Nitroglycerin

Nitroglycerin (NTG) 

Nitroglycerin (NTG) is a nitrate-class vasodilator widely used for the management of cardiovascular conditions. It primarily works by releasing nitric oxide (NO), which activates guanylate cyclase and increases cyclic GMP levels, resulting in smooth muscle relaxation and vasodilation.

Uses

• Angina Pectoris: Acute relief and long-term prophylaxis of angina attacks in ischemic heart disease.
• Heart Failure: Acute management, particularly in patients with elevated blood pressure or ischemic conditions.
• Hypertensive Emergencies: Rapid blood pressure reduction in acute hypertensive crises.
• Perioperative Hypertension: Control of blood pressure and myocardial oxygen demand during surgeries.
• Acute Myocardial Infarction (MI): Relief of ischemic pain and improved coronary perfusion.
• Esophageal Spasm (Off-label): Symptomatic relief.

Dosage and Administration

1. Sublingual Tablets (Angina Relief)

• Initial Dose: 0.3-0.6 mg sublingually at onset of chest pain.
• Maximum: Up to 3 doses within 15 minutes.

2. Transdermal Patches (Angina Prophylaxis)

• Dose: Apply a patch delivering 0.2-0.4 mg/hour.
• Administration: Wear for 12-14 hours, then remove for 10-12 hours to prevent tolerance.

3. Intravenous (IV) (Heart Failure or Hypertensive Emergencies)

• Adults: Initial 5 mcg/min IV, increase by 5 mcg/min every 3-5 minutes as needed.
• Maximum: 200 mcg/min.
• Pediatrics: Initial 0.25-0.5 mcg/kg/min IV, titrate by 0.5 mcg/kg/min.
• Maximum: 5 mcg/kg/min.

4. Oral Extended-Release (Angina Prophylaxis)

• Dose: 2.5-9 mg orally two to four times daily, ensuring a nitrate-free interval.

Dose Adjustments in Different Diseases

• Hepatic Impairment: Caution due to impaired metabolism.
• Renal Impairment: Generally no dose adjustment required, but monitor for hypotension.
• Heart Failure: Start at lower doses and titrate cautiously.

Drug Combinations in Use

Combination Drug	Indication	Clinical Benefit
Beta-blockers	Angina	Reduce myocardial oxygen demand
Diuretics	Heart Failure	Enhance preload reduction
ACE Inhibitors	Hypertension	Improve blood pressure control
Antiplatelets	MI	Reduce thrombotic events
Calcium Channel Blockers	Angina	Improve coronary blood flow

Presentation or Form

• Sublingual Tablets: 0.3 mg, 0.4 mg, 0.6 mg tablets.
• Transdermal Patches: Deliver 0.2 mg/hour, 0.4 mg/hour, 0.6 mg/hour.
• IV Solution: 25 mg/5 mL ampules.
• Oral Extended-Release Tablets: 2.5 mg, 6.5 mg, 9 mg tablets.
• Topical Ointment: 2% ointment.

Pharmacokinetics

• Absorption: Rapid absorption through mucous membranes and skin.
• Metabolism: Extensive hepatic metabolism via glutathione-organic nitrate reductase.
• Onset and Duration:
  • Sublingual: Onset within 1-3 minutes; duration 30-60 minutes.
  • IV: Immediate onset; duration ceases with infusion cessation.
  • Transdermal: Onset 30 minutes to 1 hour; duration 12-24 hours.

Pharmacodynamics

• Reduces myocardial oxygen demand by decreasing preload and afterload.
• Improves coronary blood flow.

Drug Interactions

Interacting Drug	Interaction	Clinical Impact
Phosphodiesterase Inhibitors	Profound hypotension	Avoid concomitant use
Ergot Alkaloids	Additive vasospasm	Increased ischemia risk
Heparin	Reduced anticoagulant effect	Monitor INR/PT
Other Antihypertensives	Additive hypotension	Monitor blood pressure
Alcohol	Exacerbates vasodilation	Increased hypotension risk

Comparison with Other Drugs of the Same Category

Drug	Onset	Duration	Route	Nitrate-Free Interval
Nitroglycerin	1-3 min (SL)	30-60 min (SL)	SL, IV, Transdermal	Yes
Isosorbide Dinitrate	15-30 min	4-6 hours	Oral, SL	Yes
Isosorbide Mononitrate	30-60 min	12-24 hours	Oral	Yes

Precautions and Special Considerations

• Tolerance: Develops with continuous use; ensure nitrate-free intervals.
• Hypotension: Monitor blood pressure, particularly in elderly patients.
• Headache: Common side effect; consider analgesics.
• Pregnancy: Category C; use only if benefits outweigh risks.
• Withdrawal: Gradually taper to avoid rebound angina.

Side Effects

• Common: Headache, hypotension, dizziness, flushing, syncope, tachycardia.
• Serious: Severe hypotension, reflex tachycardia, methemoglobinemia (rare).

Recent Updates and Guidelines

• Recent guidelines emphasize the use of NTG in acute coronary syndromes and its combination with antiplatelet therapy for optimal outcomes.
• Updated recommendations on nitrate-free intervals to mitigate tolerance.

Facts to Remember

• Rapid onset makes sublingual NTG ideal for acute angina relief.
• Always use a nitrate-free period to prevent tolerance.
• Avoid concurrent use with phosphodiesterase inhibitors.
• Close blood pressure and heart rate monitoring required.

References

1. NCBI StatPearls - Nitroglycerin: https://www.ncbi.nlm.nih.gov/books/NBK482382/
2. Stoelting’s Pharmacology and Physiology in Anesthetic Practice, 5th edition.
3. Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 13th edition.
4. American Heart Association Guidelines 2022.
5. European Society of Cardiology Guidelines on Nitrate Use (2021).

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