1. 1. Dr.M.Krishna Vasudev Dept of General Medicine Peptic Ulcer Disease
2. 2. Peptic Ulcer Disease Condition characterized by Erosion of GI mucosa resulting from digestive action of HCl and pepsin
3. 3. Peptic Ulcer Disease Ulcer development Lower esophagus Stomach Duodenum 10% of men, 4% of women
4. 4. Types Acute Superficial erosion Minimal erosion Chronic Muscular wall erosion with formation of fibrous tissue Present continuously for many months or intermittently
5. 5. Peptic Ulcers: Gastric & Dudodenal
6. 6. Classification Stomach (called gastric ulcer) Duodenum (called duodenal ulcer) Oesophagus (called Oesophageal ulcer) Types of Gastric ulcer(Modified johnson criteria): Type I: Ulcer along the lesser curve of stomach Type II: Two ulcers present - one gastric, one duodenal Type III: Prepyloric ulcer Type IV: Proximal gastroesophageal ulcer Type V: Anywhere(NSAID induced)
7. 7. Gastric Ulcers Commonly found on lesser curvature in close proximity to antral junction Less common than duodenal ulcers Prevalent in women, older adults, persons from lower socioeconomic class
8. 8. Gastric Ulcers Characterized by A normal to low secretion of gastric acid Back diffusion of acid is greater (chronic)
9. 9. Gastric Ulcers Critical pathologic process is amount of acid able to penetrate mucosal barrier H. pylori is present in 50% to 70%
10. 10. Gastric Ulcers H. pylori is thought to be more destructive when noxious agents are used, or patient smokes
11. 11. Gastric Ulcers Drugs can cause acute gastric ulcers Aspirin, corticosteroids, NSAIDs, reserpine Or known causative factors Chronic alcohol abuse, chronic gastritis
12. 12. Duodenal Ulcers Occur at any age and in anyone Between ages of 35 to 45 years Account for ~80% of all peptic ulcers
13. 13. Duodenal Ulcers Associated with HCl acid secretion H. pylori is found in 90-95% of patients Direct relationship has not been found
14. 14. Duodenal Ulcers Diseases with risk of duodenal ulcers COPD, cirrhosis of liver, chronic pancreatitis, hyperparathyroidism, chronic renal failure Treatments used for these conditions may promote ulcer development
15. 15. Peptic Ulcer Disease Clinical Manifestations Common to have no pain or other symptoms Gastric and duodenal mucosa not rich in sensory pain fibers Duodenal ulcer pain Burning, cramplike Gastric ulcer pain Burning, gaseous
16. 16. SYMPTOMS An early sense of fullness with eating frequent burping or hiccupping Stomach pain wakes you up at night low blood cell count (anemia) Blood in the stools Vomiting Melena Appetite changes hematemesis (vomiting of blood) Unexplained weight loss Water brash Nausea Bloating Burning pain
17. 17. DUODENAL ULCER Classic symptoms of a duodenal ulcer include burning, gnawing, aching, or hunger-like pain, primarily in the upper middle region of the abdomen below the breastbone (the epigastric region). Pain may occur or worsen when the stomach is empty, usually two to five hours after a meal. Symptoms may occur at night between 11 PM and 2 AM, when acid secretion tends to be greatest. Feel better when you eat or drink and then worse 1 or 2 hours later (duodenal ulcer) GASTRIC ULCER Symptoms of a gastric ulcer typically include pain soon after eating. Symptoms are sometimes not relieved by
18. 18. Peptic Ulcer Disease Complications 3 major complications Hemorrhage Perforation Gastric outlet obstruction Initially treated conservatively May require surgery at any time during course of therapy
19. 19. Peptic Ulcer Disease Diagnostic Studies Endoscopy procedure most often used Determines degree of ulcer healing after treatment Tissue specimens can be obtained to identify H. pylori and to rule out gastric cancer
20. 20. Peptic Ulcer Disease Diagnostic Studies Tests for H. pylori Noninvasive tests Serum or whole blood antibody tests Immunoglobin G (IgG) Urea breath test Invasive tests Biopsy of stomach Rapid urease test
21. 21. Peptic Ulcer Disease Diagnostic Studies Barium contrast studies Widely used X-ray studies Ineffective in differentiating a peptic ulcer from a malignant tumor
22. 22. Peptic Ulcer Disease Diagnostic Studies Gastric analysis Identifying a possible gastrinoma Determining degree of gastric hyperacidity Evaluating results of therapy
23. 23. Peptic Ulcer Disease Diagnostic Studies Laboratory analysis CBC Urinalysis Liver enzyme studies Serum amylase determination Stool examination
24. 24. AIMS OF ULCER TREATMENT Promotion of ulcer healing. Symptomatic relief of pain. Prevention of recurrence (relapse). Prevention of complications
25. 25. DRUG TREATMENT OF PEPTIC ULCER I. Gastric hyposecretory drugs. H2 receptor blockers Muscarinic receptor blockers Proton pump inhibitors II. Eradication of H. pylori infections To prevent relapse
26. 26. DRUG TREATMENT OF PEPTIC ULCER III. Mucosal cytoprotective agents. Sucralfate Colloidal bismuth Prostaglandin analogues IV. Neutralizing agents (antacids).
27. 27. Gastric hyposecretory drugs H2 receptor blockers Muscarinic receptor blockers Proton pump inhibitors Decreasing gastric acidity can reduce absorption of ketoconazole & iron preparation, digoxin.
28. 28. Proton Pump Inhibitors Mechanism of action Irreversible inhibition of proton pump (H+/ K+ ATPase) that is responsible for final step in gastric acid secretion from the parietal cell. PP inhibitors include: Omeprazole Lansoprazole Pantoprazole Esomeprazole
29. 29. Illustration of Gastric secretion by parietal cells
30. 30. Pharmacokinetics: They are prodrugs taken orally. are given as enteric coated capsules They are rapidly absorbed from the intestine. They are activated in the acidic medium of the secretory parietal cell canaliculus. They are inactivated if (combined with H2 receptor blockers).
31. 31. Have long duration of action (> 12 h-24 h). Once daily dose is sufficient Bioavailability is reduced by food. Given 1 h before meal. Are metabolized in the liver by CytP450. They are more potent than H2 receptor blockers Inhibits basal and stimulated-acid secretion. Dose reduction is required in severe liver failure.
32. 32. USES 1. Zollinger Ellison syndrome (First choice). 2. Resistant severe peptic ulcer ( 4-8 weeks). 3. Reflux esophagitis. 4. Eradication of H. pylori.
33. 33. ADVERSE EFFECTS GIT disturbances: nausea, vomiting, diarrhea Achlorhydria. Hypergastrinaemia Gastric hyperplasia. Increased bacterial flora (nitrosamine)
34. 34. H2 receptor blockers Mechanism of action They competitively and reversibly block to H2 receptors on the parietal cells thus reduce gastric secretion. They include: Cimetidine Ranitidine Famotidine Nizatidine
35. 35. Pharmacokinetics Good oral absorption Plasma half life (1-3 h). Duration (4-12 h). First pass metabolism (50% Except Nizatidine 100 % bioavailability). Given before meals. Metabolized by liver. Excreted mainly in urine. Cross placenta & excreted in milk
36. 36. Pharmacological actions: Inhibit histamine, gastrin, cholinergic drug -induced secretions. Reduce basal and food-stimulated gastric secretion. Reduce pepsin activity. Promote mucosal healing & decrease pain
37. 37. USES: Duodenal Ulcer (6-8 weeks). Benign gastric ulcer (8-12 weeks). Reflux esophagitis Zollinger Ellison Syndrome (large doses). Pre-anesthetic medication (To prevent aspiration pneumonitis). Eradication of H. pylori infections.
38. 38. Adverse Effects of H2 blockers: 1. GIT disturbances: nausea, vomiting 2. CNS effects: Headache, dizziness, confusion (elderly renal or hepatic dysfunction). 3. CVS effects Bradycardia and hypotension (rapid I.V.)
39. 39. Cimetidine has other adverse effects: 4. Endocrine effects Antiandrogenic actions (gynecomasteia impotence) Galactorrhea in women. 5. Cytochrome P450 inhibitor: decrease metabolism of oral anticoagulant, phenytoin, benzodiazepines.
40. 40. Precautions 1. Maintenance dose (Relapse may occur). 2. Dose reduction in severe renal or hepatic failure and elderly.
41. 41. ANTICHOLINERGIC DRUGS 1. Non selective muscarinic blockers: Oxyphenonium, dicyclomine Decreased gastric motility Delayed gastric emptying - Heart burn - Atropine like side effects.
42. 42. 2. Selective muscarinic blockers: Pirenzepine - Telenzepine Blocks M1 receptors on the parietal cells. Selectively inhibit gastric acid secretion No effect on gastric motility Less side effects of cholinergic blockade. No effect on CNS. Dose : 50 mg bid for 4-6 weeks Uses 1.Adjuvants to H2 receptor blockers. 2. decrease nocturnal pain in peptic ulcer.
43. 43. Eradication Of H Pylori Is a bacteria that causes chronic inflammation of the inner lining of the stomach. Produce enzymes (tissue damage), inflammation ulcer. Duodenal ulcer - Gastric ulcer Risk factor for esophagus and stomach cancers. Eradication is important to prevent recurrence of ulcer.
44. 44. Helicobacter pylori in association with gastric mucosa
45. 45. Treatment Combined therapy is usually used. Clarithromycin, tetracycline, amoxicillin Proton pump inhibitors or H2 receptor blockers. Bismuth compounds Metronidazole. Resistance may develop to antibiotics. Better eradication is obtained using proton pump inhibitors & clarithromycin.
46. 46. Treatment The standard first-line therapy is "triple therapy" consisting of proton pump inhibitors as omeprazole and the antibiotics clarithromycin and amoxicillin.
47. 47. REGIMEN DOSE DURATION Bismuth Metronidazole Tetracycline 525 mg qid 250 mg tid 500 mg qid 2 weeks omeprazole Metronidazole Clarithromycin 20 mg bid 500 mg bid 500 mg bid 1 week omeprazole Amoxacillin Clarithromycin 20 mg bid 500 mg qid 500 mg bid 1 week omeprazole Bismuth Metronidazole Amoxacillin or / Tetracycline 20 mg bid 525 mg qid 500 mg qid 500 mg qid week
48. 48. Mucosal protective agents. 1. Sucralfate 2. Prostaglandin analogues. 3. Colloidal bismuth
49. 49. Sucralfate Sucrose octaphosphate + aluminium hydroxide Mechanism of action 1. In acidic pH, sucralfate dissociates into its components. 2. The negatively charged sucrose octaphosphate binds with positively charged protein molecules found in damaged mucosa (Coat over the ulcer). 3. Promote ulcer healing. 4. Inhibition of pepsin.
50. 50. 3. Stimulation of mucosal protective mechanisms (mucous and bicarbonates secretion). Kinetics Orally, poor systemic absorption. Duration (6 h). Excreted in feces. Avoid co-administration of antacid or H2 blocker. Bette taken on empty stomach.
51. 51. Therapeutic Uses Benign gastric and duodenal ulcer. Chronic gastritis. Adverse effects Constipation and dry mouth. Interferes with absorption of some drugs tetracycline, theophyline, Tricyclic antidepressant.
52. 52. 2. Misoprostol Prostaglandin Analogues (PGE1 ) HCL secretion. Promote tight junction of gastric cells prevent back diffusion of HCL. mucous and bicarbonate secretion. blood flow of mucosa improve healing of ulcer. Kinetics Orally, 30 min. is converted into active metabolite. Excreted in urine- must be taken 3-4 times/day.
53. 53. Therapeutic uses Prevention of NSAIDS-induced peptic ulcer. Adverse Effects Abdominal cramps (sever colicky pain). Diarrhea. Uterine contraction dysmenorrhea or abortion. Vaginal bleeding.
54. 54. 3. Colloidal Bismuth compounds Bismuth subcitrate Tripotassium dicitrato bismuthate. Mechanism of Action 1. It forms a precipitate with mucous cover the ulcer with a protective coat that prevent effect of HCl. 2. Promote healing of ulcer. 3. Bactericidal effect against campylobacter pylori . 4. Decrease activity of pepsin 5. Mucous & bicarbonate secretion.
55. 55. Adverse Effects 1. Black stool. 2. Teeth discoloration. 3. Encephalopathy (in renal dysfunction). USES 1. Triple therapy for eradication of H. pylori. 2. Benign gastric & duodenal ulcer. 3. Travellers diarrhea
56. 56. Drugs That Neutralize HCL (Antacids) Drugs used to relief gastric pain associated with hypersecretion of HCL. Mechanism of Action Neutralization of HCL. Inhibition of pepsin (inactive at PH 5). Therapeutic Uses 1. relief pain of peptic ulcer. 2. Dyspepsia.
57. 57. I - Systemic Antacids Sodium bicarbonate NaHCO3 + HCL NaCL + CO2. Disadvantages 1. Rebound hyperacidity. 2. Stomach distension due to CO2 liberation pain sensation. 3. Sodium load salt and water retention ( # in cardiac patients). 4. Systemic alkalosis.
58. 58. Calcium Carbonate CaCO3+HCL CaCl2 + H2O + CO2 Disadvantages 1. Liberation of CO2 stomach distension 2. 10% is absorbed hypercalcemia. 3. Rebound hyperacidity. 4. Milk alkali syndrome (hypercalcemia, renal failure).
59. 59. II Non Systemic Antacids 1. Aluminum Hydroxide Gel 2. Magnesium Trisilicate Al (OH)3 + HCL HCL3 + H2O. Advantages 1. Longer duration of action. 2. Gradual neutralization of HCL No rebound hyperacidity. 3. Adsorbs pepsin. 4. Minimal change in acid base balance. 5. No stomach distention
60. 60. Disadvantages Al (OH)3 1. Constipation. 2. Drug interaction: absorption of tetracycline, digoxin, iron. Magnesium Trisilicate 1. Diarrhea 2. CNS depression (renal failure).
61. 61. Alginates (Gaviscon) Combine with antacids in reflux esophagitis to increase adherence of mucus to esophageal mucosa.