Proton Pump Inhibitors

PROTON PUMP INHIBITORS


PROTON PUMP INHIBITORS

  • Are prodrugs.
  • Active drug – Sulfenamide.

MOA: Act by irreversibly inhibiting H+ K+ ATPase in gastric parietal cells.

Steps of proton pump inhibition:

  • Prodrugs reach parietal cells –-> Sulfenamide (active moiety) formed –> Trapped inside parietal cell. 
  • Inhibits both basal acid output (nocturnal acid secretion) & meal-stimulated acid output (maximal acid output).

Drugs: Omeprazole, pantoprazole, esomeprazole, lansoprazole & rabeprazole

General drug properties:

  • Weak bases & destroyed easily by gastric acid.
    • Hence, protected as enteric coated tablets.
    • Coating dissolves in intestinal juice (alkaline medium) & prodrugs are absorbed.
  • Drug administration:
    • Given orally in early morning, empty stomach (just before breakfast).
    • Pantoprazole, esomeprazole & lansoprazole – Given as i.v.
  • Short t1/2, yet inhibits acid secretion for >24 hours.
    • Referred as “Hit & run drugs” – Inhibits proton pump irreversibly

Uses:

  • DOC for peptic ulcer disease (PUD) of any etiology, including NSAID induced.
  • DOC for gastroesophageal reflux disease (GERD).
  • DOC for Zollinger Ellison Syndrome (ZES).
  • Prevention of stress-induced gastric bleeding – H2 blockers (i.v. infusion) preferred over PPIs.
  • Patients with nasoenteric tube – Immediate omeprazole release by nasogastric tube is currently preferred.

Adverse effects:

  • Quite safe drugs.
  • Diarrhea, headache & abdominal pain.

Long-term use:

  • Causes subnormal vitamin B12 levels (due to reduced absorption).
  • Increased hip fracture risk (reduced Ca2+ absorption).
  • Increased enteric bacterial infections risk – 
  • C. difficile infections.
    • Bacterial gastroenteritis.
    • Pneumonia.

Important drug details:

  • Lanoprazole:
    • Most potent PPI & safest during pregnancy.
    • Enhances theophylline metabolism.
  • Esomeprazole, lansoprazole & pantoprazole:
    • Given as i.v.
  • Omeprazole & esomeprazole:
    • Microsomal enzyme inhibitors.
    • Decreases diazepam metabolism.
    • Induce carcinoid tumors in rats.

Exam Important

  • Despite their short half-lives (2 hours), Proton pump Inhibitors (PPIs) cause prolonged suppression of acid secretion (up to 48 hours), because they irreversibly inhibit the proton pump molecule and hence, acid secretion requires synthesis of new proton pumps.
  • Pantoprazole is a proton pump inhibitor can be used IV.
  • Drug of choice for Zollinger-Ellison syndrome is Proton pump inhibitors.
  • Most effective for healing of Non-steroidal Anti Inflammatory Drug (NSAID) induced gastric ulcer is Proton pump inhibitors.
  • Treatment of choice in duodenal ulcer without any complication of hemorrhage is Proton pump inhibitors.
  • Omeprazole induces carcinoid tumors in rats.
  • Omeprazole & esomeprazole are microsomal enzyme inhibitors & decreases diazepam metabolism.
  • Omeprazole act by inhibiting H+ K+ ATPase.
  • Proton pump inhibitors are all prodrugs, reach parietal cells, converted into sulfenamide (active moiety).
  • Proton pump inhibitors inhibit both basal acid output (nocturnal acid secretion) & meal-stimulated acid output (maximal acid output).
  • Proton pump inhibitors are weak bases & destroyed easily by gastric acid, hence protected as enteric coated tablets, coating dissolves in intestinal juice (alkaline medium) & prodrugs are absorbed.
  • Proton pump inhibitors are given orally in early morning, empty stomach (just before breakfast).
  • Pantoprazole, esomeprazole & lansoprazole are given as i.v.
  • PPI’s have short t1/2, yet inhibits acid secretion for >24 hours, hence referred as “Hit & run drugs” because inhibits proton pump irreversibly.
  • DOC for peptic ulcer disease (PUD) of any etiology, including NSAID induced is PPI.
  • DOC for gastroesophageal reflux disease (GERD) is PPI.
  • DOC for Zollinger Ellison Syndrome (ZES) is PPI.
  • H2 blockers (i.v. infusion) preferred over PPIs for prevention of stress-induced gastric bleeding.
  • On long-term use of PPI, causes subnormal vitamin B12 levels due to reduced absorption, increased hip fracture risk due to reduced Ca2+ absorption & increased enteric bacterial infections risk including C. difficile infections, bacterial gastroenteritis & Pneumonia.
  • Lansoprazole is the most potent PPI & safest during pregnancy.
  • Lanoprazole enhances theophylline metabolism.
  • Omeprazole & esomeprazole are microsomal enzyme inhibitors, by decreasing diazepam metabolism.
  • Omeprazole induces carcinoid tumors in rats.
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