Ischemic colitis

Approximately 8% to 20% of patients with UC and 7% to 26% of patients with CD are elderly at initial diagnosis.42 In general, IBD presents similarly in elderly patients compared to younger individuals. Elderly patients may have more comor-bid diseases, some of which may make the diagnosis of IBD more difficult. Such conditions include ischemic colitis, diverticular disease, and microscopic colitis. Increased age is also associated with a higher incidence of adenomatous polyps, but the onset of IBD at an advanced age does not appear to increase the risk of developing colorectal cancer. Elderly patients may also use more medications, particularly NSAIDs, which may induce or exacerbate colitis. 

Because alosetron has been associated with ischemic colitis, it may be prescribed only under strict guidelines, including signing of a consent form by both patient and physician. Patients selected for therapy should exhibit chronic IBS symptoms and have failed to respond to conventional therapy. 

Ischemic colitis has been observed in some patients taking tegaserod. The drug should be discontinued promptly if rectal bleeding, bloody diarrhea, or worsening abdominal pain occurs. 

Lotonex Irritable Bowel Syndrome Ischemic colitis/death... 

Alosetron (Lotronex) Irritable bowel syndrome Serious gastrointestinal events, especially ischemic colitis and constipation 2000 [53]... 

Alosetron hydrochloride Lotronex Glaxo Wellcome Gastrointestinal 2/9/2000 11/28/2000 9 months Ischemic colitis 50.4 million... 

Serious Gl adverse events, some fatal, have been reported with the use of alosetron. These events, including ischemic colitis and serious complications of constipation, have resulted in hospitalization, blood transfusion, surgery, and death. 

Alosetron should be discontinued immediately in patients who develop constipation or symptoms of ischemic colitis. Physicians should instruct patients to immediately report constipation or symptoms of ischemic colitis. Alosetron should not be resumed in patients who develop ischemic colitis. Physicians should instruct patients who report constipation to immediately contact them if the constipation does not resolve after discontinuation of alosetron. Patients with resolved constipation should resume alosetron only on the advice of their treating physician. 

Alosetron should be discontinued immediately in patients who develop constipation or signs of ischemic colitis. Alosetron should not be restarted in patients who develop ischemic colitis. 

Ischemic colitis Ischemic colitis and other forms of intestinal ischemia have been reported in patients receiving tegaserod during marketed use of the drug. Discontinue tegaserod immediately in patients who develop symptoms of ischemic colitis, such as rectal bleeding, bloody diarrhea, or new or worsening abdominal pain. 

Colitis Ulcerative and hemorrhagic/ischemic colitis, sometimes fatal, has been observed within 12 weeks of starting alpha interferon treatment. Abdominal pain, bloody diarrhea, and fever are the typical manifestations of colitis. 

Alosetron (Lotronex) is a 5-HT3 receptor antagonist. Blocking this receptor results in decreased GI motility. Alosetron received FDA approval in February 2000 for the treatment of women with diarrhea-predominant IBS. In November 2000, at the request of the FDA, the drug was voluntarily withdrawn due to reported cases of ischemic colitis, including some fatalities. 

Ischemic colitis, mesenteric ischemia, gangrenous bowel, rectal bleeding, syncope, hypotension, hypovolemia, electrolyte disorders, suspected sphincter of Oddi spasm, bile duct stone, cholecystitis with elevated transaminases, and hypersensitivity reaction including rash, urticaria, pruritus, and serious allergic type 1 reactions have been reported,... 

In contrast to the excellent safety profile of other 5-HT3-receptor antagonists, alosetron is associated with rare but serious gastrointestinal toxicity. Constipation occurs in up to 30% of patients with diarrhea-predominant IBS, reguiring discontinuation of the drug in 10%. Serious complications of constipation requiring hospitalization or surgery have occurred in 1 of every 1000 patients. Episodes of ischemic colitis—some fatal—have been reported in up to 3 per 1000 patients. Given the seriousness of these adverse events, alosetron is restricted to women with severe diarrhea-predominant IBS who have not responded to conventional therapies and who have been educated about the relative risks and benefits. 

Alosetron 5-HT3 antagonist of high potency and duration of binding Reduces smooth muscle activity in gut Approved for severe diarrhea-predominant IBS in women Rare but serious constipation ischemic colitis infarction... 

Glucocorticoids should be used with caution in progressive systemic sclerosis, and concomitant administration of anticoagulants to prevent ischemic colitis is recommended when administering glucocorticoids in high doses, especially by pulse therapy (SEDA-21, 415 150). 

Yamanishi Y, Yamana S, Ishioka S, Yamakido M. Development of ischemic colitis and scleroderma renal crisis following methylprednisolone pulse therapy for progressive systemic sclerosis. Intern Med 1996 35(7) 583-6. 

There is some reason to distinguish this from the ischemia that can be caused by oral contraceptives, in that it is restricted to the colon, can have a chronic or remitting course, can present with non-specific abdominal and colonic symptoms, can be reversible despite continued use of estrogen, and does not require surgical treatment. The symptoms of intestinal ischemia resolve within days to weeks after withdrawal of the estrogen. However, oral contraceptives have also been reported to cause ischemic colitis. 

McClennan BL. Ischemic colitis secondary to Premarin report of a case. Dis Colon Rectum 1976 19(7) 618-20. 

Deana DG, Dean PJ. Reversible ischemic colitis in young women. Association with oral contraceptive use. Am J Surg Pathol 1995 19(4) 454-62. 

Tongue ischemia and ischemic colitis have been described after 4-9 days of treatment with ornipressin 6 IU/hour combined with plasma volume expansion (19). 

Koga, K., et al. 2004. Membrane permeability and antipyrine absorption in a rat model of ischemic colitis. Int J Pharm 286 41. 

Episodes of ischemic colitis—some fatal—have been reported in up to 3 of every 1000 patients. Given the seriousness of these adverse events, alosetron is restricted to women with severe diarrhea-predominant IBS who have not responded to conventional therapies and who have been educated about the relative risks and benefits. 

Some patients may experience hearing loss, which may accompany diabetes. Usually, type 2 diabetes is described in individuals with MELAS, although type 1 or insulin-dependent diabetes also may be observed. Palpitations and shortness of breath may be present in some patients with MELAS secondary to cardiac conduction abnormalities such as Wolff-Parkinson-White syndrome. Acute onset of gastrointestinal manifestations (e.g., acute onset of abdominal pain) may reflect pancreatitis, ischemic colitis, and intestinal obstruction. Numbness, tingling sensation, and pain in the extremities can be manifestations of peripheral neuropathy. Some patients may have the presentation of Leigh syndrome (i.e., subacute necrotizing encephalopathy). 

Simmers TA, Vidakovic-Vukic M, Van Meyel JJ. Cocaine-induced ischemic colitis. Endoscopy 1998 30(l) S8-9. 

History of Crohn s disease, diverticulitis, G1 perforation and/or adhesions, impaired intestinal circulation or ischemic colitis, intestinal obstruction, intestinal stricture, or toxic megacolon... 

Gastrointestinal Abdominal pain, constipation, nausea, ischemic colitis... 

Five patients developed mesenteric ischemia, four with ischemic colitis, and one with abdominal angina, while taking beta-adrenoceptor antagonists (82). Although causation was not proven, it was possible. 

An acute colitis, different from pseudomembranous colitis, was observed in five patients taking penicillin and penicillin derivatives (133). There was considerable rectal bleeding. The radiographic findings were those of ischemic colitis (spasm, transverse ridging, thumbprinting, and punctuate ulceration). On sigmoidoscopy and biopsy, the mucosa was normal, except for an inflammatory cell infiltration in one case. Conservative treatment resulted in rapid remission. 

A 36-year-old man who had injected cocaine the day before admission and who occasionally sniffed, smoked, or injected cocaine, presented with a 3-day history of severe abdominal pain and bloody diarrhea (151). His mid-abdomen was very tender, with rebound tenderness and guarding bowel sounds were absent. Radiography showed a dilated transverse colon and dilated small bowel loops. He underwent emergency surgery and an edematous dilated transverse colon was removed. The pathology was consistent with ischemic colitis. The blood vessels were dilated but showed no structural abnormahties or thrombosis. 

Little is known about the effects of COX-2 inhibitors on the colon, although animal evidence suggests that they can worsen or precipitate acute colitis. Features similar to those seen in cases of ischemic colitis have been reported in a patient taking rofecoxib (98). 

The vasoconstrictor action of pseudoephedrine can predispose susceptible patients to ischemic colitis, particularly in the watershed area of the splenic flexure. Perimenopausal women may be more susceptible (19). A group from Yale have described four patients, women aged 35-50 years, who developed ischemic colitis while taking pseudoephedrine (19). Three of them had taken the drug for about 1 week, the fourth for 6 months. In all cases there was ischemic colitis affecting predominantly the splenic flexure, and there was full recovery after drug withdrawal. 

Dowd J, Bailey D, Moussa K, Nair S, Doyle R, Culpepper-Morgan JA. Ischemic colitis associated with pseudoephedrine four cases. Am J Gastroenterol I999 94(9) 2430-4. 

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