A 21-year-old woman comes with her parents to discuss therapeutic options for her Crohn's disease. She was diagnosed with Crohn's disease 2 years ago, and it involves her terminal ileum and proximal colon, as confirmed by colonoscopy 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 symptoms. 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 budesonide 9 mg/d. She appears thin and tired. Abdominal examination reveals tenderness without guarding in the right lower quadrant; no masses are palpable. On perianal examination, there is no tenderness, fissure, or fistula. Her laboratory 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?
Many of the drug groups discussed elsewhere in this book have important applications in the treatment of diseases of the gastrointestinal 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 processes 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-inflammatory drugs (NSAIDs). Drugs used in the treatment of acid-peptic disorders may be divided into two classes: agents that reduce intragastric acidity and agents that promote mucosal defense.
Agents that Reduce Intragastric Acidity
Physiology of Acid Secretion
The parietal cell contains receptors for gastrin (CCK-B), histamine (H2), and acetylcholine (muscarinic, M3) (Figure 62–1). When acetylcholine (from vagal postganglionic nerves) or gastrin (released from antral G cells into the blood) bind to the parietal cell receptors, they cause an increase in cytosolic calcium, which in turn stimulates protein kinases that stimulate acid secretion from a H+/K+-ATPase (the proton pump) on the canalicular surface.
Schematic model for physiologic control of hydrogen ion (acid) secretion by the parietal cells of the gastric fundic glands. Parietal cells are stimulated to secrete acid (H+) by gastrin (acting on gastrin/CCK-B receptor), acetylcholine (M3 receptor), and histamine (H2 receptor). Acid is secreted across the parietal cell ...
Log In to View More
If you don't have a subscription, please view our individual subscription options below to find out how you can gain access to this content.
Want remote access to your institution's subscription?
Sign in to your MyAccess profile while you are actively authenticated on this site via your institution (you will be able to verify this by looking at the top right corner of the screen - if you see your institution's name, you are authenticated). Once logged in to your MyAccess profile, you will be able to access your institution's subscription for 90 days from any location. You must be logged in while authenticated at least once every 90 days to maintain this remote access.
If your institution subscribes to this resource, and you don't have a MyAccess profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus.
AccessPharmacy Full Site: One-Year Subscription
Connect to the full suite of AccessPharmacy content and resources including 30+ textbooks such as Pharmacotherapy: A Pathophysiologic Approach and Goodman & Gilman's The Pharmacological Basis of Therapeutics, high-quality videos, images, and animations, interactive board review, drug and herb/supplements databases, and more.
Pay Per View: Timed Access to all of AccessPharmacy
24 Hour Subscription $34.95
48 Hour Subscription $54.95
Pop-up div Successfully Displayed
This div only appears when the trigger link is hovered over.
Otherwise it is hidden from view.