoket in the United Kingdom, Argentina, and Hong Kong. It is also a component of BiDil.