Inflammatory bowel disease, treatment agents

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. 

TABLE 16-3. Immunosuppressant and Biologic Agents for Treatment of Inflammatory Bowel Disease... 

ADVERSE DRUG REACTIONS TO AGENTS USED FOR TREATMENT OF INFLAMMATORY BOWEL DISEASE ... 

Kwon JH,Farrell RJ.The risk of lymphoma in the treatment of inflammatory bowel disease with immunosuppressive agents. Crit Rev Oncol Hematol 2005 56 169-78. 

Langford CA, Klippel JH, Balow JE, James SP, Sneller MC. Use of cytotoxic agents and cyclosporine in the treatment of autoimmune disease. Part 2 Inflammatory bowel disease, systemic vasculitis, and therapeutic toxicity. Ann Intern Med 1998 129 49-58. Ponticelli C. Calcineurin-inhibitors in renal transplantation. Too precious to be abandoned. Nephrol Dial Transplant 2000 15 1307-1309. 

Sulfasalazine, commonly used in the treatment of inflammatory bowel disease and rheumatoid arthritis, is selectively used as an alternative treatment, particularly in patients with concurrent psoriatic arthritis. Sulfasalazine is an anti-inflammatory agent that inhibits 5-lipoxygenase. When used as a single agent in the treatment of psoriasis, it is not as effective as is therapy with methotrexate, PUVA, or acitretin. One possible advantage of sulfasalazine therapy compared with other systemic treatments is its relatively high margin of safety. The usual dose of oral sulfasalazine is 3 to 4 g/day for 8 weeks. ... 

Most recent evidence indicates that DFAs can even protect the intestinal tract against agressive agents favor the assimilation of antioxidants, and act as a druglike food for the treatment of colon ailments such as inflammatory bowel disease (Crohn disease). The development of efficient methodologies for the preparation of DFA-enriched caramels, compatible with the food and agricultural industry regulations, may lead to new natural functional foods and nutraceuticals based on DFAs in the near future. 

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. 

Pharmacodier y of Gastric Acidity, Peptic Ulcers, and Gastroesophageal Reflux Disease 623 37. Treatment of Disorders of Bowel Motility and Water Rux Antiemetics Agents Used in Biliary and Pancreatic Disease 635 38. Pharmacotherapy of Inflammatory Bowel Disease 635... 

Chronic diarrhea may be due to laxative abuse, lactose intolerance, inflammatory bowel disease, malabsorption syndromes, endocrine disorders, irritable bowel syndrome and other disorders. Treatment with nonspecific antidiarrheal agents such as those listed in Table 6.2 may mask an underlying disorder. Treatment of chronic diarrhea should be aimed at correcting the cause of diarrhea rather than alleviating the symptoms. 

Overproduction of cytokines is observed in disease states such as inflammatory bowel disease (IBD). Crohn s disease patients have increased levels of tumor necrosis factor (TNF)-a, while interleukin (IL)-4 is increased in patients with ulcerative colitis. Elevated cytokine levels are associated with increased intestinal permeability. Herein, we investigated the effect of AT-1001, a permeability inhibitor 8-mer synthetic peptide, on TNF-a and IL-4 induced permeability of Lucifer yellow in vitro. We found that AT-1001 reduced TNF-a induced permeability after 24 and 72 hours in Caco-2 cell monolayers by 40% and 50%, respectively. Additionally, AT-1001 reduced the IL-4 induced permeability after 24 hours in T84 cell monolayers by 86%. Our data suggest that AT-1001 inhibits TNF-a and IL-4 induced permeability, and demonstrates potential as a therapeutic agent for the treatment of IBD. 

Cat s claw has long been used in South America as an anti-inflammatory, antirheumatic, and contraceptive agent. It is also traditionally used to treat gastrointestinal ulcers, tumors, gonorrhea, dysentery, various skin problems, cancers of the female genitourinary tract, and intestinal disorders. Native South Americans use cat s claw to cleanse the kidneys and treat bone pain. Some Europeans report that it is useful in the treatment of AIDS when used in combination with zidovudine (AZT). The purported usefulness of cat s claw tea in the treatment of diverticulitis, hemorrhoids, peptic ulcer disease, colitis, parasites, and leaky bowel syndrome have fueled demand for the bark in the U.S. 

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