Isosorbide dinitrate is a medication used for

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

esophageal spasms Diffuse esophageal spasm (DES), also known as distal esophageal spasm, is a condition characterized by uncoordinated contractions of the esophagus, which may cause difficulty swallowing (dysphagia) or regurgitation. In some cases, it may cause sym ...

, and to treat and prevent chest pain from not enough blood flow to the heart. 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 been ...

. It is taken

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

or under the tongue. Common side effects include

headache Headache 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 in those with severe headaches. Headaches can occur as a result ...

, lightheadedness with standing, and blurred vision. Severe side effects include

low blood pressure Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...

. It is unclear if use in

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

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

PDE5 Inhibitors A phosphodiesterase type 5 inhibitor (PDE5 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 supplyi ...

. Isosorbide dinitrate is in the

nitrate Nitrate is a polyatomic ion A polyatomic ion, also known as a molecular ion, is a covalent bonded set of two or more atoms, or of a metal complex, that can be considered to behave as a single unit and that has a net charge that is not zer ...

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 ...

. 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 2020, it was the 299th most commonly prescribed medication in the United States, with more than 1million 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 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 (proposed by Munzel et al. in 1995) 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.

Other side effects

In the short run, isosorbide dinitrate can cause severe headaches, necessitating analgesic administration for relief of pain, as well as severe hypotension, and, in certain cases,

bradycardia Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, a ...

. Rarely occurring are allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); fainting; fast or slow heartbeat; nausea; new or worsening chest pain; vomiting.

Mechanism of action

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

nitric oxide Nitric oxide (nitrogen oxide 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 denoted by a dot in its che ...

(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 guanos ...

(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.

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. (formerly Valeant Pharmaceuticals International, Inc.) is a Canadian multinational specialty pharmaceutical company based in Laval, Quebec, Canada. It develops, manufactures and markets pharmaceutical products and ...

, 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 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 (an arteriol ...

References

External links

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