Clinical data | |
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Trade names | Isordil, others [1] |
Other names | ISDN; (3R,3aS,6S,6aS)-hexahydrofuro[3,2-b]furan-3,6-diyl dinitrate |
AHFS/Drugs.com | Monograph |
MedlinePlus | a682348 |
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Routes of administration | By mouth |
ATC code | |
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Pharmacokinetic data | |
Bioavailability | 10–90%, average 25% |
Metabolism | Liver |
Elimination half-life | 1 hour |
Excretion | Kidney |
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CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.001.583 |
Chemical and physical data | |
Formula | C6H8N2O8 |
Molar mass | 236.136 g·mol−1 |
3D model (JSmol) | |
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Isosorbide dinitrate is a medication used for heart failure, esophageal spasms, and to treat and prevent chest pain from not enough blood flow to the heart. [1] It has been found to be particularly useful in heart failure due to systolic dysfunction together with hydralazine. [2] [1] It is taken by mouth or under the tongue. [1]
Common side effects include headache, lightheadedness with standing, and blurred vision. [1] Severe side effects include low blood pressure. [1] It is unclear if use in pregnancy is safe for the baby. [1] It should not be used together with PDE5 Inhibitors. [1] Isosorbide dinitrate is in the nitrate family of medications and works by dilating blood vessels. [1]
Isosorbide dinitrate was first written about in 1939. [3] It is on the World Health Organization's List of Essential Medicines. [4] Isosorbide dinitrate is available as a generic medication. [1] [5] A long-acting form exists. [1] In 2022, isosorbide was the 119th most commonly prescribed medication in the United States, with more than 5 million prescriptions. [6] [7]
It is used for angina, in addition to other medications for congestive heart failure, and for esophageal spasms. [1] 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.
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:
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: [9] these include endothelial and autonomic dysfunction. [10]
Similar to other nitrites and organic nitrates, isosorbide dinitrate is converted to nitric oxide (NO), an active intermediate compound which activates the enzyme guanylate cyclase (atrial natriuretic peptide receptor A). This stimulates the synthesis of cyclic guanosine 3',5'-monophosphate (cGMP) 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. [11]
Isosorbide dinitrate is sold in the US under the brand names Dilatrate-SR by Schwarz and Isordil by Valeant, 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.
An antianginal is a drug used in the treatment of angina pectoris, a symptom of ischaemic heart disease.
Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel walls are composed of endothelial tissue and a basal membrane lining the lumen of the vessel, concentric smooth muscle layers on top of endothelial tissue, and an adventitia over the smooth muscle layers. Relaxation of the smooth muscle layer allows the blood vessel to dilate, as it is held in a semi-constricted state by sympathetic nervous system activity. Vasodilation is the opposite of vasoconstriction, which is the narrowing of blood vessels.
Prednisone is a glucocorticoid medication mostly used to suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium due to cancer and adrenal insufficiency along with other steroids. It is taken by mouth.
Nifedipine, sold under the brand name Procardia among others, is a calcium channel blocker medication used to manage angina, high blood pressure, Raynaud's phenomenon, and premature labor. It is one of the treatments of choice for Prinzmetal angina. It may be used to treat severe high blood pressure in pregnancy. Its use in preterm labor may allow more time for steroids to improve the baby's lung function and provide time for transfer of the mother to a well qualified medical facility before delivery. It is a calcium channel blocker of the dihydropyridine type. Nifedipine is taken by mouth and comes in fast- and slow-release formulations.
Sotalol, sold under the brand name Betapace among others, is a medication used to treat and prevent abnormal heart rhythms. Evidence does not support a decreased risk of death with long term use. It is taken by mouth or given by injection into a vein.
Isosorbide mononitrate, sold under many brand names, is a medication used for heart-related chest pain (angina), heart failure and esophageal spasms. It can be used both to treat and to prevent heart-related chest pain; however, it is generally less preferred than beta blockers or calcium channel blockers. It is taken by mouth.
Vasospasm refers to a condition in which an arterial spasm leads to vasoconstriction. This can lead to tissue ischemia and tissue death (necrosis).
A phosphodiesterase type 5 inhibitor is a vasodilating 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 vessels supplying various tissues. These drugs dilate the corpora cavernosa of the penis, facilitating erection with sexual stimulation, and are used in the treatment of erectile dysfunction (ED). Sildenafil was the first effective oral treatment available for ED. Because PDE5 is also present in the smooth muscle of the walls of the arterioles within the lungs, two PDE5 inhibitors, sildenafil and tadalafil, are FDA-approved for the treatment of pulmonary hypertension. As of 2019, the wider cardiovascular benefits of PDE5 inhibitors are being appreciated.
Cilostazol, sold under the brand name Pletal among others, is a medication used to help the symptoms of intermittent claudication in peripheral vascular disease. If no improvement is seen after 3 months, stopping the medication is reasonable. It may also be used to prevent stroke. It is taken by mouth.
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 been found to be particularly useful in heart failure, together with isosorbide dinitrate, for treatment of people of African descent. It is given by mouth or by injection into a vein. Effects usually begin around 15 minutes and last up to six hours.
Variant angina, also known as Prinzmetal angina,vasospastic angina, angina inversa, coronary vessel spasm, or coronary artery vasospasm, is a syndrome typically consisting of angina. Variant angina differs from stable angina in that it commonly occurs in individuals who are at rest or even asleep, whereas stable angina is generally triggered by exertion or intense exercise. Variant angina is caused by vasospasm, a narrowing of the coronary arteries due to contraction of the heart's smooth muscle tissue in the vessel walls. In comparison, stable angina is caused by the permanent occlusion of these vessels by atherosclerosis, which is the buildup of fatty plaque and hardening of the arteries.
Nitroglycerin, also known as glyceryl trinitrate (GTN), is a vasodilator used for heart failure, high blood pressure (hypertension), anal fissures, painful periods, and to treat and prevent chest pain caused by decreased blood flow to the heart (angina) or due to the recreational use of cocaine. This includes chest pain from a heart attack. It is taken by mouth, under the tongue, applied to the skin, or by injection into a vein.
Carvedilol, sold under the brand name Coreg among others, is a beta blocker medication, that may be prescribed for the treatment of high blood pressure (hypertension) and chronic heart failure with reduced ejection fraction. Beta-blockers as a collective medication class are not recommended as routine first-line treatment of high blood pressure for all patients, due to evidence demonstrating less effective cardiovascular protection and a less favourable safety profile when compared to other classes of blood pressure-lowering medications.
Hydralazine/isosorbide dinitrate, sold under the brand name Bidil, is a fixed-dose combination medication used to treat self-identified Black people with congestive heart failure. It is a combination of hydralazine hydrochloride and isosorbide dinitrate.
Torasemide, also known as torsemide, is a diuretic medication used to treat fluid overload due to heart failure, kidney disease, and liver disease. It is a less preferred treatment for high blood pressure. It is taken by mouth or by injection into a vein.
Nebivolol is a beta blocker used to treat high blood pressure and heart failure. As with other β-blockers, it is generally a less preferred treatment for high blood pressure. It may be used by itself or with other blood pressure medication. It is taken by mouth.
Solifenacin, sold as the brand name Vesicare among others, is a medicine used to treat overactive bladder and neurogenic detrusor overactivity (NDO). It may help with incontinence, urinary frequency, and urinary urgency.
Prostaglandin E1 (PGE1) is a naturally occurring prostaglandin and is also used as a medication (alprostadil).
Beta adrenergic agonists or beta agonists are medications that relax muscles of the airways, causing widening of the airways and resulting in easier breathing. They are a class of sympathomimetic agents, each acting upon the beta adrenoceptors. In general, pure beta-adrenergic agonists have the opposite function of beta blockers: beta-adrenoreceptor agonist ligands mimic the actions of both epinephrine- and norepinephrine- signaling, in the heart and lungs, and in smooth muscle tissue; epinephrine expresses the higher affinity. The activation of β1, β2 and β3 activates the enzyme, adenylate cyclase. This, in turn, leads to the activation of the secondary messenger cyclic adenosine monophosphate (cAMP); cAMP then activates protein kinase A (PKA) which phosphorylates target proteins, ultimately inducing smooth muscle relaxation and contraction of the cardiac tissue.
A nitrovasodilator is a pharmaceutical agent that causes vasodilation by donation of nitric oxide (NO), and is mostly used for the treatment and prevention of angina pectoris.