ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Antiarrhythmic therapy would be greatly facilitated if the patients most at risk of sudden death could be identified. The Lown classification of the “severity” of arrhythmias is unsatisfactory. Recent attention has been directed to dispersion of depolarization, measured by signal averaging of the terminal QRS complex, and to dispersion of repolarization, measured by comparing QT intervals in different leads of the ECG. Since the Cardiac Arrhythmia Suppression Trial (CAST) therapy with Class 1 agents, especially Class 1c, if used at all, has been diverted from attempts to suppress arrhythmias and limited to control of symptoms. Interest in new Class 3 agents has grown and several new compounds are under trial. Low-dose treatment with the original Class 3 drug, amiodarone, has yielded promising results, in that mortality and serious arrhythmias have been reduced by regimes which do not fully abolish the arrhythmia.

ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

This study evaluated the effect of a standard meal on the multiple-peak behavior of diclofenac sodium following oral administration of a 100-mg slow-release (SR) wax-matrix tablet. The study was a randomized, 3x3 Latin-square trial balanced for residual effects, in which 18 subjects were randomly assigned to treatment sequences consisting of three treatments: (A) one 100-mg SR tablet, fasted; (B) one 100-mg SR tablet, fed; and (C) 100-mg diclofenac sodium buffered aqueous solution, fasted. Blood samples were obtained over a 24-h period for Treatments A and B, and over an 8-h period for Treatment C. Food did not significantly affect the extent of absorption but generally delayed the onset of absorption from the SR tablet. The plasma concentration-time profile for the SR tablet under fasted conditions was characterized by multiple-peak behavior. Under fed conditions, the SR tablet showed a more consistent absorption pattern, with a single peak occurring usually between 5 and 6 h. The concentration-time profile of the buffered aqueous solution showed a very rapid absorption phase followed by a rapid decline and a terminal elimination half-life of approximately 1.8 h. A single peak was observed following the buffered aqueous solution. This observation, in conjunction with evidence from other studies, leads to the conclusion that gastrointestinal pH may be responsible for the multiple-peak behavior observed following diclofenac sodium dosing. As compared to the solution, the wax-matrix tablet under both fasted and fed conditions showed slow-release characteristics.

ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The effects of quinapril on casual blood pressure (BP) and circadian variations in 24-h blood pressure (24ABPM) were studied in patients with essential hypertension. Twenty-six patients were enrolled in the study (mean age 59 ± 11 years). After a 4-week washout period, patients were treated with quinapril 5 mg, 10 mg, or 20 mg once a day until casual blood pressures become optimal within 8–10 weeks. The 24ABPM was performed before and after treatment at 30-min intervals using an ABPM-630 in patients during usual daily activities on work days. Measured BP was fitted to a periodic regression curve with 24-h and 12-h harmonics. Quinapril significantly decreased casual blood pressure but had no effect on pulse rate. It exhibited an excellent antihypertensive effect throughout 24 h; this effect, however, was stronger during the day than at night, resulting in no excessive nocturnal hypotension. The level of the periodic regression curves for systolic and diastolic blood pressures was significantly decreased following treatment but that of the pulse rate was not affected by this drug. The drug caused changes in the pattern of the periodic regression curve for blood pressure and pulse rate. This was attributed to the more prominent antihypertensive effect of quinapril in the afternoon and evening. To evaluate the efficacy of this drug semiquantitatively, the hyperbaric indices were compared before and after the treatment, and those indices for both systolic and diastolic blood pressures were significantly decreased. Adverse effects occurred in four patients (15.4%), all of which were mild and thought to be clinically insignificant. It was concluded that quinapril, 5–20 mg day−1, was considered to be useful for patients with mild to moderate essential hypertension.

ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Forearm hemodynamics using pulsed Doppler flowmetry were studied in 12 healthy volunteers and 20 patients with mild to moderate hypertension before and after acute and long-term oral administration of the β-blocking agent dilevalol. The study was performed using a double-blind design versus placebo. Both 200-mg and 400-mg dosages produced a significant acute blood pressure reduction in normotensive and hypertensive subjects. In hypertensive subjects, forearm vascular resistance was poorly modified, brachial artery diameter decreased significantly but only with long-term administration of the 400-mg dosage. A significant reduction in brachial artery tangential tension was consequently observed. The study provides evidence that Dilevalol produced a significant decrease in blood pressure in normotensive and hypertensive subjects in association with a decrease in brachial artery tangential tension.

ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The central antihypertensive drugs such as methyldopa or clonidine have been agents of importance in the therapy of hypertension. Due to the side effects and the rebound hypertensive phenomenon in the case of clonidine, the use of these agents have been clearly diminished. There are several evidences that a new type of receptor, imidazoline receptor, is present in the central nervous system and in the periphery. A specific agonist for these receptors, rilmenidine, has been studied in experimental animals and in hypertensive patients. Clinical studies have shown that rilmenidine exhibits similar efficacy but a better tolerability compared to clonidine. Rilmenidine may represent a good alternative in the therapy of hypertension.

ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Papaverine is a commonly used vasodilator of the internal mammary artery in cardiac surgery. The effects of papaverine with and without Nω-L-arginine methyl ester (L -NAME) (a nitric oxide production inhibitor) and/or zaprinast (a cyclic GMP inhibitor) or verapamil (calcium channel antagonist) on systemic vascular resistancein vivohave not been well documented. This study examines the hemodynamic responses to papaverine and attempts to identify the role of nitric oxide, cyclic guanosine monophosphate (GMP), and calcium in the vasodilation. The effects of varying doses of papaverine were evaluated with and without L-NAME and/or zaprinast or verapamil on the hindlimb vascular resistance in the male rat. With institutional approval, 40 male Sprague-Dawley rats (400–450 g) were anesthetized with intraperitoneal pentobarbital (50 mg kg−1). The carotid artery, jugular vein, and abdominal aorta were cannulated by cutdown; mean arterial pressure (MAP) and hindlimb perfusion pressure (HPP) were recorded. Rats were heparinized (1000 U kg−1). Papaverine (1,3,10,30, and 100 μg) was injected into the hindlimb, whereas MAP was maintained constant, and the HPP was recorded. Both L-NAME (25 mg kg−1) and/or verapamil and then papaverine (1, 3, and 10 μg) were injected into the hindlimb, and changes in HPP were recorded. A Student's t-test was used for statistical analysis, with ap< 0.05 considered significant. Papaverine, in increasing doses, decreased HPP incrementally. L-NAME partially blocked the effects of papaverine (p< 0.05), as did verapamil (p< 0.05). The combination of L-NAME and verapamil further decreased papaverine's vasodilation to almost eliminate it (p< 0.05). We demonstrated the effect of papaverine on the hindlimb vasculature is similar to its effects noted in the internal mammary artery. Nitric oxide is known to be an agent causing vasodilation. It was demonstrated that papaverine vasodilation in the hindlimb vascular bed is modified by L-NAME, which suggests that nitric oxide production inhibition is partially responsible for this effect. It was demonstrated that there is an effect of calcium channel blockade on the vasodilation caused by papaverine. Both L-NAME and verapamil together appear to modify further the vasodilation caused by papaverine, suggesting both calcium channel and nitric oxide mechanisms for vasodilation. Zaprinast, a specific cyclic GMP phosphodiesterase inhibitor, did not affect the vasodilation caused by papaverine, acetylcholine, nitroglycerin, or verapamil.

ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Pravastatin, an HMG CoA reductase inhibitor used in the treatment of hypercholesterolemia, is recommended for bedtime (PM) dosing. Bedtime dosing with pravastatin is slightly more efficacious but not significantly different than morning (AM) dosing in lowering LDL-C and total cholesterol. The pharmacokinetics of pravastatin and its major metabolite SQ 31,906 were determined in 20 healthy men administered a single 20-mg dose either in the morning or at bedtime in an open, randomized, crossover study. Concentrations of pravastatin and SQ 31,906 were measured in serum and urine by gas chromatograph/mass spectrometry methodology. The area under the serum concentration time curve (AUC) of pravastatin was significantly less (40%) following PM dosing compared with AM dosing. Urinary excretion of pravastatin following PM dosing was also significantly decreased. Bioavailability of SQ 31,906 was somewhat higher in the PM group (20% greater following PM administration), and urinary excretion of SQ 31,906 was significantly increased by 60% following PM dosing. The lower AUC of pravastatin following PM dosing does not diminish its efficacy, possibly because PM dosing immediately precedes the diurnal peak period of hepatic cholesterol synthesis. Lower blood levels of pravastatin following PM dosing may contribute to its favorable safety profile.

ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Ranolazine is a new, orally active pharmacologic agent that experimentally has been shown to favorably affect myocardial metabolism during myocardial ischemia. It has no direct action on myocardial hemodynamics but appears to improve ventricular functioning by blocking uptake of free fatty acids by the heart while shifting metabolism to anaerobic glycolysis during myocardial ischemia. Preliminary clinical studies suggest a dose-dependent antianginal, and anti-ischemic effect and an excellent safety profile for this unique drug. However, the results of a recent double-blind efficacy and safety study showed no antianginal effect of ranolazine (30–120 mg thrice daily) when compared to placebo.

ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

A single-center, open-label, four-way crossover study was performed in 22 healthy adult subjects to determine the relative effect and significance of certain foods on the bioavailability of nizatidine. Results indicate that administration of nizatidine mixed with apple sauce, cranberry juice, or vegetable juice reduces the bioavailability approximately 30–40% relative to administration of a nizatidine capsule with water. The reduction of bioavailability appears to be primarily due to reduced extent of absorption. The mechanism of this effect was not investigated.

ISSN:1075-2765    

出版商:OVID    

年代:1995

数据来源: OVID