| Class | Proton pump inhibitor |
|---|---|
| Chemistry |
All share a common core structure, consisting of a substituted benzimidazole ring and a pyridine rin
|
| Routes of administration |
All available as IV formulations as well as oral tablets. |
| Absorption |
Well absorbed in the small intestine; but deactivated by acid and need enteric coating. Bioavailability improves with repeat dosing from 35 to 60%, because of first pass enzyme inhibition.
|
| Solubility |
All are weak bases with a pKa of around 3.9-4.5. Vary in their water solubility, from good (pantoprazole) to minimal (lansoprazole).
|
| Distribution |
All are highly (97%) protein bound; VOD = about 0.2-0.3L/kg. Tend to accumulate (concentrated by 1000 times) in the highly acidic luminal environment of the parietal cell's secretory canaliculi, where the pH can be as low as 1.0
|
| Metabolism |
Inactive prodrugs; metabolised by CYP450 in the liver. Biotransformed into the active forms (sulfenamide derivatives) by the acidic environment of parietal cells
|
| Elimination |
Minimal renal clearance as unchaged drug - mostly inactive metabolites are excreted in this way.
|
| Time course of action |
Half-life is 0.5-1.0 hours; duration of proton pump inhibition is up to 72 hours (new pump proteins need to be made)
|
| Target receptor |
H+/K+ ATPase pumps, or "proton pumps" on the apical surface of gastric parietal cells |
| Mechanism of action |
By binding covalently to active proton pumps on the luminal surface of the gastric parietal cells, the action of the pump is disrupted, which results in the cessation of gastric acid secretion. This leads to a neutralisation of gastric pH. |
| Clinical effects |
Neutralisation of gastric pH (up to 6.0 with IV infusion). Side effects include - Hypomagnesemia - Interstitial nephritis - B12 and iron deficiency - Intestinal bacterial overgrowth - Increased risk of C.difficile infection - Increased risk of hospital-acquired pneumonia |
| Literature reference |
Fock et al (2008) |
| CICM details of understanding | Level 3 |
| Mentioned around Deranged Physiology | |
| Related SAQs |
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