ulcer Flashcards
what is peptic ulcer disease?
a peptic ulcer is a well-defined break in the gastrointestinal mucosa (greater than 3mm in diameter, as defined by many industry-sponsored studies) that results from chronic acid or pepsin secretions and the destructive effects of and host response to helicobacter pylori.
Peptic ulcers develop principally in regions of the gastro- intestinal tract that are proximal to acid and pepsin secretions (Figure 11-1). The first portion of the duode- num is the location of most ulcers in Western popula- tions, whereas gastric ulcers are more frequent in Asia.1 The upper jejunum rarely is involved. Peptic ulcer disease usually is chronic and focal in distribution; only approxi- mately 10% of patients have multiple ulcers.
when do peptic ulcers result?
Peptic ulcers result when the balance between aggressive factors that are potentially destructive to the gastrointes- tinal mucosa and defensive factors that usually are pro- tective of the mucosa is disrupted (Figure 11-2). The primary aggressive factor is H. pylori (formerly Campy- lobacter pylori). This organism is present in 60% to 90% of duodenal ulcers and in 50% to 70% of gastric ulcers.1,13
Use of NSAIDs is the second most common cause of peptic ulcer disease.
Other aggressive factors include acid hypersecretion, cigarette smoking, and psychological and physical stress.14,15 Cytomegalovirus infection is a rare cause noted in human immunode - ficiency virus (HIV)-positive patients.16,17
Non-NSAID, non–H. pylori peptic ulcers are infrequent and occur more often in elderly persons.
H. pylori is a microaerophilic, gram-negative, spiral- shaped motile bacillus with 4 to 6 flagella.18 H. pylori was first reported to reside in the antral mucosa by Marshall and Warren.19 The organism is an adherent but noninvasive bacterium that resides at the interface between the surface of the gastric epithelium and the overlying mucous gel. It produces a potent urease that hydrolyzes urea to ammonia and carbon dioxide. This urease may protect bacteria from the immediate acidic environment by increasing local pH while damaging mucosa through generation of its byproduct, ammonia. Upregulation of cyclooxygenase-2 (COX-2), chemotaxis of neutrophils, and the cellular immune response are involved in the local tissue damage that subsequently occurs.
what is up with use of NSAIDs with this?
Use of NSAIDs is an etiologic factor in 15% to 20% of cases of peptic ulcer.1,10 These drugs directly damage mucosa, reduce mucosal prostaglandin production, and inhibit mucus secretion. Ulcers caused by NSAIDs are located more often in the stomach than in the duode- num. Risk with NSAID use increases with age older than 60 years, high-dosage long-term therapy, use of NSAIDs with long plasma half-lives (e.g., piroxicam) rather than those with short half-lives (i.e., ibuprofen), and concomi- tant use of alcohol, corticosteroids, anticoagulants, or aspirin.26
Use of orally administered nitrogen-containing bisphosphonate drugs (aledronate, risedronate) for the treatment of osteoporosis and immunosuppressive medi- cations such as mycophenolate is associated with devel- opment of esophageal and gastric ulcers.1,27
what about NSAIDs and alcohol? how do NSAIDs cause problems ? smoking? hyperparathyroidism?
Alcohol and NSAIDs are directly injurious to gastric mucosa. Alcohol alters cell permeability and can cause cell death. NSAIDs including aspirin disrupt mucosal resistance by impairing prostaglandin production and denaturing mucous glycoproteins. Hyperparathyroidism enhances gastrin secretion, and renal dialysis does not adequately remove circulating gastrin. Smoking tobacco and family history are risk factors independent of gastric acid secretion for peptic ulcer disease.8,29 Tobacco smoke, similar to other aggressive factors, can affect gastric mucosa by reducing levels of nitric oxide,30 which is important for stimulating mucus secretion and maintain- ing mucosal blood ow.31
how does H. pylori work?
H. pylori is strongly associated with peptic ulcer disease32; however, the mechanism whereby infection with H. pylori results in peptic ulcer disease is not com- pletely understood. Current evidence suggests that H. pylori causes in ammation of the gastric mucosa by producing proteases and increasing gastrin release by G cells, which leads to increased gastric acid production, acute gastritis, and eventually ulcer formation.33-35
what class of drug is better to use than NSAIDs?
Acetaminophen and compounded acetaminophen products are better to prevent GI bleeding.
If an NSAID is used, celecoxib (Celebrex; [COX-2 selective inhibitor]) in combination with a PPI or misoprostol (Cytotec) is advised for short term use. (Celebrex with Tylenol or either alone would work well).
what is the four drug treatment for H. Pylori infection?
a. Four-drug treatment regimens. Includes:
i. PPI + 3 antimicrobials (clarithromycin, metronidazole or tinidazole, + amoxicillin) or
b. PPI + bismuth (peptobismol) + tetracycline and metronidazole
