3 - Peptic Ulcer

Peptic ulcer disease (PUD)

• group of disorders characterized by circumscribed lesions of the mucosa of the upper gastrointestinal (GI) tract (particularly the stomach and duodenum)

• lesions occur in regions exposed to gastric juices

• most common disorder of the upper GI tract

Gastroesophageal reflux disease (GERD)

refers to the retrograde movement of gastric contents from the stomach into the esophagus

reflux (erosive) esophagitis

When reflux leads to inflammation (with or without erosions or ulcerations) of the esophagus, it is called ______

nonerosive reflux disease; NERD

A condition when typical symptoms but lack evidence of esophageal mucosal injury

Dyspepsia

persistent or recurrent abdominal pain or abdominal discomfort centered in the upper abdomen

duodenal bulb

Duodenal ulcers almost always develop in the ______ (the first few centimeters of the duodenum)

• antrum

• antral–fundal junction

Gastric ulcers form most commonly in the _____ or at the _______

Stress ulcers

ulcer that results from serious trauma or illness, major burns, coagulopathy not related to anticoagulant therapy, need for mechanical ventilation 48 hrs, or ongoing sepsis

proximal

most common site of stress ulcer formation is the _____ portion of the stomach

Zollinger–Ellison syndrome

A form of peptic ulcer disease in which intractable ulcers are accompanied by extreme gastric hyperacidity and at least one gastrinoma

Stomal ulcers (marginal ulcers)

may arise at the anastomosis or immediately distal to it in the small intestine in patients who have undergone ulcer surgery and have experienced subsequent ulcer recurrence after a symptom-free period

Drug-associated ulcers

ulcer that occurs in patients who chronically ingest substances that damage the gastric mucosa, such as NSAIDs

Refl ux esophagitis

most often recognized by the presence of recurrent symptoms (e.g., heartburn) or altered epithelial morphology

Heartburn

substernal burning or regurgitation that may radiate to the neck.

Barrett’s esophagus

a premalignant condition that may lead to adenocarcinoma of the esophagus or esophagogastric junction

• demarcated

• round

• oval

• elliptical

Most ulcers are sharply ____ and have a ____ or _____ shape

• muscularis propria

• serosa

• pancreas.

Ulcers penetrate the ______ and, in some cases, extend into the or even into the _____

• Fibrous tissue

• granulation tissue

• necrotic debris

3 tissues that form the ulcer base

• NSAID intake: gastroduodenal mucosal injury

• pathogenesis of gastric/duodenal ulcer: Helicobacter pylori infection

2 major observations regarding PUD (causal relationship)

H. pylori

• gram-negative microaerophilic, spiral bacterium with multiple flagella that lives and infects the gastric mucosa

• able to survive in the acidic gastric environment by its ability to produce urease, which hydrolyzes urea into ammonia

H. pylori eradication

• can cure peptic ulcers and reduce ulcer recurrence

• can eliminate the need for maintenance therapy in many ulcer patients

O

People with blood type ____ have an above-normal incidence of duodenal ulcers

Smoking

• delays ulcer healing and increases the risk and rapidity of relapse after the ulcer heals

• accelerates the emptying of stomach acid into the duodenum

NSAIDs

• These drugs may injure the gastric mucosa by allowing back-diffusion of hydrogen ions into the mucosa

• inhibit the synthesis of prostaglandins, which are substances with a cytoprotective effect on the mucosa.

alcohol

• A known mucosal irritant

• causes marked irritation of the gastric mucosa if ingested in large quantities at concentrations of 20% or greater

• association in patients with portal cirrhosis.

Coffee

contain peptides that stimulate release of gastrin, a hormone that triggers the flow of gastric juice

pylorus

Degeneration of the _____ permits bile reflux into the stomach, creating an environment that favors ulcer formation

• thick mucus

• hydrogen

• bicarbonate

the mucosa secretes a _____ that serves as a barrier between luminal acid and epithelial cells. This barrier slows the inward movement of _____ ions, and allows their neutralization by ______ ions in fluids secreted by the stomach and duodenum

• Alkaline

• neutral pancreatic biliary

2 substances that help buffer acid entering the duodenum from the stomach

intact mucosal barrier

• prevents back-diffusion of gastric acids into mucosal cells

• has the capacity to stimulate local blood flow, which brings nutrients and other substances to the area and removes toxic substances (e.g., hydrogen ions)

• promotes cell growth and repair after local trauma

Esophagitis

develops when noxious substances in the refluxate (i.e., acid, pepsin) are in contact with the esophageal mucosa long enough to cause irritation and inflammation

transient lower esophageal sphincter relaxation (TLESR)

In patients with GERD, 65% of reflux events occur via ______

lower esophageal sphincter (LES)

TLESR represents a decrease in _____ pressure that is not associated with swallowing or peristalsis

hypochromic anemia

Blood tests may show ______

occult blood

Stool tests may detect ______ if the ulcer is chronic

• hypersecretion

• normal or subnormal

Gastric secretion tests may reveal _____ of HCl in duodenal ulcer patients and ______ HCl secretion in gastric ulcer patients.

duodenal

Duodenal bulb deformity suggests a _____ ulcer

Upper GI endoscopy

• most specific test

• may be done if barium x-ray yields inconclusive results

• may detect ulcers not demonstrable by radiography

Serology

• test of choice for noninvasive testing of H. pylori when endoscopy is not indicated

• inexpensive

Breath tests

• used to detect the H. pylori

• uniquely suited as noninvasive means of confirming eradication of H. pylori after therapy

• PPI

• antibiotics

• bismuth compounds

False-negative breath tests may occur in patients receiving:(3)

nocturnal acid secretion

Drug regimens that suppress _____ are found to result in the highest duodenal ulcer healing rates

Antacids

• neutralize gastric acid

• used to treat ulcer pain and heal the ulcer

• magnesium

• aluminum

• calcium

3 antacids available

antacids

• reduce the concentration and total load of acid in the gastric contents

• By increasing gastric pH, antacids also inhibit pepsin activity.

• they strengthen the gastric mucosal barrier

Nonsystemic antacids (mag/al)

are preferred compared to systemic antacids (e.g., sodium bicarbonate) for intensive ulcer therapy because they avoid the risk of alkalosis

Liquid antacid forms

antacids that have a greater buffering capacity than tablets

Antacid mixtures

• provide more even, sustained action than single-agent antacids

• permits a lower dosage of each compound

Calcium carbonate

• antacid that usually is avoided because it causes acid rebound

• may delay pain relief and ulcer healing

• induces constipation

• causes hypercalcemia and milk-alkali syndrome

acid-neutralizing capacity (ANC)

defined as the number of milliequivalents (mEq) of a 1 N solution of HCl that can be brought to a pH of 3.5 in 15 mins

severe renal

Calcium carbonate- and magnesium-containing antacids should be used cautiously in patients with ______ disease.

Sodium bicarbonate

______ is contraindicated in patients with hypertension, congestive heart failure (CHF), severe renal disease, and edema. It should not be used for ulcer therapy

Aluminum-containing antacids

______ should be used cautiously in patients who suffer from dehydration or intestinal obstruction

Diarrhea

common adverse effect of magnesium-containing antacids

aluminum hydroxide

Hypophosphatemia and osteomalacia can occur with long-term use of _______

• tetracycline

• fluoroquinolones

Antacids bind with ______ and ______ inhibiting the absorption and reducing therapeutic efficacy

enteric-coated

Antacids may destroy the coating of ______ drugs, leading to premature drug dissolution in the stomach

H₂-receptor antagonists

• preferred to other antiulcer agents because of their convenience and lack of effect on GI motility

• less reliable for healing erosive esophagitis

H2-receptor antagonists

• competitively inhibit the action of histamine at parietal cell receptor sites, reducing the volume and hydrogen ion concentration of gastric acid secretions

• accelerate the healing of most ulcers.

• cimetidine

• ranitidine

• famotidine

• nizatidine

• 4 choice of agents for H₂-receptor antagonists

• may be administered to treat peptic ulcers or hypersecretory states (e.g., Zollinger–Ellison syndrome)

Cimetidine

• first H2-receptor antagonist approved for clinical use

• reduces gastric acid secretion by approximately 50%

Ranitidine

more H₂A potent drug, causes a 70% reduction in gastric acid secretion

Famotidine

• most potent H2-receptor antagonist

• mean nocturnal gastric acid secretion is reduced by 94% for up to 10 hrs

Nizatidine

• last H2-receptor antagonist marketed

• causes a 90% reduction in nocturnal gastric acid secretion for up to 10 hrs

Cimetidine

approved for the prevention of Upper GI bleeding at a dose of 50 mg/hr continuous infusion

Ranitidine

can be administered to maintain healing of erosive esophagitis; for this purpose, it is better than placebo but less effective than the proton pump inhibitors

• ranitidine

• clarithromycin

______, combined with antibiotics such as _____, is indicated for eradication of H. pylori in patients with duodenal ulcer

hepatic

Ranitidine must be used cautiously in patients with _____ impairment

hematological

Cimetidine may cause ______ disorders

• male gynecomastia

• impotence

Cimetidine has a weak androgenic effect, possibly resulting in ______ and ______

cytochrome P450

Cimetidine binds the _______ system of the liver

• decreases

• propranolol

• lidocaine

Cimetidine _____ hepatic blood flow, possibly resulting in reduced clearance of ______ and ______

• Antacids

• 1

_____ impair absorption of cimetidine and ranitidine, and should be given____ hr apart from these drugs

Sucralfate

a mucosal protectant that is a nonabsorbable disaccharide containing sucrose and aluminum

Sucralfate

drug that adheres to the base of the ulcer crater, forming a protective barrier against gastric acids and bile salt

Constipation

most common adverse effect of sucralfate

• antacids

• 30-60

_____ may reduce mucosal binding of sucralfate, decreasing its therapeutic efficacy, and thus should be given ___ to___ mins apart from sucralfate

GI anticholinergics

• used as adjunctive agents for relief of refractory duodenal ulcer pain

• no proven value in ulcer healing

Anticholinergics

• delay gastric emptying, thereby prolonging antacid retention

• most effective when taken at night and in large doses

• used in patients who do not respond to H2RAs alone

anticholinergics

these drugs are contraindicated in:

• gastric ulcers because they prolong gastric emptying

• patients with narrow-angle glaucoma and urinary retention

Prostaglandins

These agents suppress gastric acid secretion and may guard the gastric mucosa against damage from NSAIDs

Misoprostol

• approved for use in the prevention of gastric ulcers caused by NSAIDs

• antisecretory (inhibiting gastric acid secretion) and mucosal protective properties

• increases bicarbonate and mucus production

• maintains mucosal blood flow

Omeprazole sulfonamide

MOA of this drug forms a stable disulfi de bond with this specifi c sulfh ydryl, thereby inactivating the ATPase and shutting off acid secretion.

PPIs

• more rapidly effective than other approved agents in treating peptic ulcer disease

• effective healing of duodenal ulcers

• effective in healing erosive esophagitis

• provide more rapid symptom relief and more consistent healing than H2-receptor antagonists

• dexlansoprazole

• esomeprazole

• omeprazole

• rabeprazole

• pantoprazole

5 PPIs used to manage GERD symptoms in patients who have failed previous therapy with H2-receptor antagonist therapy.

• omeprazole

• lansoprazole

• sodium bicarbonate

Suspensions of ______ or ______ in ______ have been used for administration to patients with nasogastric and jejunostomy tubes.

Dexlansoprazole

first and only PPI available as a dual delayed-release capsule formulation.

Omeprazole in sodium bicarbonate powder suspension

first PPI approved by the FDA for reduction in the risk of upper GI bleeding in critically ill patients

• omeprazole

• lansoprazole

approved for the over the-counter use of heartburn

Intravenous pantoprazole

indicated for management of erosive esophagitis and treatment of Zollinger–Ellison syndrome

• esomeprazole

• lansoprazole

• pantoprazole

3 PPIs used for the treatment of acute bleeding gastric ulcers

• IV emoprazole

• IV lansoprazole

• IV pantoprazole

approved for the short-term use in patients with GERD with a history of erosive esophagus unable to take oral medications

clopidogrel

PPIs may decrease the antiplatelet activity of ______

Bismuth

• prevents adhesion of H. pylori to gastric mucosa

• decreases resistance when used with other anti–H. pylori agents

• inhibits release of proteolytic enzymes

• suppresses H. pylori growth.

• PPIs

• antibiotics

Bismuth subsalicylate is highly effective when combined with _____ and/or _____

Sedatives

useful adjuncts in promoting rest for highly anxious ulcer patients

total gastrectomy

treatment of choice for Zollinger–Ellison syndrome that is unresponsive to medical management

• antrectomy and truncal vagotomy (Billroth I procedure)

• partial gastrectomy

• truncal vagotomy (Billroth II procedure)

• highly selective (proximal gastric) vagotomy

• total gastrectomy

6 types of surgical procedures

vagotomy

this procedure severs a branch of the vagus nerve, thereby decreasing HCl secretion

antrectomy

this procedure by removing the antrum, eliminates some acid-secreting mucosa as well as the major source of gastrin