Nitrogina SR

Approved Indications:

• Acute Angina Pectoris: For rapid relief of an acute angina attack.
• Prophylaxis of Angina Pectoris: To prevent anginal episodes in patients with chronic stable angina.
• Acute Myocardial Infarction (AMI): As adjunctive therapy to reduce myocardial oxygen demand.
• Perioperative Hypertension: Especially during cardiovascular surgeries.
• Congestive Heart Failure (CHF): Particularly when associated with acute myocardial infarction.
• Controlled Hypotension During Surgery: To reduce bleeding by lowering blood pressure.

Clinically Accepted Off-label Uses:

• Anal Fissures (topical ointment): Relieves pain and promotes healing via smooth muscle relaxation.
• Esophageal Spasm: Reduces chest pain related to esophageal motility disorders.
• Pulmonary Edema (cardiogenic): IV nitroglycerin helps reduce preload and pulmonary congestion.

Adults:

• Sublingual Tablets (Acute Angina): 0.3 mg to 0.6 mg placed under the tongue; may repeat every 5 minutes as needed, up to 3 doses in 15 minutes.
• Prophylaxis (Sublingual/Translingual): 0.4 mg 5–10 minutes before activity.
• Oral Extended-release Capsules: 2.5 mg to 6.5 mg, 3–4 times daily; titrate as needed.
• Transdermal Patch: 0.2–0.8 mg/hr applied for 12–14 hours daily; remove for 10–12 hours to avoid tolerance.
• Topical Ointment (2%): 1–2 inches applied every 6–8 hours to chest or upper arm; dosed via applicator.
• IV Infusion: Start at 5 mcg/min; increase by 5 mcg/min every 3–5 minutes up to 200 mcg/min as needed.

Pediatrics:
Not routinely used in pediatric patients; consult specialist. IV use has been reported in select critical care settings under expert supervision.

Elderly:
Initiate at lower end of the dosage range due to possible increased sensitivity and orthostatic hypotension.

Renal/Hepatic Impairment:
Use with caution; no dose adjustment clearly defined, but increased risk of hypotension exists—start low and titrate slowly.

Routes of Administration:
Sublingual, translingual, oral, topical (ointment), transdermal, intravenous.

Duration:
As needed for acute angina; continuous use for prophylaxis should include nitrate-free intervals to prevent tolerance.

Nitroglycerin is a nitrate that acts as a prodrug, releasing nitric oxide (NO) within vascular smooth muscle cells. NO activates guanylate cyclase, increasing cyclic guanosine monophosphate (cGMP), which causes dephosphorylation of myosin light chains and smooth muscle relaxation. The predominant effect is venodilation, which reduces preload and myocardial oxygen demand. At higher doses, it also dilates arteries, reducing afterload. Coronary vasodilation enhances oxygen delivery in ischemic myocardial tissue, relieving angina symptoms.

• Absorption: Rapid via sublingual and translingual routes; slower with oral or topical forms.
• Bioavailability: Sublingual: ~40%; Oral: <20% due to first-pass hepatic metabolism.
• Onset of Action:
• Sublingual: 1–3 minutes
• Oral: 20–60 minutes
• Transdermal: 30–60 minutes
• IV: Immediate
• Peak Plasma Levels:
• Sublingual: ~4–8 minutes
• Half-life: 1–4 minutes (parent drug); active metabolites may have longer half-lives (up to 2 hours).
• Metabolism: Hepatic via nitrate reductase to di- and mono-nitrates.
• Excretion: Renal (major), fecal (minor) as inactive metabolites.

• Pregnancy: FDA Category C
  Use only if potential benefit justifies potential risk. No adequate human studies; animal data show adverse fetal effects.
• Lactation:
  Excretion into breast milk is unknown. Caution advised; monitor infant for hypotension or other adverse effects.

• Primary Class: Antianginal Agent
• Subclass: Organic Nitrate Vasodilator

• Known hypersensitivity to nitroglycerin or other nitrates/nitrites
• Concurrent use with phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)
• Severe hypotension or hypovolemia
• Increased intracranial pressure or head trauma
• Pericardial tamponade or restrictive cardiomyopathy (IV use caution)
• Severe anemia

• Tolerance Development: Avoid continuous exposure; incorporate nitrate-free intervals (10–12 hours/day).
• Hypotension & Syncope: Especially in elderly or volume-depleted patients; monitor BP closely.
• Reflex Tachycardia: May require concurrent beta-blocker.
• Headache: Common and dose-dependent; may be severe but usually diminishes with continued use.
• Methemoglobinemia: Rare but serious; monitor with high doses or prolonged IV use.
• Avoid abrupt withdrawal after prolonged use—taper to reduce rebound angina.

Common:

• Cardiovascular: Headache, hypotension, dizziness, flushing, tachycardia, palpitations
• Gastrointestinal: Nausea, vomiting (rare)
• Dermatologic (with patches/ointments): Contact dermatitis, rash

Serious/Rare:

• Syncope
• Severe hypotension with bradycardia
• Methemoglobinemia
• Anaphylactic reactions (rare)
• Increased intracranial pressure (in predisposed patients)

• Phosphodiesterase-5 Inhibitors (e.g., Sildenafil, Tadalafil): Severe hypotension, syncope—contraindicated.
• Antihypertensives & Diuretics: Additive hypotensive effects; adjust doses accordingly.
• Ergot Derivatives: May reduce antianginal effect.
• Alcohol: Potentiates hypotension and dizziness.
• CYP450 Enzymes: Metabolism involves CYP3A4 and CYP2B6; clinically significant interactions are rare.

• AHA/ACC Guidelines (updated): Nitroglycerin remains first-line therapy for acute angina relief.
• Safety Labeling Updates: Reinforced contraindication with PDE-5 inhibitors.
• Topical Use (Anal Fissures): Increasing recognition as a valid off-label use for chronic fissures in select patients.

• Sublingual Tablets: Store at 20°C to 25°C (68°F to 77°F) in tightly closed glass containers, protected from light and moisture. Avoid plastic bottles.
• Topical/Ointment/Transdermal: Store at 20°C to 25°C; do not refrigerate or freeze.
• IV Formulations: Store in original containers; protect from light; avoid plastic tubing that may absorb drug.
• Spray: Store upright at room temperature; do not puncture or incinerate pressurized container.