Drug interactions between cimetidine and omeprazole
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Drug Interaction Mechanisms: Cimetidine and Omeprazole
Cimetidine and omeprazole are both commonly used to reduce stomach acid, but they work through different mechanisms and have distinct profiles for drug interactions. Cimetidine is a histamine H2-receptor antagonist, while omeprazole is a proton pump inhibitor. Both drugs can affect the metabolism of other medications by inhibiting liver enzymes, particularly those in the cytochrome P450 family, which are responsible for breaking down many drugs in the body 3467.
Effects on Drug Metabolism and Enzyme Inhibition
Both cimetidine and omeprazole inhibit several cytochrome P450 enzymes, including CYP2C9, CYP2C19, CYP2D6, and CYP3A. However, omeprazole is especially potent in inhibiting CYP2C19, while cimetidine has a broader but generally weaker inhibitory effect across multiple enzymes . This means that both drugs can slow the breakdown of medications metabolized by these enzymes, potentially increasing their levels in the blood and risk of side effects 1367.
Clinical Impact: Diazepam and Other Drugs
Studies show that both cimetidine and omeprazole decrease the clearance and increase the half-life of diazepam, a drug metabolized by the liver. The reduction in diazepam clearance is due to inhibition of hepatic metabolism by both drugs, but the effect is generally not clinically significant at recommended doses because diazepam has a wide therapeutic range 168. Other drugs affected by these interactions include tolbutamide, diclofenac, cisapride, glibenclamide, and benidipine, with omeprazole and cimetidine each showing selective inhibition depending on the specific drug and enzyme involved .
Comparative Risk of Drug-Drug Interactions
Cimetidine is known to interact with a larger number of drugs and to a greater extent than omeprazole, making it more likely to cause clinically significant drug interactions . Omeprazole, while still capable of inhibiting drug metabolism, generally has a lower risk of causing adverse interactions compared to cimetidine 78. This difference is important when choosing an acid-reducing agent for patients taking multiple medications.
Pharmacokinetic Interactions Between Cimetidine and Omeprazole
When cimetidine and omeprazole are used together, cimetidine can further inhibit the metabolism of omeprazole by reducing hepatic blood flow and inhibiting the same liver enzymes that metabolize omeprazole . This can lead to higher levels of omeprazole in the body, although the clinical significance of this interaction is not fully established and may depend on individual patient factors and dosages .
Conclusion
Cimetidine and omeprazole both inhibit liver enzymes responsible for drug metabolism, but cimetidine generally has a broader and stronger effect, leading to a higher risk of drug-drug interactions. Omeprazole is more selective, with its strongest inhibition on CYP2C19. When used together, cimetidine may increase omeprazole levels by further inhibiting its metabolism. Careful consideration should be given when prescribing these drugs, especially in patients taking other medications metabolized by the cytochrome P450 system 134678.
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