The influence of drug interactions on the international Normalized Ratio (INR) in hospitalized patients on warfarin therapy

Interakcije lijekova predstavljaju značajno područje istraživanja u suvremenoj medicini. Varfarin kao temeljni lijek pri liječenju i prevenciji duboke venske tromboze, plućne embolije i drugih bolesti, zbog svoje specifične građe, biotransformacije, metabolizma, individualnog doziranja i opasnosti od krvarenja predstavlja trajni izazov. U svrhu pokušaja evaluacije utjecaja interakcija lijekova na međunarodni normalizirani omjer (INR) kao temeljni parametar praćenja terapije varfarinom, tijekom ovog istraživanja je korišten računalni program za probir interakcija Lexi-Interact. U radu je provedena analiza 339 bolesnika kojima je tijekom hospitalizacije započeta terapija varfarinom, te su temeljem programa podijeljeni u ispitnu skupinu (223 bolesnika) sa mogućim klinički značajnim interakcijama s varfarinom i kontrolnu skupinu (116 bolesnika) bez njih. Bolesnici su u prosjeku istodobno dobivali 5,28 lijekova (od 1-13 lijekova po bolesniku). Analizom rezultata vidljivo je da je 65,8% bolesnika bilo izloženo klinički značajnim interakcijama (1-6 interakcija po bolesniku). Statistički značajna razlika između navedene dvije skupine zabilježena je samo u broju lijekova, izuzev varfarina, kojima su bolesnici bili liječeni. Interakcije nisu statistički značajno utjecale na vrijednosti INR-a sedmog dana terapije, kao ni na visinu doze varfarina istog dana. Značajan utjecaj interakcija nije zabilježen pri podjeli bolesnika na podskupine s ciljnim INR između 2 i 3, te one iznad i ispod tih vrijednosti, kao niti na učestalost zabilježenih nuspojava. Zaključno, ovim istraživanjem nije dokazan utjecaj interakcija varfarina s drugim lijekovima na međunarodni normalizirani omjer, te individualno titriranje i praćenje ostaje temelj njegova uvođenja u terapiju.Drug interactions represent an important area of research in modern medicine. Warfarin, as the basic drug for treatment and prevention of deep venous thrombosis, pulmonary embolism and other diseases, due to its specific composition, biotransformation, metabolism, individual dosing and the risk of bleeding represents a permanent challenge. In the attempt to evaluate the influence of drug interactions on the International Normalized Ratio (INR), the computer program for screening drug interactions called Lexi- Interact was used during this research as the basic parameter for monitoring warfarin therapy. In this paper, the analysis of 339 patients whose warfarin therapy began during hospitalization was conducted. Based on the program, they were divided into the group with (223 patients), and the group without (116 patients) possible clinically significant interactions. On the average, the patients were concurrently taking 5.28 drugs (1-13 drugs per patient). The analysis of results shows that 65.8% of patients were exposed to clinically significant interactions (1-6 interactions per patient). Statistically significant difference between the two groups was recorded only in the number of drugs, apart from warfarin, the patients were treated with. The interactions did not have a statistically significant impact on the INR values on the day 7 of therapy or on the dose of warfarin on the same day. A significant influence of interactions was not recorded in the division of patients into subgroups with target INR between 2 and 3, and those above and under those values; or on the frequency of recorded side-effects. In conclusion, this research did not prove the influence of warfarin interactions with other drugs on the International Normalized Ratio, and therefore individual titration and monitoring remains the basis of its introduction into therapy

The Relationship between Methylenetetrahydro-folate Reductase C677T Gene Polymorphism and Diabetic Nephropathy in Croatian Type 2 Diabetic Patients

Methylenetetrahydrofolate reductase (MTHFR) polymorphism has been shown to be associated with the development of diabetic nephropathy in many ethnic groups. In this study, we examined the correlation between MTHFR C677T poly- morphism and microalbuminuria in patients with diabetes mellitus type 2 in Croatian patients. 85 patients with diabetes mellitus type 2 were recruited. Patients were classified into two groups – with and without diabetic nephropathy ac- cording to urinary albumin excretion rate in urine collected during 24 hours. The C677T genotype was determined by real-time PCR analysis. The genotype frequencies were CC 36,5%, CT 42,3% and TT 21,2% in diabetic patients without nephropathy versus CC 39,4%, CT 45,4% and TT 15,2% in those with nephropathy. There was no statistically significant difference in allele distribution between patients with nephropathy and those without (p=0,788). Our study did not show a correlation between mutations in the MTHFR gene and diabetic nephropathy in Croatian patients. Diabetic nephropathy is influenced by multiple risk factors which can modify the importance of MTHFR polymorphism in its de- velopment

Hrvatske smjernice za farmakološko liječenje šećerne bolesti tipa 2 [Croatian guidelines for the pharmacotherapy of type 2 diabetes]

Introduction: The Croatian Association for Diabetes and Metabolic Disorders of the Croatian Medical Association has issued in 2011 the first national guidelines for the nutrition, education, self-control, and pharmacotherapy of diabetes type 2. According to the increased number of available medicines and new evidence related to the effectiveness and safety of medicines already involved in the therapy there was a need for update of the existing guidelines for the pharmacotherapy of type 2 diabetes in the Republic of Croatia. Participants: as co-authors of the Guidelines there are listed all members of the Croatian Association for Diabetes and Metabolic Diseases, as well as other representatives of professional societies within the Croatian Medical Association, who have contributed with comments and suggestions to the development of the Guidelines. Evidence: These guidelines are evidence-based, according to the GRADE system (eng. Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendations. Conclusions: An individual patient approach based on physiological principles in blood glucose control is essential for diabetes' patients management. Glycemic targets and selection of the pharmacological agents should be tailored to the patient, taking into account the age, duration of disease, life expectancy, risk of hypoglyce- mia, comorbidities, developed vascular and other complications as well as other factors. Because of all this, is of national interest to have a practical, rational and applicable guidelines for the pharmacotherapy of type 2 diabetes

CROATIAN GUIDELINES FOR THE PHARMACOTHERAPY OF TYPE 2 DIABETES

Uvod: Hrvatsko društvo za dijabetes i bolesti metabolizma Hrvatskoga liječničkog zbora izradilo je 2011. godine prve nacionalne smjernice o prehrani, edukaciji i samokontroli te farmakološkom liječenju šećerne bolesti tipa 2. Sukladno povećanom broju dostupnih lijekova te novim spoznajama o učinkovitosti i sigurnosti primjene već uključenih lijekova, pokazala se potreba za obnovom postojećih smjernica za farmakološko liječenje šećerne bolesti tipa 2 u Republici ­Hrvatskoj. Sudionici: Kao koautori Smjernica navedeni su svi članovi Hrvatskog društva za dijabetes i bolesti metabolizma Hrvatskoga liječničkog zbora, kao i ostalih uključenih stručnih društava, koji su svojim komentarima i prijedlozima pridonijeli izradi Smjernica. Dokazi: Ove su Smjernice utemeljene na dokazima, prema sustavu GRADE (engl. Grading of Recommendations, Assessment, Development and Evaluation) koji uz razinu dokaza opisuje i snagu preporuke. Zaključci: Individualan pristup temeljen na fiziološkim principima regulacije glikemije nuždan je u liječenju osoba sa šećernom bolesti. Ciljeve liječenja i odabir medikamentne terapije treba prilagoditi oboljeloj osobi, uzimajući u obzir životnu dob, trajanje bolesti, očekivano trajanje života, rizik od hipoglikemije, komorbiditete, razvijene vaskularne i ostale komplikacije, kao i ostale čimbenike. Zbog svega navedenoga od nacionalnog je interesa imati praktične, racionalne i provedive smjernice za farmakološko liječenje šećerne bolesti tipa 2.Introduction: The Croatian Association for Diabetes and Metabolic Disorders of the Croatian Medical Association has issued in 2011 the first national guidelines for the nutrition, education, self-control, and pharmacotherapy of ­diabetes type 2. According to the increased number of available medicines and new evidence related to the effectiveness and safety of medicines already involved in the therapy there was a need for update of the existing guidelines for the ­pharmacotherapy of type 2 diabetes in the Republic of Croatia. Participants: as co-authors of the Guidelines there are listed all members of the Croatian Association for Diabetes and Metabolic Diseases, as well as other representatives of professional societies within the Croatian Medical Association, who have contributed with comments and suggestions to the development of the Guidelines. Evidence: These guidelines are evidence-based, according to the GRADE system (eng. Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendations. Conclusions: An individual patient approach based on physiological principles in blood glucose control is essential for diabetes’ patients management. Glycemic targets and selection of the pharmacological agents should be tailored to the patient, taking into account the age, duration of disease, life expectancy, risk of hypoglycemia, comorbidities, developed vascular and other complications as well as other factors. Because of all this, is of national interest to have a practical, rational and applicable guidelines for the pharmacotherapy of type 2 diabetes

The relationship between methylenetetrahydrofolate reductase C677T gene polymorphism and diabetic nephropathy in Croatian type 2 diabetic patients [Povezanost polimirfizma C677T gena za metilentetrahidrofolat reduktazu i dijabetičke nefropatije u bolesnika sa šećernom bolesti tip 2 u Hrvatskoj]

Methylenetetrahydrofolate reductase (MTHFR) polymorphism has been shown to be associated with the development of diabetic nephropathy in many ethnic groups. In this study, we examined the correlation between MTHFR C677T polymorphism and microalbuminuria in patients with diabetes mellitus type 2 in Croatian patients. 85 patients with diabetes mellitus type 2 were recruited. Patients were classified into two groups--with and without diabetic nephropathy according to urinary albumin excretion rate in urine collected during 24 hours. The C677T genotype was determined by real-time PCR analysis. The genotype frequencies were CC 36.5%, CT 42.3% and TT 21.2% in diabetic patients without nephropathy versus CC 39.4%, CT 45.4% and TT 15.2% in those with nephropathy. There was no statistically significant difference in allele distribution between patients with nephropathy and those without (p = 0.788). Our study did not show a correlation between mutations in the MTHFR gene and diabetic nephropathy in Croatian patients. Diabetic nephropathy is influenced by multiple risk factors which can modify the importance of MTHFR polymorphism in its development

Povezanost polimirfizma C677T gena za metilentetrahidrofolat reduktazu i dijabetičke nefropatije u bolesnika sa šećernom bolesti tip 2 u Hrvatskoj

Methylenetetrahydrofolate reductase (MTHFR) polymorphism has been shown to be associated with the development of diabetic nephropathy in many ethnic groups. In this study, we examined the correlation between MTHFR C677T polymorphism and microalbuminuria in patients with diabetes mellitus type 2 in Croatian patients. 85 patients with diabetes mellitus type 2 were recruited. Patients were classified into two groups--with and without diabetic nephropathy according to urinary albumin excretion rate in urine collected during 24 hours. The C677T genotype was determined by real-time PCR analysis. The genotype frequencies were CC 36.5%, CT 42.3% and TT 21.2% in diabetic patients without nephropathy versus CC 39.4%, CT 45.4% and TT 15.2% in those with nephropathy. There was no statistically significant difference in allele distribution between patients with nephropathy and those without (p = 0.788). Our study did not show a correlation between mutations in the MTHFR gene and diabetic nephropathy in Croatian patients. Diabetic nephropathy is influenced by multiple risk factors which can modify the importance of MTHFR polymorphism in its development.Polimorfizam gena za metilentetrahidrofolat reduktazu (MTHFR) je povezan s razvojem dijabetičke nefropatije u mnogim etničkim skupinama.U ovoj studiji istraživali smo povezanost između polimorfizma C677T gena za MTHFR i mikroalbuminurije u bolesnika sa šećernom bolesti tip 2 u hrvatskih bolesnika. Osamdeset pet bolesnika sa šećernom bolesti je obrađivano i svrstano u dvije skupine – sa dijabetičkom nefropatijom i bez nje, ovisno o vrijednostima izlučenog albumina u 24-satnom urinu. Mutacija C677T gena za MTHFR određena je metodom izolacije DNA i alel specifične lančane reakcije polimeraze (PCR). Raspodjela genotipova u skupini bolesnika s normoalbuminurijom bila je: CC 36,5%, CT 42,3% i TT 21,2%, dok je u skupini bolesnika sa mikroalbuminurijom bila: CC 39,4%, CT 45,4% i TT 15,2%. Nije bilo statistički značajne razlike među grupama u distribuciji C677T genotipova (p=0,788). Naše istraživanje nije pokazalo povezanost između mutacije gena za metilentetrahidrofolat reduktazu i dijabetičke nefropatije u hrvatskih bolesnika. Mnogostruki čimbenici mogu modificirati značajnost utjecaja polimorfizma MTHFR na nastanak dijabetičke nefropatije

Povezanost polimirfizma C677T gena za metilentetrahidrofolat reduktazu i dijabetičke nefropatije u bolesnika sa šećernom bolesti tip 2 u Hrvatskoj

Methylenetetrahydrofolate reductase (MTHFR) polymorphism has been shown to be associated with the development of diabetic nephropathy in many ethnic groups. In this study, we examined the correlation between MTHFR C677T polymorphism and microalbuminuria in patients with diabetes mellitus type 2 in Croatian patients. 85 patients with diabetes mellitus type 2 were recruited. Patients were classified into two groups--with and without diabetic nephropathy according to urinary albumin excretion rate in urine collected during 24 hours. The C677T genotype was determined by real-time PCR analysis. The genotype frequencies were CC 36.5%, CT 42.3% and TT 21.2% in diabetic patients without nephropathy versus CC 39.4%, CT 45.4% and TT 15.2% in those with nephropathy. There was no statistically significant difference in allele distribution between patients with nephropathy and those without (p = 0.788). Our study did not show a correlation between mutations in the MTHFR gene and diabetic nephropathy in Croatian patients. Diabetic nephropathy is influenced by multiple risk factors which can modify the importance of MTHFR polymorphism in its development.Polimorfizam gena za metilentetrahidrofolat reduktazu (MTHFR) je povezan s razvojem dijabetičke nefropatije u mnogim etničkim skupinama.U ovoj studiji istraživali smo povezanost između polimorfizma C677T gena za MTHFR i mikroalbuminurije u bolesnika sa šećernom bolesti tip 2 u hrvatskih bolesnika. Osamdeset pet bolesnika sa šećernom bolesti je obrađivano i svrstano u dvije skupine – sa dijabetičkom nefropatijom i bez nje, ovisno o vrijednostima izlučenog albumina u 24-satnom urinu. Mutacija C677T gena za MTHFR određena je metodom izolacije DNA i alel specifične lančane reakcije polimeraze (PCR). Raspodjela genotipova u skupini bolesnika s normoalbuminurijom bila je: CC 36,5%, CT 42,3% i TT 21,2%, dok je u skupini bolesnika sa mikroalbuminurijom bila: CC 39,4%, CT 45,4% i TT 15,2%. Nije bilo statistički značajne razlike među grupama u distribuciji C677T genotipova (p=0,788). Naše istraživanje nije pokazalo povezanost između mutacije gena za metilentetrahidrofolat reduktazu i dijabetičke nefropatije u hrvatskih bolesnika. Mnogostruki čimbenici mogu modificirati značajnost utjecaja polimorfizma MTHFR na nastanak dijabetičke nefropatije

CROATIAN GUIDELINES FOR THE PHARMACOTHERAPY OF TYPE 2 DIABETES

Uvod: Hrvatsko društvo za dijabetes i bolesti metabolizma Hrvatskoga liječničkog zbora izradilo je 2011. godine prve nacionalne smjernice o prehrani, edukaciji i samokontroli te farmakološkom liječenju šećerne bolesti tipa 2. Sukladno povećanom broju dostupnih lijekova te novim spoznajama o učinkovitosti i sigurnosti primjene već uključenih lijekova, pokazala se potreba za obnovom postojećih smjernica za farmakološko liječenje šećerne bolesti tipa 2 u Republici ­Hrvatskoj. Sudionici: Kao koautori Smjernica navedeni su svi članovi Hrvatskog društva za dijabetes i bolesti metabolizma Hrvatskoga liječničkog zbora, kao i ostalih uključenih stručnih društava, koji su svojim komentarima i prijedlozima pridonijeli izradi Smjernica. Dokazi: Ove su Smjernice utemeljene na dokazima, prema sustavu GRADE (engl. Grading of Recommendations, Assessment, Development and Evaluation) koji uz razinu dokaza opisuje i snagu preporuke. Zaključci: Individualan pristup temeljen na fiziološkim principima regulacije glikemije nuždan je u liječenju osoba sa šećernom bolesti. Ciljeve liječenja i odabir medikamentne terapije treba prilagoditi oboljeloj osobi, uzimajući u obzir životnu dob, trajanje bolesti, očekivano trajanje života, rizik od hipoglikemije, komorbiditete, razvijene vaskularne i ostale komplikacije, kao i ostale čimbenike. Zbog svega navedenoga od nacionalnog je interesa imati praktične, racionalne i provedive smjernice za farmakološko liječenje šećerne bolesti tipa 2.Introduction: The Croatian Association for Diabetes and Metabolic Disorders of the Croatian Medical Association has issued in 2011 the first national guidelines for the nutrition, education, self-control, and pharmacotherapy of ­diabetes type 2. According to the increased number of available medicines and new evidence related to the effectiveness and safety of medicines already involved in the therapy there was a need for update of the existing guidelines for the ­pharmacotherapy of type 2 diabetes in the Republic of Croatia. Participants: as co-authors of the Guidelines there are listed all members of the Croatian Association for Diabetes and Metabolic Diseases, as well as other representatives of professional societies within the Croatian Medical Association, who have contributed with comments and suggestions to the development of the Guidelines. Evidence: These guidelines are evidence-based, according to the GRADE system (eng. Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendations. Conclusions: An individual patient approach based on physiological principles in blood glucose control is essential for diabetes’ patients management. Glycemic targets and selection of the pharmacological agents should be tailored to the patient, taking into account the age, duration of disease, life expectancy, risk of hypoglycemia, comorbidities, developed vascular and other complications as well as other factors. Because of all this, is of national interest to have a practical, rational and applicable guidelines for the pharmacotherapy of type 2 diabetes

CROATIAN GUIDELINES FOR THE PHARMACOTHERAPY OF TYPE 2 DIABETES

Uvod: Hrvatsko društvo za dijabetes i bolesti metabolizma Hrvatskoga liječničkog zbora izradilo je 2011. godine prve nacionalne smjernice o prehrani, edukaciji i samokontroli te farmakološkom liječenju šećerne bolesti tipa 2. Sukladno povećanom broju dostupnih lijekova te novim spoznajama o učinkovitosti i sigurnosti primjene već uključenih lijekova, pokazala se potreba za obnovom postojećih smjernica za farmakološko liječenje šećerne bolesti tipa 2 u Republici ­Hrvatskoj. Sudionici: Kao koautori Smjernica navedeni su svi članovi Hrvatskog društva za dijabetes i bolesti metabolizma Hrvatskoga liječničkog zbora, kao i ostalih uključenih stručnih društava, koji su svojim komentarima i prijedlozima pridonijeli izradi Smjernica. Dokazi: Ove su Smjernice utemeljene na dokazima, prema sustavu GRADE (engl. Grading of Recommendations, Assessment, Development and Evaluation) koji uz razinu dokaza opisuje i snagu preporuke. Zaključci: Individualan pristup temeljen na fiziološkim principima regulacije glikemije nuždan je u liječenju osoba sa šećernom bolesti. Ciljeve liječenja i odabir medikamentne terapije treba prilagoditi oboljeloj osobi, uzimajući u obzir životnu dob, trajanje bolesti, očekivano trajanje života, rizik od hipoglikemije, komorbiditete, razvijene vaskularne i ostale komplikacije, kao i ostale čimbenike. Zbog svega navedenoga od nacionalnog je interesa imati praktične, racionalne i provedive smjernice za farmakološko liječenje šećerne bolesti tipa 2.Introduction: The Croatian Association for Diabetes and Metabolic Disorders of the Croatian Medical Association has issued in 2011 the first national guidelines for the nutrition, education, self-control, and pharmacotherapy of ­diabetes type 2. According to the increased number of available medicines and new evidence related to the effectiveness and safety of medicines already involved in the therapy there was a need for update of the existing guidelines for the ­pharmacotherapy of type 2 diabetes in the Republic of Croatia. Participants: as co-authors of the Guidelines there are listed all members of the Croatian Association for Diabetes and Metabolic Diseases, as well as other representatives of professional societies within the Croatian Medical Association, who have contributed with comments and suggestions to the development of the Guidelines. Evidence: These guidelines are evidence-based, according to the GRADE system (eng. Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendations. Conclusions: An individual patient approach based on physiological principles in blood glucose control is essential for diabetes’ patients management. Glycemic targets and selection of the pharmacological agents should be tailored to the patient, taking into account the age, duration of disease, life expectancy, risk of hypoglycemia, comorbidities, developed vascular and other complications as well as other factors. Because of all this, is of national interest to have a practical, rational and applicable guidelines for the pharmacotherapy of type 2 diabetes