Isosorbide dinitrate
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 |
License data | |
Pregnancy category |
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Routes of administration | By mouth |
ATC code | |
Legal status | |
Legal status |
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Pharmacokinetic data | |
Bioavailability | 10–90%, average 25% |
Metabolism | Liver |
Elimination half-life | 1 hour |
Excretion | Kidney |
Identifiers | |
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Isosorbide dinitrate is a medication used for
Common side effects include
Isosorbide dinitrate was first written about in 1939.
Medical uses
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.
Side effects
Tolerance
After long-term use for treating chronic conditions, tolerance may develop in patients, reducing its effectiveness. The mechanisms of
- Impaired biotransformation of isosorbide dinitrate to its active principle NO (or a NO-related species)
- Neurohormonal activation, causing sympathetic activation and release of vasoconstrictors such as endothelin and angiotensin II which counteract the vasodilation induced by isosorbide dinitrate
- Plasma volume expansion
- The oxidative stress hypothesis[8]
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]
Other side effects
In the short run, isosorbide dinitrate can cause severe headaches, necessitating analgesic administration for relief of pain, as well as severe hypotension, and, in certain cases, bradycardia.
Rarely occurring are allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); fainting; fast or slow heartbeat; nausea; new or worsening chest pain; vomiting.
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.[11]
Society and culture
Isosorbide dinitrate is sold in the US under the brand names Dilatrate-SR by
References
- ^ a b c d e f g h i j k l "Isosorbide Dinitrate/Mononitrate". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
- PMID 18441861.
- ISBN 9783527607495. Archivedfrom the original on 20 December 2016.
- hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
- ^ "Competitive Generic Therapy Approvals". U.S. Food and Drug Administration (FDA). 29 June 2023. Archived from the original on 29 June 2023. Retrieved 29 June 2023.
- ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
- ^ "Isosorbide - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
- PMID 7814613.
- PMID 10467211.
- PMID 18634978.
- ISBN 978-0-7020-5362-7.