Can sorbitrate (isosorbide dinitrate) be given to patients with stable angina?

Isosorbide Dinitrate (Sorbitrate) in Stable Angina Management

Yes, isosorbide dinitrate (Sorbitrate) can be given to patients with stable angina as it is FDA-approved for the prevention of angina pectoris due to coronary artery disease. 1

Mechanism of Action and Benefits

Isosorbide dinitrate works through:

• Enzymatic conversion to nitric oxide in vessel walls, causing vasodilation 2
• At low doses: predominantly venodilation, reducing preload and myocardial oxygen demand
• At higher doses: coronary artery dilation, prevention of coronary spasm, improved subendocardial blood flow, and decreased ventricular diastolic pressure 2
• Improved collateral blood flow to ischemic areas 2

Dosing Considerations

When prescribing isosorbide dinitrate for stable angina:

• Oral formulation: 5-80 mg, 2-3 times daily with duration of effect up to 8 hours 2
• Slow-release formulation: 40 mg 1-2 times daily with duration of effect up to 8 hours 2
• Sublingual formulation: Can be used 15 minutes before activity expected to cause angina, but not recommended for aborting acute anginal episodes unless patient fails to respond to sublingual nitroglycerin 3

Critical Dosing Strategy to Prevent Tolerance

A nitrate-free interval of 10-12 hours daily is essential to prevent tolerance development. 4 Tolerance to nitrates can develop within 24-48 hours of continuous therapy 5, resulting in:

• Loss of anti-anginal efficacy
• Diminished vasodepressor response
• Need for increasing doses

Recommended approaches:

• Apply/take medication in the morning
• Ensure a 10-12 hour nitrate-free period (typically overnight) 4
• For patients with nocturnal angina, consider adding a beta-blocker during the nitrate-free period 4

Contraindications and Precautions

Avoid isosorbide dinitrate in patients with:

• Systolic blood pressure <90 mmHg or >30 mmHg below baseline 2, 4
• Marked bradycardia (<50 bpm) or tachycardia (>100 bpm) 2, 4
• Recent use of phosphodiesterase inhibitors:
  • Within 24 hours of sildenafil
  • Within 48 hours of tadalafil 2, 4
• Suspected right ventricular infarction 4
• Severe aortic stenosis (extreme caution) 4

Combination Therapy

For optimal management of stable angina:

• Combining isosorbide dinitrate with beta-blockers is particularly beneficial as beta-blockers counteract the reflex tachycardia caused by nitrates 2
• This combination provides synergistic anti-ischemic effects 2

Common Side Effects

• Headache (most common) - typically mild to moderate and improves with continued therapy 6
• Hypotension
• Reflex tachycardia 4

Clinical Pearls

• Starting with a lower dose (e.g., 30 mg once daily for one week before increasing to 60 mg) can reduce headache frequency and severity without compromising anti-anginal efficacy 6
• Approximately 30% of patients never experience headache from nitrate therapy 6
• Abrupt discontinuation during long-term treatment may exacerbate anginal symptoms 7
• High-dose single administration (120 mg slow-release once daily) has been shown to significantly reduce both symptomatic and asymptomatic ischemic episodes, particularly during morning and afternoon hours 8

Remember that isosorbide dinitrate is indicated for prevention of angina, not for aborting acute anginal episodes due to its relatively slow onset of action 1.