Although the etiology of
inflammatory bowel disease is unknown and specific
therapy is unavailable, enough information on existing empiric agents is available to allow rational
therapy. These agents include
sulfasalazine,
steroids, immunosuppressive drugs,
metronidazole and
cholestyramine.
Sulfasalazine is a two-part molecule that depends on bacterial cleavage in the colon to deliver locally acting
5-aminosalicylate, whose mechanism of action may relate to inhibition of
prostaglandin synthesis. The other half of the molecule,
sulfapyridine, is responsible for most of the side effects of the
drug. While the efficacy of
sulfasalazine in the treatment and prevention of attacks of
ulcerative colitis is well established, its use in
Crohn's disease appears to be limited to patients with active
colitis and ileo-
colitis.
Sulfasalazine is of major benefit in preventing relapses in patients with
ulcerative colitis in remission. New formulations of
5-aminosalicylate may allow delivery of the apparently active moiety to the small bowel and colon without concomitant
sulfapyridine toxicity.
Corticosteroids are highly effective in acute attacks of
ulcerative colitis and Crohn's
ileitis and ileo-
colitis; the mechanism of antiinflammatory action remains speculative. However, maintenance
therapy with
steroids is ineffective in preventing relapses or recurrent attacks of either
ulcerative colitis or
Crohn's disease.
Steroid enemas allow
topical administration to patients with distal
colitis and
proctitis with few systemic side effects. In children with growth failure associated with active
Crohn's disease, amelioration by
steroid therapy may actually restore normal growth.
Immunosuppressive agents such as
azathioprine and
6-mercaptopurine are of little value in active
Crohn's disease when administered alone; however, in combination with other agents they may help diminish
steroid dose, close fistulae and prevent relapse. Their mode of action likely depends on long-term
cytostatic effects on immune effector cells. Concern for
leukopenia and the development of late
malignancy has limited their use to patients not responding to other
therapies.
Metronidazole, an
antimicrobial agent that is effective against anaerobes, has recently been shown useful in
Crohn's disease involving the colon and perianal area. Its mechanism of action is uncertain, but may be related to its antibacterial actions on anaerobes.
Cholestyramine can be successfully used to control
bile salt-induced
diarrhea in Crohn's patients with terminal ileal resections. Effective
drug therapy of
inflammatory bowel disease is only part of a total program of management including reassurance, frequent explanation, well-timed use of surgery, and an understanding physician.