Peptic Ulcer Presented by Ms Dr. Fatma M Mady al 4 ae Peptic Ulcer Disease SmPeptic ulcer disease : — ws an , QA condition in which there is a discontinuity in the , entire thickness of the gastric or duodenal mucosa | rs as a result of acid and pepsin in the gastric juice. : 2 a QEsophageal ulceration due to acid reflux is classified under gastro- esophageal reflux disease (GERD). i Sr ae wae =Epidemiology: Risk factors : 1- Cigarette smoking 2- Psychological stress 3- Genetic factors 4- Fatty or Spicy food , alcohol and caffeine. _ 5- Helicobacter pylori infections. s 6- Some drugs as NSAIDs. 7- There are some diseases associated with peptic ulcer like: a- chronic renal failure. ts b- chronic pulmonary diseases. c- liver cirrhosis. d- acute pancrea’Mechanism of gastric acid secretion: P peels responsible for acid secretion in stomach is called (oxyntic cell). eee... | iF cls. G déWhy stomach is not affected by HCI: — , = i oo £5 Because of the presence of defensive mechanisms i t 1. Mucous/bicarbonate layer: which cover all mucosal lining of r stomach. s, 2. Gastric mucosal blood flow: washing out any harmful substances and essential for ulcer healing. 3. Prostaglandin and nitric oxide: enhance 1 and 2. = a ee « ePathogenesis of peptic ulcer NSAIDS _ _Drug- ~ induced”, urease enzyene leo 1-H. pylori COs hs ammonia surrounding MO) * Microorganism found in human stomach * H. pylori cause (90% of duodenal ulcers) (80% of gastric ulcers). * secretes many enzymes involved in tissue damage like 2 neuraminidase, fucosidase, and *” « Hyper acidity associated with H.pylori is due to increasing gastrin hormone secretions which stimulates gastric acid secretion. eeea. Drug induced ulcers (NSAIDS) Arachidonic acid pi >,» NSAIDS inhibit both cyclooxygenase enzymes resulting in decreasing protective mucosal prostaglandin synthesis and pain relief » Newer NSAIDS such as 1. Selective COX 2 inhibitor 2. (NO)-NSAIDS (nitric oxide-releasing prodrugs of non-steroidal anti- inflammatory drugs ) as NO exert protective effects in the Gl tractClinical manifestations: 1. Upper abdominal pain occurring 1-3 hours after meals relieved by food. NB: symptoms of peptic ulcer lack specificity as they don’t distinguish between duodenal ulcer , gastric ulcer and _ non ulcer dyspepsia. = 4,2. Anorexia =e 3. Weight loss 4. Nausea, vomiting ts 5. Heart burn. Hemorrhage . Chronic iron deficiency anemia . Pyloric stenosis (Gastric outlet obstruction (GOO)) due to pyloric muscle hypertrophy . PerforationInvestigations: 1. Endoscopy These serological tests Investigation of choice for diagnosing peptic ulcer pated ates Senstive, effective, and safe but mainly invasive. tones of 2- Radiology: mediestions to ensure complete eradication, Using barium sulfate as contrast media for X-rays 3-H. pylori detection : CS A- blood samples( H.pylori antibodies) (© | « B- urea breath test(Patients swallowablet of urea labelled with carbon eC isotope the detection of isotope-labelled carbon dioxide in exhaled breath indicates that the urea was split; this indicates presence of urease enzyme. * C- Stool test(for detection of H.pylori antigen) 4-CBC. ”GERD (gastro-esophageal reflux disease): + clinical conditions resulting from episodes of reflux of acid or pepsin and occasionally bile into esophagus from y stomach. ont * Heart pain | * Acid regurgitation : e ++ Dysphagia ( difficult swallowing) _-».* Complications: esophageal ulcer oPP* fo .Treatment of peptic ulcer: Pharmacological = ~ treatment _Non-pharmacological treatment 1. Stop smoking _ 2. Stop alcohol intake ' 3. Avoid stress vos 4. Avoid spicy food, - s 5. Avoid fatty food , chocolate and caffiene (as they " increase acid reflux ) 6. Elevation of the head on bed is helpful 7. Patients with heart burn >>avoid tight clothing specially at the waist IO PP tt eePharmacological treatmentUlcer healing agents . Hereceptor antagonist . Proton pump inhibitors . Bismuth chelates . Sucralfate . Antacids . Misoprostol ( synthetic analogue of protective prostaglandin) . Antibacterial agents1- H2 receptor antagonist: * They are structural analogues to histamine * They competitively block histamine receptors in gastric parietal cells>>> A- decreasing acid secretion>>>> B- decrease pepsin formation ( as pepsinogen requires acid for conversion to pepsin). > Examples : - 1. Cimetidine 2. Ranitidine 7 3. Famotidine a 4. Nizatidine a alantagonists * Histamine is thought to be ie most importa ant mediator of re jastric acid secretion fhrough activation o ceptors on Barietal cells. It stimulates~ the Preeti ° ¢ rotein inase whieh io ur, activates pape ra | cell proton pun s, the lrogen/potassium, adenosine —triphosp tase (HEY Rp, kbATPase), ‘0 secrete hydrogen ions into the stomach. *H2 receptor Sa interfere with this mechanism by , occupying "fig sites on the parietal cells. blocking th action imine. H2 antag nists) ave been Tsed? extensively ie Treatment peptic ulcer. H2 antagonists Crea their e fect cr lon a tp an antacids, as their action is i not mired oy the len heer et with the stomach * contents. H ntagonis suffer th Peotone in relations _ to antacids Fat they do not act quickly. . fro both raj cbid and extended relief, therefore, an antacid} an H2 antagonist can be taken together.All are eliminated via kidney >> require dose reduction in = renal failure + They don’t cause total achlorhydria ing nigCimetidine inhibit cytochrome P450 decrease clearance of 7 4. Theophylline | 2. Phenytoin 4 3. Benzodiazepines 4 4. Warfarin ; ; it increase their blood concentration >> increasing their e effect In addition, cimetidine was found to cause gynecomastia that is an enlargement or swelling of breast tissue in males _ FF? € Pe ee on2- Proton pump inhibitors (PPI): They are prodrugs >>>activated at parietal cells form>>>irreversibly bind to proton pump>>> 1-Inhibit gastric H*K+ ATPase >>>inhibit acid secretion 2-Inhibit H-pylori growth by inhibiting urease enzyme. Examples : . Omeprazole ( not affected by food) fansoprezole ( taken before food as food decrease its - bioavilability) . Pantoprazole ( not affected by food) They bind to different sites on proton pump>>>>have different _ 7 potencies » PPIs relieve symptoms and heal peptic ulcer faster than H2 receptor antagonist E giving active e* They are metabolized by CYTP450 enzyme * But having different effects on it: 1. Omeprazole >> inhibit enzyme>>>> decrease clearance y warfarin and phenytoin 2. Lansoprazole >> weak inducer of enzyme >>>>_ increase ’ rt clearance of ( phenytoin , warfarin, theophylline, oral 2 contraceptive) * 3. Pantoprazole: not affect enzyme 2Bismuth chelates: + Mode of action: 1. Has cytoprotective property 2. Toxic to H. pylori Combination of ranitidine has been introduced Which is used with one or two Ab in H.pylori eradication. Not used for long time as make: a- neurotoxicity. b- darkening in the tongue. ' * c- blackening of stool.4- Sucralfate: » Aluminum salt of sucrose octasulfate Pe ___ ° Has weak antacid activity (due to Al ~) f + Mode of action: SS re 1. Stimulate bicarbonate and mucus secretions : .- 2. Stimulate mucosal prostanoids( it decrease gastric acid “secretion and exert cytoprotective properties) ad » 3. Inacidic medium it forms a gel that adhere to the ulcer surface>>> physical protection ¥ Prevent alcoholic mucosal injury J er es+ Relief symptoms associated with peptic ulcer and GERD. * Symptomatic relief of non-ulcer dyspepsia. * Choice of antacids lies between Al based and Mg based. OCNot use: 1. Calcium based:>>Ca increase acid secretions + 2. Sodium based>>> increase Na load. Used antacids: 1. Magaldrate (combination of aluminum hydroxide and ’ 7 jagnesium (eral ul 2. Alginates: physical antacid , they swell forming gel like structure acting as physical barrier d-Misoprostol: » Prostaglandin analogue. + Provide protection to the stomach. * Contraindicated to pregnant as can cause abortion. Future treatments - Immunization against H. Pylori.Peptic ulcer associated with H.pylori * Triple therapy: ( ppi + 2 antibiotics) 1. PPI ( omeprazole) P 2. Clarithromycin 7 3. Amoxicillin ( metronidazole, tinidazole) : <- Used for 1 week e Continue PPI for 1 week for duodenal , and 3 week for . : gastric ulcer J Patient should be rechecked 4 weeks after discontinuation of therapy to avoid false —ve results J eI Ith ten. Tetracycline or amoxicillin . Metronidazole . Bismuth chelates Successful eradication relies upon patient adhering to their medication therapy rr 1. 2. 3. 4,Peptic ulcer associated with NSAIDs: » When NSAIDS is discontinued > faster healing with PPI or H2 blockers » PPIs relieve symptoms and heal peptic ulcer faster than H2 receptor antagonist _____ * Prophylaxis is done for patients at risk of further ulceration: ky t _ such as: elderly patients who have a history of GIT hemorrhage q + » For prophylaxis: t 1. Ranitidine ( reduce frequency of duodenal ulcer)(150mg twice daily) 2- Misoprostol (reduce freq. of both gastric ad duodenal ulcer but not well ' 7 tolerated)(200 mg twice daily) 3- Omeprazole (reduce both gastric and duodenal ulcer but well tolerated than misoprostol) (20mg once daily)Patient education: . Assure adherence to prescribed medication 2. Patients who are sensitive to penicillin require eradication therapy which doesn’t include amoxicillin rt Patients with renal failure requires dose adjustment with H2 antagonist 3 Patients must avoid alcohol when taking metronidazole Misoprosto! should not be used in pregnant women Aspirin and ibuprofen containing preparations should be J avoided and replaced by paracetamol containing products or COX Il selective. IT PB tn ce fe > o>