nitroglycerin topical (Rx)

Frequency Not Defined

Headache

Hypotension

Tachycardia

Dizziness

Lightheadedness

Blurred vision

Flushing

Nausea/vomiting

Nervousness

Xerostomia

Topical allergic reactions

Serious

• Methemoglobinemia (rare)
• Syncope
• Prolonged bleeding time
• Exfoliative dermatitis
• Unstable angina
• Rebound hypertension
• Thrombocytopenia

Contraindications

Hypersensitivity to organic nitrates

Recent use (within several days) of PDE-5 inhibitors (eg, avanafil, sildenafil, tadalafil, or vardenafil) may cause dangerously low hypotension; the time course of the interaction appears to be related to the PDE-5 inhibitor half-life

Riociguat; coadministration may cause hypotension

Narrow angle glaucoma (controversial: may not be clinically significant)

Severe anemia

Cautions

Alcohol use, incr ICP (head trauma, cerebral hemorrhage-potential contraindication), hyperthyroidism, hypertrophic cardiomyopathy, increase IOP, hypotension, volume depletion, low systolic BP

Do not change brands unintentionally as not all are bioequivalent

Treat drug-induced headache with aspirin or acetaminophen

Provide nitrate-free interval (10-12 hr or overnight) to avoid development of tolerance

Discontinue if blurred vision develops

Do not apply with fingers; do not rub or massage

Use supportive treatment in overdose

Pregnancy Category: C

Lactation: not known whether the drug crosses into breast milk, use caution

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Organic nitrate which causes systemic venodilation, decreasing preload

Cellular mechanism: nitrate enters vascular smooth muscle and converted to nitric oxide (NO) leading to activation of cGMP & vasodilation

Relaxes smooth muscle via dose-dependent dilation of arterial and venous beds to reduce both preload and afterload, and myocardial O2 demand

Also improves coronary collateral circulation

Lower BP, increase HR, occasional paradoxical bradycardia

Pharmacokinetics

Half-Life elimination: 1-4 min

Antianginal effects: 30 min

Hemodynamic effects: Within 1 hr

Duration antianginal effects: Up to 7 hr (topical)

Hemodynamic effects: 3-6 hr

Peak Plasma Time: 3-4 hr

Protein Bound: 60%

Vd: 3 L/kg

Metabolism: Mainly in liver, extrahepatic sites: vascular wall, RBC

Metabolites: 1,3-glyceryl dinitrate, 1,2-glyceryl dinitrate, and glyceryl mononitrate (inactive)

Clearance: 5.5-11 L/min

Excretion: Urine

Dialyzable: No