Inflammatory bowel disease corticosteroids

TABLE 16-2. Corticosteroids for Treatment of Inflammatory Bowel Disease... 

The same strategy was applied in colon-specific delivery of two corticosteroids used to treat inflammatory bowel disease [20][21], Indeed, budeso-nide /3-D-glucuronide and dexamethasone /3-D-glucuronide underwent ready hydrolysis in the luminal contents of rat colon and caecum. Rat mucosal homogenates were less active, and hydrolysis in human fecal samples was quite low. Based on these and other studies, the prodrugs were found to be suitable candidates for delivery of corticosteroids to the large intestine. 

Budesonide is used for inflammatory bowel disease. It has a high first pass metabolism. It has efficacy in the terminal ileum and the right colon. Budesonide in comparison with prednisolone has been associated with fewer bone density losses and unlike other corticosteroids has little influence on the hypothalamic-pituitary-adrenal axis. 

Therapeutic pyramid approach to inflammatory bowel diseases. Treatment choice is predicated on both the severity of the illness and the responsiveness to therapy. Agents at the bottom of the pyramid are less efficacious but carry a lower risk of serious adverse effects. Drugs may be used alone or in various combinations. Patients with mild disease may be treated with 5-aminosalicylates (with ulcerative colitis or Crohn s colitis), topical corticosteroids (ulcerative colitis), antibiotics (Crohn s colitis or Crohn s perianal disease), or budesonide (Crohn s ileitis). Patients with moderate disease or patients who fail initial therapy for mild disease may be treated with oral corticosteroids to promote disease remission immunomodulators (azathioprine, mercaptopurine, methotrexate) to promote or maintain disease remission or anti-TNF antibodies. Patients with moderate disease who fail other therapies or patients with severe disease may require intravenous corticosteroids, anti-TNF antibodies, or surgery. Natalizumab is reserved for patients with severe Crohn s disease who have failed immunomodulators and TNF antagonists. Cyclosporine is used primarily for patients with severe ulcerative colitis who have failed a course of intravenous corticosteroids. TNF, tumor necrosis factor. 

Lymphoma appears to be increased in patients with untreated inflammatory bowel disease. Anti-TNF agents may further increase the risk of lymphoma in this population, although the relative risk is uncertain. An increased number of cases of hepatosplenic T-cell lymphoma, a rare but usually fetal disease, have been noted in children and young adults, virtually all of whom have been on combined therapy with immunomodulators, anti-TNF agents, or corticosteroids. 

Lichtenstein GR et al. American Gastroenterological Association Institute technical review on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology 2006 130 940. [PMID 16530532]... 

Monk BE, Skipper D. Allergy to topical corticosteroids in inflammatory bowel disease. Gut 2003 52 597. 

Aberra FN, Lewis JD, Hass D, Rombeau JL, Osborne B, Lichtenstein GR. Corticosteroids and immunomodulators postoperative infectious complication risk in inflammatory bowel disease patients. Gastroenterology 2003 125 320-7. 

Corticosteroids are some of the most important drugs used in the treatment of patients with inflammatory bowel disease. Intrarectal administration of corticosteroids is used in order to obtain topical action of these drugs and thus to reduce adverse systemic side effects. 

Osteoporosis is also common in those on long-term corticosteroid therapy (for example patients with autoimmune hepatitis or coexisting inflammatory bowel disease). Patients with chronic liver disease may also have other risk factors for osteoporosis related to their disease state. These include vitamin D deficiency, excessive alcohol consumption, poor diet, physical inactivity and low body mass index. Oestrogen deficiency in the postmenopausal stage further increases the risk. 

A careful history should be taken when one of the differential diagnoses is ulcerative colitis because corticosteroid administration has the potential to unmask amebiasis and produce toxic megacolon. All patients diagnosed as having inflammatory bowel disease should have their stools examined carefully and serologic testing done for amebiasis to avoid the serious consequence that results from the administration of corticosteroids. 

Apart from classic analgesic nephropathy, this chapter will also handle the possible nephrotoxic role of 5-aminosalicylic acid (5-ASA) used in patients with chronic inflammatory bowel disease (IBD). During the last decade, 5-ASA replaced sulfasalazine as first-line therapy for mildly to moderately active IBD. For decades, sulphasalazine, an azo-compound derived from sulphapyridine and 5-aminosalicylic acid (5-ASA), has been the only valuable non-corticosteroid drug in the treatment of inflammatory bowel disease. Azad Kahn et al. [25] showed that the pharmacologically active moiety in sulphasalazine for the treatment of these diseases was 5-ASA. Consequently, this resulted in a number of new 5-ASA formulations (mesalazine, olsalazine, balsalazine) for topical and oral use. Since the metabolite sulphapyridine was largely responsible for the side effects of sulfasalazine, the primary advantage of the newer 5-ASA agents is their improved adverse effect profile. 

The role of both T and B lymphocytes in a variety of disease states beyond transplantation has become increasingly important in the past decade. This is especially true of those diseases frequently referred to as autoimmune in their etiology, such as rheumatoid arthritis, nephrotic syndrome, systemic lupus erythematosus, inflammatory bowel disease, and so on. In addition, several other major diseases are also known to have a component of T- or B-cell-mediated pathogenesis, for example, atopic dermatitis, psoriasis, and asthma. Until very recently, the mainstay of therapy for these diseases was the corticosteroids, which were often less than satisfactory in efficacy and often associated with undesirable side effects, especially in growing children and the elderly. Thus, the search for new agents with different mechanisms of action and which did not have the same adverse event profile as conventional corticosteroids led to the subsequent evaluation of drugs such as tacrolimus and sirolimus to treat several of these diseases. 

POSTERIOR SUBCAPSULAR CATARACTS AND RAISED INTRAOCULAR PRESSURE ARE CAUSED BY PROLONGED ORAL CORTICOSTEROID THERAPY IN ADULT PATIENTS WITH INFLAMMATORY BOWEL DISEASE... 

Inflammatory bowel disease (Crohn s disease and ulcerative colitis) occurs among all age groups but has peaks of incidence in the second and fourth decade of life. Currently, corticosteroid therapy is the most effective treatment for moderate to severe cases of IBD. Ocular pathology in the setting of IBD may be related to inflammation of the gastrointestinal tract or secondary to corticosteroid treatment. The two major ocular side effects of systemic corticosteroid therapy are posterior subcapsular cataract (PSC) and raised intraocular pressure (lOP). Recently, we reported that PSC was detected in 12 of 58 (20.7%) corticosteroid-treated pediatric IBD patients and that 21 patients of the same population (36.2%) had raised lOP. Because pediatric IBD patients continue corticosteroid therapy into adulthood, we analyzed the prevalence of PSC and raised lOP in a series of adult IBD patients. 

Karrison, and J.T. Ernest, Corticosteroid treatment for inflammatory bowel disease in pediatric patients increases intraocular pressure, Gastroenter. 102 1957(1992). 

Diarrhoea is also part of some inflammatory disorders, such as irritable bowel syndrome, ulcerative colitis and Crohn s disease. These may best be relieved by treatment with corticosteroids and aminosalicylates. Diarrhoea is commonly associated with bacterial or other pathogenic infections (e.g. food poisoning) and these may require treatment with antibiotics or other antimicrobials. 

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