Drug therapy of inflammatory bowel disease

Abstract

The drugs that are effective in inflammatory bowel disease (IBD) act by inhibiting the chronic unregulated intestinal inflammation in these patients. The mainstays of the drug therapy of IBD are a variety of formulations of 5-aminosalicylic acid (5-ASA), the conventional and newer low bioavailability glucocorticoids, the nitroimidazole antibiotic metronidazole, and certain immunomodulating agents. Increased understanding of the mechanisms of inflammation in IBD has permitted the development of effective designer drugs. These agents are products of the biotechnology industry and include antibodies to tumor necrosis factor (TNF)-alpha, antisense oligonucleotides and recombinant human interleukin (IL)-10. In addition, a number of other agents such as nicotine and n-3 fatty acids are useful in certain patients. This review first focuses on the pharmacology and mechanism of action of these drugs in IBD, followed by an approach to the treatment of patients with ulcerative colitis (UC) and Crohns disease (CD). The recommendations consider type and activity of IBD and are based largely on data from controlled trials and systematic reviews in the IBD literature.

Intestinal anti‐inflammatory activity of UR‐12746, a novel 5‐ASA conjugate, on acute and chronic experimental colitis in the rat

“…Sulphasalazine, a diazo compound with 5‐aminosalicylic acid (5‐ASA) (mesalamine) linked to sulphapyridine that acts as a carrier, has been long used as therapy for both intestinal conditions. Thus, this agent has been shown to be useful in managing mild‐to‐moderate active UC and mild active CD, as well as in maintaining remission by prevention of relapses in patients with inflammatory bowel disease (IBD) ( Egan & Sandborn, 1998 ). Unfortunately, long‐term administration of sulphasalazine is accompanied by a considerable number of side‐effects, either dose‐dependent such as headache, nausea, vomiting, etc.…”

Nanoparticles Enhance Therapeutic Efficiency by Selectively Increased Local Drug Dose in Experimental Colitis in Rats

“…Increased understanding of the mechanisms of inflammation in IBD has permitted the development of effective designer drugs (Egan and Sandborn, 1998). The proposed use of tumor necrosis factor-␣ monoclonal antibodies in the treatment of rheumatic arthritis and, more recently, in Crohn's disease showed distinct success of the therapy due to the antibody specificity, which greatly reduces adverse effects.…”

Inhibition of Interleukin-1-stimulated NF-κB RelA/p65 Phosphorylation by Mesalamine Is Accompanied by Decreased Transcriptional Activity

“…Sodium salicylate and acetyl salicylic acid inhibit NF-B by preventing inducible degradation of IB, and this action may underlie the in vivo anti-inflammatory effects of these agents (14). Aminosalicylates such as sulfasalazine (an azo-conjugated aminosalicylate) and mesalamine (5-aminosalicylic acid, a free aminosalicylate) inhibit gut inflammation in inflammatory bowel disease (15) (Fig. 1).…”