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1.
J Thromb Haemost ; 22(7): 1847-1856, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38580096

RESUMO

BACKGROUND: The effect of the vitamin K antagonist acenocoumarol on coagulation needs to be reversed when patients undergo an invasive procedure with considerable bleeding risk. A strategy to achieve this is by administering oral vitamin K before a procedure while continuing acenocoumarol. OBJECTIVES: To assess the effect on periprocedural international normalized ratio (INR) values and safety using oral vitamin K as anticoagulant reversal method. METHODS: In this prospective cohort study, consecutive patients using acenocoumarol undergoing elective procedures between 2019 and 2022 were included. According to standard of care in our hospital, patients took 10 mg oral vitamin K 36 to 48 hours before the procedure while continuing their normal use of acenocoumarol. Effectiveness to lower INR to <1.8 preprocedural was assessed. Bleeding and thrombotic complications within 30 days after the procedure were assessed. Periprocedural course of INR was monitored by collecting additional blood samples. RESULTS: Seventy-four patients were included for analysis. On the day of the procedure, an adequate INR of <1.8 was achieved in 99% of patients. One clinically relevant nonmajor bleeding complication and no thrombotic complications were observed during the first 30 days after the procedure. INR gradually restored to therapeutic level during the days after the procedure. CONCLUSION: Using oral vitamin K while patients continue acenocoumarol intake is an effective way to adequately lower INR before an invasive procedure. Low amount of bleeding complications and absence of thromboembolic complications suggest that this is a safe strategy. The INR values returned gradually to therapeutic range after the procedure, probably contributing to the observed low bleeding rate.


Assuntos
Acenocumarol , Anticoagulantes , Coagulação Sanguínea , Coeficiente Internacional Normatizado , Vitamina K , Humanos , Acenocumarol/administração & dosagem , Acenocumarol/efeitos adversos , Vitamina K/antagonistas & inibidores , Estudos Prospectivos , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Idoso , Feminino , Masculino , Coagulação Sanguínea/efeitos dos fármacos , Pessoa de Meia-Idade , Administração Oral , Idoso de 80 Anos ou mais , Hemorragia/induzido quimicamente , Resultado do Tratamento , Procedimentos Cirúrgicos Eletivos , Fatores de Tempo , Monitoramento de Medicamentos/métodos , Esquema de Medicação
2.
J Physiol Pharmacol ; 74(4)2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37865961

RESUMO

Acute pancreatitis (AP) is the most common gastrointestinal disease leading to hospitalizations and unexpected deaths. The development of AP leads to damage of the pancreatic microcirculation with a cascade of subsequent events resulting, among others, in coagulopathy. Previous research showed that anticoagulants can be important therapeutic agents. Heparin and acenocoumarol can alleviate the course of AP, as well as accelerate healing and post-inflammatory regeneration of the pancreas. The aim of this study was to determine whether warfarin, a drug with more stable effects than acenocoumarol, affects the healing and regeneration of the pancreas in the cerulein-induced AP. AP was evoked in Wistar male rats by intraperitoneal administration of cerulein. The first dose of warfarin (45, 90 or 180 µg/kg) was administered 24 hours after the first dose of cerulein and the doses of warfarin were repeated once a day in subsequent 10 days. The severity of AP was assessed immediately after the last dose of cerulein, as well as at days 1, 2, 3, 5, and 10 after AP induction. Treatment with warfarin dose-dependently increased international normalized ratio (INR) and attenuated the severity of pancreatitis in histological examination and accelerated pancreatic recovery. These effects were accompanied with a faster reduction in the AP-evoked increase in serum activity of amylase and lipase, the serum concentration of pro-inflammatory interleukin-1ß, and the plasma level of D-Dimer. In addition, treatment with warfarin decreased pancreatic weight (an index of pancreatic edema) and improved pancreatic blood flow in rats with AP. The therapeutic effect was particularly pronounced after the administration of warfarin at a dose of 90 µg/kg. We conclude that treatment with warfarin accelerated regeneration of the pancreas and recovery in the course of cerulein-induced mild-edematous acute pancreatitis.


Assuntos
Pancreatite , Ratos , Masculino , Animais , Pancreatite/induzido quimicamente , Pancreatite/tratamento farmacológico , Pancreatite/patologia , Varfarina/farmacologia , Varfarina/uso terapêutico , Ceruletídeo/toxicidade , Ratos Wistar , Acenocumarol/uso terapêutico , Doença Aguda , Pâncreas/patologia
3.
J Comp Eff Res ; 12(8): e230007, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37489950

RESUMO

Aim: Healthcare resources usage and costs associated to nonvalvular atrial fibrillation (NVAF) were analyzed in Spain. Methods: This is an observational and retrospective study on patients with NVAF who started their treatment with apixaban or acenocoumarol between 1 January 2015 and 31 December 2017. Results: 2160 patients treated with apixaban were paired (1:1) with patients treated with acenocoumarol (propensity score matching). Apixaban reduced the incidence of strokes and systemic embolisms, minor and major bleedings and deaths, versus acenocoumarol. Apixaban led to reductions of 80, 55 and 43% in costs related to nursing visits, hospitalizations, and emergency visits, respectively, leading to annual cost savings of €274/patient, from the perspective of society. Conclusion: Our results suggested that apixaban is a cost-effective alternative for patients with NVAF.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Acenocumarol/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Anticoagulantes/uso terapêutico , Espanha/epidemiologia , Estudos Retrospectivos , Piridonas/uso terapêutico , Atenção à Saúde , Rivaroxabana
4.
Molecules ; 28(5)2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36903321

RESUMO

The repurposing of already-approved drugs has emerged as an alternative strategy to rapidly identify effective, safe, and conveniently available new therapeutic indications against human diseases. The current study aimed to assess the repurposing of the anticoagulant drug acenocoumarol for the treatment of chronic inflammatory diseases (e.g., atopic dermatitis and psoriasis) and investigate the potential underlying mechanisms. For this purpose, we used murine macrophage RAW 264.7 as a model in experiments aimed at investigating the anti-inflammatory effects of acenocoumarol in inhibiting the production of pro-inflammatory mediators and cytokines. We demonstrate that acenocoumarol significantly decreases nitric oxide (NO), prostaglandin (PG)E2, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß levels in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Acenocoumarol also inhibits the expression of NO synthase (iNOS) and cyclooxygenase (COX)-2, potentially explaining the acenocoumarol-induced decrease in NO and PGE2 production. In addition, acenocoumarol inhibits the phosphorylation of mitogen-activated protein kinases (MAPKs), c-Jun N terminal kinase (JNK), p38 MAPK, and extracellular signal-regulated kinase (ERK), in addition to decreasing the subsequent nuclear translocation of nuclear factor κB (NF-κB). This indicates that acenocoumarol attenuates the macrophage secretion of TNF-α, IL-6, IL-1ß, and NO, inducing iNOS and COX-2 expression via the inhibition of the NF-κB and MAPK signaling pathways. In conclusion, our results demonstrate that acenocoumarol can effectively attenuate the activation of macrophages, suggesting that acenocoumarol is a potential candidate for drug repurposing as an anti-inflammatory agent.


Assuntos
Acenocumarol , NF-kappa B , Animais , Camundongos , Anti-Inflamatórios/farmacologia , Ciclo-Oxigenase 2/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismo
5.
Thromb Res ; 222: 43-48, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36565679

RESUMO

INTRODUCTION: The evaluation and management of patients who sustain recurrent thromboembolic events while taking therapeutic anticoagulation have not been well characterized; moreover, there has been no systematic review or randomized trial focused on treating patients with recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE) during anticoagulant treatment. Therefore, we developed a pilot trial to compare rivaroxaban plus aspirin versus acenocoumarol in patients with recurrent venous thromboembolism despite ongoing anticoagulation with rivaroxaban. MATERIALS AND METHODS: The study was a multicenter, randomized clinical trial. We randomly assigned patients with objectively documented recurrent venous thromboembolism to receive rivaroxaban (20 mg once a day) plus aspirin (300 mg once a day) or an adjusted dose of acenocoumarol. The study was designed to evaluate the incidence of recurrent thromboembolic events (recurrent ipsilateral or contralateral DVT, PE, ischemic stroke, and myocardial infarction) and hemorrhagic events. RESULTS: A total of 58 patients were randomized: 28 were allocated to the rivaroxaban plus aspirin group and 30 to the acenocoumarol group. After 90 days of follow-up, three recurrent thromboembolic events (primary outcome) occurred in the acenocoumarol group - two DVTs and one ischemic stroke - and zero events in the rivaroxaban plus aspirin group (risk ratio [RR] 0.15; 95 % confidence interval [CI] 0.008-2.83; P = 0.20). Minor bleeding occurred in five patients in the acenocoumarol group and zero in the rivaroxaban plus aspirin group (RR 0.09; 95 % CI 0.005-1.68; p = 0.10). There was one non-fatal gastrointestinal major bleed in the rivaroxaban plus aspirin group. CONCLUSIONS: In this pilot study, there were no significant differences in any outcome assessed; however, recurrent thromboembolic events and minor bleeding events occurred numerically less frequently in the rivaroxaban plus aspirin group. These data suggest the need to carry out more extensive randomized studies with sufficient statistical power to clarify these results.


Assuntos
AVC Isquêmico , Embolia Pulmonar , Tromboembolia Venosa , Trombose Venosa , Humanos , Rivaroxabana/farmacologia , Rivaroxabana/uso terapêutico , Aspirina/uso terapêutico , Acenocumarol/efeitos adversos , Tromboembolia Venosa/tratamento farmacológico , Projetos Piloto , Trombose Venosa/tratamento farmacológico , Anticoagulantes/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Embolia Pulmonar/tratamento farmacológico
6.
Comb Chem High Throughput Screen ; 26(2): 339-346, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35538833

RESUMO

BACKGROUND: Currently, there are no effective differentiation-inducing agents for gliomas. Drug repositioning is a time-saving, low-risk, and low-cost drug development strategy. In this study, drugs that could induce the differentiation of glioma cells were searched by using a drug repositioning strategy. METHODS: Data mining was used to screen for differentially expressed genes (DEGs). The STRING 11.0 database was used for enrichment analysis. The Connectivity Map database was used for drug screening. The ChEMBL and STITCH databases were used to search for drug targets. The SwissDock database was used for molecular docking. RESULTS: A total of 45 DEGs were identified. The biological processes in which the DEGs were enriched mainly involved nervous system development and the regulation of biological processes. The enriched molecular functions mainly involved transcription-related molecular binding. The enriched cellular components mainly involved membrane-bound organelles and cellular protrusions. The enriched local network clusters mainly involved autophagy, the retinoic acid signalling pathway, and DNA methylation. The drug screening results showed that the drug with the highest score was acenocoumarol. A total of 12 acenocoumarol targets were obtained, among which histone deacetylase 1 (HDAC1) was the target with the highest degree value; the lowest ΔG value for acenocoumarol docked with HDAC1 was -7.52 kcal/mol, which was between those of the HDAC1 inhibitors romidepsin and vorinostat. CONCLUSION: Acenocoumarol may be a potential differentiation-inducing agent for glioma cells.


Assuntos
Reposicionamento de Medicamentos , Glioma , Humanos , Simulação de Acoplamento Molecular , Acenocumarol , Glioma/tratamento farmacológico , Glioma/genética , Glioma/metabolismo , Diferenciação Celular
7.
Curr Drug Saf ; 18(2): 267-269, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35469571

RESUMO

BACKGROUND: Acenocoumarol is an anticoagulant with numerous drug reactions. We report here, an unusual interaction between acenocoumarol and azathioprine. CASE PRESENTATION: A 35-year-old woman, treated with acenocoumarol for thrombosis of the superior mesenteric vein, was prescribed azathioprine for Crohn's disease. Three days later, INR values decreased from 2.36 to 1.48. The dose of acenocoumarol had to almost be doubled to reach an INR value of 2.56. The interaction between azathioprine and acenocoumarol was then suspected. Few similar cases of interactions between azathioprine and another coumarin derivative, warfarin, have been reported. To our knowledge, this is the second case of such interaction reported with acenocoumarol in literature. CONCLUSION: Thus, despite the rarity of this interaction reporting, we draw attention to the importance of close monitoring of INR values in patients treated with acenocoumarol associated with azathioprine.


Assuntos
Azatioprina , Doença de Crohn , Feminino , Humanos , Adulto , Azatioprina/efeitos adversos , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Acenocumarol/efeitos adversos , Interações Medicamentosas , Anticoagulantes/efeitos adversos
8.
Artigo em Inglês | MEDLINE | ID: mdl-35843922

RESUMO

Background: Genetic factors play an important role in deep vein thrombosis (DVT). The duration of anticoagulation therapy in patients with verified genetic inheritance and previous events of DVT is still questionable. Case reports: We present three cases of siblings (two brothers and one sister) with verified Venous thromboembolism (VTE) and genetic inheritance. The first case is a 33 y.o. male who was admitted with bilateral massive pulmonary thromboembolism and DVT of the right femoral vein. He had an episode of DVT 4 years ago. Fibrinolytic therapy was introduced immediately. Afterwards, unfractionated heparin was introduced, and then switched to enoxaparin and acenocoumarol. Because of inappropriate INR, it was switched then to rivaroxaban. The imaging methods showed significant improvement, and the patient was discharged from the hospital with rivaroxaban at 2x15 mg/day for another 2 weeks and was instructed to continue 20 mg/day until his next control. In the meantime, the second case, a 36 y.o. male, brother to the first patient, came with vein thrombosis of vena saphena magna of the left leg. Treatment with Acenocoumarol was started and continued for 2 years until complete resolution of the thrombi, and then it was changed to Aspirin. The third case is the sister of the first 2 cases, a 38 y.o female with symptoms and findings almost similar to those in the second case. She was treated with Acenocoumarol for 6 months. Doppler ultrasound showed complete resolution of the thrombosis and anticoagulation therapy was stopped. Genetic investigations for mutation showed presence of homozygous gene mutation for Prothrombin (PTB G20210A) in the first patient, his brother (the second case) was compound heterozygote for PTB and for MTHFR C677T, and his sister (third case) was heterozygous only for the PTB mutation. According to the clinical (recurrent unprovoked DVT with thromboembolic complications) and genetic testing (homozygous gene mutation for PTB) in the first patient, we decided to continue the secondary thromboprophylaxis with rivaroxaban 10 mg/day indefinitely. Conclusion: Testing for genetically inherited thrombophilia should be included in the risk assessment for recurrence, and performed in all patients under 50 y.o. who have a first, non-provoked episode of thrombosis, in order to determine the duration of anticoagulation therapy.


Assuntos
Trombofilia , Trombose , Tromboembolia Venosa , Trombose Venosa , Acenocumarol/uso terapêutico , Anticoagulantes/uso terapêutico , Feminino , Heparina/uso terapêutico , Humanos , Masculino , Rivaroxabana/efeitos adversos , Trombofilia/complicações , Trombofilia/tratamento farmacológico , Trombofilia/genética , Trombose/induzido quimicamente , Trombose/complicações , Trombose/tratamento farmacológico , Trombose Venosa/tratamento farmacológico , Trombose Venosa/genética
9.
J Int Med Res ; 50(6): 3000605221103959, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35748017

RESUMO

Effective prevention of thromboembolism is essential for patients with mechanical prosthetic heart valves. For this group of patients, vitamin K antagonists (VKAs) remain the drug group of choice despite the widespread use of new anticoagulants in other diseases. As a consequence, warfarin resistance remains a serious challenge for physicians. The current report describes a 65-year-old male patient that had a mechanical prosthetic aortic valve implanted due to severe aortic insufficiency after infective endocarditis. Despite consistent increases in his warfarin dose, the level of international normalized ratio (INR) remained very low. The patient was considered to have warfarin resistance. Warfarin was successfully replaced by another VKA, acenocoumarol, which resulted in a stable INR observed over 1 year of follow-up. Achieving the target INR in patients with mechanical prosthetic heart valves using VKAs is the main goal of thromboprophylaxis. Although the genetic changes that cause warfarin resistance are understood, the options to overcome these pharmacogenetic issues remain limited. Based on the success with this current patient, physicians with similar patients with warfarin resistance might wish to consider replacing warfarin with acenocoumarol.


Assuntos
Próteses Valvulares Cardíacas , Tromboembolia Venosa , Acenocumarol/uso terapêutico , Idoso , Anticoagulantes/uso terapêutico , Fibrinolíticos/uso terapêutico , Próteses Valvulares Cardíacas/efeitos adversos , Humanos , Coeficiente Internacional Normatizado , Masculino , Erros Inatos do Metabolismo , Tromboembolia Venosa/tratamento farmacológico , Varfarina/uso terapêutico
10.
Int J Cardiol ; 362: 147-151, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35533748

RESUMO

BACKGROUND: Several studies have shown that in patients treated with vitamin K antagonists (VKAs) time spent in therapeutic range (TTR) is lower in females than in males. This retrospective study has evaluated a possible association among over-anticoagulation and gender, type and indications to VKAs, TTR and bleeding. Moreover, the decrease of the INR level, after VKAs withdrawal, was considered. METHODS: From December 2020 to January 2004, 1230 patients with venous thromboembolism or atrial fibrillation were enrolled. Age, gender, type of VKAs, clinical indications, INR values and bleeding events were recorded. TTR was calculated considering the entire period of treatment. RESULTS: A total of 1616 and 1759 over-anticoagulation episodes were found in males and females, respectively. The median INR value was 4.5 (4.0-19.04). Thirty-two percent of the patients did not have an overdose throughout the observation period. The median number of over-anticoagulation per year was significantly higher in females (0.39-year) than in males (0.28-year). After 24 h of VKAs withdrawal, INRs were similar in both genders. Logistic regression analysis showed that the episodes of over-anticoagulation per year were associated with females, atrial fibrillation, warfarin therapy, follow-up length longer than 4 years, and TTR <73%, but were not associated to bleeding episodes. CONCLUSION: The higher number of over-anticoagulation can explain the lower TTR in females. An excess of anticoagulation is not associated with bleeding events. The recovery of INR performs better when acenocoumarol is used, therefore, in patients who present several episodes of over-anticoagulation, acenocumarolo could replace warfarin.


Assuntos
Fibrilação Atrial , Varfarina , Acenocumarol/efeitos adversos , Anticoagulantes , Fibrilação Atrial/complicações , Feminino , Fibrinolíticos/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Coeficiente Internacional Normatizado , Masculino , Estudos Retrospectivos , Fatores Sexuais , Vitamina K , Varfarina/efeitos adversos
11.
Hematology ; 27(1): 318-321, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35231200

RESUMO

BACKGROUND: Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug reaction associated with thrombosis. Clinical scoring systems and the presence of anti-platelet factor 4 (anti-PF4)/heparin antibodies determine the diagnosis. CASE PRESENTATION: A 57-year-old man who was treated with acenocoumarol due to a chronic left ventricular thrombus was admitted to the hospital for severe SARS-CoV-2 pneumonia and pulmonary embolism. The patient was started on bemiparin and discharged. Left lower limb acute arterial ischemia and thrombocytopenia were diagnosed 18 days later. Computed tomography angiography revealed a large left ventricular thrombus and multiple arterial thrombi. Left femoral-popliteal thromboembolectomy was performed. Anti-PF4/heparin antibodies confirmed an HIT diagnosis. Fondaparinux (7.5 mg/24 h) was initiated, but cardiac surgery was necessary. Bivalirudin was used during surgery, with an initial load (1.25 mg/kg) and maintenance infusion (2.5 mg/kg/h). The cardiac thrombus was extracted, but the patient experienced a postsurgical myocardial infarction. Percutaneous cardiovascular intervention (PCI) required a bivalirudin load (0.75 mg/kg) and maintenance infusion (1.75 mg/kg/h). No coronary lesions were detected, and argatroban was started afterwards (0.5 µg/kg/min). When the platelet count exceeded 100 × 109/L, acenocoumarol was initiated. Thereupon, acetylsalicylic acid (100 mg/24 h) was added. No other complications have been reported to date. CONCLUSION: The clinical presentation of intraventricular and multiple arterial thrombi is remarkable. SARS-CoV-2 infection likely contributed to a hypercoagulable state. The management of patients with HIT undergoing cardiac surgery is challenging. If surgery cannot be delayed, then treatment with bivalirudin is recommended. Additionally, this drug is recommended for PCI. Bivalirudin is safe and well-tolerated in both procedures.


Assuntos
Acenocumarol/administração & dosagem , Anticoagulantes/administração & dosagem , Arginina/análogos & derivados , Tratamento Farmacológico da COVID-19 , Heparina , Hirudinas/administração & dosagem , Fragmentos de Peptídeos/administração & dosagem , Intervenção Coronária Percutânea , Ácidos Pipecólicos/administração & dosagem , SARS-CoV-2 , Sulfonamidas/administração & dosagem , Trombocitopenia , Trombose , Arginina/administração & dosagem , COVID-19/complicações , Heparina/administração & dosagem , Heparina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Trombocitopenia/induzido quimicamente , Trombocitopenia/terapia , Trombose/induzido quimicamente , Trombose/terapia
12.
Med Clin (Barc) ; 159(8): 366-371, 2022 10 28.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-35120766

RESUMO

INTRODUCTION AND OBJECTIVE: In Spain, vitamin K antagonists (VKA) remain the standard treatment for the prevention of thromboembolic and hemorrhagic complications in patients with atrial fibrillation (AF), despite the high risks of suffering adverse effects. The objective of this study was to characterize the profile of VKA-treated patients suffering from stroke/systemic embolism (SE) or major hemorrhagic episodes, their evolution and the actions taken after those episodes. MATERIALS AND METHODS: EVENTHO was an observational multicenter study conducted in 22 Anticoagulation Spanish Units. The study included patients ≥18 years with AF who suffered major hemorrhagic episodes (67.8%) or stroke/SE (32.1%) during 2016 whileon VKA treatment [acenocoumarol (98.2%) or warfarin (1.8%)]. Time in therapeutic range (TTR) was calculated according to the Rosendaal method based on the international normalized ratio (INR) values of the previous 6 months. RESULTS: The study included 585 patients (median age [range] 82.3 [43.6-96.2] years; 51.1% men; mean [95% confidence interval, CI] CHA2DS2-VASc: 4.3 [4.2-4.4] and HAS-BLED: 2.2 [2.1-2.3]). Poor anticoagulation and VKA maintenance were higher in patients with major hemorrhagic episode (p<0.0001). The most common situations after hospital discharge were: functional dependence, neurological sequelae and death. CONCLUSIONS: In the sample studied, half of the AF patients who suffered stroke/SE or major hemorrhagic episode had inadequate TTR and, despite this, after hospital discharge, they restarted treatment with VKA. These results highlight the need to evaluate safer and effective therapeutic alternatives in AF patients with poor TTR control after suffering a stroke/SE or major hemorrhagic episode.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Acenocumarol/efeitos adversos , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Feminino , Fibrinolíticos/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/complicações , Humanos , Coeficiente Internacional Normatizado/efeitos adversos , Masculino , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/prevenção & controle , Vitamina K , Varfarina/efeitos adversos
13.
Crit Rev Anal Chem ; 52(3): 627-636, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-32897755

RESUMO

Acenocoumarol is an oral anticoagulant medicinal agent is frequently prescribed for the prophylaxis and the management of thromboembolic events. Acenocoumarol is prescribed in the form of racemic mixture and S- form is a more influential isomer. Acenocoumarol starts quickly with action and absorption, and the effect lasts for 15-20 h. In most patients, the therapeutic prothrombin range is caused 36 h after the primary dose. This review offers a detailed overview of the various analytical methodologies published in the literature from 1976 to uptil now for evaluation acenocoumarol and its combinations in specimens. The present review also stated the chiral analytical methods for the quantification of its enantiomers. A detailed study of the work revealed several analytical methodologies are routinely used for estimation of acenocoumarol includes UV/Vis-Spectrophotometry, liquid chromatography-mass spectrophotometry, high-performance liquid-chromatography, gas chromatography, high-performance thin-layer chromatography, capillary electrophoresis, Fourier-transform infrared spectroscopy and many miscellaneous techniques. Pharmaceutical analysis carried out the prominent task to understand the knowledge of the physicochemical properties of the medicinal agent; since the establishment of a new analytical method is still a challenging task for a research scientist. Thus, the present review will help to research scientist for the development of new analytical methods for the acenocoumarol.


Assuntos
Acenocumarol , Eletroforese Capilar , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia em Camada Fina , Humanos , Preparações Farmacêuticas
14.
Evid. actual. práct. ambul ; 25(3): e002144, 2022. tab
Artigo em Espanhol | LILACS, UNISALUD, BINACIS | ID: biblio-1398442

RESUMO

Lograr un adecuado nivel de anticoagulación con antagonistas orales de la vitamina K suele ser un desafío frecuente en la práctica clínica, dado que su estrecho rango terapéutico suele verse afectado por diversas interacciones farmacológicas,alimentos y condiciones clínicas. A partir de un caso de un paciente anticoagulado que presenta una hemorragia gastro-intestinal posterior a realizar un tratamiento antibiótico, la autora de este artículo revisó la evidencia sobre el riesgo desangrado secundario a la interacción entre este tipo de anticoagulantes y antibióticos orales. Su conclusión tras realizar una búsqueda bibliográfica y seleccionar la mejor evidencia disponible, es que existe un aumento del riesgo relativo desangrado en pacientes anticoagulados que reciben antibióticos, por lo que deberían evitarse aquellos antibióticos con conocido potencial de interacción. Si ello no fuera posible, se recomienda monitorizar el estado de anticoagulación con dosaje de la razón internacional normatizada (RIN) posterior a la introducción del antibiótico. (AU)


Achieving an adequate level of anticoagulation with oral vitamin K antagonists is often a frequent challenge in clinical practice, given that their narrow therapeutic range is often affected by various drug interactions, food, and clinical conditions. Based on a case of an anticoagulated patient who presented gastrointestinal bleeding after antibiotic treatment, the authorof this article reviewed the evidence on the risk of secondary bleeding due to the interaction between this type of anticoagulants and oral antibiotics. Their conclusion, after performing a literature search and selecting the best available evidence, is that there is an increased relative risk of bleeding in anticoagulated patients receiving antibiotics, so antibiotics with known potential for interaction should be avoided. If it weren't possible, it is recommended to monitor the anticoagulation status with International Normalized Ratio (INR) dosing after the introduction of the antibiotic. (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Vitamina K/antagonistas & inibidores , Varfarina/efeitos adversos , Hemorragia/induzido quimicamente , Acenocumarol/efeitos adversos , Antibacterianos/efeitos adversos , Anticoagulantes/efeitos adversos , Varfarina/farmacologia , Varfarina/farmacocinética , Fatores de Risco , Medição de Risco , Coeficiente Internacional Normatizado , Interações Medicamentosas , Acenocumarol/farmacologia , Acenocumarol/farmacocinética , Antibacterianos/farmacologia , Anticoagulantes/farmacologia , Anticoagulantes/farmacocinética
15.
Ned Tijdschr Geneeskd ; 1652021 09 09.
Artigo em Holandês | MEDLINE | ID: mdl-34523845

RESUMO

Acenocoumarol and phenprocoumon are vitamin K antagonists (VKA) with average half-lives of 11 hours and 160 hours, respectively. They are used to treat and prevent thrombosis in mechanical cardiac valve replacement, atrial fibrillation and venous thromboembolism. There are historical regional differences in preferred VKA in the Netherlands. Safe and effective treatment requires the international normalized ratios (INRs) to be in the therapeutic range, and stable. Theoretically, the longer-acting phenprocoumon would yield a higher time in therapeutic range (TTR) and lower INR variability. In practice, switching from acenocoumarol to phenprocoumon eventually improves INR variability and in some patients TTR as well. However, during the preceding transition period, INRs are more often volatile and supratherapeutic. Furthermore, switching to an alternative VKA could weaken integrated care, as other healthcare providers are less experienced with it. Healthcare providers must coordinate an intended switch with the anticoagulation clinic.


Assuntos
Acenocumarol , Femprocumona , Acenocumarol/uso terapêutico , Anticoagulantes , Coagulação Sanguínea , Humanos , Coeficiente Internacional Normatizado , Femprocumona/farmacologia
16.
FEMS Microbiol Lett ; 368(18)2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34529059

RESUMO

The increased interest of consumers in probiotic foods requires a deeper knowledge on the possible interactions with drugs, because their pharmacological properties could be modified. In this context, these studies are relevant for drugs such as acenocoumarol, whose dosage must be controlled due to, among other factors, food-drug interactions. Acenocoumarol is an oral anticoagulant with a narrow therapeutic range. The aim of the present research is to evaluate, in vitro, the effect of bifidobacteria on acenocoumarol. The drug was incubated with Bifidobacterium bifidum CIDCA 5310 or Bifidobacterium adolescentis CIDCA 5317 in MRS broth at 37°C for 24 h in anaerobic conditions. The effect of incubation with sterilized spent culture supernatants (SSCS) was also evaluated. Analysis by RP-HPLC showed that both bifidobacterial strains reduced the area of the acenocoumarol peak and two new peaks were evidenced. In addition, a decrease in the intensity of the bands at 1650, 1390 and 1110/cm was observed in the FTIR spectroscopic determinations. Moreover, a new band appeared at 1720/cm. No effect on the drug was observed when incubation was performed with SSCS. The present study showed a significant change in the concentration of the anticoagulant after incubation with bifidobacteria and results are compatible with biomodification of the drug due to enzymatic activity of bifidobacteria.


Assuntos
Acenocumarol , Bifidobacterium , Acenocumarol/metabolismo , Anticoagulantes/metabolismo , Bifidobacterium/metabolismo , Interações Medicamentosas , Probióticos/metabolismo
17.
Biomédica (Bogotá) ; 41(3): 403-408, jul.-set. 2021. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1345391

RESUMO

Se presenta el caso clínico de una paciente de 10 años diagnosticada con miocardiopatía dilatada, quien registró valores en el índice internacional normalizado (International Normalized Ratio, INR) superiores a 10 con la dosis estándar de acenocumarol, además de otros valores que indicaban el estado incoagulable, lo que obligó a suspender y reiniciar el tratamiento en varias ocasiones. Después de más de 30 días de tratamiento, sorprendentemente se lograron los niveles esperados y estables en el INR con la mitad de la dosis recomendada para una paciente de su edad y peso.Se decidió hacer un análisis farmacogenético retrospectivo del caso mediante RT-PCR con sondas TaqMan™ que incluyó cinco polimorfismos de un solo nucleótido y distinto grado de asociación con la dosis-respuesta a los fármacos antivitamínicos K (AVK): rs2108622 (gen CYP4F2), rs9923231, rs7294 (gen VKORC1), rs1799853 y rs1057910 (gen CYP2C9). La paciente resultó ser homocigota para el rs9923231 (VKORC1) y heterocigota para el rs2108622 (CYP4F2). Se ha evidenciado a nivel nacional e internacional que este perfil genético está fuertemente asociado con una necesidad de dosis menores de antivitamínicos K.En conclusión, el análisis farmacogenético confirmó que la condición genética de la paciente, la cual conlleva una baja expresión de la enzima VKORC1 (blanco terapéutico de los antivitamínicos K), hacía predecible la necesidad de una dosis menor a la establecida según los protocolos clínicos recomendados por la Food and Drug Administration (FDA) y PharmGKB™ para los fármacos cumarínicos. El análisis genotípico previo de la paciente hubiese permitido alcanzar el rango terapéutico más prontamente, evitando potenciales riesgos de hemorragia, lo que demuestra la importancia de los análisis farmacogenéticos en tratamientos de gran variabilidad y estrecho rango terapéutico.


Abstract We present the clinical case of a 10-year-old patient diagnosed with dilated cardiomyopathy who registered INR values above 10 upon receiving standard doses of acenocoumarol, as well as other values reported as uncoagulable, forcing the discontinuation and restart of treatment more than once. Expected and stable INR levels were achieved after more than 30 days of treatment, surprisingly with half the recommended dose for a patient of her age and weight. We decided to conduct a retrospective pharmacogenomic analysis including nucleotide genetic polymorphisms (SNPs) with different degrees of association with the dose/response to antivitamin K (AVK) drugs: rs2108622 (gene CYP4F2), rs9923231, rs7294 (gene VKORC1), rs1799853, and rs1057910 (CYP2C9 gene) using TaqMan® RT-PCR. The patient was homozygous for rs9923231 (VKORC1) and heterozygous for rs2108622 (CYP4F2), a genetic profile strongly associated with a requirement of lower AVK doses as shown by national and international evidence. In conclusion, the pharmacogenetic analysis confirmed that this patient's genetic conditions, involving low expression of the VKA therapeutic target, required a lower dose than that established in clinical protocols as recommended by the Food and Drug Administration (FDA) and the PharmGKB® for coumarin drugs. A previous genotypic analysis of the patient would have allowed reaching the therapeutic range sooner, thus avoiding potential bleeding risks. This shows the importance of pharmacogenetic analyses for highly variable treatments with a narrow therapeutic range.


Assuntos
Farmacogenética , Acenocumarol , Vitamina K , Anticoagulantes
18.
Ann Rheum Dis ; 80(5): 598-604, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34412027

RESUMO

OBJECTIVES: Vitamin K is hypothesised to play a role in osteoarthritis (OA) pathogenesis through effects on vitamin K-dependent bone and cartilage proteins, and therefore may represent a modifiable risk factor. A genetic variant in a vitamin K-dependent protein that is an essential inhibitor for cartilage calcification, matrix Gla protein (MGP), was associated with an increased risk for OA. Vitamin K antagonist anticoagulants (VKAs), such as warfarin and acenocoumarol, act as anticoagulants through inhibition of vitamin K-dependent blood coagulation proteins. VKAs likely also affect the functioning of other vitamin K-dependent proteins such as MGP. METHODS: We investigated the effect of acenocoumarol usage on progression and incidence of radiographic OA in 3494 participants of the Rotterdam Study cohort. We also examined the effect of MGP and VKORC1 single nucleotide variants on this association. RESULTS: Acenocoumarol usage was associated with an increased risk of OA incidence and progression (OR=2.50, 95% CI=1.94-3.20), both for knee (OR=2.34, 95% CI=1.67-3.22) and hip OA (OR=2.74, 95% CI=1.82-4.11). Among acenocoumarol users, carriers of the high VKORC1(BB) expression haplotype together with the MGP OA risk allele (rs1800801-T) had an increased risk of OA incidence and progression (OR=4.18, 95% CI=2.69-6.50), while this relationship was not present in non-users of that group (OR=1.01, 95% CI=0.78-1.33). CONCLUSIONS: These findings support the importance of vitamin K and vitamin K-dependent proteins, as MGP, in the pathogenesis of OA. Additionally, these results may have direct implications for the clinical prevention of OA, supporting the consideration of direct oral anticoagulants in favour of VKAs.


Assuntos
4-Hidroxicumarinas/efeitos adversos , Acenocumarol/efeitos adversos , Anticoagulantes/efeitos adversos , Indenos/efeitos adversos , Osteoartrite/epidemiologia , Vitamina K/antagonistas & inibidores , Idoso , Alelos , Proteínas de Ligação ao Cálcio/efeitos dos fármacos , Progressão da Doença , Proteínas da Matriz Extracelular/efeitos dos fármacos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Osteoartrite/induzido quimicamente , Osteoartrite/patologia , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Vitamina K/efeitos adversos , Vitamina K Epóxido Redutases/efeitos dos fármacos , Proteína de Matriz Gla
20.
Pan Afr Med J ; 38: 324, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34285747

RESUMO

Vitamin K antagonists (VKA) based oral anticoagulation, is widely used for the prevention and treatment of thromboembolic disease. The major complication of this therapy is bleeding, and sometimes it can occur in unsuspected areas. Spontaneous pectoral hematoma is one of the rare complications due to over anticoagulation by VKA therapy, with only a few cases reported in the literature. Concomitant use of this therapy with commonly used antibiotic, especially in the elderly with multiple comorbidities, can increase the risk of bleeding. Herein, we report a case of a 72-year-old woman under VKA for the treatment of atrial fibrillation, who presented with a spontaneous massive pectoral hematoma, while using antibiotic to treat a respiratory tract infection, who was successfully managed.


Assuntos
Anticoagulantes/efeitos adversos , Hematoma/induzido quimicamente , Hemorragia/induzido quimicamente , Acenocumarol/administração & dosagem , Acenocumarol/efeitos adversos , Idoso , Anticoagulantes/administração & dosagem , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Feminino , Humanos , Tromboembolia/etiologia , Tromboembolia/prevenção & controle , Vitamina K/antagonistas & inibidores
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