Overview
Isosorbide dinitrate is an organic nitrate vasodilator used primarily for the prophylaxis and treatment of angina pectoris. It works by relaxing vascular smooth muscle, leading to venous and arterial dilation, which reduces myocardial oxygen demand and improves coronary blood flow.
Mechanism of Action
Isosorbide dinitrate is converted to nitric oxide (NO) in vascular smooth muscle cells. NO activates guanylate cyclase, increasing cyclic guanosine monophosphate (cGMP), which leads to dephosphorylation of myosin light chains and smooth muscle relaxation. This causes venous dilation (reducing preload) and arterial dilation (reducing afterload), decreasing myocardial oxygen demand while improving coronary perfusion.
Indications
- Prophylaxis and treatment of angina pectoris
- Chronic heart failure (adjunct therapy)
- Acute myocardial infarction (in some protocols)
Dosage
For angina prophylaxis: Typically 5-40 mg orally 2-3 times daily, with a nitrate-free interval of 10-14 hours to prevent tolerance. Sublingual tablets: 2.5-10 mg as needed for acute angina attacks. Dosage must be individualized based on response and tolerance.
Contraindications
- Hypersensitivity to nitrates or any component
- Concurrent use with phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil)
- Severe anemia
- Increased intracranial pressure
- Cardiogenic shock
- Hypotension
Side Effects
- Headache (most common)
- Dizziness/lightheadedness
- Hypotension
- Flushing
- Nausea/vomiting
- Tachycardia
- Weakness
- Syncope
- Rash
- Tolerance with prolonged use
Interactions
- Phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil): Severe hypotension risk
- Other vasodilators: Additive hypotensive effects
- Alcohol: Enhanced hypotensive effects
- Antihypertensives: Potentiated blood pressure lowering
- Heparin: Reduced anticoagulant effect (with IV nitroglycerin)