RESUMEN
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.
Asunto(s)
Anticoagulantes/farmacología , Inhibidores Enzimáticos/farmacología , Vitamina K Epóxido Reductasas/antagonistas & inhibidores , Administración Oral , Anticoagulantes/administración & dosificación , Línea Celular , Resistencia a Medicamentos , Inhibidores Enzimáticos/administración & dosificación , Humanos , Fenindiona/administración & dosificación , Fenindiona/análogos & derivados , Fenindiona/farmacología , Mutación Puntual , Vitamina K/metabolismo , Vitamina K Epóxido Reductasas/genética , Vitamina K Epóxido Reductasas/metabolismo , Warfarina/administración & dosificación , Warfarina/farmacologíaRESUMEN
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.
Asunto(s)
Síndrome de Hipersensibilidad a Medicamentos , Glucocorticoides/administración & dosificación , Anomalías Linfáticas , Síndrome de Noonan , Fenindiona/análogos & derivados , Microangiopatías Trombóticas , Adulto , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Diagnóstico Diferencial , Síndrome de Hipersensibilidad a Medicamentos/sangre , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Síndrome de Hipersensibilidad a Medicamentos/etiología , Síndrome de Hipersensibilidad a Medicamentos/fisiopatología , Humanos , Anomalías Linfáticas/diagnóstico , Anomalías Linfáticas/etiología , Masculino , Mediastino/diagnóstico por imagen , Mediastino/patología , Mutación , Síndrome de Noonan/genética , Síndrome de Noonan/fisiopatología , Fenindiona/administración & dosificación , Fenindiona/efectos adversos , Espacio Retroperitoneal/diagnóstico por imagen , Espacio Retroperitoneal/patología , Proteínas Son Of Sevenless/genética , Microangiopatías Trombóticas/diagnóstico , Microangiopatías Trombóticas/etiología , Privación de TratamientoRESUMEN
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.
Asunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Fibrilación Atrial/tratamiento farmacológico , Dabigatrán/administración & dosificación , Vitamina K/antagonistas & inhibidores , Síndrome Coronario Agudo/complicaciones , Administración Oral , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Aspirina/administración & dosificación , Fibrilación Atrial/complicaciones , Plaquetas/citología , Clopidogrel/administración & dosificación , Estudios de Cohortes , Angiografía Coronaria , Femenino , Tasa de Filtración Glomerular , Hemorragia/prevención & control , Humanos , Incidencia , Isquemia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Seguridad del Paciente , Fenindiona/administración & dosificación , Fenindiona/análogos & derivados , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Riesgo , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Anticoagulantes/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Fibrinolíticos/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas , Válvula Mitral/cirugía , Fenindiona/análogos & derivados , Vitamina K/antagonistas & inhibidores , Warfarina/efectos adversos , Anticoagulantes/administración & dosificación , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Enfermedad Hepática Inducida por Sustancias y Drogas/terapia , Sustitución de Medicamentos , Femenino , Fibrinolíticos/administración & dosificación , Prótesis Valvulares Cardíacas , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/instrumentación , Heparina de Bajo-Peso-Molecular/administración & dosificación , Humanos , Pruebas de Función Hepática , Persona de Mediana Edad , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/fisiopatología , Fenindiona/administración & dosificación , Fenindiona/efectos adversos , Factores de Riesgo , Resultado del Tratamiento , Warfarina/administración & dosificaciónAsunto(s)
Antagonistas de Receptores Adrenérgicos beta 1/química , Anticoagulantes/química , Errores de Medicación/prevención & control , Nebivolol/química , Fenindiona/análogos & derivados , Percepción Visual , Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Discriminación en Psicología , Composición de Medicamentos , Sobredosis de Droga/prevención & control , Femenino , Humanos , Nebivolol/administración & dosificación , Fenindiona/administración & dosificación , Fenindiona/efectos adversos , Fenindiona/química , Polifarmacia , Reconocimiento en Psicología , Factores de RiesgoRESUMEN
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.
Asunto(s)
Anticoagulantes/efectos adversos , Hematoma/inducido químicamente , Hemoperitoneo/inducido químicamente , Mesocolon/patología , Adulto , Anticoagulantes/administración & dosificación , Femenino , Hematoma/diagnóstico por imagen , Hemoperitoneo/diagnóstico por imagen , Humanos , Mesocolon/diagnóstico por imagen , Fenindiona/administración & dosificación , Fenindiona/efectos adversos , Fenindiona/análogos & derivados , Embolia Pulmonar/tratamiento farmacológico , Vitamina K/antagonistas & inhibidoresRESUMEN
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.
Asunto(s)
Acenocumarol/administración & dosificación , Anticoagulantes/administración & dosificación , Peso Corporal , Obesidad , Fenindiona/análogos & derivados , Fenprocumón/administración & dosificación , Vitamina K/antagonistas & inhibidores , Warfarina/administración & dosificación , Comorbilidad , Cálculo de Dosificación de Drogas , Humanos , Obesidad Mórbida , Fenindiona/administración & dosificaciónRESUMEN
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.
Asunto(s)
Creatinina/sangre , Pruebas de Enzimas/métodos , Fenindiona/efectos adversos , Insuficiencia Renal Crónica/diagnóstico , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Anticoagulantes/sangre , Errores Diagnósticos , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Fenindiona/administración & dosificación , Fenindiona/sangre , Insuficiencia Renal Crónica/fisiopatologíaRESUMEN
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.
Asunto(s)
Anticoagulantes/administración & dosificación , Cálculo de Dosificación de Drogas , Nomogramas , Fenindiona/análogos & derivados , Trombosis/prevención & control , Warfarina/administración & dosificación , Anciano , Anciano de 80 o más Años , Envejecimiento/metabolismo , Algoritmos , Anticoagulantes/farmacocinética , Relación Dosis-Respuesta a Droga , Sustitución de Medicamentos , Femenino , Humanos , Masculino , Fenindiona/administración & dosificación , Fenindiona/farmacocinética , Equivalencia Terapéutica , Trombosis/metabolismo , Warfarina/farmacocinéticaRESUMEN
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.
Asunto(s)
4-Hidroxicumarinas/efectos adversos , Anticoagulantes/efectos adversos , Curcuma/efectos adversos , Hemorragia/inducido químicamente , Interacciones de Hierba-Droga , Indenos/efectos adversos , Insuficiencia de la Válvula Mitral/tratamiento farmacológico , Fenindiona/análogos & derivados , Vitamina K/antagonistas & inhibidores , 4-Hidroxicumarinas/administración & dosificación , Administración Oral , Anticoagulantes/administración & dosificación , Femenino , Humanos , Indenos/administración & dosificación , Relación Normalizada Internacional , Persona de Mediana Edad , Fenindiona/administración & dosificación , Fenindiona/efectos adversos , Vitamina K/administración & dosificación , Vitamina K/efectos adversosRESUMEN
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.
Asunto(s)
Anticoagulantes/administración & dosificación , Computadoras de Mano , Medicina General/instrumentación , Relación Normalizada Internacional/instrumentación , Fenindiona/análogos & derivados , Anciano , Anciano de 80 o más Años , Femenino , Medicina General/métodos , Médicos Generales , Humanos , Relación Normalizada Internacional/métodos , Masculino , Persona de Mediana Edad , Fenindiona/administración & dosificación , Estudios ProspectivosAsunto(s)
Coagulación Sanguínea/efectos de los fármacos , Carbamazepina/efectos adversos , Carbamazepina/farmacología , Fenindiona/análogos & derivados , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/efectos adversos , Analgésicos no Narcóticos/farmacología , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Carbamazepina/administración & dosificación , Antagonismo de Drogas , Resistencia a Medicamentos/fisiología , Humanos , Masculino , Persona de Mediana Edad , Neuralgia/tratamiento farmacológico , Fenindiona/administración & dosificación , Fenindiona/uso terapéuticoRESUMEN
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.
Asunto(s)
Anestesia Local , Anticoagulantes/administración & dosificación , Inhibidores de Agregación Plaquetaria/administración & dosificación , Cirugía Vitreorretiniana , Acenocumarol/administración & dosificación , Acenocumarol/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Aspirina/administración & dosificación , Aspirina/efectos adversos , Clopidogrel , Sedación Consciente , Electrocardiografía , Hemorragia del Ojo/inducido químicamente , Femenino , Humanos , Masculino , Persona de Mediana Edad , Órbita , Oximetría , Fenindiona/administración & dosificación , Fenindiona/efectos adversos , Fenindiona/análogos & derivados , Inhibidores de Agregación Plaquetaria/efectos adversos , Hemorragia Posoperatoria/inducido químicamente , Estudios Retrospectivos , Ticlopidina/administración & dosificación , Ticlopidina/efectos adversos , Ticlopidina/análogos & derivados , Warfarina/administración & dosificación , Warfarina/efectos adversos , Adulto JovenRESUMEN
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.
Asunto(s)
Anticoagulantes/efectos adversos , Erupciones por Medicamentos/etiología , Hipersensibilidad a las Drogas/fisiopatología , Eosinofilia/etiología , Farmacovigilancia , Fenindiona/análogos & derivados , Vitamina K/antagonistas & inhibidores , Administración Oral , Adulto , Sistemas de Registro de Reacción Adversa a Medicamentos , Anciano , Anciano de 80 o más Años , Anticoagulantes/administración & dosificación , Erupciones por Medicamentos/terapia , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/terapia , Eosinofilia/inducido químicamente , Eosinofilia/terapia , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Fenindiona/administración & dosificación , Fenindiona/efectos adversos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Pruebas CutáneasRESUMEN
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.
Asunto(s)
Portadores de Fármacos/química , Griseofulvina/administración & dosificación , Fenindiona/administración & dosificación , Progesterona/administración & dosificación , Cristalización , Estabilidad de Medicamentos , Griseofulvina/química , Enlace de Hidrógeno , Fenindiona/química , Ácidos Polimetacrílicos/química , Povidona/química , Progesterona/química , Solubilidad , Temperatura de TransiciónAsunto(s)
Síndrome de Behçet/diagnóstico , Emigrantes e Inmigrantes , Administración Oral , Adolescente , Antiinflamatorios/administración & dosificación , Anticuerpos Monoclonales/administración & dosificación , Atrofia , Azatioprina/administración & dosificación , Síndrome de Behçet/tratamiento farmacológico , Síndrome de Behçet/inmunología , Proteína C-Reactiva/análisis , Ciclofosfamida/administración & dosificación , Diagnóstico Diferencial , Quimioterapia Combinada , Femenino , Humanos , Inmunosupresores/administración & dosificación , Infliximab , Infusiones Intravenosas , Imagen por Resonancia Magnética , Metilprednisolona/administración & dosificación , Mielitis Transversa/diagnóstico , Mielitis Transversa/tratamiento farmacológico , Mielitis Transversa/inmunología , Examen Neurológico , Fenindiona/administración & dosificación , Fenindiona/análogos & derivados , Prednisolona/administración & dosificación , Piodermia Gangrenosa/tratamiento farmacológico , Médula Espinal/patología , Isquemia de la Médula Espinal/diagnóstico , Isquemia de la Médula Espinal/tratamiento farmacológico , Isquemia de la Médula Espinal/inmunología , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
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.
Asunto(s)
Anticoagulantes/administración & dosificación , Cuidadores/educación , Medicamentos Genéricos/administración & dosificación , Educación del Paciente como Asunto , Fenindiona/análogos & derivados , Warfarina/administración & dosificación , Actividades Cotidianas/clasificación , Factores de Edad , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Relación Dosis-Respuesta a Droga , Medicamentos Genéricos/efectos adversos , Femenino , Francia , Humanos , Masculino , Fenindiona/administración & dosificación , Fenindiona/efectos adversos , Autoadministración , Comprimidos , Warfarina/efectos adversosAsunto(s)
Deficiencia del Factor VII/diagnóstico , Deficiencia del Factor X/diagnóstico , Fenindiona/análogos & derivados , Rodenticidas/toxicidad , Adolescente , Coagulación Sanguínea/efectos de los fármacos , Coagulación Sanguínea/genética , Dominio Catalítico/genética , China , Análisis Mutacional de ADN , Ingestión de Alimentos , Deficiencia del Factor VII/sangre , Deficiencia del Factor VII/complicaciones , Deficiencia del Factor VII/congénito , Deficiencia del Factor X/sangre , Deficiencia del Factor X/complicaciones , Deficiencia del Factor X/congénito , Humanos , Masculino , Mutación Missense/genética , Linaje , Fenindiona/administración & dosificación , Fenindiona/toxicidad , Polimorfismo Genético , Rodenticidas/administración & dosificaciónRESUMEN
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.
Asunto(s)
Síndrome de Budd-Chiari/complicaciones , Absceso Hepático Amebiano/complicaciones , Anciano de 80 o más Años , Antiinfecciosos/uso terapéutico , Anticoagulantes/administración & dosificación , Anticoagulantes/uso terapéutico , Enoxaparina/administración & dosificación , Enoxaparina/uso terapéutico , Humanos , Absceso Hepático Amebiano/tratamiento farmacológico , Masculino , Metronidazol/uso terapéutico , Ofloxacino/uso terapéutico , Fenindiona/administración & dosificación , Fenindiona/análogos & derivados , Fenindiona/uso terapéuticoRESUMEN
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.