Is isosorbide mononitrate a short-acting nitrate?

Isosorbide Mononitrate: Duration of Action

Isosorbide mononitrate is not a short-acting nitrate but rather a long-acting nitrate with effects lasting 12 to 24 hours when used in its standard formulation. 1, 2

Pharmacological Properties

• Isosorbide mononitrate is the major active metabolite of isosorbide dinitrate and works primarily through vasodilation of veins, arteries, and arterioles by promoting the release of nitric oxide 2, 3
• Unlike short-acting nitrates such as sublingual nitroglycerin (which acts for 1-7 minutes), isosorbide mononitrate has a prolonged duration of action 1
• The mean plasma elimination half-life of isosorbide mononitrate is approximately 5 hours, but its clinical effects last significantly longer 3
• According to the ACC/AHA guidelines, standard oral isosorbide mononitrate has a duration of effect of 12-24 hours 1

Formulations and Duration

• Standard oral isosorbide mononitrate is typically dosed as 20 mg twice daily with effects lasting 12-24 hours 1
• Extended-release/slow-release formulations are dosed once daily (60-240 mg) and provide sustained effects throughout the day 1, 4
• Extended-release formulations have a quick onset of action (30 minutes) with effects evident for up to 17 hours 4
• Clinical studies show that extended-release isosorbide mononitrate (120 and 240 mg) significantly prolongs exercise time 4 and 12 hours after dosing during long-term therapy 5

Comparison with Other Nitrates

• Short-acting nitrates include:
  • Sublingual nitroglycerin tablets (duration: 1-7 minutes) 1
  • Nitroglycerin spray (similar to sublingual tablets) 1
• Medium-acting nitrates include:
  • Oral isosorbide dinitrate (duration: up to 8 hours) 1
• Long-acting nitrates include:
  • Isosorbide mononitrate (duration: 12-24 hours) 1
  • Transdermal nitroglycerin patches (duration: 8-12 hours during intermittent therapy) 1

Clinical Implications

• The prolonged duration of action of isosorbide mononitrate makes it suitable for prophylactic treatment of angina rather than for acute symptom relief 6
• For acute angina attacks, short-acting nitrates like sublingual nitroglycerin are preferred 1, 7
• The extended duration of action allows for once-daily dosing with extended-release formulations, improving patient compliance compared to multiple daily dosing regimens 6, 8

Important Considerations

• Despite its long duration of action, continuous therapy with isosorbide mononitrate can lead to nitrate tolerance 2, 6
• To prevent tolerance development, a "nitrate-free interval" of at least 10 hours is recommended 1, 2
• Once-daily dosing of extended-release isosorbide mononitrate helps maintain efficacy by providing this nitrate-free interval 6, 5
• Common side effects include headaches and hypotension, similar to other nitrate preparations 1, 2

Practical Dosing Recommendations

• For angina prophylaxis, extended-release isosorbide mononitrate 60-240 mg once daily in the morning is effective and minimizes tolerance 5
• Standard isosorbide mononitrate can be given as 20 mg twice daily, with doses spaced to allow a nitrate-free interval 1, 7
• Asymmetric dosing (e.g., morning and early afternoon) may be more effective than evenly spaced doses for preventing tolerance 7