Acid peptic disorders
- 1. Presented by Dr Subhayan Das 1st year Pharmacology PGT. Midnapore Medical College,Dated:18.09.2019
- 2. Acid Peptic Disorders are a result of distinctive, but overlapping pathogenic mechanisms leading to either excessive acid secretion or diminished mucosal defence. Peptic Ulcer ( gastric and duodenal ulcer),Gastroesophageal reflux disease(GERD) and stress related mucous injuries are the most common acid peptic disorders encountered in day to day practice.
- 4. H pylori Infection Drugs like NSAIDS(Non Steroidal Anti- inflammatory drugs) Lifestyle factors such as Smoking, Alcohol Use, Caffeine etc. Severe Physiological Stress: burns, Central Nervous System (CNS) trauma, surgery , sepsis, serious systemic illness , multiple traumatic injuries increases the risk of secondary(stress) ulceration.
- 5. Hypersecretory states (uncommon): Gastrinoma (Zollinger -Ellison Syndrome)or multiple endocrine neoplasia type I(MEN-I), Antral G cell hyperplasia , Systemic mastocytosis ,Basophilic leukaemia , Cystic Fibrosis, Short bowel syndrome, Hyperparathyroidism . Physiological factors: Increased Basal Acid Output(BAO), accelerated gastric emptying , seasonal changes and climatic extremes etc.
- 6. Genetic factors: Weak associations have been observed between duodenal ulcers and Blood group O.A rare genetic association exist between familial hyperpepsinogenemia and duodenal ulcers. Additional etiological factors: Allergic gastritis ,Corrosive gastropathy , Uremic gastropathy, Henoch-Scholein gastritis ,Crohn disease etc may be associated with peptic ulcer disease.
- 8. Enterochromaffin like cells(ECL) are the major source of gastric histamine release needed for acid secretion and that histamine has a obligatory role to play , as a final chemo stimulator in all modes of acid secretion. The acidic ph<2 within the stomach cleaves pepsinogen into an active pepsin , the former being synthesised by chief cells found primarily in the gastric fundus . Too much of pepsin activity erodes gastric mucosa , to form peptic ulcer. PGE2 produced by gastric mucosa ,inhibits acid secretion by inhibiting cAMP formation , enhances mucosal blood flow and stimulates secretion of mucus and bicarbonate.
- 10. PUD affect the quality of life and productivity of affected patients . It is an cause of morbidity and mortality. The global incidence and prevalence of peptic ulcer disease ,along with the associated rates of hospitalizations and mortality have been in decline over the past couple of decades. Predominantly seen in males. Spain had the highest incidence of all peptic ulcer disease whereas the United Kingdom has the lowest.
- 11. Epigastric pain is the most common symptoms of gastric and duodenal ulcers. Pain characterised by gnawing or burning sensation and occurs after meals –classically , shortly after meals with gastric ulcer and 2- 3hrs afterward with duodenal ulcer. Duodenal ulcer pain often awakens the patient at night. Pain with radiation to the back is suggestive of a posterior penetrating gastric ulcer complicated by pancreatitis.
- 12. Dyspepsia, including belching ,bloating ,distension ,and fatty food intolerance . Heartburn Chest discomfort Hematemesis or melena resulting from gastrointestinal bleeding Symptoms consistent with anaemia, fatigue, dyspepsia may be present NSAIDS induced gastritis may be silent ,especially in elderly people. Only 20-25% of patients with symptoms suggestive of peptic ulceration are found on investigation to have a peptic ulcer.
- 13. Epigastric tenderness ( usually mild) . Right upper quadrant tenderness may suggest a biliary aetiology or, less frequently a peptic ulcer disease. Succussion splash resulting from partial or complete gastric outlet obstruction Patients with perforated peptic ulcer usually present with a sudden onset of severe sharp abdominal pain and with demonstrable signs and symptoms of septic shock such as tachycardia, hypotension and anuria .
- 14. Complete Blood Count (CBC). Liver function tests(LFT). Serum amylase and serum lipase Upper GI endoscopy Testing for H pylori infection which includes a rapid urease test, faecal antigen tests , urea breath tests, histopathology and culture. A chest radiography in case a perforation is suspected.
- 15. ACG guidelines include the following recommendations for testing for H pylori All patients with active or past history of peptic ulcer disease, low grade Mucosa associated lymphoid tissue (MALT) lymphoma , or a history of endoscopic resection of early gastric cancer. Patients with dyspepsia who are undergoing upper endoscopy (gastric biopsy specimens) Patients with long term ,low dose aspirin. Patients initiating long term therapy with NSAIDS. Patients with unexplained iron deficiency anaemia following standard workup. Adults with idiopathic thrombocytopenic purpura.
- 16. Non Pharmacological managements/Life style modifications Acid Suppression Treatment for H pylori infection Management of bleeding peptic ulcers. Management of NSAIDS induced peptic ulcers.
- 17. Cessation of smoking, alcohol intake, tobacco. Avoidance of spicy fatty foods. Small frequent meals Avoidance of stress Avoid unnecessary use of NSAIDS.
- 18. I) Drugs reducing gastric acid secretion: A) H2 receptor Antagonists Cimetidine , Ranitidine, Famotidine , Nizatidine , Roxatidine , Loxatidine . B) Proton Pump Inhibitors Omeprazole , Lansoprazole , Deslansoprazole , Pantoprazole , Rabeprazole , Esomeprazole . C) Anticholinergics Propantheline , Oxyphenonium , Pirenzipine , Telenzipine D) Prostaglandin analogues Misoprostol , Enprostil , Rioprostil .
- 19. II) Drugs which Neutralise Gastric Acid( Antacids) A) Systemic Antacids Sodium bicarbonate B) Non systemic Antacids i) Buffer Type Aluminium hydroxide, Magnesium trisilicate , Magaldrate . ii) Non Buffer Type Magnesium hydroxide, Calcium Carbonate. iii) Miscellaneous Alginates, Semethicone . III) Mucosal Protective Agents: Sucralfate , Colloidal Bismuth Subcitrate , Ranitidine Bismuth citrate. IV)Ulcer healing agents: Carbenoxolone V) Anti-Helicobacter Pylori drugs: Amoxicillin, Clarithromycin , Tetracycline, Metronidazole , Ranitidine bismuth citrate, Bismuth subsalicylate and Proton-pump inhibitors( combinations).
- 20. Examples of H2RAs include ranitidine , cimetidine , famotidine and nizatidine . Examples of Proton pump inhibitors include omeprazole , pantoprazole , lansoprazole and rabeprazole . Intravenous PPI therapy maintains haemostasis more effectively than intravenous H2RA in a case of active bleeding duodenal ulcer. Two classes of acid suppressing medications ,available in both intravenous and oral preparations are histamine-2 receptor antagonists (H2RAs) and PPIs. Reducing gastric acidity is believed to improve homeostasis primarily through the decreased activity of pepsin in the presence of a more alkaline environment. Hence , use of H2RA has been largely superseded by the use of PPI Attention must be focussed on adverse effects following long term use of PPI such as Vitamin B12 deficiency, increased chances of hip fractures etc.
- 21. TRIPLE THERAPY (14days) 1) Bismuth Subsalicylate 2tab(525mg) QID + Metronidazole 250mg QID + Tetracycline 500mg QID. 2) Ranitidine Bismuth Citrate 400mg BID +Tetracycline 500mg BID + Metronidazole 500mg BID or Clarithromycin 500mg BID. 3) Omeprazole (or Lansoprazole) 20mg (30mg) BID + Clarithromycin 500mg BID + Amoxicillin 1gm BID or Metronidazole 500mg BID.
- 22. QUADRUPLE THERAPY(14 days) Tab Omeprazole(or Lansoprazole) 20mg(30 mg) OD + Bismuth subsalicylate 2tab 525 mg QID + Metronidazole 250mg QID+ Tetracycline 500mg QID. After completion of any therapy, treatment with PPIs (once daily) is continued for another 4-6 weeks to promote ulcer healing.
- 23. HPI management regimen should take into account any previous antibiotic exposure. 10-14days of bismuth quadruple therapy is strongly recommended for particularly those with previous macrolide exposure or penicillin allergic pts. 14 days of Clarithromycin triple therapy should be reserved for patients with no previous history of macrolide exposure and in regions with low clarithromycin resistance. (Suggested option) 5-7 days of sequential therapy with PPI and amoxicillin ,followed by 5-7 days with clarithromycin , PPI and nitroimidazole (conditional recommendation) (Suggested option) 10-14 days of Levofloxacin triple therapy (levofloxacin , a PPI and amoxicillin)(conditional recommendation).
- 24. Salvage treatment if 1st line treatment fails and HPI persists include the following options Avoid previously used antibiotics ,if feasible (strong recommendation) Preferred for patients who previously received first line clarithromycin regimens Bismuth quadruple therapy or levofloxacin salvage regimens(conditional recommendation). Preferred for patients who previously received first line bismuth quadruple therapy Clarithromycin or levofloxacin containing salvage regimens(conditional recommendation).
- 25. The principles of management of bleeding peptic ulcer outlined below are equally applicable to both gastric and duodenal ulcers. Endoscopic evaluation of the bleeding ulcer can decrease the duration of hospital stay by identifying patients at low risk for rebleeding. Endoscopic therapy reduces the likelihood of recurrent bleeding and decreases the need of surgery. High risk stigmata seen in initial endoscopic examinations are : Active haemorrhage(90% risk of rebleeding ), A visible vessel (50% risk of rebleeding and a fresh overlying clot (30 % risk of rebleeding ). Several modalities of endoscopic therapy available such as injection therapy(epinephrine in a 1.10000 dilution or with absolute alcohol), coagulation therapy , haemostatic clips, argon plasma coagulator , and a combination therapy.
- 26. With the success of medical therapy, surgery has a very limited role in the management of peptic ulcer disease. In general 5% of bleeding ulcers eventually require surgical management. The appropriate surgical procedure depends on the location and nature of ulcer. Surgical procedures include Vagotomy + antrectomy ( bilroth I gastroduodenostomy , bilroth II gastrojejunostomy (recurrence rate :1%, complications: highest, Vagotomy and pyloroplasty ( recurrence rate 10%, complication rate : intermediate), Parietal cell ( proximal gastric super selective vagotomy (recurrence rate >10 %, complication : lowest).
- 27. Refractory symptomatic peptic ulcers. Perforation GI bleeding Penetration leading to formation of gastro colic fistula. Gastric malignancy( Gastric ulcers, H pylori infections are potential risk factors).
- 28. According to ACG guidelines, all patients who are beginning long term NSAID therapy should first be tested for H pylori. NSAIDS should be immediately discontinued in patients with positive H pylori tests if clinically feasible. For patients who must continue with their NSAIDS, PPI maintenance therapy is recommended to prevent recurrences even after eradication of H pylori. Active ulcers associated with NSAID use are treated with appropriate course of PPI therapy (6-8 weeks) and the cessation of NSAIDS. Patients at moderate risk of gastrointestinal complications and at high risk of cardiovascular diseases should avoid NSAIDs or COX2 inhibitors completely and should receive alternate therapy.
- 30. Gastroesophageal reflux is a normal physiologic phenomenon experienced intermittently by most people, particularly after a meal. Gastroesophageal reflux disease occurs when the amount of gastric juice that refluxes into the oesophagus exceeds the normal limit, causing symptoms with or without associated oesophageal mucosal injury( i.e. Oesophagitis ). When the endogenous defence mechanisms such as actions of lower oesophageal sphincter and normal oesophageal motility are defective or overwhelmed so that the oesophagus is bathed in acid or bile and acid containing fluid for prolonged periods, GERD can said to be exist.
- 31. Heartburn Regurgitation Dysphagia Abnormal reflux can cause atypical (extra oesophageal) symptoms such as Coughing and/ or wheezing Hoarseness, sore throat Otitis media Non cardiac chest pain Enamel erosions or other dental manifestations.
- 32. The following studies are used to evaluate patients with suspected gastroesophageal reflux disease: Upper gastrointestinal endoscopy/ oesophagogastroduodenoscopy : Mandatory. Oesophageal manometry : Mandatory. Ambulatory 24hr pH monitoring: Criterion standard in establishing a diagnosis of gastroesophageal reflux disease.
- 33. Losing weight( if overweight) Avoiding alcohol, chocolate , citrus juice, and tomato- based products. Avoiding peppermint , coffee , and possibly the onion family. Eating small frequent meals rather than large meals. Waiting 3 hours after a meal to lie down. Refraining from ingesting food ( except liquids) within 3 hours of bed time. Elevating the head of the bed by 8 inches. Avoiding bending or stooping position.
- 34. The following medications are used in the management of gastro oesophageal reflux disease: H2 receptor antagonists: ranitidine, cimetidine, famotidine, nizatidine. Proton pump inhibitors: Omeprazole, lansoprazole, rabeprazole, esomeprazole , pantoprazole. Prokinetic agents : Metoclopramide . Antacids: Aluminium hydroxide, Magnesium hydroxide.
- 35. Transthoracic and transabdominal fundoplications are performed for GERD , including partial ( anterior or posterior) and circumferential wraps. Open and laparoscopic technique may be used. Placement of a device to augment the lower oesophageal sphincter may be another surgical option. Indications for fundoplication include the following i ) Patients with symptoms not well controlled by PPI. ii) Patients with well controlled reflux disease who desire definitive one time treatment iii) Barrett oesophagus iv)young patients v) Poor pt compliance with medications.
- 36. Immaturity in lower oesophageal function manifested by transient lower oesophageal relaxations. Signs and symptoms: Typical or atypical cry/irritability, poor appetite, weight loss, vomiting, abdominal or chest pain, recurrent pneumonitis , chronic cough, significant dental problems Mostly clinical diagnosis Nonpharmacotherapy management: Providing small frequent meals, Upright positioning after feeding. Pharmacotherapy: Antacids: Aluminium hydroxide, H2 antagonists: Ranitidine, PPIs: Lansoprazole.
- 37. PUD affects quality of life and productivity of affected patients. H pylori infection and NSAID use are the two important causal factors for peptic ulcer diseases. Life style modification along with pharmacotherapy can help the patients to lead a better life with the disease.