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3 PEPTIC ULCER DISEASE
Peptic ulcer disease (PUD) refers to a group of ulcerative disorders of the gastrointestinal tract characterized by mucosal damage secondary to pepsin and gastric acid secretion. It usually occurs in the stomach and proximal duodenum; less commonly, it occurs in the lower esophagus, the distal duodenum, or the jejunum, as in unopposed hypersecretory states such as Zollinger-Ellison syndrome.
TYPES OF PEPTIC ULCER
The two most common types of peptic ulcer are called “gastric ulcers” and “duodenal ulcers”. These names refer to the location where the ulcer is found. Gastric ulcers are located in the stomach Duodenal ulcers are found at the beginning of the small intestine known as the duodenum. A person may have both gastric and duodenal ulcers at the same time. (Feldman Mark.2005)
Most peptic ulcers occur in the presence of acid and pepsin when HP, NSAIDs, or other factors that disrupts normal mucosal defense and healing mechanisms.
(Feldman Mark.2005) Table 1.3a : CAUSES OF GASTRO DUODENAL ULCERS COMMON RARE • Helicobacter pylori Infection • Acid-hypersecretory states Gram-negative, motile spiral rod found in 48 percent of (e.g. Zollinger-Ellison patients with peptic ulcer disease syndrome) Multiple gastro duodenal, jejunal, or oesophageal Ulcers • NSAIDs • Malignancy 5 to 20 percent of patients who use NSAIDs over long Gastric cancer, lymphomas, lung periods develop peptic ulcer disease.NSAID-induced cancers ulcers and complications are more common in older • Stress patients, patients with a history of ulcer or After acute illness, multiorgan failure, gastrointestinal bleeding, those who use steroids or ventilator support, extensive burns anticoagulants, and those with major organ impairment (Curling’s ulcer), or head injury • Other medications (Cushing’s ulcer) Steroids, bisphosphonates, potassium chloride, chemotherapeutic agents (e.g., intravenous fluorouracil
The normal stomach maintains a balance between protective factors, such as mucus and bicarbonate secretion, and aggressive factors, such as acid secretion and pepsin. Gastric ulcers develop when aggressive factors overcome protective mechanisms. The two major etiological factors for PUD are Helicobacter pylori infection and nonsteroidal anti-inflammatory drug (NSAID) consumption. Currently, 70% of all gastric ulcers occurring in the United States can be attributed to H pylori infection. In addition to an increase in acid secretion, H pylori infection also predisposes patients to ulcer disease by disrupting mucosal integrity. The bacterium's spiral shape and flagella facilitate its penetration into the mucous layer and its attachment to the
epithelial layer. Subsequently, it releases phospholipase and proteases, which cause further mucosal damage.
Helicobacter pylori Chronic Active Gastritis
Blocks COX-1 ↓PGs
↑Serum Gastrin ECL Cell Histamine Release HCl, Pepsin Hyper secretion
Peptic Ulcer Disease (Much More Duodenal than Gastric
Peptic Ulcer Disease (More Duodenal than Gastric)
Peptic Ulcer Disease (More Gastric than Duodenal)
(a) Helicobacter pylori induces a diffuse, chronic, active superficial gastritis, usually throughout the stomach (b) Nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) (c) Gastrinoma cells figure 1.3a: pathogenesis of peptic ulcer
NSAID-induced ulcers account for approximately 26% of gastric ulcers, and they are believed to be secondary to a decrease in prostaglandin production resulting from the inhibition of cyclooxygenase. COX-2 selective NSAIDs produce a lesser reduction in prostaglandins and are associated with fewer peptic ulcers than non selective COX-1. The greatest risk of developing an ulcer occurs during the first 3 months of NSAID use; thereafter, the risk decreases but continues to be present. Whether concurrent H pylori infection and NSAID use are synergistic in producing gastric ulcers remains unclear. Recent accumulating evidence indicates that patients with H pylori infection may be twice as likely to get a bleeding peptic ulcer. A rare cause of PUD is Zollinger-Ellison syndrome (ie, Gastrinoma). The hallmark of Zollinger-Ellison syndrome is the profound hyper secretion of gastric acid. Gastrinoma cells in the pancreas or duodenum secrete large amounts of gastrin into the circulation. Elevated serum gastrin levels promote the release of histamine by acting on receptors for cholecystokininB (CCKB) and for gastrin, which are located on gastric enterochromaffin-like (ECL) cells. Histamine acts on H2 receptors on parietal and chief cells to augment hydrochloric acid (HCl) and pepsin secretion. Significant disruption of the mucosal integrity often results in multiple duodenal and gastric ulcers. (Feldman Mark.2005)
Tests used in the diagnosis of peptic ulcer are • EGD (esophagogastroduodenoscopy ) • Diatrizoate sodium • Hypotonic duodenography • Urea breath test • Serologic ELISA 21
• • •
Urine-based ELISA and rapid urine test Endoscopic biopsy Stool antigen test
(Ramakrishnan K. 2007)
Table 1.3b: SYMPTOMS OF PEPTIC ULCER DISEASE Duodenal Ulcer 1.Pain that awakens patients from sleep symptoms: 2. Burning or gnawing sensation in the upper abdomen 3. Pain in the back, lower abdomen or chest area may occasionally occur 4. Pain that occurs when the stomach is empty (about two hours After a mean or during the night). Relief frequently occurs after eating Gastric Ulcer symptoms 1. Gastric ulcer pain may be less severe than duodenal ulcer pain and is noticeably higher in the abdomen 2. Eating may increase pain rather than relieve pain 3. Pain is described as aching, nagging, cramping or dull 4. Other symptoms may include nausea, vomiting and weight loss Some ulcers may produce no symptoms at all. However, occasional painless bleeding, anaemia or the passage of black, tarry stool may be the first sign of peptic ulcer disease. (Berardi RR, Welage LS. 2005)
Table 1.3c: RISK FACTORS FOR PEPTIC ULCER Established Risk Factors Possible Risk Factors Questionable Risk Factors • Age over 60 years • NSAIDs-related • Cigarette dyspepsia smoking • previous peptic ulcer • Duration of • Alcohol disease NSAIDs use consumption • Previous upper GI • Helicobacter bleeding pylori infection • Concomitant • Rheumatoid corticosteroid therapy arthritis • high-dose and multiple NSAIDs use • Concomitant anticoagulant use or coagulopathy • Chronic major organ impairment (e.g., cardiovascular disease)
DESIRED OUTCOME The goals of treatment are relieving ulcer pain, healing the ulcer, preventing ulcer recurrence, and reducing ulcer-related complications. In HP positive patients with an active ulcer, a previously documented ulcer, or a history of an ulcer-related complication, the goals are to eradicate the organism, heal the ulcer, and cure the disease with a cost-effective drug regimen. NONPHARMACOLOGIC TREATMENT • Patients with PUD should eliminate or reduce psychological stress, cigarette smoking, and the use of Nonselective NSAIDs (including aspirin). If possible, alternative agents such as acetaminophen, a nonacetylated salicylate (e.g., salsalate), or a COX-2 selective inhibitor should be used for pain relief. Although there is no need for a special diet, patients should avoid foods and beverages that cause dyspepsia or exacerbate ulcer symptoms (e.g. spicy foods, caffeine, and alcohol).
PHARMACOLOGIC TREATMENT • ERADICATION OF HELICOBACTER PYLORI
Treatment duration is 10 to 14 days (although courses lasting one to seven days have been reported to have Comparable effectiveness. eradication rates 80 to 90 percent or higher. • PROTON PUMP INHIBITORS Treatment duration is four weeks for duodenal ulcer and eight weeks for gastric ulcer 80 to 100 percent healing. • HISTAMINE H2 BLOCKERS 70 to 80 percent healing in duodenal ulcer after four weeks, 87 to 94 percent after eight weeks. • SUCRALFATE (CARAFATE) Treatment duration is four weeks effectiveness. • SURGERY Rarely needed similar to H2 blockers. Berardi RR, Welage LS.2005)
Table 1.3d: Drug Regimens to Eradicate Helicobacter Pylori Drug #1 Drug #2 Drug #3 Drug #4 Proton pump inhibitor–based three-drug regimens
Omeprazole 20 mg twice daily or Lansoprazole 30 mg twice daily or Pantoprazole 40 mg twice daily or Esomeprazole 40 mg daily or Rabeprazole 20 mg daily Bismuth-based four-drug regimens Omeprazole 40 mg twice daily or Lansoprazole 30 mg twice daily or Pantoprazole 40 mg twice daily or Esomeprazole 40 mg daily or Rabeprazole 20 mg daily or Standard ulcer-healing dosages of an H2-receptor antagonist taken for 4–6 weeks
Clarithromycin 500 mg twice Daily
Amoxicillin 1 g twice daily or Metronidazole 500mg twice daily
Bismuth subsalicylate 525 mg four times daily
Metronidazole 250– 500 mg four times daily
Tetracycline 500 mg four times daily or Amoxicillin 500 mg four times daily, or, Clarithromycin 250–500 mg four times daily
Although treatment is minimally effective if used for 7 days, 10–14 days of treatment is recommended. The antisecretory drug may be continued beyond antimicrobial treatment in the presence of an active ulcer. In an active ulcer, acid suppression is added to hasten
Oral Drug Regimens Used to Heal Peptic Ulcers or Maintain Ulcer Healing
Table 1.3e:Oral Drug Regimens Used to Heal Peptic Ulcers or Maintain Ulcer Healing
Drug Duodenal or Gastric Ulcer Healing (mg/dose) Maintenance of Duodenal or Gastric Ulcer Healing (mg/dose)
Proton pump inhibitors Omeprazole Lansoprazole Rabeprazole Pantoprazole Esomeprazole H2-receptor antagonists Cimetidine Famotidine Nizatidine Ranitidine Promote mucosal defense Sucralfate (g/dose)
20–40 daily 15–30 daily 20 daily 40 daily 20–40 daily 300 four times daily 400 twice daily 800 at bedtime 20 twice daily 40 at bedtime 150 twice daily 300 at bedtime 150 twice daily 300 at bedtime 1 four times daily 2 twice daily
20–40 daily 15–30 daily 20 daily 40 daily 20–40 daily 400–800 at bedtime 20–40 at bedtime 150–300 at bedtime 150–300 at bedtime 1–2 twice daily 1 four times daily
COMPARISON OF COMMON FORMS OF PEPTIC ULCER Table 1.3f: COMPARISON OF COMMON FORMS OF PEPTIC ULCER
CONDITION SITE OF DAMAGE INTRAGASTRIC PH SYMPTOMS ULCER DEPTH GI BLEEDING
H. PYLORI– INDUCED Chronic Duodenum > stomach
Chronic Stomach > duodenum Less dependent Often asymptomatic Deep More severe, single vessel
More dependent Usually epigastric pain Superficial Less severe, single vessel
Acute Stomach > duodenum Less dependent Asymptomatic Most superficial More severe, superficial mucosal capillaries
H. pylori, Helicobacter pylori; NSAID, nonsteroidal anti-inflammatory drug; SRMD, stress-related mucosal damage.
If ulcers remain untreated they may lead to: • Bleeding • Perforation (an actual puncture through the stomach) • Obstruction (repeated attacks may cause scar tissue that can block the digestive tract)
• • • Patients should be re evaluated in 6-8 weeks with a repeat endoscopy to document complete healing of the gastric ulcer. Maintenance therapy with antisecretory medications (e.g., H2 blockers, PPIs) for 1 year is indicated in high-risk patient Patients with recurrent gastric ulcers should be questioned in detail about NSAID use (particularly over-the-counter varieties), and endoscopy with biopsies should be repeated to help rule out malignancy and to check for the persistence of H pylori. Instruct patients to avoid NSAIDs. Discourage alcohol consumption and cigarette smoking because these activities impair gastric mucosal protection.
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