Organic nitrates are classic, fast-acting anti-anginal drugs that every medical student encounters early—and repeatedly. They are high-yield for exams because of their rapid symptom relief, multiple dosage forms, and the famously tested concept of nitrate tolerance.
What Are Organic Nitrates?
Organic nitrates are vasodilators that release nitric oxide (NO) in vascular smooth muscle, leading to venous > arterial dilation.
Core Clinical Effect
- ↓ Preload → ↓ myocardial oxygen demand
- Relief of angina pectoris
Mechanism of Action (Very High-Yield)
Step-by-Step
1. Nitrates are converted to nitric oxide (NO)One-Line Exam Answer
Organic nitrates release nitric oxide, increasing cGMP and causing venodilation
Why Venodilation Matters
Venodilation:
- ↓ Venous return (preload)
- ↓ LV end-diastolic volume
- ↓ Wall stress
- ↓ Myocardial oxygen demand
This is why nitrates are so effective in angina.
Major Drugs in This Class
1. Nitroglycerin (Glyceryl Trinitrate)
Prototype and most important nitrate
Key Features
- Very rapid onset
- Short duration
- Multiple dosage forms
Common Uses
- Acute angina attack
- Acute coronary syndrome
- Acute heart failure / pulmonary edema
- Hypertensive emergencies (IV)
Routes (Exam Favorite)
- Sublingual tablet
- Sublingual spray
- IV infusion
- Transdermal patch
- Ointment
- Extended-release oral forms
Sublingual nitroglycerin = drug of choice for acute angina
2. Isosorbide Mononitrate (ISMN)
Key Features
- Long-acting
- Excellent oral bioavailability
- No first-pass metabolism
Uses
- Chronic stable angina (prophylaxis)
- Long-term anti-anginal therapy
Not used for acute attacks
3. Isosorbide Dinitrate (ISDN)
Key Features
- Intermediate duration
- Undergoes first-pass metabolism
Uses
- Chronic angina
- Heart failure (with hydralazine)
- Alternative when mononitrate is unavailable
High-Yield Comparison Table
| Feature | Nitroglycerin | Isosorbide Mononitrate | Isosorbide Dinitrate |
|---|---|---|---|
| Onset | Very fast | Slow | Moderate |
| Duration | Short | Long | Moderate |
| Acute angina | Yes | No | No |
| Chronic angina | Limited | Yes | Yes |
| First-pass metabolism | High | None | High |
Clinical Uses of Organic Nitrates (Grouped)
Angina
- Acute attack → Nitroglycerin (SL)
- Prophylaxis → Isosorbide mononitrate / dinitrate
Heart Failure
- ↓ Preload
- ISDN + hydralazine improves survival in selected patients
Acute Settings
- Pulmonary edema
- Acute coronary syndrome
- Hypertensive emergencies (IV nitroglycerin)
Nitrate Tolerance (Extremely High-Yield)
What Is It?
Reduced response after continuous nitrate exposure
Why It Occurs
- Depletion of sulfhydryl groups
- Increased oxidative stress
- Neurohormonal activation
Prevention (Exam Pearl)
✔ Nitrate-free interval of 8–12 hours daily
Usually scheduled overnight.
Adverse Effects (Must Remember)
Common
- Headache (very common)
- Flushing
- Dizziness
- Postural hypotension
Cardiovascular
- Reflex tachycardia
- Syncope (high doses)
Contraindications (Very Important)
❌ Phosphodiesterase-5 inhibitors
Sildenafil, tadalafil, vardenafil→ Severe hypotension
❌ Hypotension
❌ Hypertrophic obstructive cardiomyopathy
❌ Raised intracranial pressure
Drug Interactions (Exam Favorite)
- Nitrates + PDE-5 inhibitors = dangerous
- Alcohol enhances hypotensive effect
- Beta-blockers often added to prevent reflex tachycardia
Nitrates vs Other Anti-Anginal Drugs
| Feature | Nitrates | Beta-Blockers | CCBs |
|---|---|---|---|
| Acute relief | Yes | No | No |
| Preload reduction | Yes | No | Mild |
| Heart rate | ↑ (reflex) | ↓ | ↓ / ↑ |
| Tolerance | Yes | No | No |
Important Exam-Oriented Pearls
- Nitroglycerin → acute angina
- Isosorbide mononitrate → chronic prophylaxis
- Headache is dose-limiting but benign
- Always ensure nitrate-free interval
- Never combine with sildenafil
Easy Memory Tricks
- “NITRO = Now It Treats Rapid angina Onset”
- “MONO = Maintenance Only”
- “Nitrates Need Night-off” (nitrate-free interval)
FAQs
1. Which nitrate is used for acute angina?
Sublingual nitroglycerin.
2. Why do nitrates reduce anginal pain?
They reduce preload and myocardial oxygen demand.
3. What is nitrate tolerance?
Reduced drug effect with continuous use.
4. How is nitrate tolerance prevented?
By providing a daily nitrate-free interval.
5. Which nitrate is best for chronic angina?
Isosorbide mononitrate.
6. Why do nitrates cause headache?
Due to cerebral vasodilation.
7. Can nitrates be used with sildenafil?
No, this combination can cause severe hypotension.
8. Do nitrates dilate arteries or veins more?
Veins more than arteries.
9. Are nitrates used in heart failure?
Yes, especially to reduce preload and relieve congestion.
10. Do nitrates improve survival in angina?
They relieve symptoms but do not reduce mortality alone.
