Peptic Ulcer Disease (PUD)

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PEPTIC ULCER DISEASE (PUD)

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DEFINITION

• 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.

As many as 70–90% of such ulcers are associated with Helicobacter pylori, a rod-shaped bacterium that lives in the acidic environment of the stomach; however, only 40% of those cases go to a doctor. Ulcers can also be caused or worsened by drugs such as aspirin, ibuprofen, and other NSAIDs.

• The three common forms of peptic ulcers include:

1. Helicobacter pylori (HP)– associated ulcers,

2. Non-steroidal antiinflammatory drug (NSAID)–induced ulcers,

3. And stress-related mucosal damage (also called stress ulcers).

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The parietal cell is regulated by neural, hormonal, and paracrine pathways.

Activation of vagal parasympathetic preganglionic outflow to the stomach acts in three ways to stimulate gastric acid secretion.

There is direct neural innervation and activation of the parietal cell via release of acetylcholine (ACh) from enteric neurons, which acts on the parietal cell via muscarinic receptors.

In addition, neural activation of the ECL cell stimulates the release of histamine, which acts via a paracrine pathway to stimulate the parietal cell.

Finally, G cells located in gastric glands in the gastric antrum are activated by the release of gastrin-releasing peptide from enteric neurons, which acts on the G cell to stimulate the release of gastrin. Gastrin thereafter acts via a humoral pathway to stimulate the parietal cell.

04/19/2023 5Components involved in providing gastroduodenal mucosal defense and repair

HCO3 HCO3 HCO3 HCO3

What Causes Peptic Ulcer Disease

Helicobacter Pylori (H. pylori)Most ulcers are the result of infection with H. pylori

Not all of those infected with H. pylori develop ulcers

H. pylori MAY result in a weakening of the mucosal defense systems, allowing for development of ulcer subsequent to acid/pepsin aggression;

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Pathogenesis

• In normal acid/pepsin attack is balanced by mucosal defences

• Increased attack by hyperacidity

• Weakened mucosal defence – the major factor (H. pylori related)

Figure 28.3 (still)

28 >Chapter MENU

Gram negative bacterium

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04/19/2023 10 H. pylori produces large amounts of the enzyme urease, molecules of which

are localized inside and outside of the bacterium. Urease breaks down urea (which is normally secreted into the stomach) to carbon dioxide and ammonia (which neutralizes gastric acid).

The survival of H. pylori in the acidic stomach is dependent on urease, and it would eventually die without the enzyme.

The ammonia that is produced is toxic to the epithelial cells, and, along with the other products of H. pylori—including protease, vacuolating cytotoxin A (VacA), and certain phospholipases—damages those cells.

Thus 1. H. pylori penetrate the mucus layer of host stomach and adhere the surface of

gastric mucosal epithelial cells. 2. produce ammonia from urea by the urease, and the ammonia netralize the gastric

acid to escape from elimination. 3. prolifirate, migrate, and finally form the infectious focus. 4. The gastric ulcerization is developed by destruction of mucosa, inflammation and

mucosal cell death.

What Causes Peptic Ulcer Disease• NonSteroidal AntiInflammatory Drugs (NSAIDs)

Long term use of nonsteroidal anti-inflammatory drugs. NSAIDs block COX enzymes and decrease prostaglandins (PGs).

• Gastrinoma (Zollinger-Ellison Syndrome)Tumors of the duodenum or pancreas and secrete

abnormally high amounts of gastrin which stimulates gastric acid.

• Stress ulcers Result of physical trauma

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PATHOPHYSIOLOGY• The pathogenesis of duodenal ulcers (DU) and gastric ulcers (GU) is

multifactorial and most likely reflects a combination of pathophysiologic

abnormalities and environmental as well as 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.

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PATHOPHYSIOLOGY (Cont.)

• 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-NSAID ulcers are infected with HP, and HP eradication markedly

decreases ulcer recurrence. HP may cause ulcers by direct mucosal damage,

altering the immune/inflammatory response, and by hypergastrinemia leading to

increased acid secretion.

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PATHOPHYSIOLOGY (Cont.)

• Nonselective NSAIDs (including aspirin) cause gastric mucosal damage

by two mechanisms:

• (1) A direct or topical irritation of the gastric epithelium, and

• (2) Systemic inhibition of the cyclooxygenase-1 (COX-1) enzyme, which

results in decreased synthesis of protective prostaglandins.

• Use of corticosteroids alone does not increase the risk of ulcer or

complications, but ulcer risk is doubled in corticosteroid users taking

NSAIDs concurrently.

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Other Factors:

• Epidemiologic evidence links cigarette smoking to PUD, impaired ulcer

healing, and ulcer-related GI complications.

• The risk is proportional to the amount smoked per day.

• Although clinical observation suggests that ulcer patients are adversely affected

by stressful life events, controlled studies have failed to document a cause-and-

effect relationship.

• Coffee, tea, cola beverages, beer, milk, and spices may cause dyspepsia but do

not increase PUD risk.

• Ethanol ingestion in high concentrations is associated with acute gastric mucosal

damage and upper GI bleeding but is not clearly the cause of ulcers.

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CLINICAL PRESENTATION

• Abdominal pain is the most frequent symptom of PUD. The pain is often

epigastric and described as burning but can present as vague discomfort,

abdominal fullness, or cramping.

• A typical nocturnal pain may awaken patients from sleep, especially between

12 AM and 3 AM.

• Pain from DU often occurs 1 to 3 hours after meals and is usually relieved

by food, whereas food may precipitate or accentuate ulcer pain in GU.

• Antacids provide rapid pain relief in most ulcer patients.

• Heartburn, belching, and bloating often accompany the pain.

• Nausea, vomiting, and anorexia are more common in GU than DU.

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CLINICAL PRESENTATION

• The severity of symptoms varies from patient to patient and may be

seasonal, occurring more frequently in the spring or fall.

• Pain does not always correlate with the presence of an ulcer.

• Asymptomatic patients may have an ulcer at endoscopy, and patients may

have persistent symptoms even with endoscopically proven healed ulcers.

• Many patients (especially older adults) with NSAID-induced, ulcer-related

complications have no prior abdominal symptoms.

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Complications:

• Complications of ulcers caused by HP and NSAIDs include:

1. Upper GI bleeding,

2. Perforation into the peritoneal cavity,

3. Penetration into an adjacent structure (ex., Pancreas, biliary tract, or liver),

4. And gastric outlet obstruction.

• Bleeding may be occult or present as melena or hematemesis.

• Perforation is associated with sudden, sharp, severe pain, beginning first in the

epigastrium but quickly spreading over the entire abdomen.

• Symptoms of gastric outlet obstruction typically occur over several months and

include early satiety, bloating, anorexia, nausea, vomiting, and weight loss.

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DIAGNOSIS

• The physical examination may reveal epigastric tenderness

between the umbilicus and the xiphoid process that less

commonly radiates to the back.

• Routine laboratory tests are not helpful in establishing a

diagnosis of uncomplicated PUD. The hematocrit, hemoglobin,

and stool hemoccult tests are used to detect bleeding.

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Diagnostic Procedures:

• The diagnosis of HP infection can be made using endoscopic or nonendoscopic

tests.

• The tests that require upper endoscopy are invasive, more expensive,

uncomfortable, and usually require a mucosal biopsy for histology, culture, or

detection of urease activity.

• The nonendoscopic tests include serologic antibody detection tests, the urea breath

test (UBT), and the stool antigen test.

• Serologic tests detect circulating immunoglobulin G directed against HP but are

of limited value in evaluating post-treatment eradication.

• The Urea Breath Test is based on urease production by HP.

• Testing for HP is only recommended if eradication therapy is considered.

Figure 28.2 (still)

28 >Chapter MENU

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Urease

Urease

UreaseUrease

UreaseUrease

Urease

UreaseUrease

Urease

Urease Urease Urease

UreaseUreaseUrease

UreaseUrease

Urease

Urease

Urea H2O

2CO2

Type IV secretion system

Ammonia cloud

NH3

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Diagnostic Procedures:

• If endoscopy is not planned, serologic antibody testing is reasonable to determine

HP status. The UBT is the preferred nonendoscopic method to verify HP

eradication after treatment.

• The diagnosis of PUD depends on visualizing the ulcer crater either by upper

GI radiography or endoscopy. Radiography may be the preferred initial

diagnostic procedure in patients with suspected uncomplicated PUD.

• Upper endoscopy should be performed if complications are thought to exist or if

an accurate diagnosis is warranted. If a GU is found on radiography, malignancy

should be excluded by direct endoscopic visualization and histology.

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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.

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TREATMENT

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NON-PHARMACOLOGIC 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 (celecoxib, rofecoxib) 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, alcohol).

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PHARMACOLOGIC TREATMENT

• Eradication of HP is recommended for HP-infected patients with GU,

DU, ulcer-related complications, and in some other situations.

• Treatment should be effective, well tolerated, easy to comply with,

and cost-effective.

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Helicobacter eradication

Use of multiple drugs prevents development of drug resistance

Quadruple TherapyBismuth Subsalicylate

MetronidazoleTetracycline

H2 receptor antagonist or PPI

More commonly given for 2 weeks

Gastric acid suppressors for 6-8 weeks

Eradication rate = 90%

Strategies for Protecting the Gastric Mucosa from Acid Exposure

Inhibitsecretion

Preventcontact

Neutralizeacid

Mechanisms ExampleCimetidine

OmeprazoleProstaglandins

Muscarinic antagonists

SucralfateBismuth

Antacids

H+

H+

H+

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Strategies for Inhibiting Parietal Cell Acid Secretion04/19/2023 30

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H+, K+-ATPase (the proton pump) is the final transport pathway for parietal cell hydrogen ion secretion

H+, K+-ATPase is located on the parietal cells of the gastric mucosa

The pump requires large amounts of energy that is supplied by intracellular ATP;

Inhibition of H+, K+-ATPase blocks HCL into the lumen of the stomach

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Proton-Pump inhibitors (PPIs)• These drugs are prodrugs with an acid-resistant enteric coating

to protect them from degradation in stomach.

• The coating is removed in the alkaline duodenum, and the prodrug, a weak base, is absorbed and transported to the parietal cell where it is converted to the active form forming a stable covalent (irreversible) bond (ATPase needs to be resynthesized to overcome this inhibition which takes 18 hrs).

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Omeprazole• H+/ K+-ATPase inhibitor; first of PPI class

• Profound reduction of gastric acid - elevates gastric pH significantly (20mg/day for 7days will decrease acid by 95%);

• Highly protein bound; Metabolized by CYP2C & CYP3A; plasma half life of 1 to2 hours but long duration of action;

• Should be taken just prior to a meal and should NOT be taken with other acid-suppressing agents.

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EsomeprazoleSimply the S-isomer of omeprazole;H+, K+-ATPase inhibitor;Given orally.

Pantoprazole

H+, K+-ATPase inhibitor; An acid-stable form and can be given by IV

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Proton Pump Inhibitors (PPI)

Generally well tolerated

Hypergastrinemia (can lead to tumor growth in the GI)NauseaHeadaches, skin rashes

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Figure 28.7 (still)

28 >Chapter MENU

Adverse effects of PPIs

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Histamine H2 Antagonists

• Cimetidine

• Ranitidine

• Famotidine

• Nizatidine

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Drugs for Acid-Peptic Disorders - Cimetidine

Competitive H2 receptor Antagonist;

inhibits basal acid secretion including nocturnal secretion;Readily absorbed after oral administration;Relatively brief duration of action (4-8 hr)

Given on a multiple dosing schedule; (300-400 mg, 2-4 times daily); Typical therapy is for 4-8 weeks

•.

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Figure 28.5 (still)

28 >Chapter MENU

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Figure 28.6 (still)

28 >Chapter MENU

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Drugs for Acid-Peptic Disorders - Cimetidine

• Side effects include inhibition of the microsomal metabolism of other drugs results in higher blood levels and enhancement of their effects

• Interactions have been shown with:

Diazepam Chlordiazepoxide

Theophylline Phenytoin

Warfarin Propranolol

Meperidine Pentobarbital

Lidocaine and many others...

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Drugs for Acid-Peptic Disorders - Cimetidine

Additional Side effects:• In some patients, cimetidine acts as a nonsteroidal

antiandrogen (i.e., interferes with estrogen metabolism).

• It results in gynecomastia (swelling of the breasts and soreness of the nipples in males)

• Can produce confusion and disorientation in elderly patients;• Diarrhea, rash and miscellaneous other effects in a small

number of patients.

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Drugs for Acid-Peptic Disorders – Ranitidine, Famotidine, Nizatidine

• Same mechanism of action as Cimetidine but a longer duration of action (8 to 12 hrs);

• Given orally; can be given less frequently than cimetidine

• Less interactions on P450 than Cimetidine.

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Drugs for Acid-Peptic Disorders - Anticholinergics

• General muscarinic receptor antagonists • Dicyclomine

Side-effects are typical of anticholinergics such as• Dry mouth• Tachycardia• Blurred vision• Bowel discomfort (constipation)• Difficulty in urination

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Drugs for Acid-Peptic Disorders – Prostaglandins (PGE2 & PGI2 )

Inhibits:• Acid secretion• Gastrin release• Pepsin secretion

Stimulates:• Mucus secretion• Bicarbonate secretion• Mucosal blood flow

These compounds act by both inhibition of acid production and by increasing defense.These compounds are also effective against direct damage produced by alcohol, aspirin and NSAIDs, and are therefore termed “cytoprotective mechanisms

• Act at prostaglandin EP3 receptors on parietal cells

•”

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Drugs for Acid-Peptic Disorders - Prostaglandins

Misoprostol :Synthetic Analog of Prostaglandin E1

Anti-acid secretoryPrevention of NSAID-induced gastric ulcers

Side Effects Diarrhea Stimulates uterine contractions contraindicated in

pregnancy Exacerbate IBD and should not be given

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Figure 28.8 (still)

28 >Chapter MENU

Misoprostol reduces serious GI complications in patients receiving NSAIDs

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Drugs for Acid-Peptic Disorders - Antacids

Antacids are weak bases that neutralize HCl in the stomach;

They do not decrease the secretion of acid.Neutralize acidDecrease acid load to duodenumDiminish pepsin activity

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Drugs for Acid-Peptic Disorders - Antacids

• Magnesium hydroxide

• Aluminum hydroxide

• Magnesium-aluminum mixtures

• Calcium carbonate

• Sodium bicarbonate

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Drugs used to neutralize gastric acid

(Diarrhea)(Constipation)

P - 13

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Antacids are weak bases that react with gastric hydrochloric acid to form a salt and water.

Although their principal mechanism of action is reduction of intragastric acidity, they may also promote mucosal defense mechanisms through stimulation of mucosal prostaglandin production.

A single dose of antacid given 1 hour after a meal effectively neutralizes gastric acid for up to 2 hours.

Antacids are the most rapidly acting acid suppressors because they react with acid instantaneous in the lumen of the stomach.

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Sodium bicarbonate (baking soda) It reacts rapidly with HCl to produce carbon dioxide and NaCl. Formation of carbon dioxide results in gastric distention and

belching. Sodium chloride absorption may exacerbate fluid retention in

patients with heart failure, hypertension, and renal insufficiency.

Calcium carbonate (Tums) It is less soluble and reacts more slowly than sodium bicarbonate

with HCl to form carbon dioxide and CaCl2. Like sodium bicarbonate, calcium carbonate may cause belching or

metabolic alkalosis. Excessive doses of either sodium bicarbonate or calcium carbonate

with calcium-containing dairy products can lead to hypercalcemia, renal insufficiency, renal stones, and metabolic alkalosis (milk-alkali syndrome).

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Magnesium hydroxide and aluminum hydroxide They react slowly with HCl to form magnesium chloride or aluminum

chloride and water. Because no gas is generated, belching does not occur. Patients with renal insufficiency should not take these agents long-

term. Like CaCO3, Al(OH)3 is a phosphate binder and may also lead to hypophosphatemia with prolonged use.

Note: All antacids may affect the absorption of other medications by binding the drug (reducing its absorption) or by increasing intragastric pH so that the drug's dissolution or solubility (especially weakly basic or acidic drugs) is altered. Therefore, antacids should not be given within 2 hours of doses of tetracyclines, fluoroquinolones, itraconazole, and iron.

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Drugs for Acid-Peptic Disorders – Sucralfate

• Complex of aluminum hydroxide and sulfated sucrose

• This substance adheres strongly to gastric and duodenum mucosa and adheres even more strongly to partially denatured proteins such as those found at the base of the ulcer.

• Sucralfate protects the gastric and duodenal mucosa from acid/pepsin attack.

• Must be taken every 6 hours

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Drugs for Acid-Peptic Disorders – Sucralfate

Side effects:• The compound is not really absorbed and, therefore,

side-effects are minimal:– constipation– diarrhea– nausea

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Bismuth subsalicylate• Antimicrobial properties• Effective in peptic ulcers• Inhibits pepsin activity; increase secretion of mucus, and

interact with glycoproteins in necrotic mucosal tissue to coat and protect the ulcer crater cytoprotective

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Therapeutic Options:• First-line eradication therapy is a proton pump inhibitor (PPI)–

based, three-drug regimen containing two antibiotics, usually

clarithromycin and amoxicillin, reserving metronidazole for back-

up therapy (e.g., clarithromycin– metronidazole in penicillin-allergic

patients).

• The PPI should be taken 30 to 60 minutes before a meal along

with the two antibiotics.

• Although an initial 7-day course provides minimally acceptable

eradication rates, longer treatment periods (10 to 14 days) are

associated with higher eradication rates and less antimicrobial

resistance.

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Therapeutic Options: contd

• First-line treatment with quadruple therapy using a PPI (with bismuth,

metronidazole, and tetracycline) achieves similar eradication rates

as PPI based triple therapy and permits a shorter treatment duration

(7 days).

• However, this regimen is often recommended as second-line

treatment when a clarithromycin–amoxicillin regimen is used initially.

• All medications except the PPI should be taken with meals and at

bedtime.

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Failed Eradication:

• If the initial treatment fails to eradicate HP, second-line empiric treatment should:

• (1) use antibiotics that were not included in the initial regimen;

• (2) include antibiotics that do not have resistance problems; • (3) use a drug that has a topical effect (e.g., bismuth); and • (4) be extended to 14 days. • Thus, if a PPI–amoxicillin–clarithromycin regimen fails,

therapy should be instituted with a PPI, bismuth subsalicylate, metronidazole, and tetracycline for 14 days.

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Conventional Protocols:

• Treatment with a conventional antiulcer drug (e.g., PPI,

histamine-2 receptor antagonist [H2RA], or sucralfate alone is an

alternative to HP eradication but is discouraged because of the

high rate of ulcer recurrence and ulcer-related complications.

• Dual therapy (e.g., H2RA plus sucralfate, H2RA plus PPI) is not

recommended because it increases cost without enhancing

efficacy.

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Maintenance therapy:

• Maintenance therapy with a PPI or H2RA (Table 29-2) is recommended for

high-risk patients with ulcer complications, patients who fail HP

eradication, and those with HP-negative ulcers.

• For treatment of NSAID-induced ulcers, nonselective NSAIDs should be

discontinued (when possible) if an active ulcer is confirmed.

• Most uncomplicated NSAID-induced ulcers heal with standard regimens of

an H2RA, PPI, or sucralfate (see Table 29-2) if the NSAID is discontinued.

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Patients on NSAIDs:

• If the NSAID must be continued, consideration should be given to reducing

the NSAID dose or switching to acetaminophen, a nonacetylated salicylate,

a partially selective COX-2 inhibitor, or a selective COX-2 inhibitor.

• PPIs are the drugs of choice when NSAIDs must be continued because

potent acid suppression is required to accelerate ulcer healing.

• If HP is present, treatment should be initiated with an eradication

regimen that contains a PPI.

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Special Cases:

• Patients at risk of developing serious ulcer-related

complications while on NSAIDs should receive prophylactic

therapy with misoprostol or a PPI.

• Patients with ulcers refractory to treatment should undergo upper

endoscopy to confirm a nonhealing ulcer, exclude malignancy,

and assess HP status.

• HP-positive patients should receive eradication therapy.

• In HP negative patients, higher PPI doses (e.g., omeprazole 40

mg/day) heal the majority of ulcers.

• Continuous PPI treatment is often necessary to maintain healing.

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Evaluation Of Therapeutic Outcomes:

• Patients should be monitored for symptomatic relief of ulcer pain as

well as potential adverse effects and drug interactions related to drug

therapy.

• Ulcer pain typically resolves in a few days when NSAIDs are

discontinued and within 7 days upon initiation of antiulcer therapy.

• Most patients with uncomplicated PUD will be symptom-free after

treatment with any one of the recommended antiulcer regimens.

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Evaluation Of Therapeutic Outcomes:

• The persistence or recurrence of symptoms within 14 days

after the end of treatment suggests failure of ulcer

healing or HP eradication, or an alternative diagnosis such

as gastroesophageal reflux disease.

• Most patients with uncomplicated HP-positive ulcers do not

require confirmation of ulcer healing or HP eradication.

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Evaluation Of Therapeutic Outcomes:

• High-risk patients on NSAIDs should be closely

monitored for signs and symptoms of bleeding,

obstruction, penetration, and perforation.

• Follow-up endoscopy is justified in patients with

frequent symptomatic recurrence, refractory disease,

complications, or suspected hypersecretory states.

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Case 1: • A 75-year-old retired greengrocer who presented to the Accident and

Emergency Department with shortness of breath and a history of melaena is found on endoscopy to have a bleeding gastric erosion. His drug therapy leading up to his admission consisted of digoxin, warfarin and piroxicam for a painful hip, and over-the-counter cimetidine selfinitiated by the patient for recent onset indigestion.

• Question• How may this patient’s drug therapy have precipitated or aggravated his

bleeding gastric erosion?

• Answer• NSAIDs inhibit the biosynthesis of prostaglandin E2, as well as causing

direct damage to the gastric mucosa. Warfarin is an anticoagulant and will increase bleeding. Cimetidine inhibits CYP450 enzymes and therefore inhibits the metabolism of warfarin, resulting in higher blood concentrations and an increased anticoagulant effect.

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Case 2: • A 25-year-old male estate agent complains of intermittent heartburn,

belching and sub-xiphisternal pain which has been present on most nights for two weeks. It was particularly severe the previous Saturday night after he had consumed a large curry and several pints of beer. The symptoms were not improved by sleeping on two extra pillows or by taking ibuprofen. He smokes ten cigarettes daily. Examination revealed him to be overweight, but was otherwise unremarkable.

• Question• Outline your management of this patient.• Answer• Life-style advice – stop smoking, lose weight and exercise, adopt a low-

fat diet, avoid tight clothing, avoid large meals or eating within three hours of going to bed. Raise the head of the bed (do not add pillows). Avoid NSAIDs and excessive alcohol. Prescribe alginate/antacids.

• If there is an inadequate response or early relapse, prescribe an H2-blocker or proton-pump inhibitor for six weeks. If symptoms have still not completely resolved, refer the patient for endoscopy.

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Case 3:• Mr. Sloley is a 45 year old male who presents to your

clinic with epigastric abdominal pain x 2 weeks. What is your initial differential diagnosis at this point given the limited information?

• Mr Sloley History PMH: HTN stable, Osteoarthritis in knees, treated for an ulcer 3 years ago Meds: Hydrochlorothiazide, ibuprofen prn Soc HX: Married, employed as bank manager, smokes 1ppd x 20years, drinks 2 beers per day, and 2-4 cups coffee per day. What risk factors can you identify for PUD?

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• Mr. Sloley is a 45 year old male who presents to your clinic with epigastric abdominal pain x 2 weeks. He describes it as a burning pain which is non-radiating and is worse after he eats. He has frequent belching with bloating sensation but denies nausea, vomiting, diarrhea, constipation, or weight loss. He has tried Maalox which do help a little. Which symptoms support the possible diagnosis of PUD?

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• Signs and Symptoms of PUD Epigastric pain is most common symptom Pain described as gnawing, burning or annoying May radiate to the back (consider penetration) Pain occurs when stomach is empty Relieved by food, antacids (duodenal), Dyspepsia including belching/ bloating Hematemesis or melena with GI bleeding

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Case 4

High-risk patients on NSAIDs visited a hospital with signs and symptoms of bleeding, obstruction, penetration, and perforation. What initial step to be taken up by clinician, if he has to continue with pain reliever?

Replace NSAID with COX2 inhibitorStart Triple therapyProceed with Quadruple regimenSucralfate administration  

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Case 5

Suggest most appropriate antiulcer therapy if HP is positive by serological test.

Quadruple therapyTriple therapyOnly antibiotic therapy excluding penicillinMetronidazole 

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Case 6

Choose a test for confirmation of eradication of HP in ulcer

Mantoux test Elisa TestPPI estimationUBT

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• 45-year-old woman is distressed by the dissolution of her marriage. She has been drinking heavily and overeating. She complains of persistent heartburn and an unpleasant, acid-like taste in her mouth. The clinician suspects that she has gastrointestinal reflux disease and advises her to raise the head of her bed 6 to 8 inches, not to eat for several hours before retiring, to avoid alcohol, and to eat smaller meals. Two weeks later, she returns and says the symptoms have subsided slightly but still are a concern. The clinician prescribes which one of the following drugs?

A. An antacid such as aluminum hydroxide.

B. Dicyclomine.

C. An antianxiety agent such as alprazolam.

D. Esomeprazole.

Case 7

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• D. It is appropriate to treat this patient with a proton-pump inhibitor (PPI) to reduce acid production and promote healing. An H2-receptor antagonist might also be effective, but the PPIs are preferred. An antacid would decrease gastric acid, but its effects are short-lived compared to those of the PPIs and H2-receptor inhibitors. Dicyclomine is an antimuscarinic drug and would decrease acid production, but it is not as effective as the PPIs or the H2 receptor inhibitors. An antianxiety agent might have antiemetic action but would have no effect on the acid production.

A 42-year-old overweight, though otherwise healthy, women presents with the sudden onset of right upper abdominal colicky pain 45 minutes after a meal of fried chicken. The pain is associated with nausea and vomiting, and any attempt to eat since has caused increased pain.The mostly cause is:A: Gastric ulcerB: CholelithiasisC: Duodenal ulcerD: Acute hepatitis

CASE 8

ANSWER --- B Right upper abdominal pain that has an acute onset after the ingestion of a fatty meal and that is associated with nausea and vomiting is most suggestive of biliary colic as a result of gallstones.

Duodenal ulcer pain is likely to be determined with food, and gastric ulcer pain is not likely to have the acute severe onset.

Acute hepatitis is more likely to produce dull ache and tenderness

Which of the following is not true of H.pylori infection:

A. It is more common in developing counties

B. It is associated with the development of gastric lymphoma

C. It is believed to be the cause of nonulcer dyspepsia

D. The route of transmission is believed to be fecal – oral

E. It is believed to be a cause of most duodenal and gastric ulcer

CASE 9

ANSWER --- C While H.pylori is clearly linked to gastric and duodenal

ulcers, and probably to gastric carcinoma and lymphoma,

it is unclear whether it is more common in patients with

nonulcer dyspepsia, or whether treatment in those patients

reduces symptoms.

A 45-year-old male was brought to the emergency room after vomiting bright red blood. He has a blood pressure of 88/46 mmHg and heart rate of 120 bpm. Which of the following is the best next step?

A. IV fluid resuscitation and preparation for a transfusion

B. Administration of a proton pump inhibitor

C. Guaiac test the stool

D. Treatment for H.pyroli

CASE 10

ANSWER --- A

This patient is hemodynamically unstable with hypotension and tachycardia as a consequence of the acute blood loss. Volume resuscitation, immediately with crystalloid or colloid solution, followed by blood transfusion, if necessary, is the initial step to prevent irreversible shock and death. Later, after stabilization, acid suppression and H.pylori treatment might be useful to heal an ulcer, if one is present.

Which one of the following patients should be promptly referred for endoscopy?A. A 65-year-old man with a new onset of epigastric

pain and weight lossB. A 32-year-old whose symptoms are not relieved with

ranitidineC. A 29-year-old H. pylori- positive patient with

dyspeptic symptomsD. A 49-year-old women with intermittent right upper

quadrant pain following meals

CASE 11

ANSWER --- A Patient “A” has a red flag: he is older than 45 years of age with new onset symptoms.

Patient “B” may benefit from the reassurance of a negative endoscopic exam.

Patient “C” may benefit from treatment of the her H.pylori first.

Some studies indicate this approach may be cost-saving overall.

This patient could be sent for an endoscopic examination if she doesn’t improve following therapy.

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ANY QUESTIONS?

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THANK YOU