Nitrates — Mechanism, Use & Tolerance
Module 2 · Visual Summary
Mechanism: Nitric Oxide → Vasodilation
Bioactivation
Organic nitrate prodrug converted to nitric oxide
Signaling
Nitric oxide activates soluble guanylyl cyclase, raising cyclic guanosine monophosphate
Result
Smooth muscle relaxation: veins at standard doses, arteries and coronaries at higher doses
Formulations
| Formulation | Onset | Use |
|---|
| Sublingual nitroglycerin | Minutes | Acute relief |
| Oral / transdermal | 30–60 min | Chronic prophylaxis |
| Intravenous | Immediate | Hospital, acute settings |
Tolerance and Contraindications
Predictable Phenomenon
Nitrate Tolerance
- Develops within 24–48 hours of continuous exposure
- Reduced bioactivation, weaker response
- Fixed by a daily nitrate-free interval
Preload Dependence
Three Contraindications
- Right ventricular infarction
- Severe aortic stenosis
- Hypertrophic obstructive cardiomyopathy
Critical Contraindication
Phosphodiesterase type 5 inhibitors potentiate nitrate-induced cyclic guanosine monophosphate accumulation, risking severe hypotension. Always ask about recent use before giving any nitrate.