Peptic Ulcer Disease Treatment

• The module is Metabolism & Nutrition (MEN 208) for Level 2, Semester 4 students
• The lecture is about the treatment of Peptic Ulcer Disease
• The lecturer is Prof. Samah M. Elaidy, MD, PhD, JMHPE from the Pharmacology Department

Learning Outcomes:

• Classified by drugs: Understand the different drugs used in peptic ulcer treatment
• Mechanism of action: Explain how the drugs work to treat peptic ulcers
• Adverse effects: Know the potential side effects of these drugs
• Drug therapy: Explain how to eradicate Helicobacter Pylori using drugs
• Treatment plans: Create treatment strategies for individuals suffering from peptic ulcer disease

Lecture Outline

• PUD Definition: An intro to definition and discuss the pathophysiology of peptic ulcer disease (PUD)
• Drug Classification: Categorize the drugs used in PUD treatment
• Mechanism of Action: Mechanism on how drugs act to treat PUD
• Therapeutics: The therapeutic usage of PUD treatment drugs
• Side Effects: Discuss the side effects and interactions of the drugs
• H. pylori: Identify the drugs to treat H. pylori
• Clinical case to show how to manage PUD

Acid Peptic Disease

• Conditions characterized by acid secretion and gastric mucosal defenses balances
• Manifestations include:
• Peptic ulcer disease
• Gastroesophageal reflux disease (GERD)
• Stress-related mucosal injury.

Peptic Ulcer Disease (PUD)

• Formation of a sore/focal defect that forms on the inside lining of the lower esophagus, stomach, and/or duodenum
• The defect extends from mucosa to submucosa, and even deeper to muscular layer

Gastric Secretion and Its Regulation

• Gastrin, histamine, and acetylcholine (ACh) stimulate gastric acid secretion
• Prostaglandins inhibit gastric acid secretion and promote mucosal protection.
• Proton pump inhibitors (PPIs) block the final step of acid production (H+/K+ ATPase).

Pathogenesis of PUD

• PUD is triggered by disrupted balance between gastroduodenal mucosa and aggressors
• Defense mechanisms are: mucus and bicarbonate, intrinsic epithelial cells, rich mucosal blood flow, and PGE2
• Aggressive factors are: pepsin and bile, gastric acid (HCL) secretion, H. pylori infection, and NSAIDs

Risk Factors for PUD:

• Tobacco
• Infection with Helicobacter pylori
• Alcohol and Caffeine
• Drugs like NSAIDs and Corticosteroids
• Stress, Spicy food and Steroids

Signs and Symptoms:

• Epigastric pain and discomfort
• In gastric ulcer: Pain worsens after meals
• In duodenal ulcer: Pain relieved by meals
• Heartburn and bloating
• Nausea and vomiting
• Gastrointestinal tract bleeding, including hematemesis and/or melena
• Loss of appetite and weight loss

Management of PUD

• Non-Pharmacological Treatment
• Avoidance includes: drugs that increase acid secretion (NSAIDs, Steroids), foods/drinks that cause dyspepsia, smoking, and stress
• Aim of Pharmacological Treatment
• Relieve signs and symptoms
• Heal the ulcer, reduce acid secretion
• Prevent complications, and recurrences by eradicating H. pylori

Pharmacological Therapy of PUD

• Decreased gastric acidity achieved by:
• Decrease acid production (PPIs, PCABs, H2 blockers, anticholinergics)
• Neutralizing acid (antacids)
• Enhance mucosal defenses (Prostaglandins analogues, Bismuth, Sucralfate).
• Elimination of H. pylori

Drugs Decreasing HCl Secretion

• Selective M1 Blockers: Includes Pirenzepine and Telenzepine
• Mechanism of action: Selectively block gastric M1 receptors. This results in reduced basal HCl secretion
• Uses: used as adjuvant therapy with H2 blockers
• Side effects: high doses produce atropine-like effects; dry mouth, blurred vision, tachycardia, urine retention

H2 Blockers

• Common examples: Cimetidine, Ranitidine, Famotidine, Nizatidine
• Mechanism of action: They are competitive inhibitors of H2 receptors on the parietal cells
• Uses:
• Reduce histamine-stimulated HCl secretion
• Duodenal/gastric ulcers
• GERD
• Prophylaxis & treatment of stress ulcers (e.g. after burn or major trauma)

Adverse effects of H2 Blockers

• Effects mostly associated with cimetidine
• Cimetidine has anti-androgenic effects leading to reduced sperm count, impotence and gynecomastia
• Cimetidine inhibits hepatic microsomal enzymes (P450); this affects the metabolism of other drugs. Leads to reversible hepatotoxicity and anemia
• CNS effects include headache, slurred speech, delirium, coma; occurs mainly in elderly people

Precautions of H2 Blockers

• Precautions to consider are:
• Avoid sudden withdrawal (rebound ulceration)
• Pregnancy and lactation (crosses placental barrier, secreted in milk)
• Caution if someone has a narrow therapeutic index (cimetidine inhibits microsomal P450, increasing toxicity)

Cimetidine vs Ranitidine vs Famotidine

• Weak: Cimetidine H2 Blocking effect
• Potent: Ranitidine H2 Blocking effect
• More Potent: Famotidine H2 Blocking effect
• Strong: Cimetidine anti-aderogentic effect
• Minimal: Ranitidine anti-aderogentic effect
• No anti-aderogentic effect: Famotidine
• String liver enzyme inhibition: Cimetidine
• Minimal liver enzyme inhibition: Ranitidine + Famotidine

Proton Pump Inhibitors (PPIs)

• Omeprazole, Lansoprazole, Pantoprazole are examples
• Mechanism of action: Irreversible inhibition of gastric H+/K+ ATPase enzyme
• Inhibits: basal and stimulated HCl secretion to around the zero level
• Action duration: 1-2 days
• Restoration of acid secretion: 3-5 days
• Their bioavailability is decreased significantly by food
• Should administer 1 hour before a meal.
• Therapeutic uses: Same as H2 blockers

Adverse Effects (PPIs)

• Diarrhea, abdominal colic, dizziness, skin rash, and leucopenia
• Decreases of vit B12 absorption (after 12 weeks of therapy)
• Alteration of bioavialability of some drugs e.g. ketoconazole, digoxin, and iron
• Omeprazole inhibits hepatic P450 isoenzymes causing decrease in elimination of phenytoin, diazepam, warfarin, and cyclosporine. Decreases activation of clopidogrel.
• Increase cancer risk for gastric carcinoid tumor
• Osteoporosis

Potassium Competitive Acid Blockers (P-CABs)

• Vonoprazan, Tegoprazan, Revaprazan
• Act by competing with K+
• Induces selective and reversible inhibition of the proton pump

Drugs Enhancing Mucosal Defense Mechanisms

• Sucralfate

• Needs acidic medium activated (not with antacids, H₂bl, PPIs)

• Aluminum moiety is released forming viscosity and binds to protein damaged mucosa

• Equal effects to H2 antagonists

• Binds to and inactivates pepsin/bile acids, and increase PG secretion (endogenous)

• Adverse Effects: Constipation due to presence of aluminum

• Bismuth Compounds: bismuth subsalicylate

  • Similar action of sucralfate + antimicrobial activity against H. pylori
  • Don't give simultaneously with antacids/H2 blockers
  • Stool and teeth discoloration
  • Encephalopathy if there is renal failure
  • Chronic renal failure and CNS diseases

• Carbenoxolone

• Liquorice derivative having steroid structure

• Increases production of viscosity for gastric mucus. Increases mucosal resistance

• Decreases pepsin secretion and increases endogenous PG secretion

• Salt and water retention leading to hypertension especially with cardiac/renal disease

• Synthetic PGE1 analogue: Misoprostol

• Works on specific cells to decrease histamine-stimulated HCl secretion

• Increase secretions of mucus and bicarbonate, and protects cells.

• Increase mucosal blood flow. Stimulates mucosal cellular regeneration.

• Therapeutic used for the prevention of peptic ulcers with long term use of NSAIDs

• Adverse effects due to increase in GIT motility which causes diarrhea, diarrhea, and cramping pain

• Uterine contractions during pregnancy which leads to abortion

Anti H.Pylori Drug Therapy

• First-line, Bismuth quadruple therapy include PPI(standard), Bismuth sub salicylate (300mg), Metronidazole (250-500mg), and Tetracycline (500mg) with different dosage frequencies and duration of 10-14 day
• First-line, Concomitant therapy include PPI(standard), Clarithromycin (500mg), Amoxicillin (lg), and Metronidazole (250-500mg) with different dosage frequencies and duration of 10-14 day
• First-line, Clarithromycin triple therapy include PPI (standard or double), Clarithromycin (500mg), and Amoxicillin (lg) with different dosage frequencies and duration of 14 days

Management of Peptic Ulcer in Pregnancy

• Antacids are often considered safe
• Avoid magnesium trisilicates due to potential fluid overload
• Use sucralfate with caution
• Cimetidine should be avoided, known for antiandrogenic effects