Compare and contrast the pharmacology of ranitidine and omeprazole.
These agents are both commonly used in the ICU. The expectation was weighted towards the interesting and important aspects of pharmacology as outlined for category B drugs. It was expected candidates could detail that both drugs are used to suppress acid secretion in the stomach. Ranitidine is a competitive, reversible inhibitor of the action of histamine at the histamine H2 receptors found in gastric parietal cells. This results in decreased gastric acid secretion and gastric volume, and reduced hydrogen ion concentration. In contrast to Omeprazole which is a proton pump inhibitor that irreversibly blocks the hydrogen potassium ATPase the gastric parietal cells. Some general description of dosing, route of administration, pharmacokinetics and possible adverse effects was expected.
| Name | Ranitidine | Omeprazole |
| Class | H2 receptor antagonist | Proton pump inhibitor |
| Chemistry | Guanidine derivative | Benzimidazole derivative |
| Routes of administration | Oral and IV | Oral and IV |
| Absorption | Well absorbed; 50% oral bioavailability | Well absorbed in the small intestine; need enteric coating. Bioavailability improves with repeat dosing from 35 to 60% |
| Solubility | pKa 7.8; highly water-soluble | pKa 3.97; slightly soluble in water. |
| Distribution | VOD=1.4L/kg; 13-25% protein-bound | VOD =0.3L/kg; 97% protein-bound |
| Target receptor | H2 histamine receptors, which are Gs-coupled receptors; their activation causes an increase in cAMP | H+/K+ ATPase pumps, or "proton pumps" on the apical surface of gastric parietal cells |
| Metabolism | Approximately half of a dose undergoes haptic metabolism | Inactive prodrug; metabolised by CYP450 in the liver. Biotransformed into the active form (a sulfenamide derivative) by the acidic environment of parietal cells |
| Elimination | Approximately half of a dose is cleared renally | Minimal renal clearance as unchaged drug - mostly inactive metabolites are excreted in this way. |
| Time course of action | Half-life is 2 hours; duration of effect is 4-10 hrs | Half-life is 0.5-1.0 hours; duration of proton pump inhibition is up to 72 hours |
| Mechanism of action | Histamine (H2) receptor antagonists block the effect of histamine on gastric acid production by antagonising the basolateral H2 receptor, and therefore decreasing the levels of cAMP in parietal cells. That cAMP is usually responsible for the activation of protein kinase A, which in turn phosphorylates all sorts of cytoskeletal machinery to bring H+/K+ ATPase transporters ("proton pumps") to the luminal surface. Ergo, the mechanism of action of these drugs is to reduce the expression of the acid secretion machinery. | 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 | Decreases gastric acid production by up to 70%. Minimal adverse effects; inhibits alcohol dehydrogenase | 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 |
| Single best reference for further information | Schunack, 1989 | Fock et al (2008) |