Nitroglycerin

Usage

• Medical Conditions: Nitroglycerin is primarily prescribed for angina pectoris (chest pain due to reduced blood flow to the heart), acute myocardial infarction, congestive heart failure, and hypertension. It is also used to induce controlled hypotension during surgical procedures and for the treatment of anal fissures.
• Pharmacological Classification: Vasodilator, antianginal agent, nitrate.
• Mechanism of Action: Nitroglycerin is converted to nitric oxide (NO) in vascular smooth muscle. NO activates guanylate cyclase, leading to increased cyclic guanosine monophosphate (cGMP), which ultimately results in smooth muscle relaxation and vasodilation. This reduces preload and afterload, decreasing myocardial oxygen demand and improving coronary blood flow.

Alternate Names

• Glyceryl Trinitrate (GTN)
• Trinitroglycerin
• Nitro-Bid, Nitro-Dur, Nitrolingual, Nitrostat (brand names)

How It Works

• Pharmacodynamics: Nitroglycerin’s primary effect is vasodilation, leading to decreased preload (venous return to the heart) and afterload (resistance against which the heart pumps). It also dilates coronary arteries, improving blood flow to the heart muscle.
• Pharmacokinetics:
  • Absorption: Rapidly absorbed sublingually, buccally, transdermally, and intravenously. Oral absorption is variable due to first-pass metabolism.
  • Metabolism: Primarily metabolized in the liver by nitrate reductase.
  • Elimination: Excreted mainly in the urine as metabolites. The half-life is short, ranging from 1-4 minutes for intravenous administration to 20-30 minutes for sublingual administration.
• Mode of Action: Nitroglycerin is denitrated within vascular smooth muscle cells, releasing nitric oxide (NO). NO stimulates guanylate cyclase to produce cGMP. Increased cGMP leads to a decrease in intracellular calcium levels and subsequent smooth muscle relaxation.
• Receptor Binding/Enzyme Inhibition: NO acts by binding to the heme group of guanylate cyclase, activating the enzyme.
• Elimination Pathways: Primarily hepatic metabolism followed by renal excretion of metabolites.

Dosage

Standard Dosage

Adults:

• Sublingual: 0.3-0.6 mg every 5 minutes as needed for angina, up to three doses. Prophylactically, 0.3-0.6mg 5-10 minutes before activities that may precipitate angina.
• Intravenous: 5 mcg/min initially, titrated by 5 mcg/min every 3-5 minutes up to 20 mcg/min. Further titration may be done by 10 mcg/min increments, and then 20 mcg/min if needed. Usual range 5 to 100 mcg/min up to maximum 200 mcg/min (or higher in some protocols) depending on the indication.
• Transdermal: 0.2-0.4 mg/hr applied daily for 12-14 hours, with a 10-12 hour nitrate-free interval.

Children:

• Dosage must be determined by a physician and is weight-based for intravenous administration.
• Sublingual and transdermal formulations are generally not recommended for children.

Special Cases:

• Elderly Patients: Start with lower doses and titrate cautiously.
• Patients with Renal Impairment: Careful monitoring is required, but dose adjustments are usually not necessary.
• Patients with Hepatic Dysfunction: Start with lower doses and titrate cautiously.
• Patients with Comorbid Conditions: Adjust dosage based on individual needs.

Clinical Use Cases

• Intubation: Intravenous bolus of 1-2 mcg/kg may be used to attenuate hemodynamic responses.
• Surgical Procedures: Intravenous infusion titrated to desired blood pressure (often 10-200 mcg/minute, may require up to 400 mcg/minute).
• Mechanical Ventilation: Intravenous nitroglycerin may be used to manage hypertension and heart failure.
• Intensive Care Unit (ICU) Use: Continuous intravenous infusion titrated to maintain hemodynamic stability.
• Emergency Situations: Intravenous nitroglycerin for acute coronary syndromes, hypertensive emergencies, and acute heart failure exacerbations. Bolus doses up to 2 mg may be used. High-dose nitroglycerin (up to 400 mcg/min or boluses of 2mg) has been used for the treatment of SCAPE (Systolic dysfunction in acutely decompensated heart failure with preserved ejection fraction) or acute cardiogenic pulmonary edema.

Dosage Adjustments

• Adjust dosage based on patient response, blood pressure, heart rate, and other hemodynamic parameters.
• Renal and hepatic impairment may require lower initial doses.

Side Effects

Common Side Effects

• Headache
• Dizziness
• Lightheadedness
• Nausea
• Flushing

Rare but Serious Side Effects

• Syncope
• Reflex tachycardia
• Paradoxical bradycardia
• Methemoglobinemia

Long-Term Effects

• Tolerance to nitrate effects may develop with prolonged use.

Adverse Drug Reactions (ADR)

• Severe hypotension
• Allergic reactions

Contraindications

• Hypersensitivity to nitrates
• Severe anemia
• Increased intracranial pressure
• Closed-angle glaucoma
• Concomitant use of phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil)

Drug Interactions

• Phosphodiesterase-5 Inhibitors: Can cause severe hypotension.
• Antihypertensives: Additive hypotensive effects.
• Alcohol: May potentiate hypotension.
• Heparin: Reduced anticoagulant effect of heparin has been reported.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C. Use only if potential benefits outweigh potential risks.
• Breastfeeding: Excreted in breast milk. Use with caution.

Drug Profile Summary

• Mechanism of Action: Vasodilator via NO pathway.
• Side Effects: Headache, dizziness, hypotension.
• Contraindications: Hypersensitivity, severe anemia, increased ICP, glaucoma, PDE5 inhibitor use.
• Drug Interactions: PDE5 inhibitors, antihypertensives, alcohol.
• Pregnancy & Breastfeeding: Use with caution.
• Dosage: Varies depending on formulation and indication.
• Monitoring Parameters: Blood pressure, heart rate, and other hemodynamic measures.

Popular Combinations

• Often used in combination with other antianginal agents (e.g., beta-blockers, calcium channel blockers).

Precautions

• General Precautions: Monitor blood pressure and heart rate closely.
• Specific Populations: Use with caution in elderly patients and those with hepatic or renal impairment.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Nitroglycerin?

A: Dosage varies depending on indication, formulation, and patient factors. See detailed dosage section above.

Q2: How should nitroglycerin be administered for acute angina?

A: Sublingually or as a spray under the tongue, 0.3-0.6mg every 5 minutes up to three doses.

Q3: What are the common side effects of nitroglycerin?

A: Headache, dizziness, lightheadedness, nausea, flushing.

Q4: What are the contraindications to using nitroglycerin?

A: Hypersensitivity, increased intracranial pressure, severe anemia, right ventricular infarction, concomitant PDE5 inhibitor use.

Q5: How does nitroglycerin work in heart failure?

A: Reduces preload and afterload, decreasing cardiac workload and improving cardiac output.

Q6: Can nitroglycerin be used in patients with renal impairment?

A: Yes, but careful monitoring is necessary. Dose adjustments are usually not required.

Q7: What should be done if chest pain persists after three sublingual doses of nitroglycerin?

A: Seek immediate medical attention.

Q8: Can nitroglycerin be used during pregnancy?

A: Use only if potential benefit outweighs risk (Pregnancy Category C).

Q9: How does nitroglycerin interact with other medications?

A: Can interact with PDE5 inhibitors (contraindicated) and antihypertensive medications (additive effect).

Q10: How does nitroglycerin interact with alcohol?

A: Can enhance the hypotensive effects of nitroglycerin.

The information provided above is current as of today, February 16, 2025. Medical knowledge is constantly evolving, so it’s always best to consult with up-to-date resources and guidelines for the most accurate information.