The document discusses the secretion of hydrochloric acid by gastric parietal cells and the regulation of drugs used to treat peptic ulcers and gastroesophageal reflux disease, specifically proton pump inhibitors (PPIs). It highlights various formulations, therapeutic uses, potential side effects, and drug interactions related to PPIs like omeprazole, lansoprazole, and pantoprazole. Additionally, it covers considerations for patients with renal and hepatic diseases regarding PPI dosage and effectiveness.

2. Secretion of HCl
by gastric parietal
cell and its
regulation
K.D Tripathi. Drugs for Peptic Ulcer and Gastroesophageal Reflux Disease. In: Essentials of pharmacology. 8th edition. New Delhi: Jaypee Brothers
Medical Publishers, 2019. 647

3. DRUGS
 Omeprazole
 Lansoprazole
 Pantoprazole
 Rabeprazole
 Esomeprazole

4. Mechanism of action
Keith A. Sharkey, Wallace K. McNaughton. Pharmacotherapy for Gastric Acidity, Peptic Ulcers, and Gastroesophageal Reflux Disease. In: Goodman and
Gilman’s; The Pharmacological Basis of Therapeutics.13th Edition. New York: Mc Graw Hill education; 2018. 908

5. Pharmacokinetics of PPIs
Kenneth R. McQuaid. Drugs Used in the Treatment of Gastrointestinal Diseases. In: Katzung; Basic and Clinical Pharmacology. 14th edition. New York:
Mc Graw Hill education; 2018. 1095

6. Different formulations for oral dosage forms
 Enteric-coated pellets within gelatin capsules (omeprazole, dexlansoprazole, esomeprazole,
lansoprazole, rabeprazole)
 Delayed-release tablets (omeprazole formulations)
 Delayed-release capsules (dexlansoprazole, esomeprazole formulations)
 Delayed-release oral suspension packets (esomeprazole, omeprazole, pantoprazole)
 Enteric-coated microgranules in orally disintegrating tablets (lansoprazole)
 Enteric-coated tablets (pantoprazole, rabeprazole, and omeprazole)
 Powdered omeprazole combined with sodium bicarbonate (capsules and oral suspension)

7. Therapeutic
uses
• In GERD, including erosive esophagitis.
• In conjunction with antibiotics for the
eradication of Helicobacter pylori.
• Treatment of Zollinger-Ellison syndrome.

8. Side effects
Carol Motycka. Gastrointestinal and Antiemetic Drugs. In: Lippincott Illustrated
Reviews: Pharmacology.6th edition. Philadelphia: Wolters Kluwer;2015. 404

9. Side effects (Contd.)
 Other- Subacute myopathy, arthralgias, headaches, interstitial nephritis, and skin
rashes.
 Chronic use of PPIs has been reported to be associated with increased
susceptibility to certain infections (e.g., hospital-acquired pneumonia,
community-acquired Clostridium difficile)
 Hypergastrinemia

10. Drug Interactions
• Only omeprazole inhibits CYP2C19 (thereby decreasing the clearance of disulfiram,
phenytoin, and other drugs)
• Also induces the expression of CYP1A2 (thereby increasing the clearance of imipramine,
several antipsychotic drugs, tacrine, and theophylline)
• Some evidence that PPIs can inhibit conversion of clopidogrel (at the level of CYP2C19) to
the active anticoagulating form, but this is controversial
• Concurrent use of clopidogrel and PPIs (mainly pantoprazole) significantly reduces GI
bleeding without increasing adverse cardiac events
• Methotrexate and PPI therapy because PPIs can competitively inhibit methotrexate
elimination and thereby increase methotrexate levels

11. SUMMARY OF DRUGS
Keith A. Sharkey, Wallace K. McNaughton. Pharmacotherapy for Gastric Acidity, Peptic Ulcers, and Gastroesophageal Reflux Disease. In: Goodman and
Gilman’s; The Pharmacological Basis of Therapeutics.13th Edition. New York: Mc Graw Hill education; 2018. 918

12. REFERENCES
 Keith A. Sharkey, Wallace K. McNaughton. Pharmacotherapy for Gastric Acidity, Peptic Ulcers, and
Gastroesophageal Reflux Disease. In: Goodman and Gilman’s; The Pharmacological Basis of
Therapeutics.13th Edition. New York: Mc Graw Hill education; 2018. 909-912
 Kenneth R. McQuaid. Drugs Used in the Treatment of Gastrointestinal Diseases. In: Katzung; Basic
and Clinical Pharmacology. 14th edition. New York: Mc Graw Hill education; 2018. 1091-1094
 Carol Motycka. Gastrointestinal and Antiemetic Drugs. In: Lippincott Illustrated Reviews:
Pharmacology.6th edition. Philadelphia: Wolters Kluwer;2015. 404-405
• K.D Tripathi. Drugs for Peptic Ulcer and Gastroesophageal Reflux Disease. In: Essentials of
pharmacology. 8th edition. New Delhi: Jaypee Brothers Medical Publishers, 2019. 647-654

14. • Chronic renal failure does not lead to drug accumulation with once-a-
day dosing of the PPIs. Hepatic disease substantially reduces the
clearance of esomeprazole and lansoprazole. Thus, in patients with
severe hepatic disease, dose reduction is recommended for
esomeprazole and lansoprazole.