Isosorbide dinitrate is a medication used for

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...

, esophageal spasms, and to treat and prevent

angina pectoris Angina, also known as angina pectoris, is chest pain or pressure, usually caused by insufficient blood flow to the heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typically the result of part ...

. It has been found to be particularly useful in heart failure due to systolic dysfunction together with

hydralazine Hydralazine, sold under the brand name Apresoline among others, is a medication used to treat high blood pressure and heart failure. This includes high blood pressure in pregnancy and very high blood pressure resulting in symptoms. It has bee ...

. It is taken

by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

or under the tongue. Common side effects include

headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...

, lightheadedness with standing, and

blurred vision Blurred vision is an ocular symptom where vision becomes less precise and there is added difficulty to resolve fine details. Temporary blurred vision may involve dry eyes, eye infections, alcohol poisoning, hypoglycemia, or low blood pressur ...

. Severe side effects include

low blood pressure Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...

. It is unclear if use in

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

is safe for the baby. It should not be used together with

PDE5 Inhibitors A phosphodiesterase type 5 inhibitor (PDE5 inhibitor) is a vasodilating medication, drug that works by blocking the degradative action of cGMP-specific phosphodiesterase type 5 (PDE5) on cyclic GMP in the smooth muscle cells lining the blood vess ...

. Isosorbide dinitrate is in the

nitrate Nitrate is a polyatomic ion with the chemical formula . salt (chemistry), Salts containing this ion are called nitrates. Nitrates are common components of fertilizers and explosives. Almost all inorganic nitrates are solubility, soluble in wa ...

family of medications and works by dilating blood vessels. Isosorbide dinitrate was first written about in 1939. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. Isosorbide dinitrate is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

. A long-acting form exists. In 2022, isosorbide was the 119th most commonly prescribed medication in the United States, with more than 5million prescriptions.

Medical uses

It is used for angina, in addition to other medications for congestive heart failure, and for esophageal spasms. 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 A nitrovasodilator is a pharmaceutical agent that causes vasodilation (widening of blood vessels) by donation of nitric oxide (NO), and is mostly used for the treatment and prevention of angina pectoris. This group of drugs includes nitrates (es ...

have been thoroughly investigated in the last 30 years and several hypotheses have been proposed. These include: # Impaired biotransformation of isosorbide dinitrate 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 isosorbide dinitrate # Plasma volume expansion # The oxidative stress hypothesis 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: these include endothelial and autonomic dysfunction.

Mechanism of action

Similar to other nitrites and organic nitrates, isosorbide dinitrate is converted to

nitric oxide Nitric oxide (nitrogen oxide, nitrogen monooxide, or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes den ...

(NO), an active intermediate compound which activates the enzyme

guanylate cyclase Guanylate cyclase (EC 4.6.1.2, also known as guanyl cyclase, guanylyl cyclase, or GC; systematic name GTP diphosphate-lyase (cyclizing; 3′,5′-cyclic-GMP-forming)) is a lyase enzyme that converts guanosine triphosphate (GTP) to cyclic guanosi ...

(atrial natriuretic peptide receptor A). This stimulates the synthesis of cyclic guanosine 3',5'-monophosphate (

cGMP CGMP is an initialism. It can refer to: *cyclic guanosine monophosphate (cGMP) * current good manufacturing practice (cGMP) *CGMP, Cisco Group Management Protocol, the Cisco version of Internet Group Management Protocol The Internet Group Manag ...

) 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.

Society and culture

Isosorbide dinitrate is sold in the US under the brand names Dilatrate-SR by Schwarz and Isordil by

Valeant Bausch Health Companies Inc. is a global, diversified American-Canadian pharmaceutical company. Its global corporate headquarters are located in Laval, Quebec, Canada, and its U.S. headquarters are in Bridgewater, New Jersey. It develops, manufa ...

, according to FDA Orange Book. It is sold under the trade name Isoket in the United Kingdom, Argentina, and Hong Kong. It is also a component of BiDil.

References

{{Portal bar, Medicine Nitrate esters Antianginals Furofurans World Health Organization essential medicines Wikipedia medicine articles ready to translate Drugs developed by Wyeth Drugs developed by Pfizer