Usage
- Isosorbide mononitrate is primarily prescribed for the prevention of angina pectoris due to coronary artery disease. It is important to note that it is not suitable for treating acute anginal attacks due to its relatively slow onset of action.
- Pharmacological Classification: Vasodilator, specifically a nitrate.
- Mechanism of Action: Isosorbide mononitrate is metabolized to nitric oxide, which activates guanylate cyclase within vascular smooth muscle. This enzyme catalyzes the formation of cyclic guanosine monophosphate (cGMP), leading to smooth muscle relaxation, vasodilation, and reduced cardiac workload.
Alternate Names
- While Isosorbide Mononitrate is the generic name, it is marketed under various brand names.
- Brand Names: Imdur, Monoket, Ismo, Imdur ER.
How It Works
- Pharmacodynamics: Isosorbide mononitrate, through its conversion to nitric oxide, causes vasodilation, primarily affecting veins and, to a lesser extent, arteries. This reduces venous return (preload) and peripheral vascular resistance (afterload), thereby decreasing cardiac workload and myocardial oxygen demand.
- Pharmacokinetics:
- Absorption: Isosorbide mononitrate is well-absorbed from the gastrointestinal tract. The extended-release formulations provide sustained release over time.
- Metabolism: Primarily metabolized in the liver by denitration to isosorbide and sorbitol.
- Elimination: Excreted mainly by the kidneys.
- Mode of Action: Nitric oxide, formed from isosorbide mononitrate, activates guanylate cyclase, leading to increased intracellular cGMP. cGMP activates protein kinase G, which causes dephosphorylation of myosin light chains, resulting in smooth muscle relaxation and vasodilation.
- Elimination Pathways: Primarily renal excretion.
Dosage
Standard Dosage
Adults:
- Immediate-release tablets: Initially, 5-10 mg orally twice daily, 7 hours apart. The dose can be increased to 10 mg every 12 hours, with a maintenance dose of 20 mg every 12 hours.
- Extended-release tablets: Initially, 30-60 mg orally once daily in the morning. The dose can be increased to 120 mg once daily, and rarely up to 240 mg once daily, if needed. Wait at least 3 days between dose increases.
Children: The safety and efficacy of isosorbide mononitrate have not been established in children.
Special Cases:
- Elderly Patients: Start with the lowest recommended adult dose.
- Patients with Renal Impairment: Dose adjustment may be necessary in severe renal impairment.
- Patients with Hepatic Dysfunction: Dose adjustment may be required.
- Patients with Comorbid Conditions: Caution is advised in patients with conditions like hypotension, hypovolemia, and increased intracranial pressure.
Clinical Use Cases
- The use of isosorbide mononitrate in specific clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations requires careful evaluation and is generally not recommended. It’s important to emphasize that this medication is meant for prophylactic use in chronic stable angina rather than acute settings.
Dosage Adjustments
- Dose adjustments may be necessary based on individual patient response and tolerability. Monitor patients closely for side effects, especially hypotension.
Side Effects
Common Side Effects
- Headache (most common), dizziness, lightheadedness, nausea, flushing.
Rare but Serious Side Effects
- Severe hypotension, syncope, reflex tachycardia, increased intracranial pressure, methemoglobinemia.
Long-Term Effects
- Tolerance to the drug can develop with continuous 24-hour dosing, which is why nitrate-free intervals are recommended.
Adverse Drug Reactions (ADR)
- Severe hypotension, methemoglobinemia.
Contraindications
- Hypersensitivity to nitrates.
- Severe hypotension, low cardiac filling pressures, hypertrophic obstructive cardiomyopathy, constrictive pericarditis, cardiac tamponade, aortic/mitral stenosis.
- Increased intracranial pressure.
- Concomitant use of phosphodiesterase-5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil, vardenafil) or riociguat.
Drug Interactions
- PDE-5 Inhibitors: Concomitant use can cause severe hypotension.
- Antihypertensives: Additive hypotensive effects.
- Alcohol: Increased risk of hypotension and dizziness.
- Riociguat: Can cause hypotension.
- Ergot Alkaloids: Can cause hypertension.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Data on the safety of isosorbide mononitrate during pregnancy is limited. Use only if clearly needed and the potential benefits outweigh the risks.
- Breastfeeding: It is unknown if isosorbide mononitrate passes into breast milk. Use with caution during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Relaxes vascular smooth muscle, leading to vasodilation and reduced cardiac workload.
- Side Effects: Headache, dizziness, hypotension.
- Contraindications: Hypersensitivity to nitrates, severe hypotension, PDE-5 inhibitor use, riociguat use.
- Drug Interactions: PDE-5 inhibitors, antihypertensives, alcohol.
- Pregnancy & Breastfeeding: Use with caution.
- Dosage: Varies depending on formulation and patient response. See detailed dosage section above.
- Monitoring Parameters: Blood pressure, heart rate.
Popular Combinations
- Isosorbide mononitrate may be used in combination with other antianginal medications like beta-blockers and calcium channel blockers.
Precautions
- General Precautions: Monitor blood pressure closely. Caution in patients with hypotension, hypovolemia, or increased intracranial pressure.
- Specific Populations: Use with caution in pregnancy and breastfeeding.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Isosorbide Mononitrate?
A: The dosage varies based on the formulation (immediate-release vs. extended-release) and individual patient needs. See the detailed dosage section above.
Q2: How should Isosorbide Mononitrate be administered?
A: Orally, with a glass of water. Extended-release tablets should be swallowed whole and not crushed or chewed. Immediate release tablets can be taken with or without food.
Q3: What are the most common side effects of Isosorbide Mononitrate?
A: Headache, dizziness, and lightheadedness are common side effects.
Q4: Can Isosorbide Mononitrate be used to treat an acute angina attack?
A: No, isosorbide mononitrate is not suitable for treating acute angina attacks due to its slow onset of action.
Q5: What are the contraindications for Isosorbide Mononitrate?
A: Contraindications include hypersensitivity to nitrates, severe hypotension, use of PDE-5 inhibitors or riociguat, increased intracranial pressure.
Q6: Does Isosorbide Mononitrate interact with other medications?
A: Yes, clinically significant interactions can occur with PDE-5 inhibitors (e.g., sildenafil), antihypertensives, alcohol.
Q7: Can Isosorbide Mononitrate be used during pregnancy or breastfeeding?
A: Use with caution during pregnancy and breastfeeding. Consult with a specialist to assess the risk-benefit ratio.
Q8: How does tolerance to Isosorbide Mononitrate develop, and how can it be prevented?
A: Tolerance can develop with continuous 24-hour nitrate exposure. A nitrate-free interval (typically 10-12 hours or overnight) helps prevent tolerance.
Q9: What should I do if a patient experiences severe hypotension while taking Isosorbide Mononitrate?
A: Discontinue the medication immediately and place the patient in a supine position with legs elevated. Monitor vital signs and provide supportive care as needed.
Q10: What are some patient counseling points for Isosorbide Mononitrate?
A: Advise patients to avoid alcohol, stand up slowly from a sitting or lying position, and report any severe headaches or dizziness immediately. Explain the importance of adhering to the prescribed dosing schedule and nitrate-free interval.
