What are some common nitrates used in medical practice?

Common Nitrates Used in Medical Practice

The three most common nitrate compounds available for clinical use in the United States are nitroglycerin (glyceryl trinitrate), isosorbide dinitrate (ISDN), and isosorbide-5-mononitrate (ISMN). 1

Nitroglycerin

Nitroglycerin is the most widely used nitrate and is available in multiple formulations:

• Sublingual tablets/spray: Rapid onset for immediate relief of angina attacks

  • Should be dissolved under the tongue at the first sign of angina
  • May be repeated approximately every 5 minutes until relief (up to 3 tablets in 15 minutes) 2
  • Can be used prophylactically 5-10 minutes before activities that might trigger angina 2

• Intravenous: The only nitrate available for intravenous use in the United States 1

  • Particularly useful in unstable angina and acute myocardial infarction complications

• Topical/Transdermal:

  • Ointment: Applied in a thin layer (0.2-0.8 mg/hour) for 12-14 hours daily 3
  • Patches: Provide sustained release over 12-24 hours

• Pharmacokinetics: Very short half-life of only several minutes 1

Isosorbide Dinitrate (ISDN)

• Oral formulations:

  • Standard release: 5-80 mg, 2-3 times daily (effect up to 8 hours) 3
  • Slow-release: 40 mg, 1-2 times daily (effect up to 8 hours) 3

• Pharmacokinetics: Half-life ranges from 40-90 minutes 1

  • Extensively metabolized in the liver to two active metabolites, including isosorbide-5-mononitrate

Isosorbide-5-Mononitrate (ISMN)

• Oral formulations:

  • Standard and sustained-release forms available

• Pharmacokinetics:

  • Half-life of 4-5 hours 1
  • 100% bioavailable after oral dosing (does not undergo first-pass metabolism) 1
  • Approved by FDA in 1991 1

Mechanism of Action

All nitrates work through the same primary mechanism:

• Metabolic conversion to nitric oxide (NO) near the vascular smooth muscle cell membrane 1
• NO activates guanylate cyclase, increasing cyclic guanosine monophosphate (cGMP) levels 4
• This leads to decreased intracellular calcium and subsequent vasodilation 4
• Primarily affects veins at low doses (reducing preload) and arteries at higher doses (reducing afterload) 1

Clinical Applications

Nitrates are used in:

1. Angina pectoris (stable, unstable, and variant forms) 3, 5
2. Acute myocardial infarction 1, 6
3. Heart failure (particularly with hydralazine) 1, 6

Important Considerations for Nitrate Use

Nitrate Tolerance

• Develops with continuous exposure lasting longer than 10-12 hours 3, 6
• Prevention requires a "nitrate-free interval" of at least 10 hours daily 1, 3
• For transdermal applications, patches should be removed for 10-12 hours (typically overnight) 6
• Combination with hydralazine or ACE inhibitors may help minimize tolerance 1, 6

Common Side Effects

• Headaches (most common, often diminish with continued use) 1, 2
• Hypotension and reflex tachycardia 1, 2
• Dizziness, especially when standing 2

Contraindications

• Systolic blood pressure <90 mmHg or >30 mmHg below baseline 3
• Concurrent use of phosphodiesterase-5 inhibitors (e.g., sildenafil) 2
• Right ventricular infarction (use with extreme caution) 1, 3
• Severe aortic stenosis (use with extreme caution) 3

Practical Prescribing Tips

• Start with low doses and gradually increase as needed 6
• For chronic use, schedule dosing to provide a nitrate-free interval (typically overnight) 6
• Consider combining with beta-blockers to prevent reflex tachycardia and provide coverage during nitrate-free intervals 3
• Store nitroglycerin tablets in their original glass container, tightly capped to prevent loss of potency 2

Nitrates remain a cornerstone therapy for cardiovascular disease despite being one of the oldest cardiovascular medications in use, with their efficacy well-established in reducing morbidity and mortality when appropriately prescribed.