Medical management of ulcerative colitis

The major medical therapy for active disease is to treat with corticosteroids, such as prednisolone, and when the acute disease has settled, to maintain remission with compounds containing 5-aminosalicylic acid (5-AS A). Azathioprine is used as a 'steroid sparing agent'. Anti-diarrhoea agents, anti-spasmodics, and analgesics are also sometimes used to reduce symptoms without affecting disease activity.

Corticosteroids

Steroids have a wide range of actions in the human body, one of which is a general ability to reduce inflammation. Two steroids in particular, hydrocortisone and prednisolone, have been used with good effect in the management of IBD for many years. Systemic, intravenous steroids are given for very severe or fulminant relapses of ulcerative colitis. Oral steroids are used for slightly less severe exacerbations. Active rectal and sigmoid colitis is treated using cortico-steroids in liquid or foam enema preparations. These are relatively convenient to use and have few side-effects. Corticosteroid use is associated with unpleasant side-effects including weight gain, acne, fluid retention and psychiatric symptoms such as mood swings. In the long term they also cause metabolic bone disease and hypertension. It is for these reasons that their use must be closely monitored and limited to acute exacerbations. There is no evidence that they maintain remission, and long-term use of corticosteroids is therefore avoided.

5-Aminosalicylic acid compounds

Only 4% of untreated patients with ulcerative colitis failed to have a further attack of their disease in the 15 years after onset. Maintenance of remission is therefore an important aspect of the long-term management (Jewell 2000a). Over 50 years ago it was noted that the medication, sulphasalazine, used in rheumatological conditions was efficacious in IBD. Sulphasalazine is broken down by colonic bacteria to release an active component, 5-ASA. Consequently, the active drug is only released in the colon. Newer compounds such as osalaz-ine and mesalazine deliver 5-ASA to the colon without the carrier molecule (sulphonamide). Sulphasalazine is one of the mainstays of maintenance therapy in ulcerative colitis. It reduces the frequency of recurrent attacks and is effective over many years. It is also effective in the treatment of mildly active disease.

The reported dose-related side-effects of sulphasalazine include nausea, vomiting, diarrhoea, azospermia and headaches and occur in up to 20% of patients. In cases of sulphasalazine intolerance, hypersensitivity or male infertility the use of mesalazine or olsalazine is indicated. These drugs are appreciably more expensive than sulphasalazine, but are much better tolerated (Jewell 2000a).

Immunosuppressive therapy

Azathioprine and 6-mercaptopurine have been used extensively in IBD. They have been mostly used in Crohn's disease but have also been shown to be effective in the treatment of active ulcerative colitis. They act by damping down immune reactions, probably by indirectly blocking the synthesis of DNA and by direct action on types of white blood cells associated with inflammation. However, their action is slow and they have to be taken for over three months for benefit. Immunosuppresive therapies are particularly helpful in producing remission and preventing relapse in IBD.

The main reluctance to use immunosuppressive drugs is primarily related to their potential toxicity, including bone marrow suppression, hepatotoxicity and acute pancreatitis. Therefore patients must be closely monitored using laboratory tests. Fear concerning their mutogenic and teratogenic potential has been eliminated.

Antibiotic therapy

Antibiotics have long been viewed as a potential treatment option in inflammatory bowel disease in specific clinical situations. Metronidazole is a useful agent for managing peri-anal disease and may also suppress Crohn's disease activity. Other antibiotics have a role in treating septic complications.

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