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PHARMACOLOGY: PPIs and H 2 Antagonists

Learn about the physiology of acid secretion, mechanism of action, common PPIs and H2 antagonists, indications for use, contraindications, and potential side effects of these drugs.

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PHARMACOLOGY: PPIs and H 2 Antagonists

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  1. PHARMACOLOGY: PPIs and H2 Antagonists Rebecca Bourdon-Pierre

  2. Learning Objectives • Physiology of acid secretion within the stomach • Mechanism of action of PPIs • Common PPIs, reasons for use, contraindications and side effects. • Mechanism of action of H2 antagonists • Common H2 antagonists, reasons for use, contraindications and side effects. • Summary

  3. Indications for PPIs • Gastric and duodenal ulcers • Rx of H. pylori (alongside abx) • After endoscopic Rx of bleeding peptic ulcer can reduce risk of re-bleeding • Dyspepsia • GORD • Prevention / Rx of NSAID-associated ulcers • Zollinger-Ellison syndrome

  4. Physiology of Acid Production • Patietal cells in stomach exchange H+ ions with potassium in lumen via “proton pump” • AKA hydrogen-potassium adenosine triphosphatase enzyme system • Can reduce acid production by up to 99%!!! • http://pharmacologycorner.com/proton-pump-inhibitors-ppis-mechanism-of-action-a-video-animation/

  5. Common PPIs • Omeprazole • Lansoperazole • Esemeeprazole • Pantroprazole • Rabeorazole Sodium

  6. Clinical issues to be aware of… • Decreases effectiveness of Clopidogrel (increases risk of stroke / MI) • PPIs associated with C.diff • PPIs can mask signs of gastric cancer

  7. Contraindications • Pts with liver disease • Pregnancy and breast feeding • LT use / high does  bone fractures / osteoperosis

  8. Side Effects Mostly GI: Nausea & vomiting Diarrhoea Abdo pain Flatulence Very rare / serious: Anaphylaxis Toxic epidermal necrolysis  Steven-Johnson Hepatitis

  9. H2 Antagonists **H refers to HISTAMINE** 2 mechanisms of action: • Released by ECL cells and stimulates acid secretion. • Enhances effects of other substances that promote acid secretion (acetylcholine, gastrin)

  10. H2 receptor blocker = INVERSE AGONIST rather than a true receptor antagonist. i.e. binds to same receptor but induces a pharmacological response opposite to that of the agonist (histamine)

  11. Common H2 Antagonists • Ranitidine • Cimetidine • Famotidine • Nizatidine

  12. Indications For Use *Mostly the same as for PPIs • Not used for Zollinger-Ellison Syndrome (PPI’s better) • Reduces risk of acid aspiration in obstetric pts (Mendelson’s syndrome)

  13. Contraindications & Side Effects All same as for PPIs, except caution should be applied in patients with renal impairment.

  14. Drug Interactions Cimetidine – binds to cytochrome P450 AVOID in pt is on: • Warfarin • Phenytoin • Theophylline *Others do not exibit this effect

  15. Summary • Now know the physiology of gastric acid production & how PPIs & H2s target this. • PPIs generally more effective than H2 antagonists • Useful in treating GI conditions e.g. ulcers, infection and bleeding • Side effects (usually GI upset) tend not to be serious

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