“If this blog helped you out, don’t keep it to yourself—share the link on your socials!” 👍 “Like what you read? Spread the love and share this blog on your social media.” 👍 “Found this useful? Hit share and let your friends know too!” 👍 “If you enjoyed this post, please share the URL with your friends online.” 👍 “Sharing is caring—drop this link on your social media if it helped you.”

Sunday, July 27, 2025

Isosorbide mononitrate


Isosorbide Mononitrate is a long-acting nitrate used primarily in the prevention and long-term management of angina pectoris due to coronary artery disease. It belongs to the class of organic nitrates and functions as a vasodilator, reducing myocardial oxygen demand by decreasing preload and afterload. Unlike glyceryl trinitrate (nitroglycerin), which is typically used for acute anginal attacks, isosorbide mononitrate is used for prophylaxis, not acute relief.


Brand Names

  • Imdur®

  • Monoket®

  • ISMO®

  • Isodur®

  • Elantan®

  • Mononitrate Durules®

  • Cedocard Retard®

(Brand names vary depending on country and manufacturer.)

Pharmacological Class

  • Therapeutic class: Antianginal agent

  • Pharmacologic class: Nitrate vasodilator

  • ATC code: C01DA14

  • Schedule: Prescription-only (Rx)

Mechanism of Action

Isosorbide mononitrate acts as a nitric oxide (NO) donor. After absorption, it is converted to nitric oxide, which activates guanylate cyclase in vascular smooth muscle. This leads to increased cyclic guanosine monophosphate (cGMP), causing:

  • Relaxation of vascular smooth muscle

  • Dilation of veins > arteries

  • Reduction in preload (venodilation → decreased left ventricular filling pressure)

  • Reduction in afterload (mild arterial dilation)

  • Improved myocardial oxygen supply-demand balance

Notably, isosorbide mononitrate does not undergo significant first-pass metabolism, unlike isosorbide dinitrate, making its oral bioavailability more consistent and reliable.

Therapeutic Indications

Approved Uses

  • Prophylaxis of angina pectoris due to coronary artery disease

  • Adjunct in chronic heart failure (off-label in some countries)

  • Management of esophageal spasm or pulmonary hypertension (off-label)

  • Prophylaxis of nitrate-responsive chest pain

Not for Acute Relief

  • Isosorbide mononitrate is not indicated for the immediate relief of acute angina attacks. Short-acting agents like sublingual nitroglycerin are preferred in such cases.

Formulations and Dosage

Oral Immediate-Release Tablets

  • Typical adult dose: 20 mg twice daily, 7 hours apart (e.g., 8 AM and 3 PM) to avoid nitrate tolerance.

Oral Extended-Release Tablets (Once-Daily Dosing)

  • Initial dose: 30–60 mg once daily in the morning.

  • Maintenance: May be titrated to 120 mg once daily.

  • Maximum: 120 mg once daily.

Administration Notes

  • Take on an empty stomach with a full glass of water.

  • Do not crush or chew extended-release tablets.

  • Dosing-free interval (typically overnight) is crucial to minimize nitrate tolerance.

Contraindications

  • Hypersensitivity to nitrates or formulation components

  • Concurrent use of PDE5 inhibitors (e.g., sildenafil, tadalafil, vardenafil) due to risk of profound hypotension

  • Severe hypotension (SBP < 90 mmHg)

  • Acute myocardial infarction with low filling pressures

  • Increased intracranial pressure or recent head trauma

  • Severe anemia

  • Pericardial tamponade or restrictive cardiomyopathy

Adverse Effects

Common

  • Headache (up to 50%): Due to vasodilation; usually diminishes with continued use

  • Dizziness, lightheadedness

  • Flushing

  • Orthostatic hypotension

  • Nausea

Less Common

  • Palpitations

  • Fatigue

  • Skin rash

  • Weakness

  • Syncope

Rare

  • Severe hypotension

  • Paradoxical bradycardia

  • Methemoglobinemia (rare, more common with high-dose nitrates)

Precautions and Warnings

  • Avoid abrupt discontinuation, especially in patients with angina, due to potential rebound ischemia.

  • Titrate dose carefully in elderly patients to reduce orthostatic hypotension risk.

  • Use cautiously in hypovolemia, hypertrophic cardiomyopathy, or aortic/mitral stenosis.

  • Monitor for nitrate tolerance: Ensure dosing schedule includes a daily nitrate-free interval.

  • Safety in pregnancy: Category C (risk not ruled out; use only if benefits justify potential risk).

  • Lactation: Limited data; avoid or monitor infant for hypotension.

Nitrate Tolerance

A key concern with long-acting nitrates is the development of tolerance (tachyphylaxis). This refers to a decrease in response with continuous exposure, often within 24–48 hours.

Mechanisms

  • Depletion of sulfhydryl groups

  • Increased production of superoxide radicals

  • Activation of neurohormonal pathways (e.g., renin-angiotensin)

Prevention

  • Implement nitrate-free intervals of 10–12 hours (e.g., overnight)

  • Avoid continuous exposure (e.g., transdermal patches removed for 10–12 hours/day)

Drug Interactions

Major Interactions

  • Phosphodiesterase-5 (PDE5) inhibitors: Profound hypotension, life-threatening

    • Sildenafil (Viagra®)

    • Tadalafil (Cialis®)

    • Vardenafil (Levitra®)

    • Avanafil

  • Riociguat: Additive hypotension via guanylate cyclase stimulation

  • Other antihypertensives: Potentiation of blood pressure lowering

    • Beta-blockers

    • Calcium channel blockers

    • ACE inhibitors/ARBs

  • Alcohol: Additive hypotensive effects

  • Ergot alkaloids: Nitrate-induced hypotension may enhance ischemia by reducing coronary perfusion

Pharmacodynamic Considerations

  • Combining nitrates with vasodilators or CNS depressants can amplify dizziness and hypotension

  • Avoid concurrent chronic use with other long-acting nitrates, as this can reduce efficacy due to tolerance

Pharmacokinetics

  • Absorption: Rapid and complete from GI tract

  • Bioavailability: ~90–100% (does not undergo first-pass metabolism)

  • Onset: 30–60 minutes (immediate-release); ~1–2 hours (extended-release)

  • Peak plasma: ~1 hour (immediate); ~4–5 hours (extended)

  • Half-life: ~5 hours

  • Duration of action: 6–8 hours (immediate); up to 24 hours (extended)

  • Metabolism: Hepatic to inactive metabolites

  • Excretion: Primarily via kidneys (renal)

Monitoring Parameters

  • Blood pressure and heart rate (especially with dose changes)

  • Frequency of anginal attacks

  • Signs of hypotension

  • Tolerance development (monitor efficacy over time)

  • Orthostatic symptoms

Clinical Use Notes

  • For chronic stable angina, isosorbide mononitrate is part of second-line therapy after beta-blockers or calcium channel blockers.

  • Also used in combination regimens with antiplatelets (aspirin), statins, and other antianginal agents.

  • Not suitable as monotherapy in unstable angina or acute coronary syndrome.

Use in Special Populations

Elderly

  • Start at lower doses.

  • Increased risk of postural hypotension and falls.

Renal Impairment

  • No dose adjustment usually needed.

Hepatic Impairment

  • Use caution; reduced metabolism may increase drug levels.

Pregnancy and Lactation

  • Category C: Avoid unless necessary.

  • Consider alternative agents for angina during pregnancy if possible.

Comparison with Isosorbide Dinitrate

FeatureIsosorbide MononitrateIsosorbide Dinitrate
Active MetaboliteYes (parent drug)Prodrug (converted to mononitrate)
BioavailabilityHigh (~90–100%)Variable (~20–25%)
Duration of actionLongerShorter
Dose frequencyOnce or twice daily2–3 times daily
First-pass metabolismMinimalExtensive



on
Labels:

No comments:

Post a Comment

Subscribe to: Post Comments (Atom)