Inhibitory effects of diazepam in rat vas deferens: role of calcium.

Diazepam and Ro5-4864 effects on noradrenaline-induced rat vas deferens contractions were studied. We investigated whether central or peripheral type benzodiazepine receptors were involved, by studying the effects of the selective central or peripheral benzodiazepine receptor antagonists, flumazenil (Ro 151788) or PK 11195 respectively. Diazepam interactions with GABA, adenosine, theophylline, and hypercalcic medium (3.5 mM) were studied. Also, we investigate diazepam effect on KCl depolarized vas deferens. Results showed that diazepam (10(-4) to 1.7 x 10 (-4) M) and Ro 5-4864 (10(-5) to 5.5 x 10(-5) M) inhibited NA-induced vas deferens contractions and that neither flumazenil nor PK 11195 antagonized diazepam or Ro 5-4864 inhibitory effects respectively. GABA, adenosine and theophylline did not modify neither NA vas deferens response nor diazepam inhibitory action. Diazepam effect was significantly reduced in and 3.5 mM calcium medium and KCl vas deferens response was inhibited by diazepam 1.3 x 10(-5) and 1.3 x 10(-4) M. It is concluded that in rat vas deferens diazepam effect seems to be related with calcium mobilization.

Influencia de la siesta sobre la presión arterial en pacientes hipertensos esenciales / Afternoon nap influence on blood pressure in essential hypertensives

Hay suficientes evidencias que demuestran que el descenso nocturno de la presión arterial es consecuencia de la inactividad y no depende de una hora determinada, ya que la presión arterial desciende cuando los individuos duermen durante el día. Comparamos la presión arterial sistólica, diastólica y la frecuencia cardíaca durante la siesta, el período nocturno de actividad y el sueño nocturno en 59 pacientes (32 mujeres, 27 hombres) hipertensos sin medicación (edad promedio: 53 ñ 14 años, rango: 26-84 años). La presión arterial y la frecuencia cardíaca fueron registradas utilizando un Pressurometer Del Mar IV 1990. Veintidós pacientes durmieron dos horas por lo menos luego de almorzar, 17 descansaron sin dormir y 20 permanecieron activos en el período posprandial. Evaluamos la media, el área bajo la curva y el desvío estándar de la presión arterial sistólica, diastólica y frecuencia cardíaca durante el período posprandial, el sueño nocturno y el resto del día. Tanto el sueño nocturno como el sueño posprandial disminuyeron la presión arterial sistólica, diastólica y la frecuencia cardíaca. Durante el descanso posprandial la presión arterial diastólica fue similar a la presión arterial diastólica nocturna y durante la siesta disminuyó más que durante el sueño nocturno

Steady-state hydroxyflutamide plasma levels after the administration of two dosage forms of flutamide.

A bioavailability study of randomized cross-over design was carried out in eight volunteers who were given a 48-h flutamide treatment consisting of 250-mg tablets three times daily or 400-mg sustained-release tablets twice daily, followed 3 weeks later by the alternative dosage form. Just before the last dose and 15 times during the subsequent 24 h, blood samples were obtained for the determination of plasma hydroxyflutamide (the active metabolite of flutamide) levels by high-performance liquid chromatography. No statistically significant differences between the two dosage forms were found for the lag time, rate of initial increase in concentration, peak plasma concentration, mean hydroxyflutamide concentration within one dosing interval or 24-h AUC value. One subject presented mild and transient nausea during both treatment periods. After the first treatment period (250-mg tablets), an increase in serum bilirubin was observed in another volunteer, who was withdrawn from the study. It may be concluded that both dosage forms were bioequivalent.

Effects of enalapril on renal parameters in patients with primary glomerulopathies associated with chronic renal failure.

14 patients (8 male, 6 female), aged 35 to 64 years, with glomerulopathies consisting of membranoproliferative glomerulonephritis (GN) [n = 6], membranous GN (n = 3), focal and diffuse glomerulosclerosis (n = 4), and post-streptococcal GN (n = 1) were studied. Diagnosis was established by renal biopsy in 12 of the 14 patients. All 14 patients had impaired renal function (creatinine clearance = 25 to 55 ml/min) and proteinuria (1.0 to 10.4 g/day). Five normotensive patients received enalapril 20 mg/day, whereas 9 patients with hypertension received 20 to 40 mg/day to control blood pressure. Diuretics were administered concomitantly to 8 patients. Patients attended the clinic every 14 days for 30 months and their diets were closely monitored, with sodium intake limited to between 50 and 100 mEq/day and protein to between 1.0 and 1.2 g/kg/day. Blood pressure was significantly controlled in the patients with hypertension. Serum creatinine, blood urea nitrogen, creatinine clearance and 24-hour urinary protein excretion all significantly improved during the 30-month study. No adverse clinical events were noted. Thus, over a period of time, enalapril therapy may improve the prognosis of patients with glomerulonephritis by maintaining glomerular filtration rates and decreasing proteinuria and blood pressure.

Treatment of ifosfamide-induced urothelial toxicity by oral administration of sodium 2-mercaptoethane sulphonate (MESNA) to patients with inoperable lung cancer.

The protective effect of oral administration of the thiol compound sodium 2-mercaptoethane sulphonate (MESNA) against urothelial toxicity induced by ifosfamide (IF) was tested in a group of 45 patients with inoperable lung cancer under treatment with IF (2250 mg/m2 on days 2-5) as part of a polychemotherapy regimen repeated in a 4-week cycle. MESNA was given orally on the days of treatment with IF in 3 doses of 840 mg/m2, each administered at 0 hr (= injection of IF), 4 hr and 8 hr p.i. Out of a total of 88 courses of this treatment we observed 10 episodes of asymptomatic microscopic haematuria and no episodes of gross haematuria. In this group of 45 patients under protection with MESNA there were 5 complete remissions and 9 partial remissions (total 31%). A further group of 25 patients under polychemotherapy with IF were treated by conventional prophylactic measures (raised fluid intake and forced diuresis). In this group there were 1 complete and 5 partial remissions (total 24%), but nearly all patients developed either gross haematuria and/or symptoms of bladder irritation (cystitis and pollakisuria). There were no appreciable differences between the MESNA series and the conventional prophylaxis series with respect to either haematological or systemic toxicity of the cytostatic treatment. Our results support the view that MESNA, given orally in conjunction with combined cytostatic regimens which include IF, simplifies the treatment and provides optimum protection for the urinary epithelium. Protection with oral MESNA is particularly suitable for outpatients.

Union de drogas a proteinas plasmaticas. / Union of drugs with plasma proteins

Se discute en detalle la union e las proteinas plasmaticas a las drogas, lo que constituye uno de los aspectos mas importantes de la farmacocinetica de los diferentes farmacos. En esta revision se analizan los mecanismos cineticos moleculares de la union proteina-droga; las tecnicas de estudio de este fenomeno, las modificaciones que acontecen en diferentes condiciones clinicas y terapeuticas en relacion a este importante hecho farmacocinetico. Finalmente, se describen las implicaciones terapeuticas derivadas de las modificaciones en la union proteina-droga que acontece en diferentes condiciones experimentales y clinicas