RESUMEN

Objetivo: Describir la situación de accesibilidad y adherencia a tratamientos con drogas biológicas en pacientes de un servicio público de reumatología. Métodos: Estudio de corte transversal, observacional y retrospectivo que incluyó pacientes con gestión de DB. Variables: sociodemográficas, clínicas, tratamientos, tiempo desde el diagnóstico al acceso, adherencia (porcentaje de toma mensual y adecuada de la droga ≥75%); tiempo desde prescripción a administración; trámite administrativo realizado por entidad pública u obra social; certificado único de discapacidad (CUD). Resultados: Se incluyeron 57 pacientes, 86% mujeres, edad media 47,79 años (IC 95%: 44,46-51,12); educación media 8,42 años (IC 95%: 7,68-9,16); 82,5% nivel socioeconómico medio-bajo; 63,2% etnia mestiza; 19,3% cobertura privada. Patología más frecuente: artritis reumatoidea. Tiempo medio desde el diagnóstico a la DB: 104,25 meses (IC 95%: 82,61-125,89). Tiempo medio desde la prescripción a la aplicación: 6,4 meses (IC 95%: 5,62-7,18). Adherencia del 86,0%. 50% de los pacientes contaban con CUD. No hubo diferencias en el tiempo de espera desde prescripción a administración de DB, en relación a cobertura de salud (p=0,065) y nivel socioeconómico. Conclusión: Existe un largo tiempo de evolución de la enfermedad en relación a la accesibilidad a DB y tanto el acceso como la adherencia reflejan la vulnerabilidad de estos pacientes.

Objective: To describe the situation of accessibility and adhesion treatment of patients with biological drugs (BD) from a public rheumatology service. Methods: Cross-sectional, observational and retrospective study, which includes patients who have been treated with BD. Variables: sociodemographic; clinical and treatments; time from diagnosis to BD access, adherence (monthly intake percentage of the drug ≥75%); time from the prescription to the administration of the BD; paperwork by a public or private entity; disability certificate (DC). Results: A total of 57 patients were included, 86% women, mean age being 47.79 (95% CI: 44.46-51.12) and education years being 8.42 (95% CI: 7.68- 9.16). 82.5% belonged to a medium-low socioeconomic status and 63.2% were mestizos. 19.3% had private coverage. Rheumatoid Arthritis was the most frequent disease. The mean time from diagnosis to BD: 104.25 months (95% CI: 82.61-125.89). The mean time from prescription to application: 6.4 months (95% CI: 5.62-7.18). The adherence was 86.0% and 50.0 % of patients had DC. There were no differences in the waiting time from the prescription to BD administration, taking into account the health coverage (p = 0.065) and socioeconomic status. Conclusion: There is a long time of disease evolution in regarding the accessibility to BD. In addition, accessibility and adherence reflect the vulnerability of our patients.

Asunto(s)

RESUMEN

Oral treatment with ifosfamide results in dose-limiting encephalopathy. Methylene blue is effective in reversal and prophylaxis of this side effect. In the present study, the pharmacokinetics of ifosfamide after iv and po therapy in combination with prophylactic administration of methylene blue were investigated. Nine patients with metastatic non-small cell lung cancer were treated by a combination of ifosfamide (3 days), sodium 2-mercaptoethane sulfonate (4 days), and etoposide (8 days). Cycles were repeated every 28 days. Ifosfamide was administered orally, with the exception of one of the first two cycles, when it was administered as a short infusion (randomly assigned). The patients received methylene blue in doses of 50 mg po 3 times daily; an initial dose of 50 mg was given the evening before chemotherapy. Urine samples were collected over the entire treatment period, and concentrations of ifosfamide and its major metabolite, 2-chloroethylamine, were measured by gas liquid chromatography. By the same technique, 2- and 3-dechloroethylifosfamide were determined in plasma and urine. Overall alkylating activity in urine was assayed by reaction of the alkylating metabolites with 4-(4'-nitrobenzyl)-pyridine. The chemotherapeutic regimen was well-tolerated by all of the patients studied. There was no evidence of a shift in the metabolic pattern dependent on the route of administration. From the data, we conclude that methylene blue has a neuroprotective effect and that the pharmacokinetics of ifosfamide are not influenced by its comedication.

Asunto(s)

RESUMEN

The clinical application of ifosfamide is hampered by a central nervous side effect, the so-called ifosfamide encephalopathy. Methylene blue is effective in prophylaxis and reversal of this side effect. In the present study, the in vitro inhibition of (mono)amine oxidases by methylene blue is demonstrated in two different experimental systems. The results provide an explanation for the preventive action of methylene blue in ifosfamide neurotoxicity, because the generation of chloroacetaldehyde (a potential neurotoxin of ifosfamide metabolism) is prevented in liver mitochondria and extrahepatic tissues. Generation of alkylating metabolites was also studied in rat liver perfusions, and methylene blue did not show any inhibition of ifosfamide activation. From these data, we conclude that the clinical effectiveness of methylene blue in treatment and prevention of ifosfamide encephalopathy might be based on inhibition of (mono)amine oxidases. Hepatic bioactivation of ifosfamide is not influenced by methylene blue.

Asunto(s)

Asunto(s)

RESUMEN

In cancer chemotherapy with ifosfamide the occurrence of a drug-related encephalopathy represents a severe adverse-effect of unknown origin. We found that the underlying mechanism resides in the mitochondrial toxicity of ifosfamide metabolites. The electron accepting drug methylene blue can substitute for the demonstrated flavoprotein deficiency and its administration leads to resolution of the encephalopathy in patients. The prophylactic administration of methylene blue is equally effective via another principal mechanism, namely oxidation of the excessive quantity of NADH formed during ifosfamide metabolism. The inhibition by methylene blue of multiple amine oxidase activities also prevents formation of the neurotoxic chloroacetaldehyde from ifosfamide-derived chloroethyl amine. Thus, methylene blue exhibits several synergistic modes of actions which enable the dose-limiting neurotoxicity of alkylating chemotherapy with ifosfamide in cancer patients to be overcome.

Asunto(s)

RESUMEN

The antineoplastic ifosfamide produces dose-dependent signs of neurotoxicity. After ifosfamide overdose in a patient, we found excessive urinary excretion of glutaric acid and sarcosine, which is compatible with glutaric aciduria type II, a defect in mitochondrial fatty acid oxidation that results from defective electron transfer to flavoproteins. We therefore used the electron-accepting drug methylene-blue as an antidote for ifosfamide encephalopathy. In one patient, ifosfamide neurotoxicity was rapidly reversed by methylene-blue 50 mg intravenously. In another patient with previous episodes of ifosfamide encephalopathy, methylene-blue was administered orally prophylactically. No symptoms of neurotoxicity were noted.

Asunto(s)

RESUMEN

The histologic condition of the gingival tissues was determined prior to and 4 weeks after scaling and curettage, then 4 months after periodontal osseous surgery in a group of eight patients with chronic periodontitis. The histopathologic changes were correlated with variations in mast cell population following the different modes of periodontal therapy.

Asunto(s)

Asunto(s)