| Class | H2 receptor antagonist |
|---|---|
| Chemistry |
Guanidine derivative |
| Routes of administration |
Oral and IV |
| Absorption |
Well absorbed; 60-70% oral bioavailability |
| Solubility |
pKa 6.8; modest water solubility |
| Distribution |
VOD = 0.8L/kg 13-25% protein-bound |
| Metabolism |
Some 30% of cimetidine undergoes hepatic metabolism into inactive metabolites. More interestingly, cimetidine inhibts CYP450 enzymes, impairing the metabolism of other dugs |
| Elimination |
About 70% is eliminated in the urine unchanged |
| Time course of action |
Half-life is 1-2 hours; duration of effect is 4-8 hrs |
| Target receptor |
H2 histamine receptors, which are Gs-coupled receptors; their activation causes an increase in cAMP |
| 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. |
| Clinical effects |
Decreases gastric acid production by up to 70%. Minimal adverse effects; inhibits CYP450 enzymes, can intefere with androgens and produce gynaecomastia |
| Literature reference |
Schunack, 1989 |
| CICM details of understanding | Not specifically listed in the CICM syllabus |
| Mentioned around Deranged Physiology | |
| Related SAQs |