RESUMO
Warfarin, acenocoumarol, phenprocoumon, and fluindione are commonly prescribed oral anticoagulants for the prevention and treatment of thromboembolic disorders. These anticoagulants function by impairing the biosynthesis of active vitamin K-dependent coagulation factors through the inhibition of vitamin K epoxide reductase (VKOR). Genetic variations in VKOR have been closely associated with the resistant phenotype of oral anticoagulation therapy. However, the relative efficacy of these anticoagulants, their mechanisms of action, and their resistance variations among naturally occurring VKOR mutations remain elusive. Here, we explored these questions using our recently established cell-based VKOR activity assay with the endogenous VKOR function ablated. Our results show that the efficacy of these anticoagulants on VKOR inactivation, from most to least, is: acenocoumarol > phenprocoumon > warfarin > fluindione. This is consistent with their effective clinical dosages for stable anticoagulation control. Cell-based functional studies of how each of the 27 naturally occurring VKOR mutations responds to these 4 oral anticoagulants indicate that phenprocoumon has the largest resistance variation (up to 199-fold), whereas the resistance of acenocoumarol varies the least (<14-fold). Cell-based kinetics studies show that fluindione appears to be a competitive inhibitor of VKOR, whereas warfarin is likely to be a mixed-type inhibitor of VKOR. The anticoagulation effect of these oral anticoagulants can be reversed by the administration of a high dose of vitamin K, apparently due to the existence of a different enzyme that can directly reduce vitamin K. These findings provide new insights into the selection of oral anticoagulants, their effective dosage management, and their mechanisms of anticoagulation.
Assuntos
Anticoagulantes/farmacologia , Inibidores Enzimáticos/farmacologia , Vitamina K Epóxido Redutases/antagonistas & inibidores , Administração Oral , Anticoagulantes/administração & dosagem , Linhagem Celular , Resistência a Medicamentos , Inibidores Enzimáticos/administração & dosagem , Humanos , Fenindiona/administração & dosagem , Fenindiona/análogos & derivados , Fenindiona/farmacologia , Mutação Puntual , Vitamina K/metabolismo , Vitamina K Epóxido Redutases/genética , Vitamina K Epóxido Redutases/metabolismo , Varfarina/administração & dosagem , Varfarina/farmacologiaRESUMO
RATIONALE: The life-threatening drug rash with eosinophilia and systemic symptoms (DRESS) syndrome occurs most commonly after exposure to drugs, clinical features mimic those found with other serious systemic disorders. It is rarely associated with thrombotic microangiopathy. PATIENT CONCERNS: We describe the unique case of a 44-year-old man who simultaneously experienced DRESS syndrome with thrombotic microangiopathy (TMA) after a 5 days treatment with fluindione. DIAGNOSES: Clinical evaluation leads to the discovery of an underlying lymphangiomatosis, due to a Noonan syndrome. INTERVETIONS: The anticoagulant was withdrawn, and corticosteroids (1âmg/kg/day) and acenocoumarol were started. OUTCOMES: Clinical improvement ensued. At follow-up the patient is well. LESSONS: The association of DRESS with TMA is a rare condition; we believe that the presence of the underlying Noonan syndrome could have been the trigger. Moreover, we speculate about the potential interrelations between these entities.
Assuntos
Síndrome de Hipersensibilidade a Medicamentos , Glucocorticoides/administração & dosagem , Anormalidades Linfáticas , Síndrome de Noonan , Fenindiona/análogos & derivados , Microangiopatias Trombóticas , Adulto , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Diagnóstico Diferencial , Síndrome de Hipersensibilidade a Medicamentos/sangue , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Síndrome de Hipersensibilidade a Medicamentos/fisiopatologia , Humanos , Anormalidades Linfáticas/diagnóstico , Anormalidades Linfáticas/etiologia , Masculino , Mediastino/diagnóstico por imagem , Mediastino/patologia , Mutação , Síndrome de Noonan/genética , Síndrome de Noonan/fisiopatologia , Fenindiona/administração & dosagem , Fenindiona/efeitos adversos , Espaço Retroperitoneal/diagnóstico por imagem , Espaço Retroperitoneal/patologia , Proteínas Son Of Sevenless/genética , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/etiologia , Suspensão de TratamentoRESUMO
Essentials Acute coronary syndrome (ACS) with atrial fibrillation (AF) is a therapeutic challenge. Dual and triple antithrombotic therapy showed a similar thrombotic risk in ACS patients with AF. The omission of aspirin during the first month did not increase the rate of ischemic events. Replacement of vitamin K antagonist by dabigatran leads to an increased thrombotic risk. SUMMARY: Background Dual antithrombotic therapy comprising a vitamin K antagonist (VKA) plus clopidogrel reduces the incidence of major bleeding compared with triple therapy (VKA + clopidogrel + aspirin) in acute coronary syndrome (ACS) patients with atrial fibrillation (AF), with a similar thrombotic risk. The oral thrombin inhibitor dabigatran (150 mg twice a day) showed superiority over VKA in non-valvular AF, but data supporting its use in AF patients presenting with ACS are limited. Objective We sought to evaluate the efficacy of dabigatran vs. VKA in the management of AF patients undergoing percutaneous coronary intervention for an ACS. Methods In this open-label study, 133 consecutive patients received dabigatran plus clopidogrel. Another cohort of 133 patients treated with VKA plus clopidogrel was used as the control group. Results After propensity score adjustment, the cumulative incidence of major adverse cardiovascular events over 24 months was higher with dabigatran vs. VKA (adjusted hazard ratio, 2.28; 95% confidence interval, 1.46-3.56). Similar rates of major bleeding were found (adjusted hazard ratio, 1.17; 95% confidence interval, 0.46-2.96). Conclusions In AF patients presenting with ACS, replacement of VKA by dabigatran concurrently with clopidogrel is associated with an increased thrombotic risk, without a reduction in major bleeding.
Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Fibrilação Atrial/tratamento farmacológico , Dabigatrana/administração & dosagem , Vitamina K/antagonistas & inibidores , Síndrome Coronariana Aguda/complicações , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Aspirina/administração & dosagem , Fibrilação Atrial/complicações , Plaquetas/citologia , Clopidogrel/administração & dosagem , Estudos de Coortes , Angiografia Coronária , Feminino , Taxa de Filtração Glomerular , Hemorragia/prevenção & controle , Humanos , Incidência , Isquemia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Segurança do Paciente , Fenindiona/administração & dosagem , Fenindiona/análogos & derivados , Pontuação de Propensão , Modelos de Riscos Proporcionais , Risco , Resultado do TratamentoRESUMO
Except for bleeding complications, vitamin K antagonists (VKAs) are known to have few undesirable side effects. Herein is presented the case of a 45-year-old woman in whom liver damage was induced by fluindione and warfarin after mitral valve replacement. Hepatotoxicity is a rare complication of VKAs, both in the French National and Drug Safety registry and the medical literature. A diagnosis of VKA-induced drug damage was confirmed by the absence of other etiologies, the chronological sequence, recurrence after re-exposure to VKA, and rapid improvements after discontinuation of the drug. Despite possible cross-reactions between VKAs, the re-introduction of acenocoumarol was successfully achieved, with no recurrence of biological disturbances.
Assuntos
Anticoagulantes/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Fibrinolíticos/efeitos adversos , Implante de Prótese de Valva Cardíaca , Valva Mitral/cirurgia , Fenindiona/análogos & derivados , Vitamina K/antagonistas & inibidores , Varfarina/efeitos adversos , Anticoagulantes/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/terapia , Substituição de Medicamentos , Feminino , Fibrinolíticos/administração & dosagem , Próteses Valvulares Cardíacas , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/instrumentação , Heparina de Baixo Peso Molecular/administração & dosagem , Humanos , Testes de Função Hepática , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Fenindiona/administração & dosagem , Fenindiona/efeitos adversos , Fatores de Risco , Resultado do Tratamento , Varfarina/administração & dosagemAssuntos
Antagonistas de Receptores Adrenérgicos beta 1/química , Anticoagulantes/química , Erros de Medicação/prevenção & controle , Nebivolol/química , Fenindiona/análogos & derivados , Percepção Visual , Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Discriminação Psicológica , Composição de Medicamentos , Overdose de Drogas/prevenção & controle , Feminino , Humanos , Nebivolol/administração & dosagem , Fenindiona/administração & dosagem , Fenindiona/efeitos adversos , Fenindiona/química , Polimedicação , Reconhecimento Psicológico , Fatores de RiscoRESUMO
Spontaneous hematoma of transverse mesocolon is a rare complication of anticoagulant treatment with vitamin K. We report the case of spontaneous hematoma of right angle of the transverse mesocolon associated with a hemoperitoneum in a 32-year-old patient treated by fluindione for pulmonary embolism. The diagnosis must be made urgently. The abdominal ultrasound and the scanning confirm the diagnosis. It is important to note that surgery is indicated only in the case of complications such as the risk of rupture of the hematoma.
Assuntos
Anticoagulantes/efeitos adversos , Hematoma/induzido quimicamente , Hemoperitônio/induzido quimicamente , Mesocolo/patologia , Adulto , Anticoagulantes/administração & dosagem , Feminino , Hematoma/diagnóstico por imagem , Hemoperitônio/diagnóstico por imagem , Humanos , Mesocolo/diagnóstico por imagem , Fenindiona/administração & dosagem , Fenindiona/efeitos adversos , Fenindiona/análogos & derivados , Embolia Pulmonar/tratamento farmacológico , Vitamina K/antagonistas & inibidoresRESUMO
OBJECTIVES: Numerous factors are well documented to affect the response to vitamin K antagonists (VKA), including dietary vitamin K, other drugs, age, pharmacogenetics, and disease states. Body weight is perhaps not as well known as a variable affecting VKA dose. Our aim was to review the literature regarding body weight and VKA dose requirements. METHODS: We reviewed the English-language literature via PubMed and Scopus using the search terms VKA, warfarin, acenocoumarol, phenprocoumon, fluindione, AND body weight. RESULTS: Among 32 studies conducted since the widespread use of the international normalized ratio, 29 found a correlation with body weight or body surface area and VKA dose requirement. Warfarin was evaluated in 27 studies and acenocoumarol, phenprocoumon, or fluindione were assessed in 5 investigations. CONCLUSIONS: Because of varying study methodologies, further study is warranted. Based on current evidence, clinicians should include body weight, along with other established variables when dosing VKA. Most important, obese and morbidly obese patients may require a 30% to 50% increase with the initial dosing of VKA.
Assuntos
Acenocumarol/administração & dosagem , Anticoagulantes/administração & dosagem , Peso Corporal , Obesidade , Fenindiona/análogos & derivados , Femprocumona/administração & dosagem , Vitamina K/antagonistas & inibidores , Varfarina/administração & dosagem , Comorbidade , Cálculos da Dosagem de Medicamento , Humanos , Obesidade Mórbida , Fenindiona/administração & dosagemRESUMO
INTRODUCTION: Switching from fluindione, an indanedione vitamin K antagonist derivative, to warfarin, a coumarin one, or vice versa, requires to know the relationships between dosages of these two molecules. METHODS: We conducted a prospective study in 288 consecutive patients aged 70 years and over, converted from fluindione to warfarin. Patients who were retained for the analysis were those for whom maintenance dosages were obtained for both vitamin K antagonists. RESULTS: Eighty-two patients, mean aged 83 ± 6 years, were analysed. The average daily maintenance dosages were 13.8 ± 6.7 mg (range 5-35) and 3.7 ± 1.7 mg (range 1-8) for fluindione and warfarin, respectively. Using a linear regression model, we built a transition algorithm for the maintenance dosages of warfarin and fluindione. CONCLUSION: This is the first study to propose a conversion algorithm to help prescribers to estimate the maintenance dosage when it is necessary for a patient to switch from fluindione to warfarin or conversely.
Assuntos
Anticoagulantes/administração & dosagem , Cálculos da Dosagem de Medicamento , Nomogramas , Fenindiona/análogos & derivados , Trombose/prevenção & controle , Varfarina/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Algoritmos , Anticoagulantes/farmacocinética , Relação Dose-Resposta a Droga , Substituição de Medicamentos , Feminino , Humanos , Masculino , Fenindiona/administração & dosagem , Fenindiona/farmacocinética , Equivalência Terapêutica , Trombose/metabolismo , Varfarina/farmacocinéticaRESUMO
Enzymatic creatinine assays are considered superior to Jaffe assays due to greater analytical specificity. We report a case of phenindione interference with an enzymatic assay resulting in significant misclassification in a patient with chronic kidney disease (CKD). Analysis of creatinine values of a further 36 patients who were treated with phenindione showed significant negative interference of phenindione with the Roche enzymatic creatinine assay.
Assuntos
Creatinina/sangue , Ensaios Enzimáticos/métodos , Fenindiona/efeitos adversos , Insuficiência Renal Crônica/diagnóstico , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/sangue , Erros de Diagnóstico , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Fenindiona/administração & dosagem , Fenindiona/sangue , Insuficiência Renal Crônica/fisiopatologiaRESUMO
We report a probable interaction between a vitamin K antagonist, fluindione, and the herbal medicine turmeric that resulted in the elevation of the international normalized ratio (INR). The case presented here underlines the importance of considering potential exposure to herbal medications when assessing adverse effects.
Assuntos
4-Hidroxicumarinas/efeitos adversos , Anticoagulantes/efeitos adversos , Curcuma/efeitos adversos , Hemorragia/induzido quimicamente , Interações Ervas-Drogas , Indenos/efeitos adversos , Insuficiência da Valva Mitral/tratamento farmacológico , Fenindiona/análogos & derivados , Vitamina K/antagonistas & inibidores , 4-Hidroxicumarinas/administração & dosagem , Administração Oral , Anticoagulantes/administração & dosagem , Feminino , Humanos , Indenos/administração & dosagem , Coeficiente Internacional Normatizado , Pessoa de Meia-Idade , Fenindiona/administração & dosagem , Fenindiona/efeitos adversos , Vitamina K/administração & dosagem , Vitamina K/efeitos adversosRESUMO
INTRODUCTION: Regular monitoring of the international normalized ratio (INR) is crucial for dose adjustment of vitamin K antagonists (VKA) to maximize time in therapeutic range (TTR). We compared the use of a mobile electronic assistant INRPlus which proposes patient-specific fluindione doses, to standard fluindione management in a cluster randomized controlled study. PATIENTS AND METHODS: Twenty clusters of six general practitioners were randomized to adjust fluindione doses in VKA-treated patients either using INRPlus or according to routine practice. TTR was measured over 6 months, along with time spent above or below the recommended INR range, frequency of measurements and related complications. RESULTS: Of the 595 included patients, 551 were assessable (259 INRPlus, 292 control) and had a mean of 1.6 INR measurements/month. TTR was not significantly different between the two groups, 72.7% [Q1: 58.1%; Q3: 90%] in INRPlus patients and 71.2% [Q1: 54.8%; Q3: 88.2%] in control patients (p=0.445). At least 60% time within reference ranges was reported in 73.4% of INRPlus patients and 67.1% of control patients (relative risk 1.09, 95%CI 0.98-1.22, p=0.115). No significant differences were reported between the two groups for time outside reference ranges, frequency of measurements or complications. Eighty-two percent (82%) of patients complying with INRPlus-proposed doses spent more than 60% of TTR versus 66.9% of non-compliant patients and 67.1% of reference patients. CONCLUSIONS: In this trial, the use of the INRPlus electronic assistant resulted in a non-significant improvement in TTR that may be due to a higher than expected TTR in the control group.
Assuntos
Anticoagulantes/administração & dosagem , Computadores de Mão , Medicina Geral/instrumentação , Coeficiente Internacional Normatizado/instrumentação , Fenindiona/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Feminino , Medicina Geral/métodos , Clínicos Gerais , Humanos , Coeficiente Internacional Normatizado/métodos , Masculino , Pessoa de Meia-Idade , Fenindiona/administração & dosagem , Estudos ProspectivosAssuntos
Coagulação Sanguínea/efeitos dos fármacos , Carbamazepina/efeitos adversos , Carbamazepina/farmacologia , Fenindiona/análogos & derivados , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/efeitos adversos , Analgésicos não Narcóticos/farmacologia , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Carbamazepina/administração & dosagem , Antagonismo de Drogas , Resistência a Medicamentos/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia/tratamento farmacológico , Fenindiona/administração & dosagem , Fenindiona/uso terapêuticoRESUMO
PURPOSE: To establish the prevalence of anticoagulation (vitamin K antagonists) and antiplatelet agent therapy in patients undergoing vitreoretinal surgery and to compare the outcome of peribulbar anesthesia and vitreoretinal surgery between users and nonusers. METHODS: We conducted a retrospective case series study in one academic center. No changes in the treatment regimen were made before surgery. Patients were divided into 3 groups: G1, patients with no anticoagulant or antiplatelet therapy; G2, patients treated with anticoagulants; and G3, patients treated with aspirin, clopidogrel, or both. RESULTS: Two hundred and six eyes (206 patients) were included. G1, 144 eyes (69.9%) without any anticoagulant or antiplatelet therapy (69.9%); G2, 12 eyes (5.8%) with anticoagulants; and G3, 44 eyes (21.4%) with antiplatelet agents. Six patients (6 eyes) (2.9%) received both anticoagulant and antiplatelet agents. The incidence of overall and mild postoperative hemorrhagic complications was similar between groups, P = 0.075 and P = 0.127, respectively. However, potential sight-threatening hemorrhagic complications were more frequent in patients receiving antiplatelet agents, P < 0.003. CONCLUSION: Peribulbar anesthesia for vitreoretinal surgery can probably be performed safely in patients receiving anticoagulants. However, retinal surgeons should be aware that severe bleeding complications are more frequent in patients receiving antiplatelet therapy.
Assuntos
Anestesia Local , Anticoagulantes/administração & dosagem , Inibidores da Agregação Plaquetária/administração & dosagem , Cirurgia Vitreorretiniana , Acenocumarol/administração & dosagem , Acenocumarol/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Clopidogrel , Sedação Consciente , Eletrocardiografia , Hemorragia Ocular/induzido quimicamente , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Órbita , Oximetria , Fenindiona/administração & dosagem , Fenindiona/efeitos adversos , Fenindiona/análogos & derivados , Inibidores da Agregação Plaquetária/efeitos adversos , Hemorragia Pós-Operatória/induzido quimicamente , Estudos Retrospectivos , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Ticlopidina/análogos & derivados , Varfarina/administração & dosagem , Varfarina/efeitos adversos , Adulto JovemRESUMO
PURPOSE: Fluindione is an oral vitamin K antagonist (indanedione derivative) exclusively marketed in France and Luxembourg, known to have immuno-allergic adverse effects such as hepatitis, fever or interstitial nephritis. A few cases of drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with fluindione. The aim of the present study was to investigate fluindione-induced DRESS cases reported in France and to describe their characteristics. METHODS: We searched for potential cases of DRESS with fluindione reported in the French pharmacovigilance database since 2000. RESULTS: Thirty-six cases of DRESS were included and concerned 17 women and 19 men. The mean age was 65 years (median: 68 years, range: 28-95 years). Kidneys and liver were the most frequent organs involved. Thirty-five cases were serious. In 5 cases, the effect was life-threatening. Most of the patients recovered. Fluindione was the only medicine suspected in 26 cases. Skin patch tests, performed in 10 cases, were positive with fluindione in 9 cases. CONCLUSIONS: Fluindione is not known to be a frequent cause of DRESS. However, the number of reports found is probably underestimated. The seriousness of DRESS, as all immuno-allergic adverse effects, contraindicates fluindione reintroduction. Coumarinic derivatives are the alternatives in patients who need oral anticoagulant treatment.
Assuntos
Anticoagulantes/efeitos adversos , Erupção por Droga/etiologia , Hipersensibilidade a Drogas/fisiopatologia , Eosinofilia/etiologia , Farmacovigilância , Fenindiona/análogos & derivados , Vitamina K/antagonistas & inibidores , Administração Oral , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Erupção por Droga/terapia , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/terapia , Eosinofilia/induzido quimicamente , Eosinofilia/terapia , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Fenindiona/administração & dosagem , Fenindiona/efeitos adversos , Estudos Retrospectivos , Índice de Gravidade de Doença , Testes CutâneosRESUMO
The effect of adding a third polymer to immiscible binary solid dispersions was investigated. The model actives griseofulvin (GF), progesterone (PG) and phenindione (PD) were selected because they exemplify a key property of many poorly soluble molecules of having at least one hydrogen bonding acceptor moiety while not having any hydrogen bond donating moieties. Ternary solid dispersions of the drug, PVP (polyvinylpyrrolidone) (proton acceptor) and PHPMA (poly[2-hydroxypropyl methacrylate]) (proton acceptor and donor) were prepared by spray drying. Stability results showed that binary solid dispersions (API and PVP) of GF and PVP crystallized quickly while the amorphous form was not possible to prepare for PG and PD. The amorphous form was prolonged upon the incorporation of PHPMA in the solid dispersion (API, PHPMA and PVP). Based on measuring the melting points, the energy of mixing the drug with the polymer was calculated using the Flory-Huggins theory. The results showed that GF had the lowest free energy followed by PG and finally PD which agreed well with the stability results. These results suggest that the addition of a third polymer to immiscible binary solid dispersions can significantly improve the stability of the amorphous form.
Assuntos
Portadores de Fármacos/química , Griseofulvina/administração & dosagem , Fenindiona/administração & dosagem , Progesterona/administração & dosagem , Cristalização , Estabilidade de Medicamentos , Griseofulvina/química , Ligação de Hidrogênio , Fenindiona/química , Ácidos Polimetacrílicos/química , Povidona/química , Progesterona/química , Solubilidade , Temperatura de TransiçãoRESUMO
BACKGROUND: Vitamin K antagonist tablets are often split to fractionate the dose by elderly patients. We performed a study in order to assess the divisibility of one dosage strength of score-lined warfarin and of score-lined fluindione. METHODS: Due to a recent change in the pharmaceutical form of fluindione in order to improve the divisibility, the study was performed over 2 different periods (with the « old ¼ and with the « new ¼ pharmaceutical form). In each period, 10 patients mean aged 82 years, 10 relatives, 10 nurses, 10 medical doctors) were asked to split in half warfarin tablets (W2 1(st) period et W2 2(d) period) and fluindione tablets (F2 et F'2), and to split fluindione tablets into 4 fragments (F4 et F'4). The first end-point was the accuracy of splitting estimated by the difference between the real and the expected weight of fragmented tablets. The statistical analysis was performed using an ANOVA test with 2 variables, subject and drug. The difference between the 2 periods were analyzed using an ANOVA test with 2 variables, subject and period. RESULTS: Over the 2 periods, the differences between real and expected weight were of 4.65% for W2 1(st) phase, 9.48% for F2, 15.35% for F4, 5.56% for W2 2(d )period, 4.30% for F'2, and 6.98% for F'4. The quality of splitting was statistically poorer in the elderly patient group compared to other subjects. CONCLUSION: This study was not design to assess the clinical relevance (bleeding or thromboembolism) or the anticoagulation control of the variations in drug mass due to inappropriate splitting of tablets. However, split form of drugs should be prescribe with caution to elderly patients.
Assuntos
Anticoagulantes/administração & dosagem , Cuidadores/educação , Medicamentos Genéricos/administração & dosagem , Educação de Pacientes como Assunto , Fenindiona/análogos & derivados , Varfarina/administração & dosagem , Atividades Cotidianas/classificação , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Relação Dose-Resposta a Droga , Medicamentos Genéricos/efeitos adversos , Feminino , França , Humanos , Masculino , Fenindiona/administração & dosagem , Fenindiona/efeitos adversos , Autoadministração , Comprimidos , Varfarina/efeitos adversosAssuntos
Síndrome de Behçet/diagnóstico , Emigrantes e Imigrantes , Administração Oral , Adolescente , Anti-Inflamatórios/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Atrofia , Azatioprina/administração & dosagem , Síndrome de Behçet/tratamento farmacológico , Síndrome de Behçet/imunologia , Proteína C-Reativa/análise , Ciclofosfamida/administração & dosagem , Diagnóstico Diferencial , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/administração & dosagem , Infliximab , Infusões Intravenosas , Imageamento por Ressonância Magnética , Metilprednisolona/administração & dosagem , Mielite Transversa/diagnóstico , Mielite Transversa/tratamento farmacológico , Mielite Transversa/imunologia , Exame Neurológico , Fenindiona/administração & dosagem , Fenindiona/análogos & derivados , Prednisolona/administração & dosagem , Pioderma Gangrenoso/tratamento farmacológico , Medula Espinal/patologia , Isquemia do Cordão Espinal/diagnóstico , Isquemia do Cordão Espinal/tratamento farmacológico , Isquemia do Cordão Espinal/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidoresAssuntos
Deficiência do Fator VII/diagnóstico , Deficiência do Fator X/diagnóstico , Fenindiona/análogos & derivados , Rodenticidas/toxicidade , Adolescente , Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/genética , Domínio Catalítico/genética , China , Análise Mutacional de DNA , Ingestão de Alimentos , Deficiência do Fator VII/sangue , Deficiência do Fator VII/complicações , Deficiência do Fator VII/congênito , Deficiência do Fator X/sangue , Deficiência do Fator X/complicações , Deficiência do Fator X/congênito , Humanos , Masculino , Mutação de Sentido Incorreto/genética , Linhagem , Fenindiona/administração & dosagem , Fenindiona/toxicidade , Polimorfismo Genético , Rodenticidas/administração & dosagemRESUMO
BACKGROUND: Isolated and spontaneous dissection of mesenteric arteries is a rare entity; a little more than 50 cases have been reported in medical literature. There is no therapeutic consensus concerning this type of lesion. METHODS: In this study, we report the results of our treatment based on a conservative approach. This retrospective study concerns eight patients with dissection of the celiac trunk and/or of the upper mesenteric artery (UMA) who were treated between 2002 and 2006. Because these patients were not presenting with acute intestinal ischemia diagnosed by clinical examination or paraclinical tests (medical imaging/biology) or with vital complications, they were treated with an efficient anticoagulation (heparin followed by anti-vitamin K) for 3 to 6 months. Endovascular or surgical treatment was used as the first option in patients with obvious intestinal ischemia or likely to have an arterial rupture, and also when medical treatment had failed. Clinical and radiological follow-up was at 1 month, 3 months, 6 months, and 1 year and then every year. Seven men and one woman (mean age, 48.2; age range, 38-53 years) were treated. Six patients presented with isolated dissection (celiac trunk=4, UMA=2). One patient had a celiac trunk and a UMA dissection and one had a celiac trunk and a UMA dissection along with a dissection of his two renal arteries. On entering the hospital, a patient was operated on for mesenteric ischemia related to a stenosis of the upper mesenteric artery (upper aortomesenteric bypass); a covered stent was implanted in the celiac trunk of another patient presenting with a contained rupture. RESULTS: Both patients were successfully treated. Six patients were medically treated. One of them required an aortohepatic bypass to treat an aneurysmal evolution of the celiac trunk revealed by a computed tomography scan obtained 1 month after the symptoms had begun. In one patient, the dissection remained stable on imaging. Four patients were cured, with a mean 20.1-month follow-up. CONCLUSION: Conservative treatment of spontaneous dissections of mesenteric arteries is possible when there are no complications, and it gives satisfactory results provided regular clinical and radiological checking is performed.
Assuntos
Anticoagulantes/administração & dosagem , Dissecção Aórtica/terapia , Isquemia/terapia , Artérias Mesentéricas/cirurgia , Procedimentos Cirúrgicos Vasculares , Dor Abdominal/etiologia , Dor Abdominal/terapia , Adulto , Dissecção Aórtica/complicações , Dissecção Aórtica/diagnóstico , Esquema de Medicação , Feminino , Heparina/administração & dosagem , Humanos , Isquemia/diagnóstico , Isquemia/etiologia , Masculino , Artérias Mesentéricas/diagnóstico por imagem , Pessoa de Meia-Idade , Fenindiona/administração & dosagem , Fenindiona/análogos & derivados , Estudos Retrospectivos , Ruptura , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Ultrassonografia Doppler Dupla , Vitamina K/antagonistas & inibidoresRESUMO
Amebiasis remains a major public health issue in most of the world. Amebic liver abscess is the most common extraintestinal manifestation. A complication such as venous obstruction associated with amebiais is rare. We report a thrombosis in hepatic veins associated with amebic hepatic abscess in a traveler.