Nicardipine as antihypertensive monotherapy: positive effects on quality of life.

The effects of nicardipine and propranolol on patients' quality of life were compared during a double-blind, multicentre, parallel, randomised study of hypertension therapy. After a placebo run-in period, the doses for each patient were successfully titrated to reduce supine diastolic blood pressure to less than 90 mmHg with either nicardipine 60 or 90 mg/day (123 patients) or with propranolol 90-240 mg/day (120 patients). Both drugs demonstrated similar efficacy in reducing systolic and diastolic blood pressure. Total duration of therapy ranged from 6-12 weeks. The Nottingham Health Profile questionnaire was used to assess the effect of each treatment on the patients' quality of life. The overall quality of life score for patients on nicardipine showed a tendency toward improvement, while for those on propranolol, the trend was toward overall worsening. The differences between the two treatment groups were statistically significant for males (P = 0.02). The analysis of the separate components of this evaluation demonstrated that physical mobility was reported to be decreased more for the propranolol-treated patients than for the nicardipine-treated patients (P = 0.02). In contrast to the propranolol-treated patients, the nicardipine-treated patients reported improvements for sleep, social life, work, sex life, and for activities related to hobbies and interests. A second questionnaire was used to assess the effects of the therapies on work productivity. Among those patients who worked for pay, more patients treated with propranolol than those treated with nicardipine rated themselves as less productive at work (P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Sustained-release diltiazem compared with atenolol monotherapy for mild to moderate systemic hypertension.

The daily administration of 240 to 360 mg of diltiazem lowered blood pressure in a dose-related pattern similar to that seen in patients taking a daily dosage of 50 to 100 mg of atenolol. Sustained-release diltiazem was administered twice daily and atenolol once. Goal blood pressure was defined as less than 90 mm Hg or a reduction of greater than or equal to 10 mm Hg for patients with baseline pressures of 95 to 99 mm Hg in the supine position and was achieved in 60% of diltiazem-treated and 63% of atenolol-treated patients. The mean diltiazem dosage at the end of the study was 329 mg daily; for atenolol it was 80 mg daily. Adverse reactions considered possibly or probably drug related were reported by 26% of diltiazem patients and 38% of atenolol patients. Although both drugs were associated with a slower heart rate, atenolol patients showed a significantly greater negative chronotropic effect. Diltiazem, in a sustained-release form taken twice daily, is as effective as atenolol as a sole antihypertensive agent. It has a favorable side-effect profile and may be a useful alternative antihypertensive medication compared with existing beta-blocker therapy with atenolol.

Hepatitis B surface antigenemia in a chronic hemodialysis program: lack of influence on morbidity and mortality.

One hundred one patients established on chronic hemodialysis on January 1, 1978, were retrospectively evaluated over the ensuing 8-year period to determine the effect of hepatitis B surface antigenemia on morbidity and mortality. Sixty-four patients remained HBsAg-negative after reaching end-stage renal disease; 30 were transiently or persistently HBsAg-positive; seven patients were excluded from study because of insufficient data. The HBsAg-positive and HBsAg-negative patients did not differ with respect to age, sex, race, or etiology of renal disease. There were no differences between the positive and negative groups in terms of death rates (50% v 34.4%, P = not significant), causes of death, hospitalizations (1.5 v 1.2/patient/yr), or hospitalized days (18.0 v 11.8 patient/yr). Only mild liver enzyme elevation (SGOT) was observed at the time of conversion in 13 patients with enzyme abnormalities who seroconverted after beginning hemodialysis (mean SGOT 255 micron/mL). No patient had persistent liver enzyme elevation over the 8-year period. These data suggest that chronic hepatitis B surface antigenemia is not, in itself, associated with increased morbidity or mortality in a chronic hemodialysis population.

Nephrotic-range proteinuria and hyperglycemia associated with clonidine therapy.

Glycosuria, hyperglycemia, and nephrotic-range proteinuria developed in a 68-year-old patient after clonidine was added to a stable antihypertensive regimen, which included metoprolol, of three years' duration. He later became glucose-intolerant with fasting hyperglycemia. Clonidine has been reported to transiently impair glucose tolerance. Persistent diabetes in a previously normoglycemic patient following clonidine has not been reported, and it supports the possibility that clonidine and metoprolol may have additive effects in suppressing endogenous insulin secretion.

Nomogram for bretylium dosing in renal impairment.

Bretylium (Bretylol), an antiarrhythmic agent, is currently being used in the prophylaxis and treatment of patients with life-threatening ventricular fibrillation and tachycardia not responsive to conventional therapy. Because bretylium has a delayed onset of action that commonly causes hypotension and may increase ventricular irritability, its use in patients (especially patients with renal impairment) must be exercised with caution. Our results show that the maximum plasma concentration (Cmax) observed at the end of bretylium infusion, when normalized to the dose, increases significantly as renal function diminishes. Significant reductions in renal and total body clearance of bretylium have been observed in patients with renal insufficiency. In order to minimize the risk of potential toxicity following multiple dosing in such patients, dosage adjustments are necessary. Based on correlations developed between the total body clearance of bretylium and renal function, we present a nomogram herein that can be effectively used for adjusting the dosage of bretylium in patients with renal impairment.

Bretylium kinetics in renal insufficiency.

Bretylium kinetics were examined in patients with varying degrees of renal impairment after a single intravenous dose of bretylium tosylate. Maximum plasma concentrations achieved at the end of the infusion, when normalized to the dose, correlated strongly with creatinine clearance. Drug disposition from plasma was biexponential, with a short distributive phase, but drug elimination was reduced, especially in patients with creatinine clearance below 30 ml/min X 1.73 m2. There was reduction in renal and total clearance and prolongation of t 1/2, with deteriorating renal function. In one patient who was reevaluated after a year, there was 76% reduction in the total clearance, corresponding to 43% deterioration of renal function. The difference of 33% between these values is due to a reduction of nearly 36% in volume of distribution, caused by the further deterioration of the renal function. Six-hour hemodialysis procedure on two anephric patients, resulted in an apparent one- to threefold increase in the computed bretylium clearance during dialysis, but the fraction of the total body load eliminated during the same period was not proportionally significant. The strong linear relationships between renal and total clearance, beta, and the creatinine clearance, may be helpful in adjusting dosage regimens for bretylium in patients with renal dysfunction.

Acute rhabdomyolysis associated with an echovirus 9 infection.

A 28-year-old long-distance runner experienced fever, chills, and brown urine 24 hours after a six-mile run. This was accompanied by a large rise in the creatine phosphokinase level and a rise in echovirus 9 titers from 1:16 to greater than 1:256 during a two-week period. A muscle biopsy specimen showed acute rhabdomyolysis, but no viral inclusion particles. Muscle energy metabolism analysis demonstrated no abnormalities. The patient was treated with forced saline diuresis, and he maintained normal renal function. He subsequently returned to long-distance running and has remained well for one year after the episode. This represents the first reported case, to our knowledge, of acute rhabdomyolysis associated with an echovirus 9 infection.

Pharmacokinetics of bretylium in man after intravenous administration.

The pharmacokinetic profile of bretylium was studied in four normal male volunteers using a new sensitive EC-GC procedure for its quantitative in biological fluids. The plasma concentrations and urinary excretion rates following the constant i.v. infusion of a single 4 mg/kg dose of bretylium tosylate declined biexponentially and the data were fitted to a two-compartment model with a renal and a nonrenal route of elimination. The drug had a mean half-life (t1/2 beta) of 7.8 hr and apparent volume of distribution (Vd, beta) of 8.18 liters/kg. The renal clearance, which was 6 times that of the glomerular filtration rate, accounted for almost 84% of the total body clearance and correlated linearly with the subjects' creatinine clearance. The observed side effects of bretylium were mild and similar to those of other adrenergic blocking agents.

Effect of intravenous thiamine on pralidoxime kinetics.

Subjects were given pralidoxime chloride (5 mg/kg, intravenously) alone and again while they were receiving an infusion of thiamine hydrochloride. After the addition of thiamine: (1) overall, the urinary excretion of oxime was the same but the amount excreted in the first three hours was smaller; (2) the plasma half-life of oxime lengthened; (3) the plasma concentrations of oxime rose; and (4) the intercompartmental clearances and rate constant for elimination for oxime fell. These changes suggest that thiamine and oxime compete for a common renal secretory mechanism or that thiamine alters the membrane transport of oxime.