Isosorbide dinitrate

Isosorbide dinitrate
Systematic (IUPAC) name
1,4:3,6-dianhydro-2,5-di-O-nitro-D-glucitol
Clinical data
AHFS/Drugs.com monograph
  • US: C (Risk not ruled out)
  • ℞ (Prescription only)
Oral
Pharmacokinetic data
Bioavailability 10–90%, average 25%
Metabolism Hepatic
Half-life 1 hour
Excretion Renal
Identifiers
87-33-2 Yes
C01DA08 C05AE02
PubChem CID 6883
DrugBank DB00883 Yes
ChemSpider 6619 Yes
UNII IA7306519N Yes
KEGG D00516 Yes
ChEBI CHEBI:6061 Yes
ChEMBL CHEMBL2171310 
Synonyms (3R,3aS,6S,6aS)-hexahydrofuro[3,2-b]furan-3,6-diyl dinitrate
Chemical data
Formula C6H8N2O8
236.136 g/mol
  (what is this?)  (verify)

Isosorbide dinitrate, ISDN, is a nitrate used pharmacologically as a vasodilator, e.g. in angina pectoris, but also for anal fissure, a condition known to involve decreased blood supply leading to poor healing. It is also used as a direct vasodilator to treat congestive heart failure.

It is used for heart-related chest pain, in addition to other medications for congestive heart failure, and for esophageal spasms.[1]

Isosorbide dinitrate is sold in the USA 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. It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[2]

Medical uses

It is used for angina, in addition to other medications for congestive heart failure, and for esophageal spasms.[1]

Advantages

Long-acting nitrates can be more useful as they are generally more effective and stable in the short term.

Disadvantages

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 ISDN 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 ISDN
  3. Plasma volume expansion
  4. The oxidative stress hypothesis (proposed by Munzel et al. in 1995)

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: [3] these include endothelial and autonomic dysfunction. [4] In the short run, ISDN can cause severe headaches, necessitating analgesic (very rarely up to morphine) 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.

Synthesis

Isosorbide dinitrate synthesis:[5][6] U.S. Patent 4,156,736 DE 2623800

References

  1. ↑ 1.0 1.1 "Isosorbide Dinitrate/Mononitrate". The American Society of Health-System Pharmacists. Retrieved Apr 21, 2014.
  2. ↑ "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014.
  3. ↑ (Nakamura et al.)
  4. ↑ (Gori et al.).
  5. ↑ Goldberg, L. (1948). "Pharmacological Properties of Sorbide Dinitrate". Acta Physiologica Scandinavica 15 (2): 173–87. doi:10.1111/j.1748-1716.1948.tb00494.x. PMID 18863140.
  6. ↑ Pharmacol Exp Ther October 1939 67:187-190.