Isosorbide dinitrate

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Isosorbide dinitrate
Isosorbide dinitrate.svg
Isosorbide dinitrate ball-and-stick.png
Systematic (IUPAC) name
1,4:3,6-dianhydro-2,5-di-O-nitro-D-glucitol
Clinical data
AHFS/Drugs.com monograph
Pregnancy cat. C (US)
Legal status Prescription only
Routes Oral
Pharmacokinetic data
Bioavailability 10–90%, average 25%
Metabolism Hepatic
Half-life 1 hour
Excretion Renal
Identifiers
CAS number 87-33-2 YesY
ATC code C01DA08 C05AE02
PubChem CID 6883
DrugBank DB00883
ChemSpider 6619 YesY
UNII IA7306519N YesY
KEGG D00516 YesY
ChEBI CHEBI:6061 YesY
ChEMBL CHEMBL2171310 N
Synonyms (3R,3aS,6S,6aS)-hexahydrofuro[3,2-b]furan-3,6-diyl dinitrate
Chemical data
Formula C6H8N2O8 
Mol. mass 236.136 g/mol
 N (what is this?)  (verify)

Isosorbide dinitrate or ISDN for short is a nitrate used pharmacologically as a vasodilator, e.g. in angina pectoris but also for anal fissure, a condition which is 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, a list of the most important medication needed in a basic health system.[2]

Medical uses[edit]

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

Advantages[edit]

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

Disadvantages[edit]

After long term use for treating chronic conditions, tolerance may develop in a patient 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).

Recent evidence suggests that 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, studies have shown that nitrate tolerance is associated with vascular abnormalities which have the potential to worsen patients prognosis (Nakamura et al.): these include endothelial and autonomic dysfunction (Gori et al.). 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.

References[edit]

  1. ^ a b "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.