Drugs used to treat peptic ulcer disease

BDS 2nd year theory class

1. Drugs Used to treat Peptic Ulcer Disease Dr. Pravin Prasad M.B.B.S., MD Clinical Pharmacology Assistant Professor, Maharajgunj MedicalCampus 2 March 2020 (19 Falgun 2076), Monday

2. By the end of this class, BDS 2 nd year students will be able to: Classify drugs used in Peptic Ulcer Disease (PUD) Explain the pharmacological basis of use of different drugs for the treatment of PUD List the specific adverse drug reactions of different drugs for the treatment of PUD Apply the gained knowledge to solve the clinical situations related to PUD

3. Relevant Physiology: Gastric acid secretion

4. Drugs Used in PUD: Classification Reduction of gastric acid secretion Neutralization of gastric acids Ulcer protectives Anti H pylori drugs

5. Drugs Used in PUD: Classification Reduction of gastric acid secretion Neutralization of gastric acids Ulcer protectives Anti H pylori drugs H 2 anti histamines : Cimetidine, Ranitidine, Famotidine Proton pump inhibitors : Omeprazole, Esomeprazole, Lansoprazole, Pantoprazole Anticholinergic drugs : Pirenzepine, propantheline Prostaglandin analogues : Misoprostol

6. Drugs Used in PUD: Classification Reduction of gastric acid secretion Neutralization of gastric acids Ulcer protectives Anti H pylori drugs Systemic : Sodium bicarbonate, sodium citrate Non Systemic : Calcium carbonate, Magnesium hydroxide, Magnesium trisilicate, Aluminium hydroxide gel, Magaldrate

7. Drugs Used in PUD: Classification Reduction of gastric acid secretion Neutralization of gastric acids Ulcer protectives Anti H pylori drugs Sucralfate Colloidal bismuth subcitrate

8. Drugs Used in PUD: Classification Reduction of gastric acid secretion Neutralization of gastric acids Ulcer protectives Anti H pylori drugs Amoxicillin Clarithromycin Metronidazole, Tinidazole Tetracycline

9. Anticholinergics for PUD Nonselective: Atropine, Propantheline, Oxyphenonium Selective: Pirenzepine (M 1 ) Cholinergic receptors: Muscuranic Nicotinic Muscuarnic receptors: M 1 receptors: Stimulatory Gastric glands: increased secretion

10. Anticholinergics for PUD Acts by reducing the gastric secretion volume Nonselective anticholinergics: High doses required Intolerable side effects Not used these days Selective anticholinergics: Reduces gastric secretion by 40-50% Less side effects at effective doses Not commonly used

11. Antihistamines in PUD H 2 antihistamines are used: Competitive blockers: Cimetidine, Ranitidine, Roxatidine Non-competitive blockers: Famotidine H 2 receptors: Gs coupled Increases gastric acid secretion Blocked by H 2 antihistamines Acts by decreasing gastric acid secretion Basal, psychic, neurogenic, gastric phases decreased 60-70% inhibition of acid output

12. Antihistamines in PUD Uses Promote healing of gastric and duodenal ulcers Heal uncomplicated GERD Prevent occurrence of stress ulcers Gastrinoma Famotidine: Zollinger Ellison syndrome, prevention of aspiration pneumonia PPIs preferred due to higher efficacy and equally good tolerability

13. Antihistamines in PUD Adverse Drug Reactions Well tolerated, low incidence of side effects Diarrhoea , headache, drowsiness, fatigue, muscular pain, constipation CNS side effets (confusion, delirium, hallucinations, slurred speech) Cimetidine: Galactorrhoea in females and gynaecomastia Reduced sperm count and impotence in males- rare

14. Drugs Used to treat Peptic Ulcer Disease-II Dr. Pravin Prasad M.B.B.S., MD Clinical Pharmacology Assistant Professor, Maharajgunj MedicalCampus 5 March 2020 (22 Falgun 2076), Thursday

15. By the end of this discussion, BDS 1 st year students will be able to: Explain the pharmacological basis of use of different drugs for the treatment of PUD List the specific adverse drug reactions of different drugs for the treatment of PUD Apply the gained knowledge to solve the clinical situations related to PUD

16. Proton pump inhibitors in PUD Inhibits common final steps in gastric secretion Dose-dependent action Can totally abolish HCl secretion Mechanism of action: Gets activated at pH < 5 (gastric pH) Reacts co- valently with H + K + ATPase pump (proton pump) and inhibits irreversibly: Hit and Run Drugs Acid secretion resumes only after synthesis of new pump molecules (~ 18 hrs )

17. Proton pump inhibitors in PUD Pharmacokinetics Administered orally in enteric coated ( e.c. ) form Do not be break or crush the tablets Oral bioavailability (omeprazole): ~50% Bioavailability reduced by food: should be taken in empty stomach, followed 1 hour later by a meal Omeprazole is highly plasma protein bound Rapidly metabolised in liver by CYP2C19 and CYP3A4 (plasma t½ ~1 hr ) Excreted in urine Inhibition of HCl secretion occurs within 1 hr , reaches maximum at 2 hrs , is still half maximal at 24 hrs and lasts for 2–3 days At steady state all PPIs produce 80–98% suppression of 24 hour acid output with conventional doses Secretion resumes gradually over 3–5 days of stopping the drug

18. Proton pump inhibitors in PUD Uses Promote healing of gastric and duodenal ulcer Bleeding peptic ulcer Stress ulcers Gastro-esophageal reflex disorder Erosive esophagitis Zollinger Ellison Syndrome Prevention of recurrence of NSAIDs induced ulcer

19. Proton pump inhibitors in PUD Adverse effects: Rare, well tolerated Nausea, loose stools, headache, abdominal pain, muscle and joint pain, dizziness (3-5%) Rashes, leucopenia, hepatic dysfunction Atrophic gastritis on prolonged use Accelerated osteoporosis among elderly patients: high dose and long term use Omeprazole (prolonged use): gynecomastia, erectile dysfunction Subacute myopathy, arthralgias, headache and skin rashes have been reported

20. Ulcer Protectives: Sucralfate Basic aluminum salt of sulfated sucrose Mechanism of action: Polymerizes at pH < 4 by cross linking of molecules, assuming a sticky gel-like consistency Preferentially and strongly adheres to ulcer base, especially duodenal ulcer Surface proteins at ulcer base are precipitated Acts as a physical barrier Dietary proteins get deposited on this coat

21. Ulcer protectives: Sucralfate Minimally absorbed after oral administration Should not be given with antacids Infrequently used now because of need for 4 large well-timed daily doses and the availability of simpler and more effective H2 blockers/PPIs. Indications : Ulcer healing (duodenal, gastric) Bile reflux Gastritis Prophylaxis of stress ulcers Topical: burns, bedsores, diabetic/ radiation ulcers, excoriated skin

22. Ulcer Protectives: Sucralfate Adverse drug reaction Constipation Hypophosphatemia Dry mouth and nausea

23. Ulcer Protectives: Colloidal Bismuth Subcitrate It is a colloidal bismuth compound; water soluble but precipitates at pH < 5 Mechanism of action (possibilities): May increase gastric mucosal PGE2, mucus and HCO3 ¯ production May precipitate mucus glycoproteins and coat the ulcer base May detach and inhibit H.pylori directly Milk and antacids should not be taken concomitantly

24. Ulcer Protectives: Colloidal Bismuth Subcitrate Majority eliminated unchanged in faeces Small amounts absorbed are excreted in urine Adverse drug reactions: Diarrhoea , headache and dizziness Poor patient acceptance of CBS Blackening of tongue, dentures and stools Inconvenient dosing schedule Indication: Add on drug for triple drug Anti- H. pylori therapy

25. Anti- H. pylori regimes

26. Clinical scenario 1 You attend a patient of dental pain that was not managed adequately by local measures The patient also gives a history of frequent dyspepsia You decide to start one of the NSAIDs drugs. Which NSAIDs would you choose? How will your new drug have effect on the dyspepsia of the patient? What can you do to prevent aggravating the dyspepsia of the patient?

27. Clinical Scenario 2 A patient came to you in ED with complains of pain abdomen and sour brash for 30 mins. He had spicy food in quantities more that he usually consumes for his dinner. You decide to prescribe one of the gastric acid lowering agent. Which drug would you prescribe? How is your option better that other gastric lowering agents?