RESUMEN
A randomized, single-blind, placebo-controlled study was conducted in 82 obese patients with mild to moderate essential hypertension, to determine the incidence of hyperinsulinemia, the relations between fasting insulin and dihydroepiandrosterone-sulfate (DHEA-S) levels, and the short-term effects of antihypertensives on DHEA-S and insulin serum concentrations. Increased insulin/glucose ratios (IGR) suggestive of insulin resistance were found in half of our patients. Hyperinsulinemic and normoinsulinemic obese patients with hypertension had comparable fasting glucose and DHEA-S concentrations and comparable blood pressure (BP) levels. Thus no relations were found between fasting insulin and DHEA-S levels. Fasting hyperinsulinemia was found in only half of the obese subjects with hypertension, suggesting that not all obese patients with hypertension are at the same high cardiovascular risk. Short-term treatment with captopril, prazosin, verapamil, atenolol, or hydrochlorothiazide (HCTZ) reduced BP; greater BP reduction was observed with drugs with vasodilatory effects. Captopril, prazosin, and verapamil reduced fasting insulin levels, whereas atenolol and hydrochlorothiazide did not. The former drugs reduced fasting insulin levels that were either within normal limits or in the hyperinsulinemic range. None of the drug treatments produced significant increases in serum DHEA-S concentrations, although some of them considerably reduced fasting insulin levels. No relations between insulin and DHEA-S levels were observed either at baseline or at the end of the antihypertensive treatment. The BP reduction resulting from the peripheral vasodilation may explain the insulin-reducing action of captopril, verapamil, and prazosin. These results further emphasize the large heterogeneity present in the pathophysiologic mechanisms operating in obesity and hypertension.
Asunto(s)
Antihipertensivos/uso terapéutico , Glucemia/análisis , Sulfato de Deshidroepiandrosterona/sangre , Hipertensión/sangre , Insulina/sangre , Obesidad/sangre , Ayuno , Humanos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Persona de Mediana Edad , Obesidad/complicaciones , Placebos , Método Simple CiegoRESUMEN
The antihypertensive effects of the regular immediate release formulation of verapamil (verapamil IR) and the newer sustained release formulation of verapamil (verapamil SR) were compared in Hispanic patients with untreated essential hypertension. Verapamil IR was given in 3 divided doses (80 or 160mg 3 times daily) and verapamil SR was given either as a single daily dose of 240mg or as 240mg every 12 hours. With both formulations there was a significant reduction in systolic (SBP) and diastolic blood pressure (DBP); a greater lowering of BP was observed with verapamil 480 mg/day than with 240 mg/day. With verapamil SR 480 mg/day, 91% of patients had reductions in SBP and DBP greater than 20 and 15mm Hg, respectively. In addition, 83% of patients reached normotension. With the lower dose (240mg once daily), 83% of patients had decreases in DBP greater than 10mm Hg and 73% of patients achieved normotension. Comparable effects were achieved with verapamil IR. With verapamil IR there was a more rapid fall in BP which peaked 3 to 4 hours postdose, whereas with verapamil SR a more gradual and sustained BP reduction was observed. Only small changes in heart rate (HR) were observed with verapamil IR and verapamil SR. For verapamil SR, the mean increase in HR was 5 beats/min (to 80 beats/min) and the mean decrease in HR was 13 beats/min (to 62 beats/min). Both verapamil SR and verapamil IR prolonged the PR interval of the ECG. An equal degree of PR prolongation was observed with 240 and 480 mg/day. The incidence of side effects (headache, palpitations, dizziness and flushing) was dose dependent, decreased with continuous treatment and was much higher with verapamil IR than with verapamil SR. Steady-state plasma verapamil concentrations were monitored. Compared with verapamil IR, verapamil SR produced a more gradual rise and a more sustained elevation of plasma verapamil and norverapamil concentrations. Comparable trough verapamil concentrations (Cmin) were observed with verapamil IR (98 micrograms/L) and SR (81 micrograms/L); morning Cmin verapamil concentrations were higher than daytime Cmin values. The normalised area under the plasma concentration-time curve (AUC) and maximum concentration (Cmax) were 10 to 20% greater for verapamil IR than SR. The 2-fold increase in oral dose produced a 2.2- and 2.4-fold increase in AUC for verapamil IR and SR, respectively, associated with a 20% reduction in metabolism to norverapamil. Fasting increased the rate and extent of absorption of verapamil.(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Hipertensión/tratamiento farmacológico , Verapamilo/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Preparaciones de Acción Retardada , Frecuencia Cardíaca/efectos de los fármacos , Hispánicos o Latinos , Humanos , Verapamilo/farmacocinética , Verapamilo/farmacologíaRESUMEN
We assessed the pharmacokinetics and pharmacodynamics of immediate-release (IR) and slow-release (SR) verapamil in Hispanic patients with mild to moderate essential hypertension. Area under the curve and Cmax increased linearly with the dose of IR and SR. Plasma levels showed a more gradual increase and were maintained elevated for longer periods with SR. Both IR and SR reduced blood pressure (BP) significantly. Peak BP reduction with 240 mg q.i.d. SR (6 h postdose) or 80 mg t.i.d. IR (4 h postdose) averaged 28/18 and 23/20 mm Hg, respectively. Morning predose BP levels were reduced 16/5 mm Hg by SR and 5/6 mm Hg by IR. Peak PR prolongation averaged 43 ms for SR and 56 ms with IR. Heart rate was not modified. With 480 mg/day there was a greater BP reduction with no relevant changes in HR and no further increases in PR intervals. However, incidence of side effects (headaches, dizziness) was enhanced with 480 mg/day IR but not with SR. These results suggest that Hispanic patients have a good response to verapamil. The pharmacokinetic characteristics of SR verapamil account for its more favorable side-effect profile observed with this formulation. SR is considered advantageous to IR for the chronic treatment of hypertensive patients.