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)

Riociguat; coadministration may cause hypotension

Cautions

Use caution in alcohol use, increased ICP (head trauma, cerebral hemorrhage-potential contraindication), hyperthyroidism, hypertrophic cardiomyopathy, increased IOP, hypotension, volume depletion, or 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

Amplification of vasodilatory effects of nitroglycerin by sildenafil can result in severe hypotension; time course and dose dependence of this interaction not studied; appropriate supportive care has not been studied, but seems reasonable to treat this as a nitrate overdose, with elevation of extremities and with central volume expansion

Benefits of transdermal nitroglycerin in patients with acute myocardial infarction or congestive heart failure not established; if one elects to use nitroglycerin in these conditions, use careful clinical or hemodynamic monitoring to avoid hazards of hypotension and tachycardia

Severe hypotension, particularly with upright posture, may occur with even small doses; use drug with caution in patients who may be volume depleted or who, for whatever reason, are already hypotensive; hypotension induced by therapy may be accompanied by paradoxical bradycardia and increased angina pectoris

Nitrate therapy may aggravate angina caused by hypertrophic cardiomyopathy

Effect of therapy on exercise tolerance, although still observable, may become somewhat blunted; in industrial workers who have had long-term exposure to unknown (presumably high) doses of organic nitrates, tolerance clearly occurs; chest pains, acute myocardial infarction, and even sudden death have occurred during temporary withdrawal of nitrates from these workers, demonstrating existence of true physical dependence

During nitrate-free intervals in some clinical trials, anginal attacks have been more easily provoked than before treatment, and patients have demonstrated hemodynamic rebound and decreased exercise tolerance; importance of these observations to routine, clinical use of transdermal nitroglycerin not known

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