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Isosorbide dinitrate

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Isosorbide dinitrate

Isosorbide dinitrate
Systematic (IUPAC) name
1,4:3,6-dianhydro-2,5-di-O-nitro-D-glucitol
Clinical data
AHFS/Drugs.com
Pregnancy
category
  • US: C (Risk not ruled out)
Legal status
  • (Prescription only)
Routes of
administration
Oral
Pharmacokinetic data
Bioavailability 10–90%, average 25%
Metabolism Hepatic
Biological half-life 1 hour
Excretion Renal
Identifiers
CAS Registry Number  Y
ATC code C01 C05
PubChem CID:
DrugBank  Y
ChemSpider  Y
UNII  Y
KEGG  Y
ChEBI  Y
ChEMBL  N
Synonyms (3R,3aS,6S,6aS)-hexahydrofuro[3,2-b]furan-3,6-diyl dinitrate
Chemical data
Formula C6H8N2O8
Molecular mass 236.136 g/mol
 N   

Isosorbide dinitrate, ISDN, is a nitrate used pharmacologically as a vasodilator for angina (heart-related chest pain), congestive heart failure, and esophageal spasms.[1]

Isosorbide dinitrate is sold in the USA under the brand names Dilatrate-SR by health system.[2]

Contents

  • Medical uses 1
  • Advantages 2
  • Disadvantages 3
  • Synthesis 4
  • References 5

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. ^ a b "Isosorbide Dinitrate/Mononitrate". The American Society of Health-System Pharmacists. Retrieved Apr 21, 2014. 
  2. ^ "WHO Model List of EssentialMedicines" (PDF). 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.  
  6. ^ Pharmacol Exp Ther October 1939 67:187-190.
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