Abstract
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.
Highlights
Drug interaction is currently an increasingly important problem of modern pharmacotherapy since it may considerably alter the pharmacodynamic activity of drugs and be a cause of failed therapy or a decrease of its safety [14].Widely used for treatment of acid-dependent diseases, omeprazole in the human body undergoes rapid and intensive biotrasformation mediated by isoenzymes CYP2C19 and CYP3A4, increasing the probability of the development of drug interaction with other substrates or inhibitors of these enzymes [5, 6]
At the second stage of the study we analysed pharmacotherapy of patients with accompanying pathology – acid-dependent diseases (ADDs) (analysis of the most commonly prescribed combinations of drugs, drug interactions with regard for metabolism, as well as assessment of the risk for the development of adverse drug reactions (ADRs) at the level of cytochrome P450 CYP3A4 with the help the Internet-resource drugs.com)
We examined the dynamics of arterial pressure (AP) in patients with arterial hypertension (AH) and ADD, being on adjusted antihypertensive therapy consisting of amlodipine at a dose of 10 mg, who due to exacerbation of ADD were prescribed omeprazole at a dose of 20 mg
Summary
Drug interaction is currently an increasingly important problem of modern pharmacotherapy since it may considerably alter the pharmacodynamic activity of drugs and be a cause of failed therapy or a decrease of its safety [14]. Used for treatment of acid-dependent diseases, omeprazole in the human body undergoes rapid and intensive biotrasformation mediated by isoenzymes CYP2C19 and CYP3A4, increasing the probability of the development of drug interaction with other substrates or inhibitors of these enzymes [5, 6]. The question arises of whether this alteration in the activity of isoenzyme CYP3A4 can lead to clinically significant interactions (altered activity) of drugs metabolised. Dorofeeva Chair of, of medical and social assessment, urgent and ambulatory care First Moscow State Medical University named after I.
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