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 contaminated with nitrogen-containing fertilizer run-off, and in antifreeze mixtures. Sodium nitrite, purchased in pure form, has been used in suicide attempts. Butyl, amyl, ethyl, and isobutyl nitrites often are sold as “room deodorizers” or “liquid incense” and sometimes are inhaled for sexual enhancement and other abuse purposes.

Nitrates and nitrites both cause vasodilation, which can result in hypotension and reflex tachycardia.

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, which hinders oxygen-carrying capacity and oxygen delivery. Some organic nitrites (eg, amyl nitrite and butyl nitrite) are volatile and may be inhaled.

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 compared to adults. Severe methemoglobinemia has occurred in adults when sodium nitrite marketed as a food additive or preservative is applied directly to foods and ingested or in suicide attempts. Methemoglobinemia induced by nitrite may be more severe and associated with hemolysis in the presence of G6PD deficiency.

1. Nitrates. The estimated adult lethal oral dose of nitroglycerin is 200-1,200 mg. Hypotension occurs at low doses, but massive doses of nitroglycerin are usually 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.

Headache, skin flushing, and orthostatic hypotension with reflex tachycardia are the most common adverse effects of nitrates and nitrites, even with therapeutic doses.

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. Inhaled nitrites are flammable and their accidental ignition (such as after lighting a cigarette that had been dipped in a nitrite solution) has resulted in serious burns.
3. methemoglobinemia is most common after nitrite exposure; cyanosis occurs even at low levels (eg, 15%) in patients who are otherwise asymptomatic. Hypoxic manifestations including altered mental status can be seen with high methemoglobin levels.
4. Hemolytic anemia can occur due to oxidant stress, particularly in people who have G6PD deficiency.
5. Use of sildenafil and other selective phosphodiesterase inhibitors (tadalafil, vardenafil) used to treat erectile dysfunction can prolong and intensify the vasodilating effects of nitrates, causing severe hypotension.

Is suggested by hypotension with reflex tachycardia and headache. Cyanosis with a low oxygen saturation in the absence of respiratory disease suggests methemoglobinemia. “Chocolate brown” blood when it is dried on filter paper is another clue to the diagnosis.

1. Specific levels. Blood levels are not commercially available. Nitrite can be detected in the serum of patients exposed to alkyl nitrites using a urine nitrite dipstick test (normally used to detect bacteria in urine). Very high concentrations of nitrites can be found in urine from individuals who purposefully adulterate their urine prior to workplace urine drug screening programs, to invalidate drug of abuse immunoassays. Many drug testing laboratories routinely test for the excess presence of nitrites.
2. Other useful laboratory studies include electrolytes, glucose, arterial blood gases or oximetry, methemoglobin concentration, CBC with blood smear to look for signs of hemolysis, and ECG monitoring. Note that many arterial blood gas instruments and conventional pulse oximetry do not measure methemoglobin.

1. Emergency and supportive measures
   1. Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen.
   2. Treat hypotension with supine positioning, IV crystalloid fluids, and pressors if needed
   3. Monitor vital signs and ECG for 4-6 hours.
2. Specific drugs and antidotes. Symptomatic methemoglobinemia may be treated with methylene blue. Consider blood transfusion or exchange transfusion for life-threatening methemoglobinemia, especially if methylene blue is unavailable or there is a known history of G6PD deficiency. High doses of ascorbic acid have also been used, although evidence of efficacy is limited.
3. Decontamination
   1. Inhalation. Remove victims from exposure and administer supplemental oxygen if available.
   2. Skin and eyes. Remove contaminated clothing and wash with copious soap and water. Irrigate exposed eyes with water or saline.
   3. Ingestion. Administer activated charcoal orally if conditions are appropriate (see Table I-37,). Gastric lavage is not necessary after small-to-moderate ingestions if activated charcoal can be given promptly.
4. Enhanced elimination. Hemodialysis and hemoperfusion are not effective.