2.  Peptic ulcers are the areas of degeneration and Necrosis of gastrointestinal mucosa exposed to acid-peptic secretions.  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 in the gastric juice.  Peptic ulcer is usually represented as Dyspepsia.

3.  Acute or stress ulcers : Multiple, Small mucosal erosions.  Chronic ulcers: Gastric or Duodenal ulcers.

4.  Occurs due to imbalance between the aggressive and defensive factors.  Etiological factors of Acute ulcers : A. Psychological stress B. Physiological stress  Shock  Severe trauma  Drugs and Local irritants  Cushing’s syndrome

5.  Chronic ulcer disease : Multifactoral, the main contributing factor is the H-Pylori infection.  Acid-pepsin secretions  Mucus secretion  Gastritis  Local Irritants  Dietary factors  Psychological factors  Genetic factors  Hormonal factors  Miscellaneous factors

6.  Viral Infections (cytomegalovirus)  Radiation  Chemotherapy ( e.g. hepatic artery infusions)  Idioathic  Vascular insufficiency  Cigarette smoking

7. Infection H-Pylori Infection Few months Chronic superficial gastritis Years Hyperacidity Mucosal layer erosion Peptic ulcer

12.  H-Pylori contains enzymes like urease, protease, catalase, phospholipase which damage the mucosal barrier.  Basal and Maximal acid output due to various stimuli.  Vagal stimulation  Gastric Ulcer : Impaired gastric mucosal defenses against acid-pepsin secretions.  Pathogenesis : serum gastrin levels due to ingested food leading to hyperacidity.

13.  Acid secretion because of parietal cell mass.  Inhibition of gastric acid secretion.  Hco 3 - secretion in the duodenum due to H- Pylori infection causing local release of cytokins and further damage.

14.  NSAIDS induced peptic ulcer : NSAIDS COX inhibition Adherence of leucocytes to mucosal endothelial cells Decreased prostaglan din synthesis Superficial erosions Peptic ulcer

15.  A number of other factors may contribute to the development of NSAID induced mucosal injury, neurtophils adherence may damage vascular endothelium and cause reduced mucosal blood flow or may release oxygen derived free radicals and proteases.  Leukotriens have stimulatory effect on neutrophils adherence.  Topical irritant properties associated with the acidic properties of NSAID’s e.g. aspirin and their ability to decrease hydrophobicity of mucosal gel layer

16.  Epigastric pain  Upper abdominal pain occurring 1-3 Hrs after meals and relieved by food or antacids is a classical symptom of peptic ulcer disease.  Anorexia, weight loss.  A typical nocturnal pain that awakens the patient from sleep.  Heart burn due to acid regurgitation.  Nausea may accompany the pain.

17.  Diagnosis of H-Pylori infection.  Non-Invasive techniques: A. Urea breath test B. Serological tests C. Stool test Invasive techniques A. Rapid urease test B. Culture C. Histology

18.  13 C Urea breath test : used to demonstrate eradication of organism following treatment.

19.  Serological test : used to detect antibodies  Used in diagnosis and epidemiological studies.  Stool test : Immunoassay using monoclonal antibodies for qualitative detection of H-Pylori that leads to colour change that can be detected visually or by spectrophotometer.  Used in the diagnosis and monitoring efficacy of eradication therapy.  Culture : Biopsies cultured on a special medium  Enables sensitivity testing to determine optimum treatment or antibiotic resistance.  Histology : Gastric mucosal staining, helps in the classification of gastritis.tests for active HP infection.

20.  Biopsies are done to exclude malignancy and uncommon lesions such as crohn’s disease.  Wireless capsule endoscopy : determines NSAIDS induced ulceration of small intestine.  Use of gastrograffin meal:  Gastrografin (Diatrizoate Meglumine and Diatrizoate Sodium Solution) is a iodinated radiopaque contrast medium for oral or rectal administration only.

21.  Rapid urease test : Gastric biopsies with urea solution containing phenol Urea ammoniaPHPH Rapid colour change

22.  Esophagogastroduodenoscpy : permits direct visualization of superficial erosions and sites of active bleeding.  Routine single barium contrast techniques :  Fasting serum concentration studies :

24.  Non pharmacological therapy : I. Reduce psychological stress II. Reduce physical stress III. Cessation of cigarette smoking IV. Stop use of NSAIDS V. Avoid spicy foods, caffeine, alcohol VI. Drink plenty of water VII. Avoid fasting and maintain optimum gap between meals

25.  Classification of Drugs: 1. Proton Pump Inhibitors : e.g. omeprazole, pantaprazole,Lansoprazole. 2. H 2 receptor antagonists : e.g. Ranitidine, Famotidine, cimetidine 3. Sucralfate 4. Bismuth compounds 5. Antacids : systemic e.g. Sodium bicarbonate, Non Systemic e.g. Magnesium Trisilicate. 6. Prostaglandin Analogs : e.g. misoprostol, Enprostil.  Anti H-Pylori drugs (Antibiotics) e.g. Amoxicillin, clarythromycin, tetracyclines.

26. Proton Pump Inhibitors Carried in blood stream to the parietal cells Activation Cytosol ESC Inhibition of H + K + ATPase Inhibit acid secretion

27.  PPI’s differ in their in their potencies.  Plasma concentration is reached after 2-3 hrs.  T 1/2 48 Hrs.  To be taken 30 minutes prior to food. 2. H 2 receptor antagonists :  Structural analogs of histamine.  pepsinogen pepsin  Used in symptomatic treatment.  Plasma concentration is reached within 1-3Hrs after administration.  Recommended in patients with nocturnal gastric acid secretion and management of dyspepsia symptoms. ( )

28.  Sucralfate : Basic aluminium salt of sulfated sucrose Polymerizes at pH < 4.0 by cross linking of molecules Gel Adheres to the ulcer base Precipitates surface proteins and acts as a physical barrier Antacids are contraindicated when sulfates are taken

29.  Prostaglandin Analogs :cytoprotective properties 1. Increase mucus and bicarbonate production. 2. Increase mucosal blood flow 3. Inhibit gastrin production  Antacids : ANC--- No of Meq of 1N Hcl that are brought to pH 3.5 in 15 minutes by unit dose of antacid preparation. Mgsio3Cl - saltCl - + HCo3 - No acid-base disturbance

30.  Decision algorithm for management of uninvestigated Dyspepsia

34.  BLEEDING PEPTIC ULCER :  Patients with high risk of bleeding are given high dose of infusion of omeprazole ( 80 mg bolus followed by 8mg/Hr) for 72 Hrs to reduce rebleeding.  LATE COMPLICATIONS OF PEPTIC ULCER:  Reactive hypoglycaemia, diarrhoea, weight loss, anaemia, flushing, plapitation, sweating tachycardia, postural hypotension.

35.  Treatment :  Somatostatin analogs for reactive hypoglycaemia.  Antibiotics  metachlopramide  Zollinger-ellison syndrome: use of octreotide, surgical.

36.  Assess patient allergies  Assess patient use of alcohol or alcohol- containing products with metronidazole and oral birth control medications with antibiotics and counsel appropriately.  Inform the patient of change in stool color when bismuth salicylate is included in an HP eradication regimen.  Assess and monitor patients for potential adverse effects.  Assess and monitor patients for potential drug interactions.  Monitor patients for salicylate toxicity.

37. o Provide education to patients who are receiving HP eradication therapy, including why antibiotic and antiulcer combinations are used, when and how to take medications, adverse effects, alarm symptoms, when to contact their health care provider, and the importance of compliance to drug treatment. NSAID-induced ulcer Recommend drug treatment Assess risk factors for NSAID-induced ulcers and ulcer-related complications, and when indicated recommend appropriate strategies for reducing ulcer risk. Assess and monitor patients for potential drug interactions and adverse effects (especially misoprostol).

40.  Misoprostol, 200 mcg four times a day, markedly reduces the risk of NSAID-induced gastric ulcer, duodenal ulcer, and ulcer-related GI complications, but diarrhea and abdominal cramping limit its use  H2-RECEPTOR ANTAGONIST COTHERAPY WITH A NONSELECTIVE NSAID  Standard H2-receptor antagonist dosages (e.g., famotidine 40 mg/day) are effective in reducing the risk of NSAID-induced duodenal ulcer.

41.  Patients with refractory ulcers should undergo upper endoscopy to confirm a non healing ulcer, exclude malignancy, and assess HP status. HP-positive patients  should receive eradication therapy  In HP-negative patients, higher PPI dosages (e.g.,  omeprazole 40 mg/day) heal the majority of ulcers.  Continuous treatment with a PPI is often necessary to maintain healing, as refractory ulcers typically recur when therapy is discontinued or the dose is reduced

42.  Poor Patient compliance  Resistant organisms  Increased bacterial load  Missed dose in a 7 day regimen may also contribute towards failure of eradication.  Tolerability  Preexisting antimicrobial resistance.

43.  Proton pump inhibitors : 1. Diarrhea 2. Headache 3. Abdominal pain 4. Nausea and vomiting 5. Microscopic colitis  H 2 receptor antagonists : 1. Anti-androgeniceffects gynaecomastia. 2. Impotence

44.  Bismuth chelate: 1. Neurotoxicity  Sucralfate : 1. Constipation 2. Hypophosphataemia  Prostaglandin analogs : 1. Diarrhea 2. Abdominal cramps 3. Uterine bleeding 4. Abortion  Antacids : alkalosis, increase sodium load.

45. CONSQUENCE OF PROLONGED HYPOCHLORHYDRIA

46.  PPI’s are metabolised by cytochrome p450 isoenzymes,the affinity of individual proton pump inhibitors for these enzymes influence the incidence of clinically relevant drug interactions.  E.g. omeprazole+warfarin warfarin levels.  benzodiazepines + omeprazole benzodiazepines levels.  PPI’s also alter the absorption of other drugs du to altered pH  E.g. decreased absorption of Ketoconazole  increased absorption of Digoxin  Cimetidine interacts with Thiophylline, Diazepam, Flurazepam, Triazolam.  All acid suppressing drugs decrease absorption of pH dependent control release tablets.  Antacids interact with tetracyclines, ciprofloxacin forming insoluble complexes or chelates.

47.  Weight loss  Avoid spicy foods  Avoid hot beverages  Maintain optimum time interval between meals  Reduce psychological stress  Reduce physical stress  Cut off irregular eating habits  Educate the patient about the current principles of therapeutic management  Patient should be warned about the specific side effects to be expected from the regimen and what to do if they experience any of these side effects.  Avoid drugs e.g. TCA’s, CCB’s, Anticholinergics, NSAIDS.

48.  Pharmacotherapy by Dipiro  Clinical Pharmacy and Therapeutics by Roger Walker  Pharmacology by Thripati  Clinical Medicine by Kumar and Clark  Pathology By Harsh Mohan

50.  Gastro-oesophageal reflux disease is the term used to describe a histopathological alteration resulting from episodes of reflux of acid, pepsin and occasionally bile into the oesophagus from the stomach.

52.  Pathogenesis :  abnormal reflux of gastric contents from the stomach into the esophagus.  Decreased gastroesophageal sphincter pressures related to spontaneous transient LES relaxations, transient increases in intraabdominal pressure, all of which may lead to the development of gastroesophageal reflux.

53.  Other factors : mucosal resistance, gastric emptying, epidermal growth factor, and salivary buffering.  Abnormal oesophageal acid clearence.  Endoscopy-negative reflux disease : GORD with normal endoscopy.  Hiatus hernia

54.  Patients should be assessed for symptoms, such as heartburn and for signs and symptoms of complications (e.g., dysphagia)that require immediate medical attention.  The goals of GERD treatment are to alleviate symptoms, decrease the frequency of recurrent disease, promote healing of mucosal injury, and prevent complications.

55.  Many patients with GERD will relapse if medication is withdrawn,so long-term maintenance treatment may be required.A proton pump inhibitor is the drug of choice for maintenance of patients with moderate to severe GERD.