7. Management of Peptic Ulcer

Define and describe peptic ulcer.

• An ulcer of the alimentary tract mucosa, usually stomach or duodenum, rarely in lower esophagus, where mucosa is exposed to gastric acid secretion

• A localized loss of gastric as well as duodenal mucosa leads to the formation of peptic ulcer

• Common disorder affecting millions worldwide

How do peptic ulcers come about?

• When normal mucosal defense mechanisms (mucus, mucosal blood flow, formation of HCO₃^- and PGE₂) are impaired

• When normal mucosa is overpowered by damaging factors (acid, pepsin, NSAIDs, and H. pylori)

Ulcers occur 5 times more commonly in

duodenum

Gastroduodenal mucosal integrity is determined by __________ (defensive) and ________ (aggressive) factors.

protective

damaging

List protective/defensive factors that determine gastroduodenal mucosal integrity.

1. Gastric mucus

2. Prostaglandins

3. Bicarbonate

4. Mucosal blood flow

5. Local nitric acid

List aggressive/damaging factors that determine gastroduodenal mucosal integrity.

1. Acid

2. Pepsin

3. H. pylori

4. Bile

5. NSAIDs

6. Tobacco

7. Alcohol

8. Emotions (stress and anger)

Mechanism of Acid Secretion

Gastric acid is secreted by ________ cells in the gastric mucosa. They contain receptors for 3 main stimulants: _________, _______, and _____________. _________ binds to H₂ receptors. Gastrin and ACh exert their effects by increasing _________ ____. They stimulate acid secretion through ___ ______ (______ ____).

parietal

histamine

gastrin

acetylcholine

Histamine

cytosolic Ca²⁺

H⁺/K⁺ ATPase (proton pump)

List the 3 classes of drugs used to treat peptic ulcers.

1. Drugs which reduce gastric acid secretion

2. Mucosal/ulcer protective agents

3. Anti-H. pylori drugs

List the 4 categories of drugs which reduce gastric acid secretion.

1. H₂ receptor antagonists

2. Proton-pump inhibitors

3. Anticholinergics

4. Prostaglandin analogues

Drugs Which Reduce Gastric Acid Secretion

List H₂ receptor antagonists used to treat peptic ulcers.

1. Cimetidine

2. Ranitidine

3. Famotidine

4. Roaxitidine

5. Ioxatidine

Drugs Which Reduce Gastric Acid Secretion

List proton-pump inhibitors used to treat peptic ulcers.

1. Omeprazole

2. Pantoprazole

3. Rabeprazole

4. Lansoprazole

5. Esomeprazole

6. Dexlansoprazole

Drugs Which Reduce Gastric Acid Secretion

List anticholinergics used to treat peptic ulcers.

1. Pirenzipine

2. Propantheline

Drugs Which Reduce Gastric Acid Secretion

List prostaglandin analogues used to treat peptic ulcers.

1. Misoprostol

2. Enprostil

List mucosal/protective agents used to treat peptic ulcers.

1. Sucralfate (aluminum salt of sulfate sucrose)

2. Colloidal Bismuth Subcitrate (CBS)

List anti-H. pylori drugs used to treat peptic ulcers.

1. Amoxicillin

2. Clarithromycin

3. Metronidazole

4. Tetracylin

5. Tinidazole

Drugs Which Reduce Gastric Acid Secretion

How do H₂ receptor antagonists work?

They block histamine-induced gastric acid secretion.

Drugs Which Reduce Gastric Acid Secretion

Describe the mechanism by which H₂ receptor antagonists work.

Competitively inhibit H₂ receptors on parietal cells and suppress basal and food-stimulated acid secretion

Drugs Which Reduce Gastric Acid Secretion

List the uses of H₂ receptor antagonists.

1. Duodenal and gastric ulcers

2. NSAIDs-induced ulcer (PPIs preferred if NSAIDs have to be continued)

3. Prevention of stress-related gastric bleeding and gastritis

Drugs Which Reduce Gastric Acid Secretion

List the adverse effects of H₂ receptor antagonists.

Safe drugs

• Headache

• Fatigue

• Constipation (rare)

Drugs Which Reduce Gastric Acid Secretion

How are H₂ receptor antagonists administered?

• Cimetidine, slow infusion should be given

• Rapid IV injection may cause bradycardia, arrythmia/cardiac arrest

Drugs Which Reduce Gastric Acid Secretion

Describe proton pump inhibitors (PPI) and their mechanism of action.

• Most widely used, good efficacy, safe

• Prodrugs requiring activation in acidic environment

• Activated form binds irreversibly to H⁺/K⁺- ATPase enzyme system (proton pump) and inhibit it

• Dose-dependent suppression of gastric acid secretion, powerful inhibitor of gastric acid; can fully abolish HCl secretion (basal/food stimulated)

Drugs Which Reduce Gastric Acid Secretion

How are the PPIs esomeprazole, lansoprazole, and pantoprazole administered?

IV

Lists the uses of PPIs.

1. Duodenal and gastric ulcers

2. Bleeding peptic ulcers

3. Gastroesophageal reflux disease (GERD)

4. H. pylori associated ulcers

List the adverse effects of PPIs.

Quite safe

• Diarrhea

• Headache

• Abdominal pain

• Reduction in oral Vitamin B₁₂ absorption occurs with prolonged therapy

Drugs Which Reduce Gastric Acid Secretion - Anticholinergics (M₁/M₃)

Describe pirenzipine and list its adverse effects

• M₁ anticholinergic

• Gastric secretion reduced by 40-50%

• Effectively heal and prevent recurrence of duodenal ulcers

1. Dry mouth

2. Blurred vision

3. Constipation

4. Urinary retention

Drugs Which Reduce Gastric Acid Secretion - Anticholinergics

Which anticholinergic is 25 times more potent than pirenzipine?

Telenzepine

Drugs Which Reduce Gastric Acid Secretion - Anticholinergics

Which anticholinergic drug has intolerable adverse effects?

Propantheline

Drugs Which Reduce Gastric Acid Secretion

Prostaglandin (PG) analogues play an important role in

gastric defense mechanism

Drugs Which Reduce Gastric Acid Secretion

Which PG is produced by the gastric mucosa? List its functions.

PG-E

1. Inhibits secretion of acid

2. Stimulates secretion of mucus and bicarbonate

3. Cryoprotective effect

4. Enhances blood flow

Drugs Which Reduce Gastric Acid Secretion

What is misoprostol? What is it used for? What is it contraindicated in and why?

• Analog of PGE₁

• Approved for healing of NSAID-induced gastric ulcers and in chronic heavy smokers

• Contraindicated in pregnancy, since it can stimulate uterine contraction and cause miscarriage

Drugs Which Reduce Gastric Acid Secretion

List the adverse effects of PG.

1. Diarrhea

2. Colic pain

3. Uterine bleeding

4. Abortion

5. Needs multiple daily doses (short t_1/2)

6. Patient acceptability is poor (PPIs are preferred)

List and describe the mechanisms of mucosal protective drugs.

1. In acidic pH (<4), polymerizes by cross-linking of molecules; forms sticky gel, which acts as acid-resistant physical barrier

   • Dietary and mucosal proteins get deposited on this coat, forming another protective layer

2. Stimulates PGE₂ synthesis and HCO₃^- secretion

3. Promotes healing of both duodenal and gastric ulcers by binding to epithelial and growth factors

List the uses of mucosal protective drugs.

1. Gastritis

2. Bile Reflux

3. Prophylaxis of stress ulcers

Mucosal Protective Drugs

List and describe the mechanisms of colloidal bismuth subcitrate (CBS).

1. Form acid-resistant protective coating over ulcer base

2. Stimulate PGE₂

3. Mucus and bicarbonate secretion

4. Dislodges H. pylori from surface of gastric mucosa

5. Has antimicrobial activity

6. Used in H. pylori treatment

Mucosal Protective Drugs

List the adverse effects of CBS.

Safe

1. Blackening of stools

2. Darkening of tongue

3. Prolonged use may lead to bismuth toxicity

Describe Helicobacter pylori and its role in peptic ulcers.

• Gram negative bacillus

• Can survive in acidic gastric environment

• 90% of duodenal ulcers

• 50-60% of gastric ulcers

• Disturbs normal feedback mechanism of acid release

• Produce other proteolytic enzymes that decrease defense

Why is single therapy relatively ineffective to treat H. pylori?

Resistance develops rapidly

How is H. pylori eradicated? Why is it beneficial?

• Concurrently with PPI/H₂ blocker therapy

• Faster ulcer healing

• Low relapse rate

Anti H. pylori Drugs

List the drugs used for triple therapy. How many days is it administered for?

Omeprazole + Clarithromycin + Amoxicillin/Metronidazole

14 days

Anti H. pylori Drugs

List the drugs used in quadruple therapy. How long is it administered for?

Omeprazole + Bismuth subsalicylate + Tetracycline + Metronidazole

14 days

Anti H. pylori Drugs

List the drugs used in sequential therapy. How long is it administered for?

1. Omeprazole + Amoxicillin (1-5 days)

2. Omeprazole + Clarithromycin + Tinidazole (next 6-10 days)

After completion of any therapy, what is done to promote ulcer healing?

Treatment with PPIs (once daily) for another 4-6 weeks