Pharm 101: Pantoprazole

Class

Proton Pump Inhibitor (PPI)

Pharmacodynamics
  • Inhibit both fasting and meal-stimulated secretion by irreversibly inhibiting H/K ATPase in parietal cell canaliculus:
    • Concentrated and activated near site of action
    • Prodrug is rapidly protonated within the parietal cell canaliculus and is concentrated more than 1000-fold by Henderson-Hasselbach trapping
    • Undergoes rapid molecular conversion to active form which forms covalent disulfide bond with H/K ATPase, irreversibly inactivating enzyme
  • In fasting state, only 10% of proton pumps are actively secreting acid and susceptible to inhibition. PPIs should thus be administered one hour before a meal so that peak serum concentration coincides with maximal activity of proton-pump secretion
  • Effects of acid inhibition last up to 24 hours because of time required (at least 18 hours) to synthesise new H/K ATPase pump molecules
Pharmacokinetics
  • Administered as inactive prodrug
  • Lipophilic weak base (pKa 4-5)
  • Bioavailability 77% (decreased 50% by food)
  • Rapid first-pass and systemic hepatic metabolism*
  • Negligible renal clearance
  • Serum half life 1-2 hours, but acid inhibition lasts up to 24 hours due to irreversible inactivation of proton pump
  • 3-4 day onset and offset:
    • Not all proton pumps are inactivated with first dose, 3-4 days of daily medication are required before full acid-inhibiting potential is reached
    • Similiar after stopping drug, 3-4 days for full acid secretion to return
Clinical uses
  • Gastro-oesophageal reflux disease (GORD)
  • Peptic ulcer disease
  • H Pylori-associated ulcers
  • Eradication of H Pylori (clarithromycin, amoxicillin, pantoprazole)
  • Upper gastrointestinal bleeding
Adverse effects
  • Gastrointestinal:
    • Diarrhoea, headache, abdominal pain in 1-5%
    • Increased risk of C difficile infection
  • Metabolic:
    • B12 deficiency
    • Low Mg with secondary Low Ca
    • Osteoporotic fractures with long-term PPI
  • Renal:
    • Acute interstitial nephritis
    • Chronic kidney disease
Precautions/contraindications
  • *Dose reduction in severe liver impairment
  • Drug interactions:
    • Decreased gastric acidity alters absorption of drugs for which intra-gastric acidity affects drug bioavailability e.g. digoxin, ketoconazole
    • PPIs can reduce clopidogrel activation
Further Reading
Pharm 101 700

Pharmacology 101

Top 200 drugs

MBBS (UWA) CCPU (RCE, Biliary, DVT, E-FAST, AAA) Emergency Medicine Advanced Trainee in Melbourne, Australia. Special interests in diagnostic and procedural ultrasound, medical education, and ECG interpretation. Editor-in-chief of the LITFL ECG Library. Twitter: @rob_buttner

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