PEPTIC ULCER DISEASE AND ITS EFFECTIVE MANAGMENT (1).pptx

a presentation on GERD

1. PEPTIC ULCER DISEASE

2. MODULE OUTLINE Background Pathophysiology Etiology Prognosis Patient Education Clinical Presentation Diagnosis Management of PUD Medications Role of the Pharmacist Patient Case studies and breakout session Conclusion

3. OBJECTIVES Classification of PUD Pathophysiology Classification of drugs used in peptic ulcer Mechanism of action, Uses & Adverse effects, drug interactions of H2 Blockers Proton pump inhibitors Antacids Ulcer protectives Drugs for eradication of H.pylori

4. WHAT IS PEPTIC ULCER DISEASE??

5. BACKGROUND – True or false Gastric and duodenal ulcers usually cannot be differentiated based on history alone Epigastric pain is the most common symptom of both gastric and duodenal ulcers G nawing or burning sensation occurs after meals Patients with perforated PUD usually DO NOT present with a sudden onset of severe, sharp abdominal pain Documentation of PUD depends on radiographic and endoscopic confirmation In most patients with uncomplicated PUD, routine laboratory tests usually are helpful Most patients with PUD are treated successfully with cure of H pylori infection and/or avoidance of nonsteroidal anti-inflammatory drugs (NSAIDs)

6. ETIOLOGY Peptic ulcer disease (PUD) may be due to any of the following: H pylori infection Drugs Lifestyle factors Severe physiologic stress Hypersecretory states (uncommon) Genetic factors

7. NSAID MEDICATIONS These drugs disrupt the mucosal permeability barrier, rendering the mucosa vulnerable to injury. As many as 30% of adults taking NSAIDs have GI adverse effects. Risk Factors include history of previous peptic ulcer disease advanced age, female sex high doses or combinations of NSAIDs, long-term NSAID use concomitant use of anticoagulants, and severe comorbid illnesses.

8. OTHER ETIOLOGICAL FACTORS Low-dose aspirin for secondary prevention of cardiovascular Previous history of peptic ulcer disease Current use of NSAIDs, oral steroid agents, or acid suppressive agents Tobacco use Stress Depression Anemia Social deprivation Most evidence now supports the assertion that H pylori and NSAIDs are synergistic with respect to the development of peptic ulcer disease.

9. NSAID GASTROPATHY IN CHILDREN P revalence in children unknown Seems to be increasing, especially in children with chronic arthritis treated with NSAIDs. Case reports have demonstrated gastric ulceration from low-dose ibuprofen in children, even after just 1 or 2 doses.

10. CORTICOSTEROIDS AND OTHERS Corticosteroids alone do not increase the risk for PUD; however, they can potentiate ulcer risk in patients who use ------------- drugs concurrently . S pironolactone or serotonin reuptake inhibitors with moderate to high affinity for serotonin transporter may increase the risk of upper GI tract bleeding

11. LIFESTYLE FACTORS Evidence that tobacco use is a risk factor for duodenal ulcers is not conclusive. Ethanol is known to cause; gastric mucosal irritation, and nonspecific gastritis. Little evidence suggests that caffeine intake is associated with an increased risk of duodenal ulcers.

12. SEVERE PHYSIOLOGIC STRESS Stressful conditions that may cause PUD include : Burns central nervous system (CNS) trauma surgery , and severe medical illness. The risk for secondary (stress) ulceration Serious systemic illness, sepsis hypotension , respiratory failure, and multiple traumatic injuries Have you heard of Stress ulcer prophylaxis?

13. GENETICS More than 20% of patients have a family history of duodenal ulcers, compared with only 5-10% in the control groups. A rare genetic association exists between familial hyperpepsinogenemia type I (a genetic phenotype leading to enhanced secretion of pepsin) and duodenal ulcers.

14. Any of the following may be associated with PUD Hepatic cirrhosis Chronic obstructive pulmonary disease Allergic gastritis and eosinophilic gastritis Cytomegalovirus infection Graft versus host disease Uremic gastropathy Henoch- Schönlein gastritis Corrosive gastropathy Celiac disease Bile gastropathy Autoimmune disease Crohn disease Other granulomatous gastritides ( eg , sarcoidosis histiocytosis X, tuberculosis) Chemotherapeutic agents, such as 5-fluorouracil (5-FU), methotrexate (MTX), and cyclophosphamide Local radiation resulting in mucosal damage Use of crack cocaine, which causes localized vasoconstriction

15. PROGNOSIS Most patients treated successfully with; Eradication of H pylori infection Avoidance of nonsteroidal anti-inflammatory agents (NSAIDs ), and The appropriate use of antisecretory therapy Studies have shown eradication of H pylori infection changes the natural history of the disease, and decrease the ulcer recurrence rate from 60-90% to approximately 10-20%.

16. DIAGNOSTIC TESTS Test-and-treat strategy for H. pylori is recommended for patients < 55 YEARS with dyspepsia who have no alarm symptoms Endoscopy With Biopsy Urea Breath Tests Stool Monoclonal Antigen Tests Serologic Tests

17. CLINICAL PRESENTATION Dyspepsia, including; Belching , bloating, distention Fatty food intolerance, fullness, Pain radiating to the back Heartburn Chest discomfort Hematemesis or melena resulting from gastrointestinal bleeding. Melena may be intermittent over several days or multiple episodes in a single day.

18. OTHER POSSIBLE MANIFESTATIONS Rarely, a briskly bleeding ulcer can present as hematochezia. Symptoms consistent with anemia ( e.g , fatigue, dyspnea) Sudden onset of symptoms may indicate perforation. NSAID-induced gastritis or ulcers may be silent, especially in elderly patients. Only 20-25% of patients with symptoms suggestive of peptic ulceration are found on investigation to have a peptic ulcer.

19. Alarm features These warrant prompt gastroenterology referral Bleeding or anemia Early satiety Unexplained weight loss Progressive dysphagia or odynophagia Recurrent vomiting Family history of gastrointestinal cancer

20. PATIENT EDUCATION Patient education should cover the following: nonsteroidal anti-inflammatory drugs (NSAIDs) Aspirin Alcohol Tobacco Caffeine ( eg , coffee, tea, cola) Others include Obesity and weight reduction Stress reduction in individual cases

21. PHYSICAL EXAMINATION In uncomplicated peptic ulcer disease (PUD), the clinical findings may be few, nonspecific and include the following: Epigastric tenderness (usually mild) Right upper quadrant tenderness may suggest a biliary etiology or, less frequently, PUD. Guaiac-positive stool resulting from occult blood loss Melena resulting from acute or subacute gastrointestinal bleeding Succussion splash resulting from partial or complete gastric outlet obstruction Patients with perforated PUD usually present with ; a sudden onset of severe, sharp abdominal pain .

22. PHYSICAL EXAMINATION – con’t Most patients describe generalized pain A few present with severe epigastric pain. Even slight movement can tremendously worsen their pain, these patients assume a fetal position. Abdominal examination usually discloses; generalized tenderness, rebound tenderness, guarding, and rigidity. These patients may also demonstrate signs and symptoms of septic shock tachycardia , hypotension, and anuria These indicators of shock may be absent in elderly or immunocompromised patients or in those with diabetes. Patients should be asked if retching and vomiting occurred before the onset of pain.

23. COMPLICATIONS OF PUD Refractory, symptomatic peptic ulcers Obstruction Perforation Ulcer bleeding - especially in patients with a history of massive hemorrhage and hemodynamic instability Recurrent bleeding on medical therapy Failure of therapeutic endoscopy to control bleeding Gastric malignancy.

24. TREATMENT OF PEPTIC ULCER DISEASE Goals of Therapy: to eradicate H pylori infection to reduce morbidity, and to prevent complications in patients with peptic ulcers

25. Classification of drugs used in peptic ulcer Drugs that inhibit gastric acid secretion Drugs that neutralize gastric acid (Antacids) Ulcer protectives Anti H. pylori drugs

26. TREATMENT OF PEPTIC ULCER DISEASE General Principles : P harmacologic management of acute bleeding from PUD Acid suppression, using histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs). Both classes available in intravenous or oral preparations. Discontinue NSAIDs if clinically feasible. PPI maintenance is recommended to prevent recurrences f or patients who must continue with their NSAIDs, even after eradication of H pylori .

27. TREATMENT OF PEPTIC ULCER DISEASE Principles Cont’d Recommended primary therapy for H pylori infection is proton pump inhibitor (PPI)–based triple therapy Emergency room treatment may include; Antacids or GI cocktail (typically an antacid with an anesthetic such as viscous lidocaine and/or an antispasmodic) for symptomatic therapy H igh risk patients should be t reated with PPIs or H2RAs for 1 year Patients with refractory ulcers may continue receiving once-daily PPI therapy indefinitely

28. EMERGENCY DEPARTMENT CARE Presentations of peptic ulcer disease (PUD) and gastritis usually are indistinguishable Treatment goals in the acute setting are; R elief of discomfort protection of the gastric mucosal barrier to promote healing. Most patients with gastritis or peptic ulcer disease do not require acute interventions.

29. TREATMENT IN THE EMERGENCY DEPARTMENT Antacids or a gastrointestinal (GI) cocktail may be used as symptomatic therapy ( typically an antacid with an anesthetic such as viscous lidocaine and/or an antispasmodic) Empiric treatment of H pylori is not recommended WITHOUT confirmation of infection. Anticholinergic agents are contraindicated.

30. BLEEDING PEPTIC ULCERS Upper GI bleeding is a common medical condition The principles of management equally applicable to both gastric and duodenal ulcers . Endoscopy is indicated for appropriate rapid diagnosis and treatment Endoscopic therapy reduces the likelihood of recurrent bleeding and decreases the need for surgery . Decreases hospital stay

31. MASSIVE BLEEDING MANAGEMENT Difficult complication to treat. Mainstays of resuscitation include the following: Establishment of adequate intravenous (IV) access, and volume replacement, initially with crystalloid If patient hypotensive after 2L , consider blood transfusion. A central venous catheter to monitor such resuscitation may be considered. Airway protection with intubation should be considered in the case of massive bleeding.

32. MASSIVE BLEEDING MANAGEMENT Nasogastric suction helps to keep the stomach empty and contracted. emergent surgical or endoscopic intervention may be required IV PPI has been shown to reduce: mortality in upper GI bleeds reduce the incidence of rebleeding and the need for surgical intervention; Patients with significant or potentially significant hemorrhage require admission, usually to the intensive care unit.

33. ENDOSCOPY Provides an opportunity to visualize the ulcer to determine the degree of active bleeding , to attempt hemostasis by direct measures. Primary endoscopic hemostatic therapy (EHT) is successful in about 90% of patients Medical management usually serves as an adjunct to direct endoscopic therapy.

34. ENDOSCOPIC THERAPY Several Modalities Available; injection therapy coagulation therapy hemostatic clips argon plasma coagulator, and combination therapy. Injection therapy is performed with epinephrine in a 1:10,000 dilution or with absolute alcohol . NOTE: Combination therapy with epinephrine injection followed by thermal coagulation appears to be more effective than monotherapy for ulcers with a visible vessel, active hemorrhage, or adherent clot.

35. LONG TERM MONITORING Maintenance therapy with antisecretory medications ( eg , H2 blockers, PPIs) for 1 year is indicated in high-risk patients . recurrent ulcers and those with complicated or giant ulcers . Patients with refractory ulcers may continue receiving once-daily PPI therapy indefinitely Peptic ulcer rebleeding is extremely rare after H pylori eradication. If H pylori eradication is not achieved despite repeat treatment, maintenance antisecretory therapy should be recommended . NSAID use may cause rebleeding even in patients in whom H pylori has been eradicated

36. ACID SUPPRESION FOR BLEEDING ULCER Mainstay in medical management Reducing gastric acidity believed to improve hemostasis primarily through the decreased activity of pepsin Presents a more alkaline environment. Pepsin believed to antagonize the hemostatic process by degrading fibrin clots. By suppressing acid production and maintaining a pH above 6, pepsin becomes markedly less active. Eradicate H pylori infection in the setting of bleeding peptic ulcers to lower the rate of rebleeding .

37. ACID SUPPRESION FOR BLEEDING ULCER Acute management of an actively bleeding ulcer in hospital setting traditionally requires the use of intravenous PPI or H2RAs. H2RAs have largely been superseded by PPIs in the setting of an actively bleeding duodenal ulcer Many gastroenterologists assert that intravenous PPI therapy maintains hemostasis more effectively than intravenous H2RA. Thus , intravenous H2RA no longer has a role in the management of bleeding peptic ulcers

38. ACID SUPPRESION FOR BLEEDING ULCER Parenteral PPI administration indicated after successful endoscopic therapy for ulcers with high-risk signs, such as active bleeding, visible vessels, and adherent clots. When indicated, intravenous pantoprazole or omeprazole is administered as an 80-mg bolus followed by a continuous 8-mg/h infusion for 72 hours. This treatment is changed to oral PPI therapy after 72 hours if no rebleeding occurs. Esomeprazole 20-40 mg intravenous qDay up to 10 days; switch to PO once patient able to swallow Oral lansoprazole (120-mg bolus, followed by 30 mg every 3 h). A study by Chan et al determined that intravenous, standard-dose omeprazole was inferior to high-dose omeprazole in preventing rebleeding after endoscopic therapy for peptic ulcer bleeding.

39. INTRAVENOUS PPI THERAPY In a study by Andriulli et al, standard-dose PPI infusion was found to be as effective as a high-dose regimen in reducing the risk of recurrent bleeding following endoscopic hemostasis of bleeding ulcers. Many researchers have compared parenteral PPI therapy with placebo, and overall, the results have demonstrated a shorter period of bleeding and a decreased incidence of rebleeding with PPI therapy. a decreased need for emergency surgery and blood transfusion; p ossible mortality reduction from ulcer bleeding

40. Medical Management of NSAID Ulcers According to the American College of Gastroenterology (ACG) guideline all patients who are beginning long-term NSAID therapy should first be tested for H pylori . Discontinue NSAIDS in patients with positive H pylori test results if clinically feasible PPI maintenance is recommended to prevent recurrences even after eradication of H pylori , if NSAID discontinuation is not feasible If NSAIDs must be continued, a cyclooxygenase (COX)-2 selective inhibitor is a better option. Use of a traditional NSAID and once-daily proton pump inhibitor (PPI) is comparable to a selective COX-2 inhibitor with respect to ulcer bleeding in patients with a history of peptic ulcer disease . In general, 6-8 weeks of therapy with a PPI is required for complete healing of a duodenal ulcer.

41. Medical Management of NSAID Ulcers – cont’d Active ulcers associated with NSAID use Discontinue NSAIDs and treat with an appropriate course of PPI therapy For patients with a known history of ulcer and in whom NSAID use is unavoidable Use of lowest possible dose and duration of the NSAID and co-therapy with a PPI or misoprostol are recommended. 2009 ACG guideline recommendation for patients treated with NSAIDs, who also require low-dose aspirin therapy for cardiovascular disease Give naproxen plus misoprostol or a PPI. Patients at moderate risk for gastrointestinal complications and at high risk for cardiovascular disease should avoid NSAIDs or COX-2 inhibitors entirely and receive alternative therapy.

42. PREVENTION OF NSAID-INDUCED ULCERS Primary prevention of NSAID-induced ulcers includes the following: Avoid unnecessary use of NSAIDs Use acetaminophen or nonacetylated salicylates when possible Use the lowest effective dose of an NSAID and switch to less toxic NSAIDs, such as the newer NSAIDs or COX-2 inhibitors, in high-risk patients without cardiovascular disease Consider prophylactic or preventive therapy for the following patients: Patients with NSAID-induced ulcers who require chronic, daily NSAID therapy Patients older than 60 years Patients with a history of peptic ulcer disease (PUD) or a complication such as gastrointestinal bleeding Patients taking concomitant steroids or anticoagulants or patients with significant comorbid medical illnesses

43. PROPHYLACTIC THERAPIES Misoprostol 100-200 mcg PO 4 times per day Omeprazole 20-40 mg PO every day Lansoprazole 15-30 mg PO every day Esomeprazole 20 to 40 mg daily Chan FK, Ching JY, Hung LC, et al, in 2005 study showed that in patients with aspirin-induced ulcer, contrary to popular belief, aspirin plus esomeprazole (Nexium) was superior to clopidogrel (Plavix) in preventing recurrent gastric ulcer bleeding. This was further confirmed in a double-blind randomized study in 2006 by Lai and colleagues. [ 51 ]

44. PROTON PUMP INHIBITER SAFETY AND MONITORING PPIs typically have a very good safety profile Adverse effects: (especially with long-term and/or high-dose therapy) Clostridium difficile infection community-acquired pneumonia hip fracture, and vitamin B12 deficiency decreased absorption of some medications such ketoconazole and iron salt iron deficiency anemia, due to achlorhydria (absence of intragastric acidity) ** ferric form of iron must be converted to the ferrous form by gastric acid**

45. CLOSTRIDIUM DIFFICILE INFECTION Gram (-) rod Associated with gastritis, gastric & duodenal ulcers, gastric adenocarcinoma Transmission route fecal-oral Secretes urease → convert urea to ammonia Produces alkaline environment enabling survival in stomach

46. CLOSTRIDIUM DIFFICILE INFECTION R ecommended primary therapy for H pylori infection is proton pump inhibitor (PPI)–based triple therapy These regimens result in a cure of infection and ulcer healing in approximately 85-90% of cases. Ulcers can recur in the absence of successful H pylori eradication . Dual therapy regimens for H pylori infection, are usually not recommended as first-line therapy Spouses and H pylori –positive family members of H pylori –positive persons should be considered for testing and treatment

47. PPI-based triple therapies for 14-day regimen Omeprazole (Prilosec): 20 mg PO bid or Lansoprazole ( Prevacid ): 30 mg PO bid or Rabeprazole ( Aciphex ): 20 mg PO bid or Esomeprazole (Nexium): 40 mg PO qd Plus Clarithromycin ( Biaxin ): 500 mg PO bid and Amoxicillin ( Amoxil ): 1 g PO bid (Metronidazole for PCN allergic patients)

48. Quadruple therapies for H pylori infection G enerally reserved for patients in whom the standard course of treatment has failed . Quadruple treatment includes the following drugs, administered for 14 days: PPI, standard dose, or ranitidine 150 mg, PO bid Bismuth 525 mg PO qid Metronidazole 500 mg PO qid Tetracycline 500 mg PO qid Eradication rate = 75-90%

49. Tinidazole Based Therapy PPI Amoxicillin 1 g Clarithromycin 500 mg, and tinidazole 500 mg or metronidazole 500 mg twice daily Eradication rate = 90%

50. Levofloxacin Based Triple Therapy PPI amoxicillin 1 g twice daily levofloxacin 500 mg (Levaquin) once daily

51. Sequential Therapy (5 days for each) PPI and amoxicillin 1 g twice daily for 5 days followed by PPI, clarithromycin 500 mg, and tinidazole 500 mg ( Tindamax ) or metronidazole 500 mg twice daily for 5 days Eradication rate = > 84%

52. ROLE OF THE PHARMACIST

53. CASE STUDIES

54. SUMMARY Upper GI endoscopy is the preferred diagnostic test in the evaluation of patients with suspected PUD . Recommend early endoscopy in patients older than 45-50 years and in patients with associated so-called alarm features . PUD can be treated successfully with; cure of H pylori infection and/or avoidance of nonsteroidal anti-inflammatory drugs (NSAIDs), along with appropriate use of antisecretory therapy. In patients with NSAID-associated peptic ulcers, discontinuation of NSAIDs is paramount, if clinically feasible P rostaglandin analog or a PPI regimens are recommended prophylactically to dramatically reduce the risk of NSAID-induced gastric and duodenal ulcers Maintenance therapy with antisecretory medications ( eg , H2 blockers, PPIs) for 1 year is indicated in high-risk patients

55. MEDICATIONS

56. H2 ANTAGONISTS Mechanism of action Competitively block H2 receptors on parietal cell & inhibit gastric acid production Supress secretion of acid in all phases but mainly nocturnal acid secretion Also reduce acid secretion stimulated by Ach, gastrin, food, etc.

57. H2RA Pharmacokinetics Absorption is not interfered by food Can cross placental barrier and reaches milk, Poor CNS penetration The serum half-lives range from 1.1 to 4 hours Cleared by a combination of hepatic metabolism, glomerular filtration, and renal tubular secretion. Dose reduction needed in moderate to severe renal insufficiency

58. H2 antagonists - Uses Promote the healing of gastric and duodenal ulcers Duodenal ulcer – 70 to 90% at 8 weeks Gastric Ulcer – 50 to 75% NSAID ulcers induced ulcers Stress ulcer and gastritis GERD Zollinger -Ellison syndrome Prophylaxis of aspiration pneumonia

59. H2RA Adverse effects Headache Dizziness, bowel upset, dry mouth CNS: Confusion, restlessness Bolus IV – release histamine – bradycardia, arrhythmia, cardiac arrest Cimetidine has antiandrogenic actions

60. H2RA Drug interactions Cimetidine inhibits several CYP-450 isoenzymes and reduces hepatic blood flow, so inhibits metabolism of many drugs like theophylline, metronidazole, phenytoin, imipramine etc. Antacids reduce the absorption of all H2 blockers

61. Proton Pump Inhibitors Most effective drugs in antiulcer therapy Prodrugs requiring activation in acid environment Activated forms binds irreversibly to H+K+ATPase and inhibit it Available options: Omeprazole Pantoprazole Lansoprazole Esomeprazole Rebeprazole

62. PPI - Mechanism of Action Prodrugs inactive at neutral pH At pH < 5 rearranges to two charged cationic forms ( sulfenamide + sulphenic acid) that bind covalently with SH groups of H⁺K⁺ ATPase and inactivate it irreversibly Also inhibits gastric mucosal carbonic anhydrase

63. Pharmacokinetics - PPI Available as enteric coated tablets They should be given 30 minutes to 1 hour before food intake half life is very short and only 1-2 Hours BUT the action persists for 24 Hours to 48 hours after a single dose Action lasts for 3-4days even after stoppage of the drug

64. PPI – Therapeutic uses Gastroesophageal reflux disease (GERD) Peptic Ulcer - Gastric and duodenal ulcers Bleeding peptic Ulcer Zollinger Ellison Syndrome Prevention of recurrence of nonsteroidal antiinflammatory drug (NSAID) - associated gastric ulcers in patients who continue NSAID use. Reducing the risk of duodenal ulcer recurrence associated with H. pylori infections Aspiration Pneumonia

65. PPI - Adverse Effects Common Nausea, loose stools, headache abdominal pain, constipation Muscle & joint pain, dizziness, rashes Rare Adverse Effects Gynaecomastia , erectile dysfunction Leucopenia and hepatic dysfunction Osteoporosis in elderly on prolonged use Hypergastrinemia

66. Drug interactions Drug interactions Omeprazole inhibits the metabolism of warfarin, phenytoin, diazepam, and cyclosporine. However, drug interactions are not a problem with the other PPIs .

67. Proton Pump Inhibitors Lansoprazole: Partly reversible, more potent, slightly more against H pylori, Higher BA, rapid onset.  Pantoprazole More acid stable, I.V, CYP450 less affinity Rabeprazole : claimed to be most rapid Esomeprazole Better intragastric pH and higher healing rates.

68. Prostaglandin analogues - Misoprostol Inhibit gastric acid secretion Enhance local production of mucus or bicarbonate Help to maintain mucosal blood Therapeutic use: Prevention of NSAID-induced mucosal injury (rarely used because it needs frequent administration – 4 times daily)

69. Misoprostol Doses: 200 mcg 4 times a day ADRs: Diarrhoea and abdominal cramps Uterine bleeding Abortion Exacerbation of inflammatory bowel disease and should be avoided in patients with this disorder Contraindications: Inflammatory bowel disease Pregnancy (may cause abortion)

70. Antacids Weak bases that neutralize acid Also inhibit formation of pepsin (As pepsinogen converted to pepsin at acidic pH) Acid Neutralizing Capacity: Potency of Antacids Expressed in terms of Number of mEq of 1N HCl that are brought down to pH 3.5 in 15 minutes by unit dose of a preparation (1 gm)

71. Systemic antacids Sodium Bicarbonate: Potent neutralizing capacity and acts instantly 1 gm = 12 mEq DEMERITS: Systemic alkalosis, Distension, discomfort and belching – CO2 Rebound acidity Sodium overload

72. Non systemic antacids Insoluble and poorly absorbed basic compounds React in stomach to form corresponding chloride salt The chloride salt again reacts with the intestinal HCO3-so that HCO3- is not spared for absorption

73. Non systemic Antacids Magnesium hydroxide Aqueos suspension is called Milk of magnesia Magnesium trisilicate Aluminium Hydroxide ( Magaldrate ) – hydrated hydroxy magnesium aluminate)

74. Non systemic antacids Duration of action : 30 min when taken in empty stomach and 2 hrs when taken after a meal Adverse effects: Aluminium antacids – constipation (As they relax gastric smooth muscle & delay gastric emptying) – also hypophosphatemia and osteomalcia Mg2+ antacids – Osmotic diarrhoea In renal failure Al3+ antacid – Aluminium toxicity & Encephalopathy

75. Miscellaneous drugs Simethicone : Decrease surface tension thereby reduce bubble formation - added to prevent reflux Alginates: Form a layer of foam on top of gastric contents & reduce reflux Oxethazaine : Surface anaesthetic

76. Drug interactions By raising gastric pH & forming insoluble complexes ↓ absorption of many drugs Tetracyclines iron salts, H2 Blockers, diazepam , phenytoin , isoniazid , ethambutol

77. Sucralfate – ulcer protective Aluminium salt of sulfated sucrose MOA: In acidic environment ( pH <4) it polymerises by cross linking molecules to form sticky viscous gel that adheres to ulcer crater - more on duodenal ulcer Astringent action and acts as physical barrier Dietary proteins get deposited on this layer forming another coat

78. Sucralfate – contd. Concurrent antacids avoided, (as it needs acid for activation) Uses: Prophylaxis of Stress ulcers Bile reflux gastritis Topically – burn, bedsore ulcers, excoriated skins Dose: 1 gm 1 Hr before 3 major meals and at bed time for 4-8 weeks ADRs: Constipation, hypophosphatemia Drug interactions : adsorbs many drugs and interferes with their absorption

79. Colloidal Bismuth Subcitrate (CBS) Mechanism of action CBS and mucous form glycoprotein bi complex which coats ulcer crater ↑ secretion of mucous and bicarbonate, through stimulation of mucosal PGE production Detaches H.pylori from surface of mucosa and directly kills them

80. Colloidal Bismuth subcitrate Dose: 120 mg 4 times a day Adverse effects blackening of tongue, stools, dentures Prolonged use may cause osteodystrophy and encephalopathy Diarrhoea , headache, dizziness

81. REFERENCES Please see Notes section below