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Contributed by Deepak Mohan, MD, James Harrison MD and Mohamed A Virji, MD, PhDFINAL DIAGNOSIS: SUICIDE ATTEMPT WITH INGESTION OF PYRIDIUM TABLETS
DISCUSSION:
This 14-year old female presented to the emergency room with vomiting and cyanosis after ingestion of 15 Pyridium tablets. She was found to have significant methemoglobinemia and was treated with methylene blue. To rule out other toxic exposures, a urine drug analysis was performed and was essentially negative. The patient's cyanosis resulted from methemoglobinemia, a known toxic effect of Pyridium.
Pyridium or phenazopyridine is in the pharmacological category of urinary analgesics. The indications are painful or burning urination, urgency and/or frequency due to irritation of the lower urinary tract mucosa. The drug belongs to the physicochemical group of synthetic azo dye and has molecular weight of 249.70. It occurs as a light or dark red to dark violet, crystalline powder.
Phenazopyridine is absorbed from the gastrointestinal tract and is biotransformed primarily in the liver. One of its metabolites is acetaminophen. Johnson(4) showed that 90% of a dose of Pyridium is excreted from the kidneys within 24 hours, as 41% unchanged phenazopyridine, 6.9% aniline (known to be linked with methemoglobin in humans), 18% N-acetyl-p-aminophenol, and 24% p-aminophenol.
In this case, methemoglobinemia was the primary toxic symptom. Methemoglobinemia after phenazopyridine exposure is probably mediated by one or more metabolites of the parent compound or of aniline, which are known to directly oxidize hemoglobin iron from Fe++ to Fe+++. Methemoglobinemia occurs early in the course of the toxicity; later effects may include hemolytic anemia, which is also produced by aniline metabolites (6). The treatment for methemoglobinemia is induced emesis, gastric lavage, activated charcoal, or whole-bowel irrigation. The specific antidote is methylene blue IV 1-2 mg/kg, or 0.1 mL/kg of a 1% solution, given intravenously over 5 minutes. Methylene blue reduces methemoglobin to hemoglobin through conversion to leucomethylene blue (Fig.6) Methemoglobinemia occurs when >15% of hemoglobin is oxidized to methemoglobin. The blood appears chocolate-brown when it is dripped onto filter paper. The exact concentration of methemoglobin in the blood may be determined spectrophotometrically. The PO2 and calculated oxyhemoglobin on routine arterial blood gases are usually normal even though the oxygen carrying capacity of the blood may be substantially decreased, and the measured saturation by pulse oximetry is unreliable in these cases.
On the 3rd hospital day the patient showed lab findings of hemolytic anemia and degmacytes or "bite cells" in the peripheral smear. Hemolysis, in these patients, usually occurs 24 to 48 hours after exposure and is characterized by diminished hemoglobin and hematocrit, increase in reticulocyte count, increase in total bilirubin, anisocytosis, poikilocytosis, "bite" cells or degmacytes, and Heinz bodies. The urine may become deep orange-red in color due to the dye properties of the drug, which can also mask colored urine of hemolytic jaundice. The hemolytic anemia in these patients may occur with and without Glucose 6-Phosphate deficiency. Ironically, hemolysis can occur with methylene blue treatment which may lead to confusion of the cause of hemolysis. The normal course of methemoglobinemia and hemolytic anemia are generally self-limited with full recovery; the hemolysis is usually mild. Patients that have non-oliguric acute renal failure usually present with both hemolysis and methemoglobinemia.
Although, this patients emesis was probably due to the toxic levels of Pyridium, patients on long term therapeutic treatment have shown symptoms of hypersensitivity hepatitis with nausea, vomiting, epigastric or right upper quadrant pain, myalgias, fever, jaundice, hepatomegaly, eosinophilia, and elevated liver enzymes.
Pyridium being an azo dye, may interfere with urinalysis based on spectrometry or color reactions. Interference may occur with the phenolsulfonphthalein excretion test of renal function and urinary glucose, steroid, and urobilinogen tests.
REFERENCES
Contributed by Deepak Mohan, MD, James Harrison MD and Mohamed A Virji, MD, PhD
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