ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03230.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03231.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

The effects of placebo, propranolol, and clonidine on blood pressure and blood pressure variability were examined in 14 subjects who had moderate essential hypertension. Hydrochlorothiazide was given throughout successive 4‐ to 5‐week periods of placebo, propranolol, and clonidine administration. During each treatment period, subjects were admitted twice to the clinical research unit for 24‐hour blood pressure monitoring performed during administration of placebo, propranolol and clonidine and repeated 1 to 2 weeks later during the first 24 hours after the abrupt cessation of placebo or drug administration. Blood pressure was recorded at 15‐minute intervals using an automated noninvasive recorder (Arteriosonde, Roche, New Jersey). Systolic and diastolic blood pressure readings were averaged and the standard deviation taken as the measure of long‐term variability (LTV). Systolic and diastolic blood pressure in sequential overlapping blocks of seven readings were averaged and the standard deviation calculated. Short‐term variability (STV) was estimated as the average of the standard deviations of the running means. During placebo administration and withdrawal, systolic and diastolic blood pressures as well as LTV and STV were unchanged. Systolic and diastolic pressures did not differ during propranolol administration from those during propranolol withdrawal or placebo withdrawal. Systolic and diastolic LTV and STV did not differ during propranolol administration and withdrawal from those observed during placebo administration or withdrawal. After clonidine withdrawal, both systolic and diastolic pressures increased to values significantly greater than during clonidine administration. These values were significantly greater than those observed after placebo withdrawal, thereby indicating rebound hypertension. After clonidine withdrawal, seven of fourteen subjects developed systolic pressure rebound; diastolic pressure rebound was observed in three patients. During clonidine withdrawal, LTV and STV of both systolic and diastolic pressures increased significantly compared with placebo

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03232.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

After a 2–4 week no‐treatment period, 24 patients (12 young, age 29–45 yr.; 12 elderly, age 65–81 yr.; 20 black, 4 white) with an untreated sitting diastolic blood pressure between 91–120 mm Hg received the nonsulfhydryl angiotensin converting enzyme inhibitor, lisinopril for three weeks in a singleblind, parallel group comparison. Patients who did not achieve goal blood pressure with the initial low‐dose (10 mg/day) were treated with a high‐dose regimen (40 mg/day) for three weeks. In those who remained incompletely responsive, hydrochlorothiazide 25 mg/day was added for four weeks in an attempt to normalize blood pressure (≤90 mm Hg). Low‐dose lisinopril monotherapy produced comparable reductions in the mean systolic and diastolic blood pressures (approximately −15/−8 mm Hg in both younger and older patients). Increasing the dose produced a slightly greater fall in mean blood pressures which normalized the blood pressure in five of six elderly patients unresponsive to the lower dose; addition of hydrochlorothiazide normalized three of the five remaining subjects from both groups who were unresponsive to high dose lisinopril. Lisinopril administration resulted in a rise in plasma renin activity and a fall in plasma aldosterone concentrations which were similar in both groups and which returned over time toward the baseline. The drug was well tolerated, producing one episode of symptomatic hypotension following the addition of hydrochlorothiazide to lisinopril monotherapy. Lisinopril alone or in combination with hydrochlorothiazide produces favorable antihypertensive effects in both younger and older predominantly black, low‐renin patients with

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03233.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Pinacidil is a potassium channel opener that decreases blood pressure by reducing peripheral arterial resistance. In two multicenter trials, we studied the concentrations and apparent clearance of pinacidil (406 patients) and concentrations of its pyridyl‐N‐oxide metabolite (147 patients). Responding patients had plasma samples collected hourly for 12 hours on 2 occasions after weeks to months of treatment. Pinacidil dose was titrated from 12.5 to 75 mg b.i.d. The peak concentration of pinacidil and N‐oxide and the area under the concentration‐time curve (AUC) were proportional to the dose of pinacidil, with an average pinacidil concentration of 268 μg/L (1.02 μM) and N‐oxide concentration of 172 μg/L (0.65 μM) for every 1 mg/kg pinacidil administered. Clearance of pinacidil (Clp= Dose/AUC) was 31 L/hr in patients younger than 45 years and 27 L/hr in those older than 60. Clpwas significantly smaller in white patients compared with other races (Clp= 28 vs. 34 L/hr). Clpwas significantly less in patients taking hydrochlorothiazide (27 vs. 31 L/hr) and greater in smokers (33 vs. 29 L/hr). Concomitant propranolol use did not

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03234.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

An observation of a treatment with digitalis antibodies (Fab‐fragments) in a young child is presented. The elimination of this antidotum proved to be much slower than normally expected. In the patient's history, the disappearance of the Fab‐fragments out of the blood lasted 142 days with a half‐life of 15.6 days, whereas an elimination with a T½of 28 hours is accepted. Probably there has been intracellular penetration of the antibodies into the liver, caused by concomitant diseases (Hepatitis A and B infections). An “in vitro” experiment is reported. It demonstrates the equimolar binding of the Fab‐fragments for digoxin and shows that the elimination of the Fab‐fragments can be established by a routine radioimmunoassay of digoxin, in a

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03235.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Previous reports have suggested an interaction between propafenone and digoxin. We investigated the pharmacokinetics of IV digoxin when given alone (Phase I), after pretreatment with propafenone 150 mg every 8 hours for seven days (Phase II), and after propafenone 300 mg every 8 hours for 7 days (Phase III). The total body clearance of digoxin during Phase I was 2.45 ml/min/kg and was 2.17 ml/min/kg during Phase II (NS) and decreased to 1.92 ml/min/kg during Phase III (P<0.05). The renal clearance and half‐life of digoxin were not significantly altered by propafenone. There was a trend towards a decrease in the volume of distribution of digoxin from 9.43 L/kg in Phase I, to 9.33 L/kg in Phase II, and 8.02 L/kg in Phase III. Similarly there was a trend towards a decreased nonrenal clearance of digoxin from 1.21 ml/min/kg during Phase I to 1.01 ml/min/kg during Phase II and to 0.75 ml/min/kg during Phase III. The changes in volume of distribution and nonrenal clearance parallel each other resulting in no change in the elimination half‐life of digoxin. It is postulated that the mechanism of this interaction is due to decreases in the volume of distribution and nonrenal elimination of digoxin by propafenone. The degree of this interaction was related to the dose of propafenone. The magnitude of this interaction may be greater in patients and, thus, may require a reduction in the digoxin d

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03236.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Furegrelate sodium (U‐63,557A), a pyridine‐derivative thromboxane synthase inhibitor, was administered orally in single doses of 200 to 1600 mg to normal male subjects. Furegrelate produced a dose‐related inhibition of thromboxane synthesis for 8–12 hours when measured either ex vivo from platelet‐rich plasma (PRP) or in vivo from urine. In general, the extent of thromboxane synthesis inhibition was greater in PRP than in urine. Furegrelate significantly inhibited platelet aggregation, but the effect was variable and measurements of thromboxane synthase did not predict the impact on platelet aggregation. Bleeding times and coagulation parameters were not altered significantly. Furegrelate was well absorbed orally with Tmax= 1 hr and t½= 3.5 to 5 hrs. There was no marked metabolism; elimination was primarily by renal excretion of parent compound. Thus, furegrelate is an effective inhibitor of thromboxane synthase in man with a relatively long biologic and circulating

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03237.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Although it is well known that calcium channel blockers can influence contraction of vascular smooth muscle, there is less knowledge on its effect on excitation contraction coupling in the endocrine glands and more specifically on insulin and glucagon release. In this study, nifedipine was administered in doses of 40 to 80 mg/day to 14 patients with essential hypertension, and its hemodynamic effects were evaluated by non‐invasive methods, and its effect on glucose metabolism by an arginine infusion test Nifedipine produced a significant reduction in systolic and diastolic blood pressure, both after the first dose (30/12 mm Hg) and after 8 weeks of administration (19/12 mm Hg). There were no significant changes in cardiac output (5.1 to 4.9 L/min), muscle (2.4 to 3.2 mL/sec/min) or cutaneous basal flow (9.8 to 8.6 mL/100 mL) as measured non‐invasively by echocardiogram and by plethysmography. Insulin and glucagon release were evaluated by the arginine infusion test. Nifedipine produced a tendency toward an increase in glucagon release and a reduction in insulin release although these changes did not reach statistical significance. In this group of patients, nifedipine produced a significant reduction in systolic and diastolic pressure, but no significant changes in insulin or glucagon plasma lev

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03238.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

A decrease in dietary protein intake lowers the clearance of a number of substances excreted principally by the kidney including uric acid and oxypurinol, the major metabolite of allopurinol. We studied the kinetics of uric acid and oxypurinol in seven healthy volunteers on a normal protein diet (2600 calories; 100 g protein) followed by a 400 calorie, protein‐free diet. A 600 mg dose of allopurinol was given orally after 6 days of the normal protein diet and again after 2 days of the 400 calorie, protein‐free diet. Two major findings emerged: first, the renal clearance of oxypurinol was reduced from 21.2 ± 1.9 ml/min during the normal protein diet to 12.3 ± 1.2 ml/min (P<.05) during the 400 calorie, protein‐free diet, and second, there was a striking diurnal difference in oxypurinol renal clearance with a 41% decrease in the oxypurinol clearance at night (8pmto 8am) versus day (8amto 8pm) on the 400 calorie, protein‐

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1989.tb03239.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY