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      Adherence to oral anticoagulation therapy

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          Abstract

          Introduction:

          Warfarin is the most frequently prescribed anticoagulant. Clinical treatment is demanding because of the narrow therapeutic range and considerable differences between the patients. The aim of this survey is to establish adherence to warfarin in subjects who have been prescribed warfarin as a long-term therapy.

          Methods:

          The survey included 30 subjects, and was conducted at local pharmacy store. Statistical processing was carried out using the SPSS (ver. 21.) software. Used for qualitative variables was the Chi-square test, and for quantitative ones the ANOVA test. Data were provided in the form of tables and charts. Level of significance was p=0.05.

          Results:

          The survey included 30 subjects, 14 men and 16 women. Of the total number of polled subjects, 15 were informed by a health care professional about the specificities of warfarin use, 7 said they were not informed, while 8 said they did not know. Most compliant in terms of regularly taking their medicines were pensioners, followed by the unemployed, χ 2=13.231; p<0.05. The number of subjects within the expected therapeutic INR range was 22 (p<0.05).

          Conclusion:

          Strict compliance with the warfarin regimen is important in order to increase its effectiveness, extend the time and strengthen the intensity of anticoagulant action in the body. That is why the target groups of patients, who use warfarin, need additional information before and during therapy, in order to avoid side effects, and at the same time maintain therapeutic efficacy of the medicine throughout the treatment.

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          Most cited references14

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          An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation.

          To avert major hemorrhage, physicians need to know the lowest intensity of anticoagulation that is effective in preventing stroke in patients with atrial fibrillation. Since the low rate of stroke has made it difficult to perform prospective studies to resolve this issue, we conducted a case-control study. We studied 74 consecutive patients with atrial fibrillation who were admitted to our hospital from 1989 through 1994 after having an ischemic stroke while taking warfarin. For each patient with stroke, three controls with nonrheumatic atrial fibrillation who were treated as outpatients were randomly selected from the 1994 registry of the anticoagulant-therapy unit (222 controls). We used the international normalized ratio (INR) to measure the intensity of anticoagulation. For the patients with stroke, we used INR at admission; for the controls, we selected the INR that was measured closest to the month and day of the matched case patient's hospital admission. The risk of stroke rose steeply at INRs below 2.0. At an INR of 1.7, the adjusted odds ratio for stroke, as compared with the risk at an INR of 2.0, was 2.0 (95 percent confidence interval, 1.6 to 2.4); at an INR of 1.5, it was 3.3 (95 percent confidence interval, 2.4 to 4.6); and at an INR of 1.3, it was 6.0 (95 percent confidence interval, 3.6 to 9.8). Other independent risk factors were previous stroke (odds ratio, 10.4; 95 percent confidence interval, 4.4 to 24.5), diabetes mellitus (odds ratio, 2.95; 95 percent confidence interval, 1.3 to 6.5), hypertension (odds ratio, 2.5; 95 percent confidence interval, 1.1 to 5.7), and current smoking (odds ratio, 5.7; 95 percent confidence interval, 1.4 to 24.0). Among patients with atrial fibrillation, anticoagulant prophylaxis is effective at INRs of 2.0 or greater. Since previous studies have indicated that the risk of hemorrhage rises rapidly at INRs greater than 4.0 to 5.0, tight control of anticoagulant therapy to maintain the INR between 2.0 and 3.0 is a better strategy than targeting lower, less effective levels of anticoagulation.
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            Nuclear receptors and the regulation of drug-metabolizing enzymes and drug transporters: implications for interindividual variability in response to drugs.

            Erratic or unpredictable response to drugs remains a challenge of modern drug therapy. An important determinant of such interindividual differences in drug response is variability in the expression of drug-metabolizing enzymes and/or transporters at sites of absorption and/or tissue distribution. Variable drug-metabolizing enzyme and transporter expression can result in unpredictable exposure and tissue distribution of drugs and may manifest as adverse effects or therapeutic failure. In the past decade, important new insights have been made relating to the regulatory mechanisms governing the expression of drug-metabolizing enzymes and transporters by ligand-activated nuclear receptors. Specifically, there is compelling evidence to demonstrate that PXR, CAR, FXR, LXR, VDR, HNF4alpha, and AhR form a battery of nuclear receptors that regulate the expression of many important drug-metabolizing enzyme and transporters. In this review, the authors focus on clinically important drug-metabolizing enzymes such as CYP3A4, CYP2B6, CYP2C9, CYP2C19, UGT1A1, SULT2A1, and glutathione S-transferases and their regulation by nuclear receptors. They also review the nuclear receptor-mediated regulation of drug transporters such as MDR1, MRP2, MRP4, BSEP, BCRP, NTCP, OATP1B3, and OATP1A2. Finally, they outline how the drug development process has been affected by the current understanding of the involvement of nuclear receptors in the regulation of drug disposition genes.
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              Genetic polymorphism of metabolic enzymes P450 (CYP) as a susceptibility factor for drug response, toxicity, and cancer risk.

              The polymorphic P450 (CYP) enzyme superfamily is the most important system involved in the biotransformation of many endogenous and exogenous substances including drugs, toxins, and carcinogens. Genotyping for CYP polymorphisms provides important genetic information that help to understand the effects of xenobiotics on human body. For drug metabolism, the most important polymorphisms are those of the genes coding for CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5, which can result in therapeutic failure or severe adverse reactions. Genes coding for CYP1A1, CYP1A2, CYP1B1, and CYP2E1 are among the most responsible for the biotransformation of chemicals, especially for the metabolic activation of pre-carcinogens. There is evidence of association between gene polymorphism and cancer susceptibility. Pathways of carcinogen metabolism are complex, and are mediated by activities of multiple genes, while single genes have a limited impact on cancer risk. Multigenic approach in addition to environmental determinants in large sample studies is crucial for a reliable evaluation of any moderate gene effect. This article brings a review of current knowledge on the relations between the polymorphisms of some CYPs and drug activity/toxicity and cancer risk.
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                Author and article information

                Journal
                JHS
                Journal of Health Sciences
                University of Sarajevo Faculty of Health Studies (Bosnia )
                2232-7576
                1986-8049
                2014
                : 4
                : 2
                : 114-119
                Affiliations
                [1 ]Boehringer Ingelheim RCV GmbH&Co.KG, Representative Office, Grbavička 4, 71000 Sarajevo, Bosnia and Herzegovina
                [2 ]Sanofi-aventis Groupe, Representative Office in Bosnia and Herzegovina, Fra Anđela Zvizdovića 1/VIII, 71000 Sarajevo, Bosnia and Herzegovina
                [3 ]Clinic for Vascular Diseases, Clinical Center of Sarajevo University, Bolnička 25, 71000 Sarajevo, Bosnia and Herzegovina
                Author notes
                [* ]Corresponding Author: Lana Lekić, mr sci pharm spec Boehringer Ingelheim RCV GmbH&Co.KG, Representative Office Grbavička 4, 71000 Sarajevo, Bosnia and Herzegovina Phone: +387 62 205950 E-mail: lana.lekic@ 123456hotmail.com
                Article
                JHS-4-114
                bd6021ca-f761-495c-93eb-2f1a93098333
                Copyright: © Lana Lekić, et al.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 August 2014
                : 11 September 2014
                Categories
                RESEARCH ARTICLE

                Nursing,General medicine,Medicine,Molecular medicine,Life sciences
                compliance,adherence,anticoagulation therapy

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