Peptic ulcer disease

Peptic ulcer disease (PUD) refers to a group of ulcerative disorders of the upper GI tract that require acid and pepsin for their formation. Ulcers differ from gastritis and erosions in that they extend deeper into the muscularis mucosa. The three common forms of peptic ulcers include Helicobacter pylori (HP)-associated ulcers, nonsteroidal antiinflammatory drug (NSAlD)-induced ulcers, and stress-related mucosal damage (also called stress ulcers). 

The pathogenesis of duodenal ulcers (DU) and gastric ulcers (GU) is multifactorial and most likely reflects a combination of pathophysiologic abnormalities and environmental and genetic factors. 

Most peptic ulcers occur in the presence of acid and pepsin when HP, NSAIDs, or other factors disrupt normal mucosal defense and healing mechanisms. Acid is an independent factor that contributes to disruption of mucosal integrity. Increased acid secretion has been observed in patients with DU and may result from HP infection. Patients with GU usually have normal or reduced rates of acid secretion. 

Alterations in mucosal defense induced by HP or NSAIDs are the most important cofactors in peptic ulcer formation. Mucosal defense and repair mechanisms include mucus and bicarbonate secretion, intrinsic epithelial cell defense, and mucosal blood flow. Maintenance of mucosal integrity and repair is mediated by endogenous prostaglandin production. 

HP infection causes gastritis in all infected individuals and is causally linked to PUD. However, only about 20% of infected persons develop symptomatic PUD. Most non-NSAlD ulcers are infected with HP, and HP eradication markedly decreases ulcer recurrence. HP may cause ulcers by direct mucosal damage, altering the immune/inflanunatory response, and by hypergastrinemia leading to increased acid secretion. 

Peptic ulcer disease is associated with Helicobacter pylori infection in 90% of patients with gastric and duodenal ulceration. Elimination of H. pylori infection with antibiotics heals the peptic ulcer and the associated symptoms. Combination therapy with antibiotics, anti-secretory agents, namely H2-receptor antagonists or proton pump inhibitors, and bismuth salts has significantly improved the clinical outcome of peptic ulcer disease. Not all strains of H. pylori cause peptic ulcer disease, and other factors are necessary for H. pylori colonization and disease to occur. Flagellated motile bacteria resist peristalsis and adhere to gastric epithelium in a highly specific manner. 

Several adhesins and their ligands have been identified on the host cells. Lewis blood group antigen has been 

Infection by H. pylori is detected by serological markers produced by host immune responses (e.g., antibodies to antigens of H. pylori) and a breath test. The latter, known as the urea breath test, consists of oral administrations of radioactively labeled urea. This is metabolized to labeled CO2 and ammonia by the urease of H. pylori present in the gastric mucosa. The presence of labeled CO2 measured in the exhaled air confirms infection. 

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The sales of antagonists of receptors, eg, diphenhydramine, terfenadine, and astemizole, used in the treatment of allergic diseases, represent 1% of the overall pharmaceutical market, ie, 1.7 biUion (U.S.). antagonists, eg, cimetidine and ranitidine, are effective in peptic ulcer disease and esophageal reflux. Sales represent 3.5% of the world market, ie, 6 biUion (U.S.). agonists or antagonists have not yet found a clear indication. 

Bismuth subsahcylate [14882-18-9] Pepto-Bismol, is a basic salt of varying composition, corresponding approximately to i9-H0CgH4C02(Bi0). Like a number of other insoluble bismuth preparations, it is not currentiy approved in the United States for the treatment of peptic ulcer disease but is under active investigation for this purpose (180). It does appear to be effective for the rehef of mild diarrhea and for the prevention of travelers diarrhea (181). The ready availabiUty of this dmg, however, may lead to its ovemse and result in toxic effects caused by both the saUcylate and bismuth components. It has been suggested that bismuth subsahcylate is somewhat effective in the symptomatic treatment of isosporiasis, a disease caused by the intracellular parasite Isospora belli (182). 

The drugp used for gout are contraindicated in patients with known hypersensitivity. Probenecid is contraindicated in patients with blood dyscrasias or uric acid kidney stones and in children younger than 2 years. Sulfinpyrazone is contraindicated in patients with peptic ulcer disease and gastrointestinal inflammation. Colchicine is contraindicated in patients with serious gastrointestinal, renal, hepatic, or cardiac disorders and those with blood dyscrasias. 

These drugp are contraindicated in patients with known hypersensitivity to die drugs, asthma, peptic ulcer disease, coronary artery disease, and hyperthyroidism. Bethanecol is contraindicated in those with mechanical obstruction of die gastrointestinal or genitourinary tracts. Fhtients with secondary glaucoma, iritis, corneal abrasion, or any acute inflammatory disease of the eye should not use die ophtiialmic cholinergic preparations. 

Chap. 31), and during lactation. Levodopa is used cautiously in patients with cardiovascular disease, bronchial asthma, emphysema, peptic ulcer disease, renal or hepatic disease and psychosis. Levodopa and combination antiparkinsonism drugs (eg, carbidopa/levodopa) are classified as Pregnancy Category C and are used with caution during pregnancy and lactation. 

The glucocorticoids are administered with caution to patients with renal or hepatic disease hypothyroidism, ulcerative colitis, diverticulitis, peptic ulcer disease, inflammatory bowel disease hypertension, osteoporosis, convulsive disorders, or diabetes. The glucocorticoids... 

There is now a considerable body of evidence to suggest that ROMs are involved in the pathophysiology of gastroduodenal damage. However, we await confirmation that antioxidants, such as allopurinol, are beneficial in human peptic ulcer disease. Salim (1990c) found... 

Jankowski, J., Bridges, A.B., Scott, N., Wormsley, K.G. and Belch, J.J.F. (1991). Circulating free-radical markers and peptic ulcer disease. Eur. J, Gastroenterol. Hepatol. 3, 823-828. 

Salim, A.S. (1992f). Alopurinol and dimethyl sulphoxide improve treatment outcomes in smokers with peptic ulcer disease. J. Lab. Clin. Med. 119, 702-709. 

Lumbar puncture within 7 d Noncompressible vascular punctures Active peptic ulcer disease Pregnancy For streptokinase/... 

O Patients with peptic ulcer disease should avoid exposure to factors known to worsen the disease, exacerbate symptoms, or lead to ulcer recurrence [e.g., non-steroidal anti-inflammatory drug (NSAID) use or cigarette smoking]. 

TABLE 15-1. Characteristics of Common Causes of Peptic Ulcer Disease... 

Previous peptic ulcer disease or upper gastrointestinal bleeding Cardiovascular disease and other comorbid conditions Multiple NSAID use (e.g., low-dose aspirin in conjunction with another NSAID)... 

H2RA, histamine2-receptor antagonist NSAID, nonsteroidal anti-inflammatory drug PPI, proton pump inhibitor. (Adapted from Berardi RR, Welage LS. Peptic ulcer disease. In DiPiro JT, Talbert RL,... 

Chan FKL, Leung WK. Peptic ulcer disease. Lancet 2002 360 933-941. Howden CW, Hunt RH. Guidelines for the management of Helicobacter pylori infection. Ad hoc committee on practice parameters of the American College of Gastroenterology. Am J Gastroenterol 1998 93 2330-2338. 

Superior mesenteric artery syndrome Enteric infections Inflammatory bowel diseases Pancreatitis Appendicitis Cholecystitis Biliary colic Gastroparesis Postvagotomy syndrome Intestinal pseudo-obstruction Functional dyspepsia Gastroesophageal reflux Peptic ulcer disease Hepatitis Peritonitis Gastric malignancy Liver failure... 

Patients at increased risk of NSAID-induced gastrointestinal adverse effects (e.g., dyspepsia, peptic ulcer formation, and bleeding) include the elderly, those with peptic ulcer disease, coagulopathy, and patients receiving high doses of concurrent corticosteroids. Nephrotoxicity is more common in the elderly, patients with creatinine clearance values less than 50 mL/minute, and those with volume depletion or on diuretic therapy. NSAIDs should be used with caution in patients with reduced cardiac output due to sodium retention and in patients receiving antihypertensives, warfarin, and lithium. 

A 48-year-old man with a history of hypertension, peptic ulcer disease (gastric ulcer 1 year ago), and morbid obesity presents to the emergency department complaining of excruciating pain in his left big toe and both ankles. This is similar to a painful episode he had with his left toe and ankle 6 months ago. On examination, his left great toe and both ankles are red, swollen, and warm to the touch. He describes the pain as throbbing and rates it as a 1 0 of 1 0 (where 1 0 is the worse pain he has ever experienced). He admits to drinking a six-pack of beer on weekends. 

The analgesic effects of NSAIDs are attributed to inhibition of the COX-2 enzyme, whereas the negative GI effects are due to inhibition of COX-1.28 Patients taking oral anticoagulants, those with a history of peptic ulcer disease, or others at high risk for GI complications may be considered candidates for a COX-2 inhibitor or a combination of a nonselective NSAID with a gastroprotective agent such as a proton pump inhibitor (PPI). Because most PPIs are available by prescription only, such patients should be referred to a physician. 

The patient is taking glyburide for non-insulin-dependent diabetes mellitus and has been treated in the past for peptic ulcer disease with ranitidine and omeprazole. He has a history of allergy to various types of pollen but reports no allergies to drugs. He reports moderate consumption of alcohol and smoking 2 packs of cigarettes per day. 

There are certain histologic subtypes of diffuse, aggressive NHL that respond less well to treatment with conventional regimens such as CHOP. Burkitt s lymphoma, lymphoblastic lymphoma, mantel cell lymphoma, and primary CNS lymphoma are examples of disease that benefit from more intensive therapy. Regimens such as hyper-CVAD, which alternate cycles of hyperfractionated cyclophosphamide, doxorubicin, vincristine, and dexamethasone with high-dose cytarabine and methotrexate, often are substituted for CHOP. Intrathecal therapy with methotrexate is indicated with documented CNS infiltration of tumor or involvement of the sinuses. The recent appreciation of the etiology of Helicobacter pylori in the etiology of peptic ulcer disease and the association between colonization and mucosal-associated lymphoma (MALT) has spurred... 

Intravenous histamine-2-receptor antagonists such as ranitidine, famotidine, and cimetidine are compatible with PN and can be added to the daily PN for prevention of stress-related mucosal damage and peptic ulcer disease. This provides a continuous acid suppression and reduces nursing time by avoiding intermittent scheduled infusions. 

PUD Peptic ulcer disease SBP Systolic blood pressure... 

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