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PEPTIC ULCER PEPTIC ULCER Definitions: Stomach or duodenal mucosal lesions Occurrence: due to imbalance between aggressive factors and mucosal protective.

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Presentation on theme: "PEPTIC ULCER PEPTIC ULCER Definitions: Stomach or duodenal mucosal lesions Occurrence: due to imbalance between aggressive factors and mucosal protective."— Presentation transcript:

1 PEPTIC ULCER PEPTIC ULCER Definitions: Stomach or duodenal mucosal lesions Occurrence: due to imbalance between aggressive factors and mucosal protective mechanisms.

2 PEPTIC ULCER PEPTIC ULCER Aggressive factors Pepsin secretion - acid secretion Protective factors Prostaglandins (E2 & I2 ) Mucus/bicarbonate secretion Mucosal blood flow Rapid turnover of gastric mucosa

3 Risk factors H Pylori infections H Pylori infections Alcohol Alcohol Smoking Smoking Diet Diet Drugs (NSAIDs, corticosteroids). Drugs (NSAIDs, corticosteroids). Stress Stress Genetic factors Genetic factors Diseases (Zollinger Ellison Syndrome). Diseases (Zollinger Ellison Syndrome).

4 SYMPTOMS: Nausea – Vomiting – Anorexia Nausea – Vomiting – Anorexia Upper abdominal pain. Upper abdominal pain. Weight loss. Weight loss. Heart burn. Heart burn.

5 COMPLICATIONS: Gastrointestinal hemorrhage Gastrointestinal hemorrhage Chronic iron deficiency anemia Chronic iron deficiency anemia Pyloric stenosis Pyloric stenosis Perforation Perforation

6 Gastric secretions 1. Pepsinogens (Chief cells). 2. HCl and intrinsic factor (Parietal cells). 3. Gastrin (G-cells). 4. Mucus, bicarbonate (mucus-secreting cells).

7 Regulation of Gastric secretions 1. Histamine (local hormone) 2. Acetylcholine (neurotransmitter). 3. Gastrin (hormone).

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10 AIMS OF ULCER TREATMENT Promotion of ulcer healing. Promotion of ulcer healing. Symptomatic relief of pain. Symptomatic relief of pain. Prevention of recurrence (relapse). Prevention of recurrence (relapse). Prevention of complications Prevention of complications

11 DRUG TREATMENT OF PEPTIC ULCER I. Gastric hyposecretory drugs. H2 receptor blockers H2 receptor blockers Muscarinic receptor blockers Muscarinic receptor blockers Proton pump inhibitors Proton pump inhibitors II. Eradication of H. pylori infections To prevent relapse

12 DRUG TREATMENT OF PEPTIC ULCER III. Mucosal cytoprotective agents. Sucralfate Sucralfate Colloidal bismuth Colloidal bismuth Prostaglandin analogues Prostaglandin analogues IV. Neutralizing agents (antacids).

13 Gastric hyposecretory drugs H2 receptor blockers H2 receptor blockers Muscarinic receptor blockers Muscarinic receptor blockers Proton pump inhibitors Proton pump inhibitors Decreasing gastric acidity can reduce absorption of ketoconazole & iron preparation, digoxin.Decreasing gastric acidity can reduce absorption of ketoconazole & iron preparation, digoxin.

14 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: Omperazole Omperazole Lansoprazole Lansoprazole Pantoprazole Pantoprazole

15 Illustration of Gastric secretion by parietal cells

16 Pharmacokinetics: They are prodrugs – taken orally. They are prodrugs – taken orally. are given as enteric coated capsules are given as enteric coated capsules They are rapidly absorbed from the intestine. They are rapidly absorbed from the intestine. They are activated in the acidic medium of the secretory parietal cell canaliculus. They are activated in the acidic medium of the secretory parietal cell canaliculus. They are inactivated if (combined with H2 receptor blockers). They are inactivated if (combined with H2 receptor blockers).

17 Have long duration of action (> 12 h-24 h). Have long duration of action (> 12 h-24 h). Once daily dose is sufficient Once daily dose is sufficient Bioavailability is reduced by food. Bioavailability is reduced by food. Given 1 h before meal. Given 1 h before meal. Are metabolized in the liver by CytP450. Are metabolized in the liver by CytP450. They are more potent than H2 receptor blockers They are more potent than H2 receptor blockers Inhibits basal and stimulated-acid secretion. Inhibits basal and stimulated-acid secretion. Dose reduction is required in severe liver failure. Dose reduction is required in severe liver failure.

18 USES 1. Zollinger Ellison syndrome (First choice). 2. Resistant severe peptic ulcer ( 4-8 weeks). 3. Reflux esophagitis. 4. Eradication of H. pylori.

19 ADVERSE EFFECTS GIT disturbances: nausea, vomiting, diarrhea GIT disturbances: nausea, vomiting, diarrhea Achlorhydria. Achlorhydria. Hypergastrinaemia Hypergastrinaemia Gastric hyperplasia. Gastric hyperplasia. Increased bacterial flora (nitrosamine) Increased bacterial flora (nitrosamine)

20 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

21 Pharmacokinetics Good oral absorption Good oral absorption Plasma half life (1-3 h). Plasma half life (1-3 h). Duration (4-12 h). Duration (4-12 h). First pass metabolism (50% Except Nizatidine 100 % bioavailability). First pass metabolism (50% Except Nizatidine 100 % bioavailability). Given before meals. Given before meals. Metabolized by liver. Metabolized by liver. Excreted mainly in urine. Excreted mainly in urine. Cross placenta & excreted in milk Cross placenta & excreted in milk

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23 Pharmacological actions: Inhibit histamine, gastrin, cholinergic drug - induced secretions. Inhibit histamine, gastrin, cholinergic drug - induced secretions. Reduce basal and food-stimulated gastric secretion. Reduce basal and food-stimulated gastric secretion. Reduce pepsin activity. Reduce pepsin activity. Promote mucosal healing & decrease pain Promote mucosal healing & decrease pain

24 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.

25 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.)

26 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.

27 Precautions 1. Maintenance dose (Relapse may occur). 2. Dose reduction in severe renal or hepatic failure and elderly.

28 ANTICHOLINERGIC DRUGS 1. Non selective muscarinic blockers: Oxyphenonium, dicyclomine - Decreased gastric motility - Delayed gastric emptying - Heart burn - Atropine like side effects.

29 2. Selective muscarinic blockers: Pirenzepine - Telenzepine Blocks M1 receptors on the parietal cells. Blocks M1 receptors on the parietal cells. Selectively inhibit gastric acid secretion Selectively inhibit gastric acid secretion No effect on gastric motility No effect on gastric motility Less side effects of cholinergic blockade. Less side effects of cholinergic blockade. No effect on CNS. No effect on CNS. Dose : 50 mg bid for 4-6 weeks Dose : 50 mg bid for 4-6 weeksUses 1.Adjuvants to H2 receptor blockers. 2. decrease nocturnal pain in peptic ulcer.

30 Eradication Of H Pylori Is a bacteria that causes chronic inflammation of the inner lining of the stomach. Is a bacteria that causes chronic inflammation of the inner lining of the stomach. Produce enzymes (tissue damage), inflammation – ulcer. Produce enzymes (tissue damage), inflammation – ulcer. Duodenal ulcer - Gastric ulcer Duodenal ulcer - Gastric ulcer Risk factor for esophagus and stomach cancers. Risk factor for esophagus and stomach cancers. Eradication is important to prevent recurrence Eradication is important to prevent recurrence of ulcer. of ulcer.

31 Helicobacter pylori in association with gastric mucosa

32 Treatment Combined therapy is usually used. Combined therapy is usually used. –Clarithromycin, tetracycline, amoxicillin –Proton pump inhibitors or H 2 receptor blockers. –Bismuth compounds –Metronidazole. Resistance may develop to antibiotics. Resistance may develop to antibiotics. Better eradication is obtained using proton pump inhibitors & clarithromycin. Better eradication is obtained using proton pump inhibitors & clarithromycin.

33 Treatment The standard first-line therapy is "triple therapy" consisting of proton pump inhibitors as omeprazole and the antibiotics clarithromycin and amoxicillin. first-line therapyproton pump inhibitorsomeprazole clarithromycinamoxicillinfirst-line therapyproton pump inhibitorsomeprazole clarithromycinamoxicillin

34 DURATIONDOSEREGIMEN 2 weeks525 mg qid 250 mg tid 500 mg qid Bismuth Metronidazole Tetracycline 1 week20 mg bid 500 mg bid omeprazole Metronidazole Clarithromycin 1 week20 mg bid 500 mg qid 500 mg bid omeprazole Amoxacillin Clarithromycin week20 mg bid 525 mg qid 500 mg qid omeprazole Bismuth Metronidazole Amoxacillin or / Tetracycline

35 Mucosal protective agents. 1. Sucralfate 2. Prostaglandin analogues. 3. Colloidal bismuth

36 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.

37 3. Stimulation of mucosal protective mechanisms (mucous and bicarbonates secretion). Kinetics Orally, poor systemic absorption. Orally, poor systemic absorption. Duration (6 h). Duration (6 h). Excreted in feces. Excreted in feces. Avoid co-administration of antacid or H2 blocker. Avoid co-administration of antacid or H2 blocker. Bette taken on empty stomach. Bette taken on empty stomach.

38 Therapeutic Uses Benign gastric and duodenal ulcer. Benign gastric and duodenal ulcer. Chronic gastritis. Chronic gastritis. Adverse effects Constipation and dry mouth. Constipation and dry mouth. Interferes with absorption of some drugs tetracycline, theophyline, Tricyclic antidepressant. Interferes with absorption of some drugs tetracycline, theophyline, Tricyclic antidepressant.

39 2. Misoprostol Prostaglandin Analogues (PGE1 ) Prostaglandin Analogues (PGE1 )  HCL secretion.  HCL secretion. Promote tight junction of gastric cells  prevent back diffusion of HCL. Promote tight junction of gastric cells  prevent back diffusion of HCL.  mucous and bicarbonate secretion.  mucous and bicarbonate secretion.  blood flow of mucosa improve healing of ulcer.  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.

40 Therapeutic uses Prevention of NSAIDS-induced peptic ulcer. Prevention of NSAIDS-induced peptic ulcer. Adverse Effects Abdominal cramps (sever colicky pain). Abdominal cramps (sever colicky pain). Diarrhea. Diarrhea. Uterine contraction dysmenorrhea or Uterine contraction dysmenorrhea or abortion. abortion. Vaginal bleeding. Vaginal bleeding.

41 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.

42 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. Traveller’s diarrhea

43 Drugs That Neutralize HCL (Antacids) Drugs used to relief gastric pain associated with hypersecretion of HCL. Mechanism of Action Neutralization of HCL. Neutralization of HCL. Inhibition of pepsin (inactive at PH 5). Inhibition of pepsin (inactive at PH 5). Therapeutic Uses 1. relief pain of peptic ulcer. 2. Dyspepsia.

44 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). ( # in cardiac patients). 4. Systemic alkalosis.

45 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).

46 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

47 Disadvantages Al (OH)3 1. Constipation. 2. Drug interaction:  absorption of tetracycline, digoxin, iron. Magnesium Trisilicate 1. Diarrhea 2. CNS depression (renal failure).

48 Alginates (Gaviscon) Combine with antacids in reflux esophagitis to increase adherence of mucus to esophageal mucosa.


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