Gastric and Duodenal Peptic Ulcer

Peptic ulcer is a break in the gastric or duodenal mucosa that arises when the normal mucosal defensive factors are impaired or are overwhelmed by aggressive luminal factors such as acid and pepsin. This imbalance results in any degree of gastrointestinal mucosal irritation, inflammation or ulceration. * Patho-physiology: Aggressive Factors a- HCl. b- Pepsin. c- Helicobacter Pylori. d- Bile salts. Defense Mechanisms a- Prostaglandins. b- Mucus. c- Bicarbonates. d- Blood supply. e- Mucosal regeneration.
Peptic Ulcer Disease

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* Clinical Features: 1- Symptoms & Signs: a- Epigastric pain & tenderness. b- Anorexia, Nausea & Vomiting. c- Hemorrhage. 2- Endoscopy. 3- Presence of H. pylori : Endoscopic biopsy, serological test & Urea breath test. * Goals of Therapy: 1- Pain Relief. 2- Promotion of healing. 3- Prevention of recurrence. 4- Preventing ulcer complications e.g. bleeding, perforation.

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* Drug Therapy: A) Antacids (Neutralization of secreted HCl): - Aluminum Hydroxide + Magnesium hydroxide or Trisilicate. B) Antisecretory Drugs (Reduction of Acid Secretion): 1- H2-Receptor Blockers: Cimetidine. 2- Proton Pump Inhibitor (H+/K+ ATPase Inhibitors): Omeprazole. 3- Antimuscarinic Drugs: Pirenzepine. 4- Gastrin Antagonists: Proglumide. 5- Prostaglandins: Misoprostol. C) Mucosal Protectives (Enhancement of Mucosal Resistance): 1- Sucralfate. 2- Colloidal bismuth. 3- Carbenoxolone. 4- Prostaglandins : Misoprostol.
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D) Eradication of H. pylori: 1- Metronidazole. 2- Bismuth compounds. 3- Amoxicillin. 4- Tetracycline. 5- Clarithromycin. E) Other Drugs: 1- Sedatives or Tranquillizers e.g. Diazepam # Psychic effect on acid secretion. 2- Tricyclic Antidepressants Psychic effects + Anti-cholinergic + H2block. 3- Estrogen on Males But feminization

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Management of peptic ulcer: * General Measures I- Rest: 1- Mental diazepam 2- Physical only in presence of complications. II- Diet: 1- Small frequent light meals. 2- Milk in reasonable amounts is suitable. Milk contains: a- Proteins i- Colloids Demulcent effect on mucosa & adsorption of HCl and pepsin. ii- Amphoteric Chemical neutralization of HCl. b- Fats Enterogastrone hormone Acidity and motility. c- However Excess milk Excess Ca & Proteins Gastrin Rebound hyperacidity
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3- Avoid: a- Heavy meals, spicy foods, vinegar, fried meat & meat extract. b- Beverages : Xanthines (Coffee & tea), Carbonated & Alcoholic. c- Smoking . d- Chewing gum.

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III- Drugs to be avoided: 1-Anti-Inflammatory drugs : a- NSAID e.g. Aspirin Irritation, PGs & Bleeding. Paracetamol is allowed. b- SAID e.g. Glucocorticoids & ACTH. 2- KCl oral preparation. 3- Xanthines : Caffeine Gastric secretions. Theophylline Irritation. 4- Tobacco Irritation and ganglion stimulation (Nicotine SD). 5- Alcohol : Up to 10% Conc. Gastric secretions & conc. > 40% Irritation. 6- Reserpine. 7- Tolazoline & Phentolamine Histamine like. 8- Parasympathomimetics. 9- Histamine, Histamine like & Histamine releasers. 10- Stomachics & Digestatnts.
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Medical Treatment * Drugs A- Active ulcer + H pylori infection Anti-microbials + Anti-secretory 1- First Line: PPI-based triple therapies for H pylori are considered the first-line therapies for the treatment of H pylori. a- For eradication of H.pylori: Double antimicrobial therapy for 1 - 2 weeks. 1- Clarithromycin: 500 mg twice per day orally + 2- Amoxicillin: 1 gm twice per day orally OR Metronidazole: 500 mg twice per day orally (for penicillin-allergic patients).

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b- Anti-secretary Drug: 1- Proton pump inhibitor Twice per day orally for two weeks, then continue once per day for 4- 8 weeks. Omeprazole (Prilosec): 20 mg orally twice/day. Lansoprazole (Prevacid): 30 mg orally twice/day. or Rabeprazole (Aciphex): 20 mg orally twice/day. or Esomeprazole (Nexium): 40 mg orally /day. OR in patients who can NOT tolerate proton pump inhibitors 2- H2-blocker for 6-8 weeks Cimetidine 800 mg at bed time or 400 mg bid. Ranitidine 300 mg at bed time or 150 mg bid. Nizatidine 300 mg at bed time or 150 mg bid. Famotidine 40 mg at bed time or 20 mg bid.
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NB) Quadruple therapies for H pylori infection are generally reserved for patients who have failed a course of treatment and are administered for 14 days. The treatment includes the following drugs: - PPI orally four times /day and - Bismuth 525 mg orally four times /day and - Metronidazole 500 mg orally four times /day and - Tetracycline 500 mg orally four times /day B- Active ulcer with No H pylori infection Either : Proton Pump Inhibitor (Omeprazole) OR H2 blockers (Ranitidine) For 4 weeks in duodenal ulcer and 8 weeks in gastric ulcer.

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NB) Active ulcers associated with NSAID use are treated with an appropriate course of PPI therapy and the cessation of NSAIDs. For patients with a known history of ulcer, and in whom NSAID use is unavoidable, the lowest possible dose and duration of the NSAID and co-therapy with a PPI or misoprostol (analog of PGE1) are recommended. C- Prevention of relapse: Therapy given for 6 months, Either: - Proton Pump Inhibitor e.g. Omeprazole 20 mg 30 minutes before breakfast. OR - H2 -Blockers: Half dose.g. Ranitidine (150mg).

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D- Treatment of acute hemorrhage complicating an ulcer: 1- General Measures: Bed rest + Fresh blood transfusion + Oxygen. 2- Gastric lavage with ice cold saline. 3- Local injection of adrenaline. 4- After control of bleeding give milk 50 100 ml by gastric drip + antacid. 5- After 48 hours treatment as active stage. E- Surgery: in severe hemorrhage or perforation. - - - - - - - - - - - - - - - - - -

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* Sample of Prescriptions: 1- Eradication Therapy: Omeprazole 20 mg Capsules Clarithromycin 500 mg Tablets Amoxicillin 1000 mg Tablets

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2- Eradication Therapy in a Patient Allergic to Pednicillins: Omeprazole 20 mg Capsules Clarithromycin 500 mg Tablets Metronidazole 400 mg Tablets

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* Points for Discussion: For EVERY drug or group of drugs used in treatment of peptic ulcer, kindly discuss the following points: 1- Role of this drug / group in peptic ulcer: a- Mechanism of action. b- Beneficial effects in peptic ulcer. c- Use in peptic ulcer: i- Eradication of H. pylori. ii- Inhibition of recurrence. iii- Compelling indications. iv- Compelling contraindications. 2- Adverse effects. 3- Contraindications. 4- Drug interactions. 5- Patient education and counseling.
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* Sample of Patient Education and Counseling: A) Antacids: 1- Shake the suspension well, drink 175 240 ml water after swallowing the suspension. 2- Do not use other drugs such as H-2 blockers, misoprostol and suceralfate, within 1 2 hours of antacid administration. 3- Separate the administration of ant acids and enteric coated drugs by 1 hour to avoid premature release of enteric coated drugs in the stomach. 7- If constipation especially with calcium and aluminum salts: a- Take high fiber diet. b- Drink 8 -13 glasses of water (240 ml). c- Combine with a magnesium containing antacid. 8- Antacid therapy normally makes stools appear speckled or whitish. 9- Antacids contain hidden sodium and potassium. 10- Bismuth: The mouth, tongue and stool may become blackened and that this is a temporary effect. 3- Aluminum may produce:
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a- Hyperaluminemia: Osteomalacia and dementia. Ask the patient's relative to monitor his cognitive functions and memorization. b- Hypophosphatemia manifested by malaise, anorexia and muscle weakness. B) Others: 1- H-2 Blockers e.g. Cimetidine: a- Do not use an antacid within 1 hour of H-2 blocker, decrease h-2 blocker absorption. b- Be aware of bradycardia. c- Take seizure precautions with cimetidine. d- Avoid any activity that requires alertness. e- Sexual dysfunction may occur with the intake of cimetidine.

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2- Omeprazole: a- Inhibits the metabolism of other drugs such as diazepam, phenytoin and warfarin. b- Omeprazole and lasoprazole interferes with absorption of ampicillin, ketoconazole and iron salts. c- Not to perform any activity that requires alertness. 3- Misoprostol: a- Taken with food. b- May produce diarrhea. c- May produce miscarriage. - Obtain a serum pregnancy test 2 weeks before beginning therapy. - Use effective contraceptive methods. - Notify the physician if planning to become pregnant. - If pregnancy is suspected, stop misoprostol immediately.

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2- Sucralfate: a- should be administered: - 2 hours before or after all other medications. - One hour before meals and at bed time. b- May produce nausea and metallic taste.

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Case No 1: A 42 year old man presented with a 5 weeks history of epigastric pain and endoscopy revealed a duodenal ulcer and tests were positive for helicobacter pylori. 1- General measures that the patient should follow: a- Excessive intake of milk. b- Small frequent meals. c- Mental rest. d- Avoid spices and stomachics. e- Smoke at ease. 2- Drugs that should be avoided: a- Paracetamol b- Corticosteroids. c- Metronidazole. d- KCl. e- Diclofenac sodium. 3- To eradicate helicobacter pylori infection the following drugs are given: a- Omeprazole. b- Sucralfate. c- Amoxicillin. d- Misoprostol. d- Clarithromycin

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4- Which drug of the ones chosen in question 3 decreases gastric acid secretion: (a b c d e) 5- The following may be used to prevent the recurrence of the duodenal ulcer: a- Famotidine. b- Prednisolone. c- Bethanechol. d- Aspirin. e- Reserpine. 6- The drug chosen in question 5 acts by: a- Blocking 5HT3 receptors. c- Blocking H2 receptors. e- Blocking gastrin receptors. b- Blocking M1 receptors. d- Blocking H1 receptors.

7- The dose of the selected drug in Q-5 is: a- 150 mg per day orally. b- 150 mg per day IM. c- 400 mg per day orally. d- 20 mg per day orally. e- 300 mg per day orally.

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8- Which drug is used to prevent aspirin induced peptic ulcer: a- Diclofenac b- Prednisolone. c- Misoprostol. d- Rifampicin. d- Amoxicillin. 9- The drug in question 8 is: a- Stimulates H2 receptors. c- Stimulates M1 receptors. e- Inhibits H K ATPase enzyme. KEY: 1- b, c, d. 9- b. b- Analogue of PGE1. d- stimulates gastrine receptors.

2- b, d, e. 3- a, c, d. 4- a.

5- a.

6- c.

7- d.

8- c.

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