Isosorbide mononitrate

Drug Information: Isosorbide mononitrate

Isosorbide mononitrate is a vasodilator belonging to the nitrate class of medications. It is primarily used to prevent angina pectoris (chest pain) caused by coronary artery disease. It works by relaxing blood vessels, making it easier for the heart to pump blood and reducing the heart’s oxygen demand. Isosorbide mononitrate is a long-acting nitrate, meaning its effects last for a longer period compared to other nitrates like nitroglycerin. It’s often prescribed for daily use to prevent angina attacks, unlike nitroglycerin which is used for acute relief.

Category

Vasodilator (including nitrates)

Mechanism of Action

Isosorbide mononitrate exerts its vasodilatory effects by being converted to nitric oxide (NO) in the body. Nitric oxide is a potent vasodilator. Here’s a detailed breakdown:

*Nitric Oxide Release: Once administered, isosorbide mononitrate is metabolized, leading to the release of nitric oxide in vascular smooth muscle.

*Guanylate Cyclase Activation: Nitric oxide activates guanylate cyclase, an enzyme that catalyzes the conversion of guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP).

*Smooth Muscle Relaxation: Increased levels of cGMP then activate protein kinases, leading to the dephosphorylation of myosin light chains. This dephosphorylation inhibits the interaction of myosin with actin, the process responsible for muscle contraction. As a result, the vascular smooth muscle relaxes.

*Vasodilation: This relaxation of smooth muscle causes vasodilation, meaning the blood vessels widen. This vasodilation occurs in both arteries and veins. Venous dilation reduces preload (the amount of blood returning to the heart), while arterial dilation reduces afterload (the resistance the heart must pump against).

*Reduced Cardiac Workload: By reducing both preload and afterload, isosorbide mononitrate decreases the heart’s workload and oxygen demand. This is particularly beneficial in patients with angina, where the heart muscle isn’t receiving enough oxygen.

*Coronary Artery Dilation: Isosorbide mononitrate can also dilate coronary arteries, improving blood flow to the heart muscle itself, further alleviating angina symptoms.

Clinical Uses

Isosorbide mononitrate is primarily used for the prophylaxis (prevention) of angina pectoris due to coronary artery disease. It’s not intended for immediate relief of acute angina attacks, for which shorter-acting nitrates like nitroglycerin are used. Here’s a more detailed look at its clinical applications:

*Prevention of Angina: The main use of isosorbide mononitrate is to reduce the frequency and severity of angina episodes. It is typically prescribed for long-term management to improve exercise tolerance and overall quality of life in patients with stable angina.

*Combination Therapy: Isosorbide mononitrate is often used in conjunction with other anti-anginal medications, such as beta-blockers or calcium channel blockers, to provide comprehensive management of angina symptoms.

*Heart Failure (Less Common): In some cases, nitrates like isosorbide mononitrate may be used (often in combination with hydralazine) to treat heart failure, particularly in patients who cannot tolerate ACE inhibitors or ARBs. This is because nitrates can reduce preload and afterload, easing the strain on the heart.

*Esophageal Spasms (Off-Label): Although not a primary indication, isosorbide mononitrate has been used off-label to treat esophageal spasms, as its vasodilatory effects can relax the esophageal muscles.

Dosage

Adults: The typical starting dose of isosorbide mononitrate is 30-60 mg once daily. Depending on the patient’s response and tolerance, the dose may be increased gradually to a maximum of 240 mg daily, usually administered in divided doses (e.g., 120 mg twice daily). Extended-release formulations allow for once-daily dosing.

Route of Administration: Oral (tablets or extended-release capsules).

Pediatrics: The safety and efficacy of isosorbide mononitrate in pediatric patients have not been established. Therefore, it is generally not recommended for use in children. If used, dosing would be based on weight and clinical indication and would require careful monitoring by a physician. Consult a pediatric cardiologist or specialist before administering.

Important Notes: To minimize the development of tolerance, some healthcare providers recommend a nitrate-free interval of 10-14 hours each day. The timing of doses should be carefully considered to allow for this nitrate-free period, typically at night. Always consult a doctor before starting this medication.

Indications

* Prevention of angina pectoris due to coronary artery disease.
* Management of chronic stable angina.
* Adjunctive treatment in heart failure (less common).

Contraindications

* Hypersensitivity to isosorbide mononitrate or other nitrates.
* Concurrent use with phosphodiesterase-5 (PDE5) inhibitors (e.g., sildenafil, tadalafil, vardenafil) due to the risk of severe hypotension. A minimum of 24-48 hours (depending on the PDE5 inhibitor) should pass between taking a PDE5 inhibitor and a nitrate.
* Acute circulatory failure or shock.
* Severe anemia.
* Marked hypotension (systolic blood pressure <90 mmHg).
* Hypertrophic obstructive cardiomyopathy (HOCM), also known as idiopathic hypertrophic subaortic stenosis (IHSS), as nitrates can worsen the outflow obstruction.
* Increased intracranial pressure.

FAQ

Q: What is Isosorbide mononitrate used for?
A: Isosorbide mononitrate is primarily used to prevent angina (chest pain) caused by heart disease. It helps to relax blood vessels, making it easier for the heart to pump blood.

Q: How should I take Isosorbide mononitrate?
A: Take Isosorbide mononitrate exactly as prescribed by your doctor. It is usually taken once or twice daily. Follow your doctor’s instructions carefully, and do not change the dose without consulting them.

Q: What are the common side effects of Isosorbide mononitrate?
A: Common side effects include headache, dizziness, lightheadedness, and flushing. These side effects are usually mild and tend to decrease with continued use.

Q: Can I take Isosorbide mononitrate with other medications?
A: Isosorbide mononitrate can interact with other medications, especially those used to treat erectile dysfunction (PDE5 inhibitors) and other blood pressure medications. Tell your doctor about all the medications you are taking.

Q: What should I do if I experience a severe headache while taking Isosorbide mononitrate?
A: Headaches are a common side effect. You can try taking an over-the-counter pain reliever like acetaminophen. If the headache is severe or persistent, contact your doctor.

Q: How long does it take for Isosorbide mononitrate to start working?
A: Isosorbide mononitrate is a long-acting medication, so it may take several days or weeks to reach its full effect in preventing angina. It is not for immediate relief of chest pain.

Q: Can I stop taking Isosorbide mononitrate suddenly?
A: Do not stop taking Isosorbide mononitrate suddenly, as this can lead to angina symptoms returning. Talk to your doctor about gradually reducing the dose before stopping the medication completely.

Q: Is there a way to prevent tolerance to this medication?
A: Yes, to prevent tolerance, your doctor might prescribe a regimen that includes a “nitrate-free interval,” typically overnight. This allows your body to remain responsive to the medication.