Prescripción inapropiada de benzodiazepinas en la población mayor de la Comunidad Valenciana / The inappropriate prescription of benzodiazepines in the elderly population of the Community of Valencia

Si bien la capacidad oxidativa metabólica de la función hepática disminuye con la edad, el metabolismo conjugativo resulta menos afectado. La mayoría de las benzodiazepinas requieren para su eliminación del metabolismo oxidativo y conjugativo; lorazepam, en cambio, sólo precisa de la conjugación, lo que lo convierte en la benzodiazepina más indicada para el tratamiento del paciente anciano. Métodos: Se realizó un estudio transversal retrospectivo de las prescripciones oficiales realizadas durante el periodo 2000-2003, y se utilizó la dosis diaria definida por mil habitantes por día (DHD) como medida del consumo de fármaco. Esta medida es la recomendada por la Organización Mundial de la Salud para comparar la evolución del consumo de principios activos en una población. Resultados: Durante el citado periodo se prescribieron más de 4.000 recetas de benzodiazepinas en la Comunidad Valenciana. El 65% fueron dispensadas con recetas de pensionista. Lorazepam fue el fármaco más prescrito, aunque sólo representó el 34% del total recetado a pensionistas. Conclusiones: En los pacientes ancianos, la prescripción de benzodiazepinas que se eliminan por metabolismo oxidativo debería reevaluarse y reemplazarse por la de otras de metabolismo conjuntivo con vistas a disminuir las reacciones adversas, como podrían ser la excesiva sedación, el riesgo de caídas y las fracturas asociadas a éstas (AU)

The metabolic oxidative capacity of the hepatic function decreases with age, whereas the conjugative metabolism is less affected. Most benzodiazepines require elimination by oxidative and conjugative metabolism, whereas lorazepam requires conjugation only. Accordingly, the most appropriate benzodia zepine for the treatment of elderly patients would be lorazepam. Methods: A retrospective cross-sectional study was conducted of the official prescriptions issued during 2000-2003, and the defined daily dose per thousand patients/day (DHD) was used as a measure of the drug consumption. That measure is the measure recommended by the WHO for the comparison of the evolution of the consumption of active principles in a population. Results: During those years more than 4,000 prescriptions for benzodiazepines were issued in the Community of Valencia. 65% were dispensed with pensioners’ prescriptions. Lorazepam was the most commonly prescribed drug although it represents just 34% of the total prescribed to pensioners. Conclusions: In the case of elderly patients the prescription of benzodiazepines that are eliminated by oxidative metabolism should be re-evaluated and modifi ed with others that are metabolised by conjugation, in order to reduce adverse reactions like excessive sedation, risk of falls and associated fractures (AU)

[Are benzodiazepines correctly used in the elderly?]. / 'Se hace un buen uso de las benzodiazepinas en el anciano?

Benzodiazepines are substances susceptible of producing drug dependence in addition to tolerability to sedative effects and frequent interactions when associated with other drugs. Thus, use of long half life benzodiazepines and inadequate intermediate and short half life dosage is related with falls and fractures in elderly patients. A retrospective study was conducted on the official prescriptions made during 2000-2003 and the daily dose defined per thousand patients/day (DDD/I) was used as a measurement of drug consumption. Prescription of benzodiazepines that are eliminated by oxidative metabolism should be revaluated and modified by other of conjunctive metabolism when treating elderly patients to decrease adverse reactions such as excess sedation, risk of falls and associated fractures.

¿Se hace un buen uso de las benzodiazepinas en el anciano? / Are benzodiazepines correctly used in the elderly?

Las benzodiazepinas son sustancias susceptibles de ocasionar farmacodependencia, además de producir tolerancia a los efectos sedantes y frecuentes interacciones al asociarlas con otros fármacos. El uso de benzodiazepinas de vida media larga y la inadecuada dosificación de las de vida intermedia y corta se relaciona con caídas y fracturas en pacientes ancianos. Se realizó un estudio retrospectivo de las prescripciones oficiales realizadas durante 2000-2003 y se utilizó la dosis diaria definida por mil pacientes y día como medida del consumo de fármaco. La prescripción de benzodiazepinas que se eliminan por metabolismo oxidativo debería de reevaluarse y modificarse por otras de metabolismo conjuntivo cuando se trate de pacientes ancianos para disminuir reacciones adversas como excesiva sedación, riesgo de caídas y fracturas asociadas (AU)

Benzodiazepines are substances susceptible of producing drug dependence in addition to tolerability to sedative effects and frequent interactions when associated with other drugs. Thus, use of long half life benzodiazepines and inadequate intermediate and short half life dosage is related with falls and fractures in elderly patients. A retrospective study was conducted on the official prescriptions made during 2000-2003 and the daily dose defined per thousand patients/day (DDD/I) was used as a measurement of drug consumption. Prescription of benzodiazepines that are eliminated by oxidative metabolism should be revaluated and modified by other of conjunctive metabolism when treating elderly patients to decrease adverse reactions such as excess sedation, risk of falls and associated fractures (AU)

Selective serotonin reuptake inhibitors: effects of chronic treatment on ethanol-reinforced behavior in mice.

Several lines of evidence suggest that aspects of ethanol drinking are mediated, at least in part, by serotonergic (5-HT) neurotransmitter systems. Ethanol-preferring animals show decreases in serotonin function and receptor densities. In addition, serotonin uptake inhibitors have been shown to decrease ethanol consumption in animal models and in humans. However, the time course of these effects and their duration remain undetermined. In the present studies, C57BL/6J male mice were treated with one of three selective 5-HT reuptake inhibitors (SSRIs): fluoxetine, sertraline, or paroxetine. All three drugs produced initial decreases in operant lever pressing behavior for ethanol followed by a return to baseline on subsequent days. Immediately following 14 days of this initial treatment, subsequent treatment with higher SSRI doses was ineffective in decreasing ethanol-reinforced behavior. However, after a several week "washout period," SSRI pretreatment again produced an initial decrease in responding for ethanol, again followed by a return to baseline. Thus, suppression of ethanol drinking may be related to immediate changes in 5-HT function following treatment with SSRIs, and tolerance to this effect appears to develop rapidly.

Regulation of operant ethanol-reinforced behavior is genetically independent of regulation of withdrawal severity in WSP and WSR mice.

Selectively bred withdrawal seizure prone (WSP1 and WSP2) and withdrawal seizure resistant (WSR1 and WSR2) mice were used to test the extent to which severity of ethanol withdrawal response is predictive of the reinforcing effects of ethanol. Mice were systematically introduced to ethanol under a fixed ratio 1 (FR 1) schedule using adjunctive drinking methods. There were no significant differences in ethanol consumption between the lines during training. Subsequently, responding for ethanol concentrations of 8%, 0% (vehicle control), and 8% retest under a FR 1 schedule in the absence of food induction was measured. Group data showed that ethanol did not serve as a reinforcer in the test phase within any of the four lines, and there were no significant line differences in rate of responding, intake, or blood ethanol concentrations (BEC). Mice were next tested for responding for ethanol under a FR 4 schedule. Again, ethanol did not serve as a reinforcer for any of the four groups, and there were no significant differences between the lines. However, further analysis showed that there were individual differences in responding within each group, some animals were apparently reinforced by ethanol, while others showed no reinforcement and some appeared to avoid ethanol. There was no systematic pattern within or between groups for these individual differences in responding. Thus, both the group results as well as the behavior patterns of individual animals are consistent with the conclusion that genes regulating rewarding effects of ethanol appear to be segregating randomly across groups and are independent of genes mediating ethanol withdrawal severity.(ABSTRACT TRUNCATED AT 250 WORDS)