QUESTION:
I'm currently taking 90mg of isosorbide dinitrate every 4.5 hours for angina (450+ mg/day). The maximum recommended dosage is 240 mg/day. I'm thinking of increasing my dosage to 120mg hoping to extend its effects. How long would it need to be effective in order to justify the additional 30mg.
I need to be very careful here, because this involves cardiac medication at a very high dose, and changing it on your own could be dangerous.
Short answer (important)
Increasing isosorbide dinitrate from 90 mg to 120 mg is very unlikely to meaningfully extend its duration of action, and it significantly increases the risk of side effects (low blood pressure, dizziness, syncope, reflex tachycardia). Dose escalation does not reliably overcome nitrate tolerance, which is usually the limiting factor—not insufficient milligrams.
You should not change this dose without your cardiologist’s explicit guidance.
Why a higher dose usually doesn’t “last longer”
1. Pharmacokinetics
- Oral isosorbide dinitrate:
- Onset: ~15–30 minutes
- Peak effect: ~1–2 hours
- Typical anti-anginal effect: 3–6 hours
- Increasing the dose raises peak concentration, not duration in a linear way.
Once hepatic metabolism and vasodilatory pathways are saturated, extra drug mostly increases side effects, not therapeutic time.
2. Nitrate tolerance is the key issue
When nitrates are given frequently or continuously, the body rapidly becomes tolerant:
- Tolerance can develop within 24–48 hours
- The effect shortens even if the dose is increased
- Increasing dose accelerates tolerance
That’s why standard nitrate regimens include a daily nitrate-free interval of 10–14 hours.
Your schedule of every 4.5 hours suggests tolerance may already be playing a role.
What would “justify” an extra 30 mg — in theory
From a pharmacologic standpoint, an additional 30 mg would only be justified if it:
- Extended symptom relief by at least 1–2 additional hours, without
- Causing hypotension, headaches, or tachycardia
In practice, studies and clinical experience show:
- Duration rarely extends meaningfully
- Side effects increase disproportionately
- Anti-anginal benefit plateaus
Specific risks at 120 mg per dose
At that level, concerns include:
- Orthostatic hypotension
- Syncope (especially at night or on standing)
- Reflex tachycardia (which can worsen angina)
- Severe headaches
- Dangerous interactions (especially if any PDE-5 inhibitors are involved)
What cardiologists usually consider instead
If angina control is inadequate at high-dose dinitrate, clinicians typically consider:
- Switching to isosorbide mononitrate ER (more predictable kinetics)
- Re-structuring dosing to restore a nitrate-free interval
- Adding or optimizing:
- Beta-blocker
- Calcium channel blocker
- Ranolazine
- Reassessing ischemic burden (stress testing, imaging)
Please don’t adjust this alone
Given the dose and frequency you’re already on, this is well beyond a “minor tweak.”
The right next step is a cardiology discussion, not a self-trial.
If you want, I can help you:
- Frame a clear question for your cardiologist
- Compare dinitrate vs mononitrate regimens
- Understand how tolerance might be affecting your symptoms
Just tell me how you’d like to proceed.
