Effect of omeprazole on antihypertensive efficacy of amlodipine in patients with comorbid pathology – arterial hypertension and acid-dependent disease
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01.01.2018 |
Dorofeeva M.
Shikh E.
Sizova Z.
Shindryaeva N.
Lapidus N.
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Electronic Journal of General Medicine |
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© 2018 by the authors; licensee Modestum Ltd., UK. Objective: The problem of drug interactions is increasingly important today because they may induce serious adverse events as well as interfere with efficacy of pharmacotherapy. Combinations of drugs are most often prescribed to patients presenting with comorbid pathology. The incidence of a combination of arterial hypertension (AH) and acid-dependent diseases (ADDs) varies widely ranging from 11.6 to 50%. One of combinations of drugs prescribed to such patients is a combination of calcium channel blocker amlodipine and proton pump inhibitor omeprazole. The latter in the human body undergoes biotransformation mediated at the level of cytochrome P450 by isoenzymes CYP2C19 and CYP3A4. Amlodipine is a substrate of the isoenzyme CYP3A4, which increases the probability of the development of interaction between these drugs. The purpose of our study was to investigate antihypertensive efficacy of amlodipine in patients suffering from arterial hypertension combined with acid-dependent diseases and additionally taking omeprazole. Method: Study included a total of 150 patients with AH and ADD. Antihypertensive therapy was evaluated by means of office measuring of arterial pressure (AP) and circadian monitoring of AP (CMAP). The followed-up patients with AH and ADD were divided into 2 groups. Group One was composed of hypertensive patients undergoing pharmacotherapy with 10 mg amlodipine, whose condition required due to exacerbation of ADD administration of omeprazole at a dose of 20 mg for a period from 3 to 4 weeks. Group Two comprised hypertensive patients receiving antihypertensive therapy consisting of 10 mg amlodipine, who were found to have remission of acid-dependent diseases, with no additional medication taken. Results: The obtained findings demonstrated that one of the commonly used drug combinations in treatment of patients with AH and ADD in ambulatory conditions was a combination of omeprazole and amlodipine, accounting for 7.1%. The results of office measurement of arterial pressure (AP) 2 weeks after initiating pharmacotherapy with omeprazole in patients with AH and ADD demonstrated that the patients receiving omeprazole in addition to antihypertensive therapy were found to have a statistically significant decrease in systolic arterial pressure (SAP) and statistically significantly more pronounced dynamics of a decrease in diastolic arterial pressure (SAP) (p<0.05) compared with those not receiving therapy with omeprazole. Also, in the group of patients taking omeprazole, the findings of circadian monitoring of blood pressure (CMAP) showed a statistically significant decrease in average circadian SAP, average circadian DAP, mean value of daytime SAP and mean value of nighttime SAP (p<0.05). Conclusion: The obtained findings demonstrated that simultaneous prescription of amlodipine and omeprazole to patients with concomitant pathology, i.e., AH and ADD, turned out to enhance the antihypertensive affect of amlodipine, which probably resulted from substrate competition of amlodipine and omeprazole at the level isoenzyme CYP 3A4 of cytochrome P450.
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Modern aspects of domperidone safety
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01.01.2018 |
Kareva E.
Serebrova S.
Drozdov V.
Kurguzova D.
Starodubtsev A.
Vasil N.
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Eksperimental'naya i Klinicheskaya Farmakologiya |
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© 2018 Izdatel'stvo Meditsina. All rights reserved. This review summarizes the state-of-the-art in the problem of assessment of the safety of domperidone - a prokinetic and anti-emetic drug belonging to those most widely used in clinical practice. Special attention is devoted to the potential cardiotoxicity of domperidone, mechanisms of adverse effects development, and risk factors. For reducing the risk of development of dose-dependent side effects, new drugs have been created and used so as to maintain the active agent concentration in the blood plasma within the therapeutic range. Another method of increasing the efficacy and safety of domperidone treatment is based on the potentiation effect. An example is the use of domperidone in a fixed combination with omeprazole (Omez-DSR), in which a the prokinetic is present in a modified release form, which ensures uniform delivery of the acting agent into blood flow (without drug concentration +AJM-peaks+AJQ-related to increased risk of dose-dependent adverse drug reactions.
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