Isosorbide dinitrate

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Isosorbide dinitrate
Clinical data
Trade namesIsordil, others[1]
Other namesISDN; (3R,3aS,6S,6aS)-hexahydrofuro[3,2-b]furan-3,6-diyl dinitrate
AHFS/Drugs.comMonograph
MedlinePlusa682348
License data
Pregnancy
category
  • AU: B1
Routes of
administration
By mouth
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability10–90%, average 25%
MetabolismLiver
Elimination half-life1 hour
ExcretionKidney
Identifiers
  • 1,4:3,6-dianhydro-2,5-di-O-nitro-D-glucitol
JSmol)
  • [O-][N+](=O)O[C@H]1[C@H]2OC[C@H](O[N+]([O-])=O)[C@H]2OC1
  • InChI=1S/C6H8N2O8/c9-7(10)15-3-1-13-6-4(16-8(11)12)2-14-5(3)6/h3-6H,1-2H2/t3-,4+,5-,6-/m1/s1 checkY
  • Key:MOYKHGMNXAOIAT-JGWLITMVSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Isosorbide dinitrate is a medication used for

systolic dysfunction together with hydralazine.[2][1] It is taken by mouth or under the tongue.[1]

Common side effects include

nitrate family of medications and works by dilating blood vessels.[1]

Isosorbide dinitrate was first written about in 1939.

generic medication.[1][5] A long-acting form exists.[1] In 2021, isosorbide was the 111th most commonly prescribed medication in the United States, with more than 5 million prescriptions.[6][7]

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

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[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

BiDil
.

References

  1. ^ 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.
  2. PMID 18441861
    .
  3. from the original on 20 December 2016.
  4. . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  5. ^ "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.
  6. ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  7. ^ "Isosorbide - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  8. PMID 7814613
    .
  9. .
  10. .
  11. .