nitroglycerin PO (Rx)

Common

Headache

Hypotension

Tachycardia

Dizziness

Lightheadedness

Blurred vision

Flushing

N/V

Nervousness

Xerostomia

Serious

Methemoglobinemia (rare)

Syncope

Prolonged bleeding time

Exfoliative dermatitis

Unstable angina

Rebound hypertension

Thrombocytopenia

Contraindications

Hypersensitivity, acute MI, severe anemia

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

Coadministration with soluble guanylate cyclase stimulators, including riociguat

Cautions

Use caution in increased ICP (eg, head trauma, cerebral hemorrhage; potential contraindication), hyperthyroidism, increased IOP, postural 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

Angina long term prophylaxis, NOT for acute relief

Lack of burning/tingling does not indicate loss of potency

Discontinue if blurred vision occurs

Use supportive treatment in overdose

Benefits of oral nitroglycerin in patients with acute myocardial infarction or congestive heart failure not established; if administered in these conditions, use careful clinical or hemodynamic monitoring to avoid hazards of hypotension and tachycardia; because effects of capsules are so difficult to terminate rapidly, not recommended in these settings

Severe hypotension, particularly with upright posture, may occur with even small doses; should be used 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

Therapy may aggravate angina caused by hypertrophic cardiomyopathy

As tolerance to other forms of nitroglycerin develops, effect of sublingual nitroglycerin on exercise tolerance, although still observable, is somewhat blunted

In industrial workers who have had long-term exposure to unknown (presumably high) doses of organic nitrates, tolerance clearly occurs; chest pain, acute myocardial infarction, and even sudden death have occurred during temporary withdrawal of nitrates from these workers, demonstrating existence of true physical dependence

Some clinical trials in angina patients have provided nitroglycerin for about 12 continuous hours of every 24-hour day; during nitrate-free intervals in some of these 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 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

onset: within 1- hr4

Duration antianginal effects: Up to 12 hr

Bioavailability: 38.5%

Protein Bound: 11-60%

Vd: 3 L/kg

Metabolism: Liver, extrahepatic sites: vascular wall, RBC

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

Clearance: 5.5-11 L/min

Excretion: urine

Dialyzable: No