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Organic nitrates (eg, nitroglycerin, isosorbide dinitrate, and isosorbide mononitrate) are widely used as vasodilators for the treatment of ischemic heart disease and heart failure. Organic nitrates such as nitroglycerin also are used in explosives. Bismuth subnitrate, ammonium nitrate, and silver nitrate are used in antidiarrheal drugs, cold packs, and topical burn medications, respectively. Sodium and potassium nitrate and nitrite are used in preserving cured foods and may also occur in high concentrations in some well water. Butyl, amyl, ethyl, and isobutyl nitrites often are sold as “room deodorizers” or “liquid incense” and sometimes are inhaled for abuse purposes.

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  1. Mechanism of toxicity. Nitrates and nitrites both cause vasodilation, which can result in hypotension.

    1. Nitrates relax veins at lower doses and arteries at higher doses. Nitrates may be converted into nitrites in the GI tract, especially in infants.

    2. Nitrites are potent oxidizing agents. Oxidation of hemoglobin by nitrites may result in methemoglobinemia (See Methemoglobinemia), which hinders oxygen-carrying capacity and oxygen delivery. Many organic nitrites (eg, amyl nitrite and butyl nitrite) are volatile and may be inhaled.

  2. Toxic dose. In the quantities found in food, nitrates and nitrites are generally not toxic; however, infants may develop methemoglobinemia after ingestion of sausages or well water because they readily convert nitrate to nitrite and because their hemoglobin is more susceptible to oxidation than is that of adults.

    1. Nitrates. The estimated adult lethal oral dose of nitroglycerin is 200–1200 mg. Hypotension occurs at low doses, but massive doses are required to produce methemoglobinemia.

    2. Nitrites. Ingestion of as little as 15 mL of butyl nitrite produced 40% methemoglobinemia in an adult. The estimated adult lethal oral dose of sodium nitrite is 1 g.

  3. Clinical presentation. Headache, skin flushing, and orthostatic hypotension with reflex tachycardia are the most common adverse effects of nitrates and nitrites and occur commonly, even with therapeutic doses of organic nitrates.

    1. Hypotension may aggravate or produce symptoms of cardiac ischemia or cerebrovascular disease and may even cause seizures. However, fatalities from hypotension are rare.

    2. Workers or patients regularly exposed to nitrates may develop tolerance and may develop angina or myocardial infarction owing to rebound coronary vasoconstriction upon sudden withdrawal of the drug.

    3. Methemoglobinemia (See Methemoglobinemia) is most common after nitrite exposure; the skin is cyanotic even at levels low enough for the individual to be otherwise asymptomatic (eg, 15%).

    4. Use of sildenafil (Viagra) and other selective phosphodiesterase inhibitors (tadalafil [Cialis], vardenafil [Levitra]) used to treat erectile dysfunction can prolong and intensify the vasodilating effects of nitrates, causing severe hypotension.

  4. Diagnosis is suggested by hypotension with reflex tachycardia and headache. Methemoglobinemia of 15% or more may be diagnosed by noting a chocolate brown coloration of the blood when it is dried on filter paper.

    1. Specific levels. Blood levels are not commercially available. With a urine nitrite dipstick (normally used to detect bacteria in urine), nitrite can be detected in the serum of patients intoxicated by alkyl nitrites.

    2. Other useful laboratory studies include electrolytes, glucose, arterial blood gases ...

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