Isosorbide dinitrate
Encyclopedia
Isosorbide dinitrate (also known as Dilatrate) 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.
Isosorbide dinitrate is sold under the brand names Isordil by Biovail
, Cedocard, Sorbitrate and Isotrate. In UK, Argentina and Hong Kong, a trade name of it is Isoket. It is also a component of BiDil.
Recent evidence suggests that the latter 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.
Nitrate
The nitrate ion is a polyatomic ion with the molecular formula NO and a molecular mass of 62.0049 g/mol. It is the conjugate base of nitric acid, consisting of one central nitrogen atom surrounded by three identically-bonded oxygen atoms in a trigonal planar arrangement. The nitrate ion carries a...
used pharmacologically
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
as a vasodilator
Vasodilation
Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...
, e.g. in angina pectoris but also for anal fissure
Anal fissure
An anal fissure is a break or tear in the skin of the anal canal. Anal fissures may be noticed by bright red anal bleeding on the toilet paper, sometimes in the toilet. If acute they may cause severe periodic pain after defecation but with chronic fissures pain intensity is often less...
, 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.
Isosorbide dinitrate is sold under the brand names Isordil by Biovail
Biovail
Biovail Corporation was a Canadian pharmaceutical company, operating internationally in all aspects of pharmaceutical products. Its major production facility was located in Steinbach, Manitoba...
, Cedocard, Sorbitrate and Isotrate. In UK, Argentina and Hong Kong, a trade name of it is Isoket. It is also a component of BiDil.
Uses
It is more useful in preventing angina attacks than reversing them once they have commenced. It may be given as a tablet for the treatment of an angina attack.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 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:- Impaired biotransformation of ISDN 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 ISDN
- Plasma volume expansion
- The oxidative stress hypothesis (proposed by Munzel et al. in 1995).
Recent evidence suggests that the latter 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.