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 Emergency Medicine Trainee with interests in medical education, ECG interpretation, and the use of point-of-care ultrasound in the undifferentiated patient. Co-author of the LITFL ECG Library | Twitter

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