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Biomedical subjects

B R Walker

Publications and source records attributed to B R Walker.

At least 199 records · Page 11Linked to original sources
PubMed1982

Comparative antihypertensive effects of guanabenz and clonidine.

The safety and efficacy of guanabenz and clonidine were compared in 188 hypertensive patients during a 6-month double-blind trial. Mean supine diastolic blood pressure (SDBP) decreased from 103 to 88 mm Hg (p less than 0.01) among guanabenz patients and from 101 to 88 mm Hg (p less than 0.01) among clonidine patients who completed 6 months of b.i.d. therapy. Clinically significant individual SDBP decreases occurred in 85% of the guanabenz patients and 83% of the clonidine patients after 6 months. Adverse effects, consisting primarily of drowsiness, dry mouth, dizziness, and weakness, were similar in the two therapy groups. The responses obtained with guanabenz (b.i.d.) were maintained, along with a decrease in adverse effects, by an equivalent single daily dose of guanabenz during a second 6 months of therapy. Seventy-six per cent (13/17) of the patients whose blood pressure was not adequately controlled by guanabenz alone after 8 weeks of therapy subsequently responded to a combination of guanabenz and hydrochlorothiazide. Similarly, 85% (17/20) of the patients who failed to respond to clonidine alone subsequently responded to guanabenz either alone or in combination with hydrochlorothiazide. These results suggest that guanabenz or the combination of guanabenz and hydrochlorothiazide is effective therapy for the majority of hypertensive patients.

Adult↗
PubMed1982

Evaluation of guanabenz added to hydrochlorothiazide therapy in hypertension.

Guanabenz, a centrally acting alpha-adrenergic antihypertensive agent, produces neither the sodium retention seen with other centrally acting agents nor the metabolic abnormalities characteristic of diuretics. In this study, which involved 204 hypertensive out-patients, the additive effects of guanabenz and hydrochlorothiazide were compared with the effects of hydrochlorothiazide therapy alone. Before randomization to the 6-month blinded addition of either guanabenz or placebo, hydrochlorothiazide (50 or 100 mg/day; mean, 70 mg/day) was administered as sole therapy for 6 weeks. During this time, mean supine diastolic blood pressure (SDBP) decreased from 102 to 94 mm Hg (p less than 0.01), with a satisfactory clinical response rate of 62% and a mean weight loss of 2 lbs (p less than 0.01). No further change in mean SDBP occurred during the next 6 months of diuretic therapy, whereas the addition of guanabenz (mean dose, 24 mg/day) caused a further decrease in mean SDBP to 88 mm Hg (p less than 0.01), an increase in the response rate to 86%, and no weight change. Pulse rates in both groups were unchanged. The principal side-effects in both groups were dry mouth, drowsiness, weakness, and dizziness, with a greater incidence of each during the combination therapy. The usual laboratory abnormalities were associated with hydrochlorothiazide. Guanabenz was found to enhance the antihypertensive efficacy of hydrochlorothiazide without compromising its natriuretic properties or producing additional metabolic abnormalities.

Adult↗
PubMed1981

Gastroscopic evaluation of the effect of aspirin and oxaprozin on the gastric mucosa.

Oxaprozin, a new long-acting, antiinflammatory agent, and aspirin were compared utilizing gastroscopic evaluation and photography of the gastric mucosa in a double-blind, crossover study in normal volunteers. Submucosal hemorrhages or mucosal bleeding was observed in seven of eight subjects on aspirin and in only two of eight on oxaprozin (P = 0.061). Adverse effects were experienced by seven of eight subjects after the aspirin treatment period--tinnitus in five and gastrointestinal symptoms in four. Only one patient had mild diarrhea on oxaprozin. The incidence of adverse effects was found significantly higher with aspirin therapy (P less than 0.001). No laboratory abnormalities of clinical significance were attributed to either drug administration. Results after ten days of treatment show that oxaprozin in therapeutic dose levels (1200 mg once a day) produces significantly fewer changes in the gastric mucosa than aspirin (975 mg administered four times a day, total daily dose 3.9 Gm) in the same subjects, who received both drugs in this double-blind, crossover experiment with a four-week washout period between treatments.

Anti-Inflammatory Agents↗
PubMed1981

Renal disease, age, and oxazepam kinetics.

Effects of renal insufficiency and age on oxazepam kinetics were assessed in 13 normal subjects (21 to 72 yr old), four patients with renal insufficiency, and eight patients on hemodialysis. Normal intact oxazepam results were: mean elimination half-life (t1/2), 10 hr; area under the curve (AUC), 6.0 microgram.hr/ml; unbound oxazepam fraction (fup), 3.2%; maximum concentration of unbound oxazepam (Cmax,u), 16 ng/ml; and intrinsic (unbound drug) clearance (Clint), 2.9 l/hr/kg. Less than 1% of the dose was excreted intact in urine. Age differences had no influence on results. In renal insufficiency patients, t1/2 was prolonged to 25 hr, fup increased to 7%, and Cmax,u and Clint were unchanged. Volume of distribution of unbound oxazepam (Vu) increased, thereby prolonging t1/2. In dialysis patients, t1/2 was prolonged to 33 hr, fup increased to 6.2%, and Cmax,u and Clint again were unchanged. Oxazepam was undialyzable; since unbound oxazepam disposition kinetics are not altered, no dosage adjustment for patients is necessary.

Adult↗
PubMed1981

Suppressed renin release during hyperoxia in the conscious dog.

Recent studies have documented a marked inhibition of renal prostaglandin E2 excretion during hyperbaric oxygenation (HBO) in the conscious dog. Numerous other studies have shown that pharmacological inhibition of prostaglandin synthesis is associated with diminished renin release. The current experiments were designed to test whether HBO is also accompanied by reduced renin secretory rate (RSR) in conscious dogs. Dogs were implanted with electromagnetic flow probes on the left renal artery as well as with chronic arterial and renal venous catheters. Renal blood flow, peripheral plasma renin activity, and renal venous renin activity were measured, which allowed calculation of RSR for the left kidney. The dogs were studied at normal atmospheric pressure while breathing room air, followed by exposure to 100% oxygen at 2 or 3 ATA. The dogs were then returned to room air. The RSR decreased from 153.6 +/- 51.6 (ng . h-1) . min-1 to 72 +/- 21 (ng . h-1) . min-1 during HBO. Upon return to normoxia, RSR rose to 345 +/- 140.4 (ng . h-1) . min-1. This renin response to HBO seems best related to the previously documented inhibition of renal prostaglandin synthesis. These experiments provide nonpharmacological evidence that there may be a functional relationship between the renin-angiotensin system and renal prostaglandin release in awake animals.

Animals↗
PubMed1981

Long-term therapy of hypertension with guanabenz.

Guanabenz, a centrally acting antihypertensive (alpha-agonist) that does not induce secondary sodium retention or other metabolic disturbances, was evaluated for up to two years at 19 investigational sites. In 329 patients completing six months of therapy, the mean supine diastolic blood pressure (SDBP) fell from 101 to 90 mmHg (P less than 0.01). Clinically significant individual SDBP decreases occurred in 74% of the patients by week 2, and these reductions were maintained in 72% at six months. Mean weight was reduced 1.4 lb (P less than 0.01), and mean supine pulse rate was decreased 5 beats/min (P less than 0.01). The most frequent effective doses were 8 and 16 mg BID (range, 2 to 32 mg BID). Principal side effects, usually mild, were sedation (31%), dry mouth (24%), dizziness (6%), and weakness (6%). Postural hypotension, impotence, and abrupt discontinuation symptoms were rare or absent. There were no clinically significant drug-related laboratory changes other than a 10 mg/100 ml mean serum cholesterol decrease. Two hundred twenty-two patients completed one year of therapy, and 80 completed two years, with little change in any parameters other than improvement in mean SDBP to 85 mmHg and in individual response rate to 84%. These results suggest that guanabenz is safe and effective for initial and sole therapy of hypertension.

Adult↗
PubMed1981

Comparative antihypertensive effects of guanabenz and methyldopa.

The effects of guanabenz acetate, a centrally acting alpha-adrenergic, non-sodium-retaining antihypertensive agent, were compared with those of methyldopa in 248 hypertensive outpatients during a one-year, double-blind, multi-center study. Mean supine diastolic blood pressure (SDBP) decreased from 102 to 91 mmHg (P less than 0.01) among 78 guanabenz-treated patients and from 101 to 92 mmHg (P less than 0.01) among 89 methyldopa-treated patients who completed six months of treatment. Clinically significant individual SDBP decreases occurred in 76% of the guanabenz-treated patients and in 63% of the methyldopa-treated patients (P less thn 0.05). Blood pressure remained unchanged during the second six months, with response of 82% and 60%, respectively, for guanabenz and methyldopa (P less than 0.05). Although drowsiness and dry mouth occurred more frequently with guanabenz, evidence of fluid retention, such as weight gain, edema, and congestive heart failure, was significantly more frequent with methyldopa than with guanabenz. Because it does not induce volume expansion, guanabenz, unlike methyldopa, may be useful as sole initial antihypertensive therapy.

Blood Pressure↗
PubMed1980

Effects of two nonsteroidal anti-inflammatory drugs, indomethacin and oxaprozin, on the kidney.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been found to cause sodium retention and to decrease glomerular filtration rate (GFR). We studied the effects of two such drugs, indomethacin and oxaprozin, a new propionic acid derivative, on renal function of awake, normal human subjects during sustained water diuresis. Although neither drug had a long-term effect on GFR or sodium clearance (CNa), indomethacin (six subjects) but not oxaprozin (seven subjects) transiently reduced GFR and CNa. Given over the short term, oxaprozin caused a reduction in GFR from 113.7 +/- 5.7 to 99.8 +/- 4.7 ml/min (p < 0.01) and CNa from 0.84 +/- 0.07 to 0.61 +/- 0.08 ml/min (p < 0.005). The results were much the same when an additional dose of indomethacin was given to subjects who had been receiving the drug for a week. Inference from clearance data at a time when urinary osmolality (Uosm) remained constant but urine flow per GFR (V/GFR) fell suggests that both drugs stimulated proximal tubular sodium and fluid resorption. Both suppressed renin and aldosterone levels comparably and reduced potassium excretion transiently, but only indomethacin caused a sustained change in serum potassium concentration; serum potassium rose from 4.32 +/- 0.10 to 4.56 +/- 0.11 mEq/l (p < 0.05) after 1 wk. These disparate findings suggest that prostaglandin synthesis inhibition may not be the sole mechanism of action of NSAIDs.

Aldosterone↗
PubMed1980

Effects of methyldopa on renal hemodynamics and tubular function.

To determine the effects of methyldopa on renal function, clearance studies were performed on hypertensive subjects during sustained steady-state water diuresis. The data reveal an acute fall in glomerular filtration rate and sodium clearance, whereas renal blood flow was unchanged. The antinatriuresis was the result of decreased filtration of sodium and possibly enhanced proximal tubular sodium reabsorption. These changes occurred before any demonstrable fall in systemic blood pressure; thus a direct effect of the drug on arteriolar resistance within the renal circulation is suggested. Chronic administration of methyldopa for 1 wk induced sustained reduction in blood pressure and resulted in the same changes in renal hemodynamics and sodium excretion noted after acute administration. These data suggest that methyldopa, like other antihypertensives, reduces glomerular filtration rate and increases sodium retention.

Adult↗
PubMed1980

Effects of placebo versus guanabenz on hypertensive out-patients.

The objectives of this study were two-fold: (1) 1 4-week multicentre, randomized, double-blind efficacy comparison of placebo and guanabenz acetate, a new centrally acting antihypertensive drug, in 168 hypertensive out-patients and (2) a more accurate determination of the incidence of drug-related, non-specific side-effects. Both treatment groups were comparable: 68% female, 63% black, mean age 53 years; 57% mild, 32% moderate, 11% moderately severe hypertensives. Seventy-six placebo patients completed 4 weeks and had a mean supine diastolic blood pressure (SDBP) decrease from 105 to 101 mm Hg (p < 0.01). Seventy-nine guanabenz patients completing 4 weeks had a mean SDBP decrease from 104 to 92 mm Hg (p < 0.01). All of the placebo responses and 10/12 mm Hg of the guanabenz response occurred during Week 1. Clinically significant individual SDBP decreases occurred in thirty-one (41%) placebo and fifty-five (70%) guanabenz-treated patients (p < 0.01). Mean daily guanabenz dose was 24 mg. Drug-related biochemical or electrocardiographic abnormalities were absent. Side-effects of sedation and dry mouth were recorded two and three times more frequently, respectively, in guanabenz as compared to placebo patients. Side-effects usually occurred within Week 1 and diminished in incidence thereafter. Consequently, in these patients it appeared that: (1) guanabenz was an effective, well-tolerated drug, (2) placebo effects on efficacy were significant, occurred early and remained stable, and (3) placebo and guanabenz side-effects were mainly sedation and dry mouth.

Adult↗
PubMed1980

Antidiuresis and inhibition of PGE2 excretion by hyperoxia in the conscious dog.

Experiments were performed to determine the influence of varying inspired oxygen tension on renal prostaglandin E2 (PGE2) excretion, renal hemodynamics, and water and electrolyte excretion in the conscious dog. Hypoxic exposure (PIO2 = 56 torr) resulted in a 13% increase in renal blood flow (RBF), while hyperoxic breathing with PIO2 of 700, 1426, or 2139 torr, all resulted in significant 5--7% decline in RBF, a response that was significantly attenuated compared to the striking renal vasoconstriction caused by hyperoxia in anesthetized dogs. Hyperbaric oxygenation (HBO) (1426 torr O2, 2139 torr O2) was associated with unexpected decreases in urine flow (V) of 61% and 70%, respectively. The antidiuresis and mild hemodynamic adjustments were correlated with a 67% decline in urinary PGE2 excretion (UPGE2 x V) when the dogs breathed 700 torr O2, while exposure to 1426 torr O2 and 2139 torr O2 diminished UPGE2 x V by 92% and 99%, respectively. Plasma antidiuretic hormone (ADH) concentration, measured during exposure to 1426 torr O2, was unchanged. In addition, this nonpharmacologic hyperbaric decline in PGE2 excretion was not associated with any changes in sodium excretion of renin secretion, in contrast to the usual depression of these variables with pharmacologic PG inhibition (indomethacin). The HBO antidiuresis may be a consequence of an increased medullary osmotic gradient secondary to reduced vasa recta blood flow. Alternatively, this antiduresis could occur as a consequence of a lowering of the normal functional antagonism existing between PGE2 and ADH, such that the influence of endogenous ADH is potentiated.

Animals↗
PubMed1979

Double-blind clinical trials of oral cyclacillin and ampicillin.

A double-blind study was performed to compare the clinical response and the incidence of side effects in 2,581 patients administered ampicillin or cyclacillin for infections of the genitourinary or respiratory tract, infections of the skin and soft tissues, or for otitis media. There was no significant difference in clinical response and bacterial eradication. All side effects, including diarrhea and skin rash, were approximately twice as frequent in patients treated with ampicillin.

Administration, Oral↗
PubMed1979

A multicentre double-blind comparison of oxaprozin aspirin therapy on rheumatoid arthritis.

Preliminary clinical studies showed that oxaprozin (4,5 Diphenyl-2-oxazolepropionic acid) has anti-inflammatory and analgesic properties with a plasma half-life of about 40 hours. Consequently, a multicentre, double-blind parallel trial was conducted for 12 weeks at thirteen investigator sites, utilizing 212 patients with classic rheumatoid arthritis and comparing oxaprozin 600 mg/day, oxaprozin 1200 mg/day and aspirin 3900 mg/day. Both the oxaprozin and aspirin-treated patients had statistically significant improvement from baseline periods, in most key categories evaluated. Oxaprozin administered twice a day (b.i.d.) was as effective as aspirin administered four times a day (q.i.d.) and caused significantly less tinnitus (p less than 0.001). Fewer patients receiving high dose oxaprozin (2%) dropped out of the study because of unsatisfactory response than did those receiving aspirin (10%). There were no clinically significant laboratory abnormalities in the gastro-intestinal, renal, hepatic or haematological parameters monitored. This study suggests that oxaprozin is effective and well tolerated in the treatment of rheumatoid arthritis.

Adult↗
PubMed1977

Guanabenz and methyldopa on hypertension and cardiac performance.

In previous placebo-controlled studies, guanabenz was shown to be a safe and effective antihypertensive drug without acute effects on cardiac function. In view of its therapeutic advantages, a double-blind comparison of guanabenz with methyldopa was performed in a group of 36 patients over 6 mo. Both drugs produced statistically and clinically significant decreases in blood pressure with similar side effects. No laboratory or electrocardiographic abnormalities were found other than positive Coombs' tests which developed in 3 patients during methyldopa therapy. Cardiac performance in 26 of the patients, as measured by noninvasive techniques, showed no significant changes from either drug except for a progressive and statistically significant increase in systolic time interval (QS2) and the ratio of the pre-ejection period to left ventricular ejection time (PEP/LVET) during methyldopa therapy. For an additional 6 mo, continued efficacy and safety were shown under open conditions in those patients who had received guanabenz. The study suggests that guanabenz may be an important new antihypertensive drug because of effectiveness, absence of adverse cardiac effects, and paucity of side effects.

Adult↗