peptic ulcer masters 2024.pdf

Peptic Ulcer Part I Pathophysiology of Peptic Ulcer Dr. Omaima Ahmedy  Definition 🞭 It is a condition in which there is a discontinuity in the entire thickness of the gastric duodenal mucosa that persist as a resul...

Peptic Ulcer Part I Pathophysiology of Peptic Ulcer Dr. Omaima Ahmedy  Definition 🞭 It is a condition in which there is a discontinuity in the entire thickness of the gastric duodenal mucosa that persist as a result of acid & pepsin in the gastric juice 🞭 Peptic ulcer disease is manifested to clinicians as dispepsia (persistent or recurrent pain or discomfort in the upper abdomen).  Ulcer Ulcer is a painful sore or small holes that form on skin or human membranes which is usually caused by infection, inflammation or non-steroidal anti-inflammatory drugs GIT Ulcer Classification Peptic (Gastric) ulcer is a sore that’s on the inside of the stomach lining — a gastric ulcer (Upper GIT) An esophageal ulcer is a type of peptic ulcer that develops in the lining of the esophagus. Esophageal ulcers occur when the layer of mucus, which lines and protects the gastrointestinal tract, wears away. (Upper GIT) Duodenal ulcer is a sore that’s on the inside of the upper part of the small intestine. (Lower GIT)  Epidemiology 🞭 Peptic ulcer is very common among the population. 🞭 Ulcers can develop at any age 🞭 They most often occur from early middle age onwards (30 - 50), with gastric ulcers being more common in elderly people ( > 60). 🞭 Affect both men & women. Acute Chronic 🞭 Maybe acute or chronic No. Multiple Individual (deeper) Symptoms No Yes Healing scar No Yes  Etiology 🞭 Genetic 🞭 Mind - Stress & strain 🞭 Foods - Spicy & chilly foods 🞭 Mechanical – Any investigative procedures. 🞭 Habits - Smoking 🞭 Neurological : Peptic ulcer may be due to return of GIT contents in case of: 🞤 In-coordination of nerves may lead to relaxation of pylorus which may permit bile int the stomach, causing gastric ulcer. 🞤 Also relaxation of oesophageal end may produce gastro oesophageal reflux & produce ulcer in oesophagus, which is felt as heartburn.  Etiology  If the digestive tract obeys the rule of one way, then there won’t be any ulcer  FORMATION  🞭 Vagus nerve stimulates excessive acid secretion.  🞭 Increased acid secretion - due to nerve stimulation or local factors (diseases of the stomach or diets) or hormonal factors (tumors of thyroid, pancreas & adrenal glands)  🞭 Drugs - long-term use of NSAIDs  🞭 Infection by gram - ve bacteria → Helicobacter pylori  Pathogenesis There are two common forms of peptic ulcer disease: 1. Those associated with the organism H. pylori 2. Those associated with the use of NSAIDs.  Prevalence Patients may present with signs and symptoms that range from benign with no sequelae to serious complications as: 1. GI bleeding 2. Strictures and perforation Prevention of risk factors can minimize these complications  Clinical Presentation Signs And SymptomsAssociated With Drug- Induced Upper GIT Ulceration  Causative agents It is a major cause ofulceration Causative Agents Non-selective NSAIDs 10-25% A Potassium chloride 8-19% A Aspirin 10-15% A Selective COX-2 NSAIDs 5-8% A Ferrous sulfate 5% B Bisphosphonates 0.2-0.4% A  How drugs-induced GIT Ulcer (Mechanisms) Drug Mechanism Aspirin COX inhibition-Platelet effect-Direct irrritant Oral bisphosphonates Direct irritant Clindamycin Direct irritant Clopidogrel Direct irritant Corticosteroids Platelet effects Erythromycin Direct irritant Ferrous sulfate Direct irritant NSAIDs COX inhibition-Direct irritant-Platelet effect Potassium chloride Direct irritant SSRIs Platelet effects Tetracyclins Direct irritant 1- HELICOBACTER PYLORI Location gastric Antrum of the stomach Incidence 95 % of duodenal ulcers & 85% of gastric ulcers It produces cytotoxins which activate the inflammatory cascade. It expresses a lipid binding adhesion that mediate binding to mucosal surface Enzymes (urease, neuraminidase) produced by the bacteria cause tissue damage. HP secretes enzymes that neutralize the acid → make its way to the "safe" area the protective Survival mucous lining. Once there, the bacterium's spiral shape helps it burrow through the lining. HP weakens the protective mucous coating of the stomach & duodenum → allows acid to get Ulcer through to the sensitive lining beneath. Both the acid & the bacteria → irritate the lining & cause ulcer. 🞭 Hyperacidity resulting from H. pylori-induced hypergastrinaemia. Elevation of gastrin is a consequence of: 1. Bacterially mediated decrease of Antral D cells that secrete somatostatin, thus losing the inhibitory modulating effect of somatostatin on gastrin 2. Direct stimulation of gastrin cells by certain cytokines liberated during the inflammatory process. 🞭 Most infected people, however, do not develop ulcers. 🞭 Why H. pylori does not cause ulcers in every infected person is not known. 🞤 Most likely, infection depends on characteristics of the infected person, the type of H. pylori. 🞭 Researchers think infection may be through food or water.  2- NSAIDS Non-specific NSAIDs → acute superficial erosionsvia: 1. Inhibition of COX. 2. Mediating the adherence of leucocytes to mucosal endothelial cells. Another types 1. Selective COX-2 inhibitors 2. Nitric oxide (NO) NSAIDS NO is coupled to the NSAID via an ester, resulting in prolonged release of NO. NO itself has anti-inflammatory effects adding to the potency of the NSAID  Risk Factors For NSAID Ulcers Uncontroversial risk factors Controversial risk factors Age > 60 years Smoking Previous peptic ulceration Alcohol High dose of NSAID or more than one NSAID Sex of patient Concomitant corticosteroid use H. pylori  Gastric ulcer Duodenal ulcer Age > 60 20-50. Signs & Symptoms pain is very marked, i.e. appears 1-2 hours pain occurs immediately after food after food i.e. Pain is felt when the stomach Pain and finally pain persists gets empty, so the pain is often felt during middle of the night or sleep Pain Pain is felt over the umbilicus and Pain is felt above umbilicus and right to the location left to midline and no radiation of midline and it may radiate to back pain is felt Pain Fullness, indigestion and heartburn Bloated feeling of intestinal gas sensation feelings noticed immediately after eating. Pain Pain is relieved by vomiting or alkali foods Pain is usually better after taking food Relief Eating & Fear of eating due to pain No weight loss will be there since patient weight loss Weight loss due to reduced intake feels better with eating and goes on eating Nausea & vomit that looks like Clinical coffee grounds Black or bloody stools (melena) may be picture Hametemesis (blood vomiting) may be present present CLINICAL MANIFESTATIONS Clinical Manifestation 🞭 Upper abdominal pain 🞭 Anorexia, weight loss, nausea, vomiting & heartburn 🞭 Complications: Haemorrhage, anemia, pyloric stenosis 🞭 Relapse is ↓ by eradication of H. pylori  Patient Assessment & Diagnosis 🞭 Endoscopy 🞭 Radiology Urea Breath Test  Complications Of Peptic Ulcer 1. Bleeding peptic ulcer (Thermocoagulation, epinephrine, H. thrombin) 2. Pyloric stenosis (endoscopic balloon dilatation) 3. Late complications of peptic ulcer surgery Uncomplicated peptic ulcer The key elements for successful management of PU: 1. Helicobacter pylori eradication 2. Discontinuation of NSAIDs  Gastro-esophageal Reflux Disease (GERD) 🞭 GERD is defined as any symptomatic clinical condition or histopathological alteration resulting from episodes of acid reflux, pepsin &, occasionally, bile into the oesophagus from the stomach. 🞭 Heartburn is the characteristic symptom, & the patient may complain of acid regurgitation & dysphagia. The mechanism of acid reflux is multifactorial 1. Reduced tone of the lower oesophageal sphincter 🞭 The most effective therapy is standard dose of PPI therapy. 🞭 Long-term management should consist of least expensive but effective Drug.  Part II Clinical Pharmacology of Peptic Ulcer  Prevention Approaches to help prevent drug-induced upper GI ulceration Aspirin -Use lowest possible dose- Avoid other ulcerogenicmedication-Use acetaminophen instead of aspirin to treat osteoarthritis elderly patients Bisphosphonates -Take with 8 oz of water- Remain upright for 30 min after taking medication Corticosteroids Avoid concomitant use of NSAIDs or aspirin,if possible NSAIDs -Use lowest possible dose – Use least ulcerogenic NSAIDs -Consider addition of PPI or misoprostol -Avoid other ulcerogenic medication -Treat H. pylori if found Potassium chloride Microencapsulated formulation preferred -Avoid slow-release wax-matrixformulations SSRIs Use alternative class of antidepressants- Avoid concomitant use of NSAIDs if possible Tetracyclines Use tablet formulation rather than capsuleformulation Treatment  A) HELICOBACTER A) HELICOBACTER PYLORI PYLORI ERADICATION ERADICATION The highest eradication rates was achieved by 1 week twice daily triple therapy consisting of a PPI (or RBC) & 2 specified antibiotics RBC= ranitidine bismuth citrate Triple therapy 1. OCA: Omeprazole 20mg, Clarithromycin 500mg, Amoxicillin 1g 2. OCM: Omeprazole 20mg, Clarithromycin 500mg, Metronidazole 400mg (Tinidazole in resistant individuals) Failure of the first line regimen necessitates the shift to another triple therapy or starting quadruple regimen. Quadruple therapy Bismuth subsalicylate, Metronidazole, Tetracycline or Amoxicillin & PPI.  B) TREATMENT OF NSAID-ASSOCIATED ULCERS Using standard doses of: 1. Proton pump inhibitors (PPIs) 2. H2-receptor antagonist 3. Misoprostol 4. Sucralfate 🞤 Due to their rapid rate of ulcer healing, PPIs are drugs of choice for patients with large or complicated NSAID-induced ulcers. 🞤 Healing is impaired if NSAID is continued.  Prophylaxis Of NSAID Ulceration 🞭 NSAIDs should be avoided in patients who are at risk of GIT toxicity BUT 🞤 Patients with chronic rheumatological conditions require long-term NSAID treatment, in this case, the lowest effective dose should be used. 🞤 It is recommended to take PPI for prophylaxis of ulceration in patients who must continue NSAIDs. 🞤 Future studies are required to compare the cost- effectiveness of cytoprotective prophylaxis with the safer COX2inhibitors.  Ulcer Healing Drugs Proton-pump inhibitors (PPIs) H2-receptor antagonists (H2RAs) Bismuth chelate Sucralfate Antacids Misoprostol  1- Proton Pump Inhibitors (PPI) 🞭 They control gastric acid secretion by inhibition of gastric H+, K+ ATPase, which is responsible for the final step in gastric acid secretion. 🞭 Under acidic conditions, they are converted to their active form. Then, irreversibly, they bind the proton pump, inhibiting acid secretion. 🞭 Rapidly absorbed producing sustained duration of action. 1. Omeprazole, 2. Lansoprazole, 3. Pantoprazole, 4. Rabeprazole. 🞭 Esomeprazole is the 1st PPI developed as a single optical isomer. 🞭 It is the S-isomer from the racemic mixture (omeprazole) 🞭 Compared with Omeprazole, Esomeprazole provides greater & more sustained acid control.  Adverse Effects 1. Diarrhea 2. Headache 3. Dizziness 4. Rash Drug interactions - All PPIs are metabolized by cytochrome P450 isoenzymes. - Omeprazole inhibits CYPs isoenzymes involved in the metabolism of phenytoin & diazepam.  Clinical Use 🞭 Relieve symptoms & heal peptic ulcers faster than H2RAs. 🞭 Heal ulcers refractory to H2RAs. 🞭 Only omeprazole & lansoprazole are currently used for healing & preventing NSAID-induced ulcers. 🞭 In GERD, they heal oesophagitis & control symptoms more rapidly than H2RAs.. 2- H2 Receptor Antagonists Cimetidine, Ranitidine, Famotidine, 🞭 They competitively block histamine ( H 2 ) receptors in gastric parietal cells, preventing acid secretion. 🞭 They are less effective than PPIs in eradication regimens, in treating ulcers when NSAIDs are continued & in prophylaxis of NSAID-induced ulcers Adverse effects Safe group of drugs Drug interactions 🞭 Cimetidine is a cytochrome P450 inhibitor, it retards the oxidative metabolism of a number of drugs, e.g. Phenytoin, Theophylline, Diazepam & Flurazepam.  3- Bismuth Chelate 🞭 Bismuth subsalicylate (Stomach-liningprotector) 🞭 Bismuth chelate is a safe form of bismuth that has ulcer healing properties comparable to those of H2antagonists. 🞭 Bismuth is toxic to H. pylori & was one of the first agents to be used to eradicate the organism & reduce ulcer recurrence. 🞭 A combination of Ranitidine & bismuth as Ranitidine bismuth Citrate (RBC) in combination with two antibiotics results in H. pylori eradication rates greater than 90%. Adverse effects 🞭 Nausea, vomiting, blackened tongue & dark faeces.  4- Sucralfate 🞭 It is the Al salt of sucrose octasulphate. 🞭 It has mucosal protective effects, stimulation of HCO3 & mucus secretion & stimulation of mucosal prostanoids. 🞭 At pH < 4.0, it forms a sticky viscid gel that adheres to the ulcer surface & results into physical protection. 🞭 It can be used to treat ulcers but it is mainly used inthe prophylaxis of stress ulceration. Adverse drug reactions 🞭 Al toxicity is produced with long-term treatment. 🞭 This is greater in patients with renal impairment.  5- ANTACIDS Antacids are used for: 🞭 Symptomatic relief of dyspepsia, GERD. 🞭 Al-based & Mg-based products N.B. 1. Calcium stimulates acid secretion (Rebound hyperacidity). 2. NaHCO3 is unsuitable for regular use because they deliver a ↑ Na load & generate ↑ quantities of CO2. 3. Mg trisilicate mixtures contain a ↑ amount of NaHCO3 Adverse drug reactions 1. Al-based antacids cause constipation 2. Mg-based products cause diarrhea.  6 - Misoprostol 🞭 Misoprostol is a synthetic prostaglandin E1 (PGE1) analogue 🞭 It stimulates increased secretion of the protective mucus that lines the GIT & ↑ mucosal blood flow → ↑ mucosal integrity. 🞭 It is sometimes co-prescribed with NSAIDs to prevent their common adverse effect of gastric ulceration (e.g. with Diclofenac in Arthrotec) 🞭 It is commonly prescribed off-label to cause birth induction by uterine contractions & the ripening of the cervix Adverse drug reactions 🞭 ↑ doses can cause uterine rupture (especially in women who have previously had a caesarean section), fetal death & severe fetal brain damage  Future Treatment Immunization against H. pylori will be a future option in the management of peptic ulcer disease.  PATIENT CARE Patient education Patient monitoring 🞭 Smoking delays ulcer healing 🞭 treatment success in PUD is 🞭 Anticholinergics,TCAs, Cachannel blockers measured by review of the patient in terms of symptom control. Lower oesophageal sphincter tone 🞭 Following eradication therapy, some giving rise to GERD, eventually patients continue to experience leading to oesophagitis. symptoms of abdominal pain. 🞭 Patients should be warned of GIT risk 🞭 Patients should be reassured that before beginning NSAID or aspirin these symptoms will resolve 🞭 Patients sensitive to penicillin need spontaneously. an eradication regimen without 🞭 Anaemic patients following bleeding amoxicillin ulcer are prescribed iron therapy 🞭 Patients receiving eradication therapy should be advised of the need of a combination of 3 drugs for a short period of time.