Drug Interactions With Proton Pump Inhibitors
Drug-drug interaction is the change that occurs in a drug’s effect because of the co-administration of two or more drugs. This may result in a decrease or increase in the effect of one of the drugs. These interactions are not desired because they may lead to sub-optimal clinical effects or serious adverse drug effects.
Clopidogrel is an antiplatelet drug. Its mechanism of action involves binding and irreversibly blocking the P2Y12 receptor on platelets, which results in the inhibition of the adenosine diphosphate pathway of platelets. This then leads to reduced platelet aggregation (Helton TJ et al., 2007). Proton pump inhibitors act by irreversibly blocking hydrogen/potassium ATPase, preventing the secretion of hydrogen ions into the gastric lumen and inhibiting acid secretion (Sach G et al., 2006).
Clopidogrel interacts with proton pump inhibitors, especially omeprazole. Clopidogrel, used for preventing ischemic events, has some drawbacks because of its gastrointestinal bleeding effect. This is a result of the inhibition of platelet aggregation at the site of ulceration. To reduce this side effect, clopidogrel is administered with omeprazole (Sach G et al., 2006). Also, gastrointestinal bleeding is associated with morbidity in people with an underlying cardiovascular disease requiring co-administration of clopidogrel and omeprazole, especially in patients at a greater risk of gastrointestinal bleeding.
Clopidogrel is administered as a prodrug, which is then metabolized to its active form by the liver enzyme CYP2C19 (Helton TJ et al., 2007). Omeprazole, when administered, is metabolized by the same enzyme and has a competitive inhibitory effect on the enzyme reducing the conversion of clopidogrel to its active form. This contributes to the lower efficacy of the clopidogrel antiplatelet effect.
Even though drug-drug interaction occurs between clopidogrel and omeprazole, these two drugs can still be co-administered, yielding reasonable clinical activity. These strategies may include increasing the clopidogrel maintenance dose and dose separation, but only during acute treatment. Alternative ways can be employed, which involve replacing omeprazole with another proton pump inhibitor such as rabeprazole, which is not metabolized by the CYP2C19 enzyme, or the use of alternative antacids such as H2 receptor blockers such as cimetidine (Helton TJ et al., 2007).
References
Helton, T. J., Bavry, A. A., Kumbhani, D. J., Duggal, S., Roukoz, H., & Bhatt, D. L. (2007). Incremental effect of clopidogrel on important outcomes in patients with cardiovascular disease: A meta-analysis of randomized trials. American Journal of Cardiovascular Drugs, 7(4), 289–297. https://doi.org/10.2165/00129784-200707040-00006
Sachs, G., Shin, J. M., & Howden, C. W. (2006). Review article: The clinical pharmacology of proton pump inhibitors. Alimentary Pharmacology and Therapeutics, 23(SUPPL. 2), 2–8. https://doi.org/10.1111/j.1365-2036.2006.02943.x
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Question 
Drug Interactions With Proton Pump Inhibitors
Drug Interactions With Proton Pump Inhibitors
Select a medication and apply the available evidence and treatment guidelines to determine appropriate therapeutic options that have a drug-drug interaction with proton pump inhibitors or antacids.
Describe the interaction and the clinical management of the situation.
Provide rationale and justification for continuing both medications, or discuss alternative therapy that could eliminate the drug-drug interaction.
Include references using APA format.