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Peptic ulcer disease pharmacotherapy

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Drugs used in Peptic ulcer disease

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Peptic ulcer disease pharmacotherapy

  1. 1. Management of Peptic ulcer disease Dr. Bushra Hasan Khan Junior Resident-1, Department Of Pharmacology, JNMC,AMU,Aligarh. 1
  2. 2. CONTENTS  Physiology of Gastric acid secretion  An introduction to Peptic Ulcer Disease  Drugs used in PUD 2
  3. 3. PHYSIOLOGY OF GASTRIC ACID SECRETION • Food is broken into macroparticles • Acid causes hydrolysis, sterilizes the meal content & activates pepsinogen to pepsin • Acid secretion: • Basal • Stimulated 3
  4. 4. 4 DIAGRAM SHOWING OXYNTIC GASTRIC GLAND
  5. 5. GASTRIC PARIETAL CELL UNDERGOING TRANSFORMATION AFTER SECRETAGOGUE MEDIATED STIMULATION 5
  6. 6. PHASES OF GASTRIC ACID SECRETION AND THEIR REGULATION 6
  7. 7. 7 PATHOPHYSIOLOGY
  8. 8. 8 PHYSIOLOGICAL REGULATION OF GASTRIC ACID SECRETION
  9. 9. HCL GASTRIN HISTAMINE ACETYLCHOLINE 9 ECL
  10. 10. PEPTIC ULCER DISEASE • PEPTIC ULCER is defined as disruption of the mucosal integrity of the stomach and/or duodenum leading to a local defect or excavation due to active inflammation. Epidemiology • Middle-age to older age . • peptic ulcers - first portion of the duodenum or in the stomach, in a ratio of about 4:1. • Male/female ratio is 3:1 10
  11. 11. PEPTIC ULCER DISEASE Acid Pepsin Bile acids NSAIDs H. pylori Alcohol Pancreatic enzymes 11 IMBALANCE FACTORS THAT PROTECT AGAINST ACIDITY FACTORS THAT INCREASE ACID SECRETION Mucus bicarbonate layer Blood flow cell renewal Prostaglandins Tight junction b/w epithelium
  12. 12. 12 CLINICAL PRESENTATION • Epigastric pain • Burning, aching, gnawing, hunger pain  aggravated by food in Gastric ulcer ,  relieved by food in Duodenal ulcer • Bloating and nausea • Loss of appetite and weight loss in Gastric ulcer • In Severe Cases - Vomiting blood or coffee ground like material - Black tarry stools
  13. 13. CLASSIFICATION OF ANTI-ULCER DRUGS 1.Drugs for reduction of acid secretion:  Proton Pump Inhibitors: Omeprazole , Lansoprozole, Dexlansoprazole , Pantoprozole , Rabeprozole, Esomeprozole  H2 receptor antagonists: Ranitidine, Famotidine, Cimetidine ,Roxatidine  Anticholinergics: Pirenzepine, Propantheline ,Oxyphenonium  Prostaglandin analogues: Misoprostol 13
  14. 14. 2.Drugs to neutralize gastric acid (antacids):  Nonsystemic:- Aluminium hydroxide , Mag. hydroxide Magaldrate , Mag. trisilicate , Calcium carbonate .  Systemic:- Sodium bicarbonate , Sodium citrate MISCELLANEOUS ADJUVANTS-Simethicone Sodium alginate 14
  15. 15. 3.Ulcer Protectives: • Sucralfate, • Colloidal Bismuth Subcitrate and Bismuth Subsalicylate • Ranitidine bismuth citrate Newer cytoprotectives- Rebamipide,Ecabet 4.Antimicrobial drugs for H. pylori eradication: • Amoxycillin • Clarithromycin • Metronidazole •Tinidazole •Tetracycline 15
  16. 16. 16 PHYSIOLOGICAL AND PHARMACOLOGICAL REGULATION OF GASTRIC ACID SECRETION
  17. 17. PROTON PUMP INHIBITORS • Diminish daily acid production (basal and stimulated) by 80-95% • Absorbed from small intestine at a pH of 6 • PPIs are prodrugs - acidic environment needed for activation. • MECHANISM OF ACTION • After absorption prodrug gets activated to a tetracyclic sulfenamide cation . • Activated form then binds covalently with sulfhydryl groups of cysteines in the H+, K+-ATPase, irreversibly inactivating the pump molecule. 17
  18. 18. •Maximum acid inhibitory effect between 2 and 6 hours after administration and duration of inhibition lasting up to 72–96 hours. • Because the pumps need to be activated for these agents to be effective, their efficacy is maximized if they are administered before meal. 18
  19. 19. DOSAGE OF PPIs : •Omeprazole 20 mg OD • Esomeprazole 20 - 40 mg OD • Rabeprazole 20 mg OD • Lansoprazole 30 mg OD • Pantoprazole 40 mg OD 19
  20. 20. PPIs: ADRs • Nausea, Diarrhea, Abdominal pain, Flatulence. • Nosocomial pneumonia • Clostridium difficle diarrhoea • Hypergastrinemia, REBOUND hypersecretion of acid • Arthralgia, headache, skin rashes. • Drug interactions : Decreased acidity may decrease the absorption of Ketoconazole, Ampicillin esters, Iron salts, Digoxin CYP2C19 and CYP3A4 enz inhibition   metabolism of benzodiazepines, warfarin, phenytoin, diazepam, theophylline etc 20
  21. 21. H2 RECEPTOR ANTAGONISTS • Inhibit acid production by reversibly competing with histamine for binding to H2 receptors on the basolateral membrane of parietal cells. • Suppress acid production by 70% • Inhibit basal and stimulated acid secretion, which accounts for their efficacy in suppressing nocturnal acid secretion. • Ranitidine, Famotidine, Roxatidine, Nizatidine. 21
  22. 22. Adverse Drug Reactions of H2 antagonists • Diarrhea, headache, drowsiness, fatigue, muscular pain, and constipation. • Confusion, delirium, hallucinations, slurred speech • REBOUND hyperacidity • Pancytopenia, neutropenia, anemia, and thrombocytopenia 22
  23. 23. Dose of H2 antagonists  Ranitidine 300 mg hs  Famotidine 40 mg hs  Nizatidine 300 mg hs 23
  24. 24. PROSTGLANDIN ANALOGUES MISOPROSTOL- PGE1 ANALOGUE •MOA- Binds to EP3 receptor on parietal cells and stimulate Gi pathway- thereby decreasing intracellular cAMP & gastric acid secretion. • Cytoprotective effects Daily dose – • The usual recommended dose for ulcer prophylaxis is 200 micrograms four times a day. 24
  25. 25. Pharmacokinetics • Inhibit acid sec.in 30 min.,peaks at 60-90 min.,lasts for 3 hrs. Adverse effects • Diarrhea • Exacerbations of IBD • C/I in pregnancy as increases uterine motility 25
  26. 26. ANTICHOLINERGICS (rarely used now) SELECTIVE M1 BLOCKERS-PIRENZEPINE,TELENZEPINE The ACh receptor on the parietal cell is of the M3 subtype. Suppress neural stimulation of acid production via actions on M1 receptors of intramural ganglia. Poor efficacy, significant and undesirable anticholinergic side effects, and risk of blood disorders (pirenzepine) 26
  27. 27. ANTACIDS • ALUMINIUM HYDROXIDE, MAGNESIUM HYDROXIDE, MAGNESIUM TRISILICATE, CALIUM CARBONATE, MAGALDRATE •MOA-neutralises HCL and form AlCl3 and MgCl2 & Carbonates • Fixed combinations of magnesium and aluminum (Al3+ can relax gastric smooth muscle, producing delayed gastric emptying and constipation; Mg2+ causes loose stools). 27
  28. 28. • The magnesium-containing preparations : contraindicated in chronic renal failure patients because of possible hypermagnesemia. • Aluminum causes chronic neurotoxicity. ( Calcium Carbonate and Sodium Bicarbonate rarely used now a days.) 28
  29. 29. DRUG INTERACTIONS • Aluminium and Magnesium ions form inert complexes- Tetracyclines, Fluoroquinlones, Itraconazole, Digoxin or Iron salts • Aluminium group of antacids decrease the bioavailability of Phosphates, Iron salts and Digoxin •By raising gastric pH and ionization, antacids decrease the absorption of acidic drugs- Barbiturates, Phenytoin, NSAIDS . 29
  30. 30. SIMETHICONE • Silicon polymer, reduces flatulence and hiccups • Surfactant,antifoaming agent, cause proper dispersal of antacid over gastric surface , coats ulcer base. SODIUM ALGINATE- • Hydrophilic colloidal carbohydrate derived from seaweeds • Used with antacid & H2 antagonist-heart burn & GERD 30
  31. 31. ULCER PROTECTIVES • SUCRALFATE- •Complex sucrose salt - the hydroxyl groups substituted by aluminum hydroxide and sulfate. •MOA: Enhances prostaglandin synthesis, Stimulates mucus and bicarbonate secretion, and Enhances mucosal defense and repair. 31
  32. 32. Dose: • 1 g four times daily (for active duodenal ulcer) • 1 g twice daily (for maintenance therapy) SIDE EFFECTS • Constipation •Avoided in pts. with chronic renal insufficiency to prevent aluminum-induced neurotoxicity • The "sticky" nature of the viscous gel - bezoars in some patients with underlying gastroparesis. 32
  33. 33. COLLOIDAL BISMUTH SUBCITRATE & BISMUTH SUBSALICYLATE • In acidic media CBS- forms acid resistant protective coating over ulcer base • Also stimulates mucosal PGE2 synthesis & HCO3- secretion • Dislodges H.PYLORI from gastric mucosa –antimicrobial activity. • Dose: 120 mg qid • Heals ulcer in 4 – 8 wks • ADRs- blackening of stool,darkening of tongue • Prolonged use –Neuropathy,osteodystrophy, encephalopathy.33
  34. 34. 34
  35. 35. Anti H.pylori drugs • Helicobacter pylori: gram negative bacillus • Attaches to gastric epithelium: gastritis, dyspepsia, peptic ulcer, gastric lymphoma, gastric carcinoma. • No single agent is effective in eradicating the organism. • Combination therapy for 14 days provides the greatest efficacy • The agents used with the greatest frequency include amoxicillin, metronidazole, tetracycline, clarithromycin, and bismuth compounds. 35
  36. 36. 36
  37. 37. • Choice of a particular regimen will be influenced by -  Efficacy,  Patient tolerance,  Existing antibiotic resistance,  Cost of the drugs • Two anti-H. pylori regimens available in prepackaged formulation:  Prevpac (lansoprazole, clarithromycin, and amoxicillin) The contents taken twice per day for 14 days  Helidac (BSS, tetracycline, and metronidazole). Helidac constituents taken four times per day with an antisecretory agent (PPI or H2 blocker), also for at least 14 days. 37
  38. 38. TRIPLE THERAPY The BEST among all the Triple therapy regimens is Omeprazole / Lansoprazole - 20 / 30 mg BD Clarithromycin - 500 mg BD Amoxycillin - 1gm BD Given for 14 days followed by P.P.I for 4 – 6 weeks 38
  39. 39. QUADRUPLE THERAPY GIVEN WHEN TRIPLE THERAPY FAILS Omeprazole/lansoprazole - 20 / 30 mg OD Bismuth subsalycilate - 525 mg Metronidazole - 250 mg QID Tetracycline - 500 mg QID 39
  40. 40. SEQUENTIAL THERAPY (10 DAYS) For 1-5 days • Omeprazole /lansoprazole -20 mg/30mg BD • Amoxicillin -1 g BD Followed by 6-10 days • Omeprazole/lansoprazole -20mg/30mg BD • Clarithromycin -500 mg BD • Tinidazole -500 mg BD 40
  41. 41. Major SIDE EFFECTS of drugs •Bismuth : black stools, constipation, or darkening of the tongue. • Amoxicillin : nausea, vomiting, skin rash, allergic reaction , pseudomembranous colitis , antibiotic-associated diarrhea. • Tetracycline : rashes and, very rarely, hepatotoxicity and anaphylaxis. 41
  42. 42. Treatment of patients infected with resistant strains of H.pylori •Regimens considered for second-line therapy include: • Combi. of Pantoprazole, Amoxicillin, and Rifabutin for 10 days (86% cure rate) • Levofloxacin-based triple therapy (Levofloxacin, Amoxicillin, PPI) for 10 days . • furazolidone-based triple therapy (Furazolidone, Amoxicillin, PPI) for 14 days. 42
  43. 43. 43 THANK YOU

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