Peptic ulcer disease

Peptic ulcer disease
Pharmacotherapeutics I
Common GI disorder
M.Pharmacy
Pharmacy practice
1st Year

1. Peptic ulcer disease PRESENTED BY: LINCY ASHA.S M.PHARM 1 ST YEAR PHARMACY PRACTICE

2. DEFINITION The term ‘peptic ulcer’ describes a condition in which there is a discontinuity in the entire thickness of the gastric or duodenal mucosa that persists as a result of acid and pepsin in the gastric juice. Peptic ulcer disease differs from gastritis and erosions in that ulcers typically extends through the muscularis mucosa into the deeper layers of the submucosa. It is one of the common gastrointestinal disorders in clinical practice. Gastric acid is a critical component of upper gastrointestinal tract Complications including gastritis, erosions and peptic ulcer.

3. TYPES OF PEPTIC ULCER ACUTE PEPTIC ULCER 1.CUSHING ULCER Gastric, duodenal or esophageal ulcer arising in patients with intracranial injury or operations. 2.CURLING ULCER It occurs mostly in the proximal duodenum and associated with severe burns and trauma . CHRONIC PEPTIC ULCER 1.GASTRIC ULCER It is a sore that is on the inside of the stomach . 2.DUODENAL ULCER The peptic ulcer having a sore on the upper part of small intestine 3.ESOPHAGEAL ULCER Open sores or lesions in the lining of esophagus . 4.BLEEDING ULCER Internal bleeding is caused by a peptic ulcer which has been left untreated. Most dangerous type of ulcer. 5.REFRACTORY ULCER These are peptic ulcers that have not healed after at least 3 months of treatment.

4. COMMON FORMS OF ULCER GASTRIC ULCER DUODENAL ULCER Develop in the stomach region Develop in the duodenal region Pain increases while eating a meal due to the physical presence of food and hydrochloric acid production stimulated by the process of eating. Pain decreases while eating a meal. Pain will start after 1-3 hours of eating food. Pain relieved by vomiting Pain relieved by meal

5. ETIOLOGY: Helicobacter pylori H. pylori are spiral, microaerophilic, gram-negative bacteria with flagella that has urease, catalase and oxidase activity. These factors allow the bacterium to survive in the acidic environment of the stomach. 95% or more of duodenal ulcers and 80-85% of gastric ulcers are associated with H. pylori. Mode of transmission: Primarily transmitted via person to person by either gastro-oral (vomitus) or fecal-oral ( diarrhoea ) contact. Risk factors for acquiring H. pylori: close contact within households, low socioeconomic status.

6. 2. Nonsteroidal Anti-Inflammatory Drugs Non-steroidal anti inflammatory drugs such as aspirin, naproxen, ibuprofen can irritate or inflame the lining of stomach and small intestine. Even safety coated aspirin and aspirin in powdered form can frequently cause ulcers. NSAID-induced ulcer have been found to increase with geriatric population, previous history of peptic ulceration and the first three months of NSAID treatment. Risk factors for NSAID ulcers: Age greater than 65 years Previous peptic ulceration/bleeding High dose of NSAID or more than one NSAID (including aspirin) Short-term history of NSAID use (<1 month) Concomitant corticosteroid or anticoagulant use Cardiovascular disease

7. 3.Stress People with ulcers often report that emotional stress increases ulcer pain. Physical stress may increase the risk of developing ulcers, particularly in the stomach. Eg. People with injuries such as severe burns and people undergoing major surgery often require treatment to prevent ulcers. 4.Acid Hydrochloric acid is secreted by the parietal cells of the gastric glands. Tumors of parietal cells of stomach increases acid output leading to ulceration. 5.Smoking People who regularly smoke tobacco are more likely to develop peptic ulcers compared to non-smokers. Cigarette smoking impairs ulcer healing, promotes ulcer recurrence and increases ulcer risk.

8. 6.Alcohol consumption Regular heavy drinkers of alcohol have a higher risk of developing peptic ulcers where the defense mechanism is weakened. In normal person, the defense mechanism is adequate, no ulcer develops. 7.Genetics A significant number of individuals with peptic ulcers have close relatives with the same problem, suggesting that genetic factors may also be involved. The genetic disorder Zollinger-Ellison syndrome is a rare disorder in which tumors secrete large amounts of the hormone gastrin. This hormone causes the stomach to produce excess acid which attack the lining of the stomach and cause ulcers. 8.Dietary factors Carbonated beverages, coffee, tea, beer, milk and spices often cause dyspepsia, but they do not appear to increase the risk of PUD. Caffeine is a gastric acid stimulant, beer, wine, carbonated beverages increases gastric acid secretion.

9. EPIDEMIOLOGY Peptic ulcer disease is a global problem with a lifetime risk of development ranging from 5% to 10%. Duodenal ulcers are four times more common than gastric ulcers. Also, duodenal ulcers are more common in men than in the woman. Gastric ulcers occur mostly in the lesser curvature of the stomach. They are benign, sometimes develop as tumors (5%). The global prevalence of H. pylori is greater than 50%. Helicobacter pylori is sometimes associated with socioeconomic status and poor hygiene. In developed countries, percentage of NSAID induced ulcer has increased and prevalence of H.pylori has declined. Mortality rates are higher among those older than or 65 years and in males compared to females. Peptic ulcer disease death in India reached to 1.20% of total death. India ranks 5 th in the world.

10. PATHOPHYSIOLOGY LAYERS OF GIT: There are 4 layers 1. Mucosa Epithelial layer Lamina propria Muscularis mucosa 2. Submucosa 3. Muscularis Circular Longitudinal Oblique 4. Serosa

11. Ulcer develops when there is an imbalance between the aggressive and defensive factors . Aggressive factors Defensive factors HCl Bicarbonates Pepsin Mucus Gastrin In physiological state there is a balance between these 2 factors so no ulcer develops.

12. HELICOBACTER PYLORI INDUCED ULCER H.Pylori Produces enzyme urease Produces enzyme catalase Adhesion molecules It splits urea into ammonia It inactivates neutrophil action leads to sticking of H.pylori to the surface of GIT Release of ammonia neutralize the acidic environment in the Stomach Ammonia is toxic to the mucosa Release of inflammatory mediators Damage mucosa of GIT ulcer formation

13. NSAID-INDUCED ULCER

14. SIGNS AND SYMPTOMS: Epigastric pain Heartburn Weight loss Nausea/vomiting Melena (Black, tarry stool) Hematochezia (Red bloody stool) Anemia Indigestion (Dyspepsia) B loating (feeling of fullness) B elching (Burping) Intolerance to fatty foods Anorexia (fear of gaining weight)

15. COMPLICATIONS 1.GASTROINTESTINAL BLEEDING It is the most common complication. Sudden large bleeding can be life-threatening. It occurs when the ulcer erodes one of the blood vessels such as the gastroduodenal artery. 2.PERFORATION A hole in the wall of the GIT often leads to catastrophic consequences if left untreated. 3.PENETRATION The ulcer may penetrate into an adjacent structure (pancreas, liver or biliary tract). 4.GASTRIC OUTLET OBSTRUCTION It is the narrowing of pyloric canal by scarring and swelling of gastric antrum and duodenum due to peptic ulcers. 5. GASTRIC CANCER Helicobacter pylori as the etiological factor make it 3 to 6 times more likely to develop stomach cancer from the ulcer.

16. DIAGNOSTIC TESTS 1 . Physical examination and recording of patient’s history. 2 . Culture of biopsy 3,Polymerase chain reaction – H.pylori DNA detected in gastric tissue. 4.Histology H,pylori can be seen in hematoxylin & eosin staining. 5.Urea breath test During the test, a special substance that has urea is swallowed. If H.pylori are present, the bacteria convert the urea into CO2, which is detected and recorded in the exhaled breath after 10 minutes. Use of antibiotics, bismuth medicines and proton pump inhibitors should be stopped 2 weeks before the test.

17. 6.Rapid urease test H.pylori in the biopsy specimen splits the urea to ammonia in the test container. Elevation of pH by ammonium hydroxide are detected as color change of pH indicator. 7.Blood tests Blood tests are used to measure antibodies to H.pylori It can only detect H.pylori antibodies and cannot be used to see if the infection has been cured after treatment. 8.Stool test It can detect traces of H.pylori in the feces . This test can be used to diagnose the infection and confirm that it has been cured after treatment.

18. 9.Radiology (Barium swallow) It examines the organs of the upper part of the digestive system: the esophagus , stomach and duodenum. Fluid called Barium is swallowed , a liquid used to coat the inside of organs so that they will show up on an X-ray. X-rays are then taken to evaluate an ulcer, scar tissue or a blockage. 10.Endoscopy It is the most accurate diagnostic test for PUD. It involves inserting a small, lighted tube (endoscope) through the throat and into the stomach to look for abnormalities. Endoscopies are performed if the patient has symptoms such as weight loss, vomiting, black stools, anemia and swallowing difficulties. 11.Endoscopic biopsy During the endoscopy, a piece of stomach tissue is removed , so that it can later be analysed for exact cause of peptic ulcer development. This type of test is typically used for older people, or those that have experienced weight loss or bleeding.

19. PHYSIOLOGY OF ACID RELEASE

20. RECEPTORS ON THE PARIETAL CELL M3 – Muscarinic acetylcholine M3 receptor CCK2 – Cholecystokinin 2 receptor H2 – Histamine type 2 receptors EP3 – Prostaglandin receptor TARGETED APPROACHES 1.Reduce HCl secretion – H2 receptor antagonist, Proton pump inhibitors, Anticholinergics, Prostaglandin analogues 2.HCl Neutralization - Antacids 3.Mucous protectives 4.Ulcer healing 5.Anti-H.pylori drugs

21. Drug Regimens Used to Eradicate Helicobacter pylori Regimen Duration Drug #1 Drug #2 Drug #3 Drug #4 Proton Pump Inhibitor- Based Triple Therapy 14 days PPl once or twice daily Clarithromycin 500 mg twice daily Amoxicillin 1g twice daily or metronidazole 500 mg twice daily Bismuth Quadruple Therapy 10-14 days PPl or H2RA once or twice daily Bismuth subsalicylate 525 mg four times daily Metronidazole 250-500 mg four times daily Tetracycline 500 mg four times daily Non-Bismuth Quadruple or "Concomitant“ Therapy 10-14 days PPl once or twice daily on days 1-10 Clarithromycin 250-500 mg twice daily on days 1-10 Amoxicillin 1g twice daily on days 1-10 Metronidazole 250-500 mg twice daily on days 1-10 Sequential Therapy 10 days PPI once or twice daily on days 1-10 Amoxicillin 1g twice daily on days 1-5 Metronidazole 250-500 mg twice daily on days 6-10 Clarithromycin 250-500 mg twice daily on days 6-10

22. Regimen Duration Drug #1 Drug #2 Drug #3 Drug #4 Hybrid Therapy 14 days PPl once or twice daily on days 1-14 Amoxicillin 1 g twice daily on days 1-14 Metronidazole 250-500 mg twice daily on days 7-14 Clarithromycin 250-500 mg twice daily on days 7-14 Levofloxacin triple 10-14 days PPl twice daily Levofloxacin 500 mg daily Amoxicillin 1 g twice daily Levofloxacin Sequential 10 days PPI twice daily on days 1-10 Amoxicillin 1g twice daily on days 1-10 Levofloxacin 500 mg once daily on days 6-10 Metronidazole 500 mg twice daily on days 6-10 LOAD 7-10 days Levofloxacin 250 mg once daily Omeprazole (or other PPI) at high dose once daily Nitazoxanide 500 mg twice daily Doxycycline 100 mg once daily

23. DRUG DOSING CATEGORY DRUG INITIAL DOSE USUAL RANGE ADVERSE EFFECT Proton pump inhibitors Omeprazole 40 mg daily 20-40 mg/day Diarrhoea, headache, abdominal pain, nausea, fatigue, dizziness Lansoprazole 30 mg daily 15-30 mg/day Rabeprazole 20 mg daily 20-40 mg/day Pantoprazole 40 mg daily 40-80 mg/day Esomeprazole 40 mg daily 20-40 mg/day Dexlansoprazole 30-60 mg daily 30-60 mg/day H2-Receptor Antagonists Cimetidine 300 mg four times daily, 400 mg twice daily, or 800 mg at bedtime 800-1,600 mg/day in divided doses Diarrhoea, headache, abdominal pain, confusion Famotidine 20 mg twice daily, or 40 mg at bedtime 20-40 mg/day Nizatidine 150 mg twice daily, or 300 mg at bedtime 150-300 mg/day Ranitidine 150 mg twice daily, or 300 mg at bedtime 150-300 mg/day

24. CATEGORY DRUG INITIAL DOSE USUAL RANGE ADVERSE EFFECT Mucosal Protectants Sucralfate 1g four times daily, or 2g twice daily 2-4 g/day Constipation Misoprostol 100-200 mcg four times daily 400-800 mcg/day Diarrhoea, abdominal pain, headache, flatulence, nausea/vomiting

25. SURGERY In very rare cases, a complicated stomach ulcer will require surgery, especially people who do not respond to medication or who develop complications . 1. Vagotomy It involves cutting the vagus nerve to interrupt messages sent from the brain to the stomach to reduce acid secretion. 2. Antrectomy It involves the removing of lower part of the stomach (antrum ) which produces a hormone that stimulates the stomach to secrete digestive juices 3. Pyloroplasty It is an elective surgical procedure in which the lower portion of stomach, the pylorus, cut and resutured to relax the muscle and widen the opening into small intestine, enabling contents to pass more freely from the stomach.

26. 4.Gastrectomy To treat stomach cancer Gastrectomy is surgery to remove part or all of the stomach If the whole stomach is removed, it is called total gastrectomy If only part of the stomach is removed, it is called partial gastrectomy or subtotal gastrectomy Remainder must be reattached to the rest of the bowel – Billroth I Billroth II 5.Billroth I Distal portion of the stomach is removed. The remainder is anastomosed t o the duodenum . 6.Billroth II The lower portion of the stomach is removed and the remainder is anastomosed to the jejunum

27. TREATMENT ALGORITHM

28. NON PHARMACOLOGICAL TREATMENT Stress reduction and smoking cessation , should be implemented in patients with PUD. Patients should be advised to reduce alcohol consumption and NSAID use if possible. Patients should avoid foods and beverages ( eg , spicy foods, caffeine and alcohol ) that cause dyspepsia or that exacerbate ulcer symptoms. Avoid fasting and maintain optimum gap between meals. Avoid heavy meals . Night feeds should be avoided. Edible vegetable oils, ghee and butter taken as such may be helpful, as these have an inhibitory effect on gastric acid secretion. Should drink plenty of water . Bed rest promotes ulcer healing. Hands must be thoroughly washed after using the bathroom and before eating or preparing food.

29. REFERENCES 1.Pharmacotherapy- A pathophysiologic approach by Joseph T.DiPiro , Gary C.Yee , L.Michael Posey, Stuart T.Haines , Thomas D.Nolin , Vicki Ellingrod - 11 th Edition. 2.Clinical pharmacy and Therapeutics edited by Roger Walker and Cate Whittlesea - 5 th Edition 3.Pharmacotherapy principles & practice by Marie A.Chisholm -Burns, Terry L.Schwinghammer , Patrick M.Malone , Jill M.Kolesar , Kelly C.Lee , P.Brandon Bookstaver – 5 th edition. 4. https://www.ncbi.nlm.nih.gov/books/NBK534792/ 5. https://youtu.be/c0KZk985PKE 6. https://pubmed.ncbi.nlm.nih.gov/12607319/ 7. https://youtu.be/DEOu8YXz5Jo 8. https://youtu.be/BQVzqJm30YA 9. https://youtu.be/a_4Y24IyLkE 10. https://medlineplus.gov/ency/article/007501.htm 11. https://www.healthline.com/health/peptic-ulcer

30. Thank you