Abstract
OBJECTIVE
To report a case of acute self-limiting ischemic colitis in a patient who was self-medicating with a proprietary over-the counter oral decongestant containing pseudoephedrine.
CASE SUMMARY
A 46-year-old white man developed clinical, endoscopic, and histologic features of acute ischemic colitis after taking a proprietary oral decongestant containing pseudoephedrine 240 mg/day for one week. The total daily dose was at the upper limit of recommended doses for pseudoephedrine (as a single drug or in combination products). The patient was also taking tramadol 150 mg/day for chronic back pain. He made a complete recovery. There were no other explanations for the episode of ischemic colitis.
DISCUSSION
An objective causality assessment based on the Naranjo probability scale revealed pseudoephedrine to be a probable cause of ischemic colitis in our patient. Pseudoephedrine occasionally causes vascular insufficiency due to intense vasoconstriction, even at standard doses. Although our patient was not taking an excessive dose of pseudoephedrine, it is possible that the concurrent use of pseudoephedrine and tramadol may have increased adrenergic vasoconstriction, predisposing to ischemic colitis.
CONCLUSIONS
Prolonged or intensive use of medications containing pseudoephedrine should be avoided, and the package information should contain advice that the medication should be ceased if abdominal pain or other ischemic symptoms occur.
Pseudoephedrine, a stereoisomer of ephedrine, is a sympathomimetic that acts predominantly by a direct action on α1-adrenergic receptors, with minimal effect on β-adrenergic receptors. However, it has both direct and indirect sympathomimetic effects. It has less potent pressor effects than ephedrine and causes little or no central nervous system stimulation. It is a common constituent of over-the-counter oral and topical decongestants. The mechanism of decongestant action may be due to vasoconstriction from activation of α1-adrenergic receptors in nasal capacitance vessels, thus decreasing blood flow through the nasal mucosa and reducing nasal airway resistance. 1
We report a case of nongangrenous, self-limiting ischemic colitis in a man with a one-week history of pseudoephedrine use who was also taking long-term tramadol and had no underlying clinical or laboratory evidence of vascular disease or coagulopathy.
Case Report
A 46-year-old white man presented to the hospital in October 2002 with a one-day history of recurrent episodes of severe central colicky abdominal pain associated with rectal passage of blood clots, dizziness, nausea, and sweating. The pain was severe enough to wake him at night. Each episode lasted approximately 3 minutes and was partially relieved by defecation. Although his stools became loose and bloody, he did not describe diarrhea. On clinical examination, he had moderate left-sided and lower abdominal tenderness, but no other clinical signs. There were no abnormal cardiac signs, blood pressure was normal, and he was afebrile.
The patient underwent a colonoscopy 48 hours after admission, which revealed a 10- to 12-cm segment of reddened, edematous, slightly narrowed colon in the descending colon below the splenic flexure, this region being the vascular watershed area between the areas supplied by the superior and inferior mesenteric arteries. The remainder of the colon and ileum were normal. A gastroscopy was normal apart from gastritis that was subsequently found to be Helicobacter pylori–positive. There was no evidence of blood in the upper or lower gastrointestinal tract. He was treated conservatively and made a full recovery within one week. He has had no further symptoms after 20 months of follow-up.
Histologic examination of colonoscopic biopsies of the affected colonic segment showed changes strongly suggestive of ischemic colitis. There was coagulative necrosis of epithelial cells, congestion of the lamina propria, submucosal edema, and minimal inflammatory infiltrate. Histologic examination of biopsies from adjacent normal-appearing colon showed normal mucosa.
The night prior to presentation, the patient had completed a 7-day course of an oral proprietary over-the-counter nasal decongestant containing dextromethorphan hydrobromide 10 mg, pseudoephedrine HCl 30 mg, guaifenesin 100 mg, and acetaminophen 250 mg. He had consumed pseudoephedrine 240 mg/day for 7 days (the maximum recommended dose for this product). This medication was ceased on admission and was not resumed after discharge or in the following 20 months. He had used the same medication for only one week about 3 months previously; on that occasion, he noted similar but milder abdominal discomfort and bowel irregularity that resolved when the medication was ceased.
His medical history consisted of only chronic low back pain for several years, for which he had taken tramadol 150 mg/day, diazepam 5 mg/day, and celecoxib 200 mg/day. Tramadol caused him some constipation, but no other adverse effects. He was taking no other medications or over-the-counter or herbal products. There was no previous personal or family history of gastrointestinal or vascular disease. He had been a non-smoker for the past 10 years. There was no history of cocaine use. Tramadol, diazepam, and celecoxib were ceased on admission and all were resumed after discharge.
Full blood examination and routine blood chemistry were normal. Thrombophilia screening for protein C, protein S, antithrombin III, factor V Leiden mutation, lupus anticoagulant, prothrombin mutation G20210, activated protein C resistance, cardiolipin antibody, and homocysteine was negative. Serum immunoglobulin and complement levels, acute phase proteins, autoantibodies, and cryoglobulin studies were also negative. Stool culture for enteric pathogens was negative. Doppler ultrasound examination of the abdomen and abdominal blood vessels showed no abnormality. An electrocardiogram was normal.
Discussion
Pseudoephedrine was found to be the probable cause of our patient's acute self-limiting ischemic colitis based on the Naranjo probability scale. 2 It is possible that our patient had experienced a previous, less severe, episode of ischemia. To date, there have been 8 cases of pseudoephedrine-induced ischemic colitis published in the literature. 3–7 Pseudoephedrine intake in these patients varied from 60 to 600 mg/day for approximately one week's duration. The age range of these subjects was 26–58 years and 6 were women. All presented with a history of acute severe colicky abdominal pain and rectal bleeding associated with the use of oral pseudoephedrine in the week prior to presentation. Pseudoephedrine in over-the-counter medications has also been associated with acute myocardial ischemia 8 and cerebral ischemia. 9
Tramadol is an opioid-type analgesic. Its precise mechanism of analgesic action is uncertain. However, it is known to inhibit the uptake of norepinephrine 10 and raise serum epinephrine levels. 11 In our patient, it is possible that the use of pseudoephedrine combined with a history of long-term tramadol use resulted in a higher than expected level of adrenergic stimulation. As of October 16, 2004, this possible tramadol–pseudoephedrine interaction has not been reported. However, there are reports of interactions between other direct-acting sympathomimetics (eg, epinephrine) and norepinephrine-reuptake–inhibiting antidepressants. Most reports concern tricyclic antidepressants and a variety of sympathomimetics. 12 The postulated mechanism is that norepinephrine is inactivated by uptake into the presynaptic neuron, and this is blocked by the antidepressant. The clinical effects of this established interaction include pressor responses, tachycardia, and ischemia, although we are unaware of any published reports of ischemic colitis. There is only one other reported case that suggests this mechanism may also be important for pseudoephedrine (whose main mechanism of action is through sensitization of α1-adrenergic receptors to circulating norepinephrine). Cardiac ischemia in the absence of coronary artery disease was reported in a 21-year-old man after pseudoephedrine was taken with bupropion, another norepinephrine-reuptake inhibitor. 8 He had previously taken pseudoephedrine on a number of occasions without bupropion, which had not precipitated ischemia. A similar interaction in our patient may have contributed to arterial vasoconstriction in the mesenteric bed, leading to colonic ischemia.
Interestingly, abdominal pain and hematochezia were not listed as possible adverse effects in the product information of the over-the-counter medication used by our patient. 13 Although ischemic colitis is an uncommon adverse effect of pseudoephedrine use, it can be associated with severe sequelae. With the widespread use and availability of over-the-counter pseudoephedrine-based decongestants and 9 cases now reported, it is suggested that the main symptoms of ischemic colitis, severe abdominal pain and rectal bleeding, should be routinely noted as a potential adverse effect in the product information. Our case also reinforces the importance of taking a thorough medical history of nonprescription medicines consumed.
Summary
We report a case of acute self-limiting ischemic colitis in a patient who was self-medicating with a proprietary over-the-counter oral decongestant containing pseudoephedrine. It is possible that the concurrent use of pseudoephedrine and tramadol may have increased adrenergic vasoconstriction, predisposing the patient to ischemic colitis. We recommend that prolonged or intensive use of medications containing pseudoephedrine should be avoided and that the package information should contain advice that the medication be ceased if abdominal pain or other ischemic symptoms occur.