| Abstract|| |
Various papers have been published on inflammatory bowel disease in the Kingdom of Saudi Arabia and other Gulf States during last decade. Apparently, the published data contradict previous belief and indicate that, we might deal here with a medical problem. However, data on the magnitude of this disease in our community remains uncertain. Could we attribute this possible change to the improvement in diagnostic procedure or to the change in life style? Unfortunately, the literature does not provide us with a convicting answer to this question yet.
However, at this stage a review of the medical management in inflammatory bowel disease seems to be justified. Hence currently used drugs in the management in inflammatory bowel disease are reviewed in this paper. Some of the potentially effective drugs for the future are also summarized.
|How to cite this article:|
Al-Gindan YM. Inflammatory bowel disease: Medical management. Saudi J Gastroenterol 1995;1:16-9
Inflammatory bowel disease (IBD) was believed to be rare among Arabs in general. However, anecdotal reports from various sources indicate that, IBD is not as rare as thought to be in the Kingdom of Saudi Arabia and other Gulf States. [1,,, The uncertainty about the pathogenesis is probably behind the frustration in the management of this disease. What is believed to play the major role in the pathogenesis? Is it autoimmunity,  genetic , environmental factors,  infectious agents,  or all of these combined? Hence, the management is supposed to be directed against one or all of the above possible etiological factors. Considering the fact that, the etiology and inflammation inducing mechanisms in IBD are still poorly understood, the mainstay of medical treat
ment in IBD has remained the same four categories of drugs, namely sulfasalazine (1940s), steroids (1950s), immunosuppressives (1960s), Metronidazole and other antibiotics (1970s). However, development of new agents, better analogues of older agents, and improved modes of drug delivery offer great promise for the future of drug therapy of this disease. 
Sulfasalazine is the most widely prescribed drug for patients with inflammatory bowel disease. In this drug 5-aminosalicylic acid is linked by an azo bond to sulfapyridine. The development of this agent by Nana Savartz in the late 1930s for the treatment of rheumatoid arthritis triggered its use in a group of patients with colitis. The results were impressive.  Sulfasalazine is a potent inhibitor of prostaglandin synthase and 5 lipoxygenase , Clinical trials have established its usefulness in the management of IBD. , Sulfasalazine is generally safe, however, approximately 30% of patients taking the agent report adverse reactions; many are idiosyncratic but others are dose related.  Skin rash, arthritis, pericarditis, pancreatitis, pleuritis, reversible infertility in men and hematological disorders are the usual or expected side effects. Constitutional symptoms such as nausea and headache are dose related.
Azad Khan  and others  were able to prove, that 5-Aminosalicylic acid (5- ASA) was the active moiety of sulfasalazine. On the other hand, the sulfa part of the sulfasalazine molecule functioned only as a carrier. Moreover, the hypersensitivity and intolerance induced were largely attributed to the sulfapyridine moiety.  The above studies called for more work on this subject. As a result various 5-ASA preparations were released into the market such as Mesalazine, Olsalazine sodium, Pentasa among others. All 5-ASA agents are better tolerated by patients who have problems with sulfasalazine. They vary in their release in the large bowel. However, none of them is more effective than sulfasalazine  Topical 5ASA in form of enema has proven to be useful in the control of distal procto colitis. , For distal Colitis, 5-ASA is also available in form of suppository.
Steroids have been used in IBD since the 1950s. This second group of drugs in the management of IBD continues to be highly useful in patients with moderate-to-severe ulcerative colitis or Crohn's disease.  Efforts have been made to alter the chemistry of this group to increase their local action in the gut without systemic glucocorticoid adverse effects. From this group, beclamethasone dipropionate, budesonide  and tixocortol pivalate are worth mentioning. These preparations allow a safe delivery of higher and more effective doses of steroids to the affected areas without adverse effects.  As a result, topical preparations with enhanced potency have proved in the last few years, to be effective in clinical trials. ,
Since the 1960s, azathioprine and 6-mercaptopurine have been used for IBD. These agents are effective in sparing steroids, closing fistulas, healing perianal disease, maintaining remissions and enhancing well being. ,,, Concern about potential adverse effects of the immunosuppressive agents has made many clinicians wary of using them.  However, with appropriate monitoring, these agents are safe and well tolerated.  The results of previous studies ,, were impressive and have served as a cornerstone for the increasing use of 6-mercaptopurine as well as azathioprine in the treatment of IBD. The steroid-sparing property of these agents in IBD has been confirmed in many studies. , Moreover, azathioprine and 6mercaptopurine proved to be useful as prophylactic agents in patients with Crohn's disease.  Neither sulfasalazine nor corticosteroids have the same property. Methotrexate at a low dose (25 mg per week) was reported in an uncontrolled study to be useful in refractory Crohn's disease and ulcerative colitis.  Cyclosporine has been found to be useful in a group of patients with severe ulcerative colitis, otherwise requiring colectomy.  This group of patients responded dramatically to cyclosporine therapy. However, the high incidence of side effects and the limited experience with this drug in the small numbers of patients with IBD, may limit its wide acceptability in patients with this disease for the foreseeable future.
Chron's disease has long been suspected of having a mycobacterial cause.  Mycobacterium para-tuberculosis has been cultured from some patients with Crohn's disease.  Beside this finding, the similarities between intestinal tuberculosis and Crohn's disease have justified the attempt to treat Crohn's disease with streptomycin and rifabutin  and later with four-drug regimen over - a 6-month period.  Other antimicrobial agents are also found to be useful for specific complications of IBD. Metronidazole was shown by various studies to be effective in healing perianal Crohn's disease as well as in treating colonic Crohn's disease.
Potentially New Drugs
Beside the above mentioned and commonly used therapeutic drugs, there are potentially new agents for the management of IBD.
Chloroquine and Hydroxychloroquine sulfate (plaquenil)
Both drugs work on the intestinal epithelial cells by activating the T-suppressor cells. The effect of these agents has been found to be useful in Ulcerative Colitis but not in Crohn's disease. 
As alpha-2 agonist, this drug is known in the treatment of hypertension. A trial, comparing the effect of this drug on ulcerative colitis with prednisone and sulfasalazine, has shown that, clonidine was as effective as prednisone and more effective than sulfasalazine in improving symptoms and endoscopic findings.  The action of clonidine on Ulcerative Colitis is not explained. More studies are needed before this drug is given a place in the management of IBD.
The finding of increased eosinophils and mast cells in the rectal mucosa in patients with ulcerative colitis justified the trial of oral sodium cromoglycate in the management of ulcerative colitis. However, the results were not encouraging.  Topical treatment seems to be much more promising.  On-going and future studies are expected to give the final answer on the possible role of this agent in the management of ulcerative colitis.
One of the possible actions of some drugs used in the management of ulcerative colitis is inhibition of the lypoxygenase pathway of arachidonic acid metabolism (see above under sulfasalazine). The consequence would be decreased production of Leukotriens. The result of a trial with eicosapentaenoic acid, which is known to inhibit the arachidonic acid metabolism, may open a new field in the management of IBD for the future.  A subsequent study confirmed the role of this group of drugs in the management of IBD. 
Oxygen - Derived Free Radical Scavengers
One of the hypothetical explanations for the action of 5-ASA in the management of IBD is through its role as a scavenger of the oxygenderived radicals. Superoxide dismutase, as a free radical scavenger, was used in different trials in both ulcerative colitis and Crohn's disease. ,,
The results indicate, that this drug might be considered as a rising star in the field of IBD management.
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Yusuf M Al-Gindan
Department of Internal Medicine. King Fahad Hospital of the University, Al-Khobar 31952
Source of Support: None, Conflict of Interest: None