Drugs Used in the Treatment of Gastrointestinal Diseases
Many of the drug groups discussed elsewhere in this book have important applications in the treatment of diseases of the gastro-intestinal tract and other organs. Other groups are used almost exclusively for their effects on the gut; these are discussed in the following text according to their therapeutic uses.
Acid-peptic diseases include gastroesophageal reflux, peptic ulcer (gastric and duodenal), and stress-related mucosal injury. In all these conditions, mucosal erosions or ulceration arise when the caustic effects of aggressive factors (acid, pepsin, bile) overwhelm the defensive factors of the gastrointestinal mucosa (mucus and bicarbonate secretion, prostaglandins, blood flow, and the pro-cesses of restitution and regeneration after cellular injury). Over 90% of peptic ulcers are caused by infection with the bacterium Helicobacter pylori or by use of nonsteroidal anti-inflammatorydrugs (NSAIDs). Drugs used in the treatment of acid-peptic dis-orders may be divided into two classes: agents that reduce intra-gastric acidity and agents that promote mucosal defense.
A 21-year-old woman comes with her parents to discuss therapeutic options for her Crohn’s disease. She was diag-nosed with Crohn’s disease 2 years ago, and it involves her terminal ileum and proximal colon, as confirmed by colonos-copy and small bowel radiography. She was initially treated with mesalamine and budesonide with good response, but over the last 2 months, she has had a relapse of her symp-toms. She is experiencing fatigue, cramping, abdominal pains, and nonbloody diarrhea up to 10 times daily, and she has had a 15-lb weight loss.She has no other significant medical or surgical history. Her current medications are mesalamine 2.4 g/d and budes-onide 9 mg/d. She appears thin and tired. Abdominal exam-ination reveals tenderness without guarding in the right lower quadrant; no masses are palpable. On perianal exami-nation, there is no tenderness, fissure, or fistula. Her labora-tory data are notable for anemia and elevated C-reactive protein. What are the options for immediate control of her symptoms and disease? What are the long-term management options?
The immediate goals of therapy are to improve this young woman’s symptoms of abdominal pain, diarrhea, weight loss, and fatigue. Equally important goals are to reduce the intes-tinal inflammation in hopes of preventing progression to intestinal stenosis, fistulization, and need for surgery. One option now is to “step up” her therapy by giving her a slow, tapering course of systemic corticosteroids (eg, prednisone) for 8–12 weeks in order to quickly bring her symptoms and inflammation under control while also initiating therapywith an immunomodulator (eg, azathioprine or mercaptopu-rine) in hopes of achieving long-term disease remission. If satisfactory disease control is not achieved within 3–6 months, therapy with an anti-TNF agent then would be recom-mended. Alternatively, patients with moderate-to-severe Crohn’s disease who have failed mesalamine may be treated upfront with both an anti-TNF agent and immunomodula-tors, which achieves higher remission rates than either agent alone and may improve long-term outcomes.