PubMed · 4153470
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H R Brunner. 1974. Renin suppression.. https://doi.org/10.1080/00325481.1974.11713889
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An original dosage form for oral delivery based on the encapsulation of both, lipophilic and hydrophilic drugs, in poly(epsilon-caprolactone) (PCL) microparticles prepared either by the oil-in-water (o/w) or the water-in-oil-in-water (w/o/w) solvent evaporation method was developed. Microparticles were characterized in terms of morphology, size, encapsulation efficiency and drug release. The physical state of the drugs and the polymer was determined by scanning electron microscopy (SEM), X-ray powder diffractometry, and differential scanning calorimetry (DSC). Nifedipine (calcium antagonist) and propranolol HCl (beta-blocker), used for the treatment of hypertension, were chosen as lipophilic and hydrophilic drugs. The microparticles were spherical with diameters in the range of 191-351 microm by the o/w-method, and in the range of 302-477 microm by the w/o/w-method. The encapsulation efficiency (EE) was 91% for nifedipine and 37% for propranolol HCl with the o/w-method, and 83% for nifedipine and 57% for propranolol HCl with the w/o/w-method. DSC and X-ray diffraction studies showed that PCL maintained its semi-crystalline structure, while the drugs were either dispersed or dissolved in the polymer. In vitro release studies revealed a controlled release of nifedipine and propranolol HCl from microparticles prepared by the o/w-method; a burst release of propranolol HCl was observed from microparticles prepared by the w/o/w-method. In conclusion, microparticles containing both a hydrophilic and a lipophilic drug were successfully prepared.
BACKGROUND: To date, the use of beta-blockers in treating patients with chronic heart failure gains support, this since several large clinical trials reported reduced mortality after chronic beta-blockade. Part of these beneficial effects may result from inhibition of deleterious neurohormone activation that accompanies progression of chronic heart failure. The present study evaluates whether this neurohormone inhibition is preserved after chronic beta-blockade. METHODS: In a retrospective analysis the neurohormonal profiles of patients with moderate to severe chronic heart failure were studied from three treatment subgroups: (1) Without beta-blockers or ACE-inhibitors (n=15), (2) without beta-blockers, with ACE-inhibitors (n=324), (3) with beta-blockers and ACE-inhibitors (n=31). Patients were on beta-blockers for an average period of 3.8 years. Plasma samples were obtained under controlled conditions. RESULTS: Despite uneven group sizes, the groups were well matched for clinical characteristics. Plasma renin levels were significantly lower in patients treated adjunctively with beta-blockers. Plasma aldosterone and endothelin-I levels also tended to be lower after chronic beta-blockade, however, this did not reach statistical significance. CONCLUSIONS: Chronic adjunctive beta-blocker treatment shows significantly lower plasma renin levels when compared to single ACE-inhibition. This persistent reduction of plasma neurohormone activation may concomitantly reduce the chance of neurohormones to escape from inhibition.
BACKGROUND: beta-blocker therapy for dilated or ischemic cardiomyopathy is now an accepted and effective treatment. However, little is known about its efficacy in patients with postoperative impaired left ventricular function. This retrospective study was designed to assess the effects of beta-blocker therapy in patients after aortic valve replacement (AVR) for aortic regurgitation (AR). METHODS: A total of 59 patients who underwent AVR for chronic AR were assigned to four groups. Twelve patients were treated with both ACE inhibitors and beta-blockers, 12 patients with only ACE inhibitors, eight patients with only beta-blockers, and 27 patients without beta-blockers or ACE inhibitors. A postoperative echocardiographic study was performed one year after surgery. RESULTS: The heart rate was significantly reduced in patients with beta-blockers despite the use of ACE inhibitors after surgery. Postoperative left ventricular volume was more significantly decreased in beta patients than in non-beta patients despite the use of ACE inhibitors. There were also significant reductions in left ventricular mass index in ACE+beta patients compared to ACE+non-beta patients. However, there were no significant differences in NYHA functional class and survival rate between beta patients and non-beta patients. CONCLUSIONS: beta-blocker therapy may improve cardiac performance by reducing cardiac volume and mass in patients with impaired LV function after AVR for AR.