Inflammatory bowel disease, treatment

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. 

In murine models of experimental autoimmune encephalomyelitis (multiple sclerosis), diabetes mellitus type 1, and inflammatory bowel disease, treatment with 1,25-hydroxycholecalciferol (in conjunction with adequate calcium intake) has been shown to inhibit the development of disease (Froicu et al., 2003 Hypponen, 2004 Van Amerongen et al., 2004). In lupus mouse strains, however, a more complex situation is seen, with some evidence of worsening of disease (particularly with respect to measures of renal damage) with 1,25-hydroxycholecalciferol treatment (Vaisberg et al., 2000). 

Halpin, T. C., Bertino, J. S., Rothstein, F. C., Kurczinski, E. M., and Reed, M. C., 1982, Iron deficiency anemia in childhood inflammatory bowel disease Treatment with intravenous iron dextran, J. Parent. Enter. Nutr. 6 9. 

Anticytokine antibodies Infliximab Chimeric (mouse/human) monoclonal antibody against TNEa. Effective in the treatment of severe forms of rheumatoid arthritis where it can halt disease progression, or inflammatory bowel disease (EBD). 

In addition to those described above, some of the newest compounds emerging in SERM development are ER 3-selective ligands and pathway-selective modulators that target the interaction of the ERs with the transcription factor NFkB. While such compounds are in the early stages of clinical evaluation, thus far they demonstrate great potential for use in the treatment of inflammatory disorders such as arthritis, inflammatory bowel disease, and like other SERMs, cancer [4]. 

Edwards-Levy, F., Andry, M. C. Levy, M. C. (1994). Determination of free amino group content of serum-albumin microcapsules. II. Effect of variations in reaction-time and terephthaloyl chloride concentration. International Journal of Pharmaceutics, Vol. 103, 3, (March 1994), pp. (253-257), ISSN 0378-5173 Friend, D. R. (2005). New oral delivery systems for treatment of inflammatory bowel disease. Advanced Drug Delivery Reviews, Vol. 57, 2, (January 2005), pp. (247-265), ISSN 0169-409X... 

AUgayer, H., Gugler, R., Bohme, P., Schmidt, M., Hofer, P. and Kruis, W. (1991). Is free radical scavenging necessary in the treatment of inflammatory bowel disease Gastroenterology 100, 581-582. 

Williams, J.G. (1990). Phagoeyftes, toxic oxygen metabolites and inflammatory bowel disease, implications for treatment. Ann. R, Coll. Sutg. Engl. 72, 253-262. 

Within the gut, oxidative damage may be prevented by phytic acid, obtained from cereals and vegetables (Graf et al., 1987), and by soluble non-starch polysaccharides like pectin (Kohen et al., 1993). The use of antioxidant vitamins in the treatment of inflammatory bowel disease has also been su ested (Evans et al., 1990). 

The inhibition of the phosphorylation of IkBoc by celastrol in the NF-kB signaling pathway is not cell specific72-75 and thus significantly broadened the potential medicinal applications of natural triterpene QMs. Celastrol 76 has been evaluated in the treatment of Crohn s disease,76 which is a chronic relapsing inflammatory bowel disease. In the peripheral blood mononuclear cells, celastrol 76 reduced the levels of... 

TABLE 16-1. Aminosalicylates for Treatment of Inflammatory Bowel Disease... 

Navarro F, Hanauer SB. Treatment of inflammatory bowel disease Safety and tolerability issues. Am J Gastroenterol 2003 98(12 Suppl) S18-S23. 

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

Emmrich, J. et al., Treatment of inflammatory bowel disease with anti-CD4 monoclonal antibody, Lancet, 338, 570, 1991. 

Other studies describe similar beneficial effects for PUFA-enriched diets to treat Crohn s disease, other inflammatory bowel diseases such as ulcerative colitis, as well as psoriasis, asthma, systemic lupus erythematosus, and multiple sclerosis [57], Thus, immunomodulation by PUFAs appears to be a promising intervention for the treatment of many autoimmune and inflammatory diseases. 

Pathway selective ER ligands have been reported that selectively inhibit nuclear factor kB (NF-kB) mediated gene expression [71], Since NF-kB is a pivotal regulator of pro-inflammatory gene expression, ligands that selectively inhibit the NF-kB pathway could be developed for the treatment of chronic inflammatory diseases such as arthritis, atherosclerosis, sepsis, and inflammatory bowel disease... 

Chemical enhancers have been demonstrated to produce transport windows in eolonie epithelia large enough for the passage of many bacterial toxins. Patients suffering from inflammatory bowel diseases and colitis typically have increased colonic permeability [45] due to bacterial toxins, both entertoxins and cytotoxins that increase eapillary permeability. Increased colon permeability associated with a diseased state may be useful in treatment where improvement of the condition might reduce mucosal permeability and naturally reduce drug transport. 

Su, C., and Lichtenstein, G. R. (2004) Treatment of inflammatory bowel disease with azathro-prine and 6-mercaptopurine. Gastroenterol. Clin. North Am. 33, 209-234. 

Winter, J., Walker, A., Shapiro, D., et al. (2004) Cost-effectiveness of thiopuiine methyltransferase genotype screening in patients about to commence azathioprine therapy for treatment of inflammatory bowel disease. Aliment. Pharmacol. Ther. 20, 593-599. 

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