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Biomedical subjects

D T Lowenthal

Publications and source records attributed to D T Lowenthal.

At least 127 records · Page 7Linked to original sources
PubMed1980

The effect of long-distance running on plasma immunoreactive glucagon levels.

Twelve highly conditioned long-distance runners were studied to determine the effects of marathon (42 km) and 10,000 m running on plasma immunoreactive glucagon (IRG), serum immunoreactive insulin (IRI), and serum glucose (G) levels. Blood samples were drawn just prior to and immediately upon completion of the run. Marathon running resulted in no significant change in G, IRI, or IRG levels. After running 10,000 m, plasma IRG levels did not change significantly, while IRI and G increased significantly. In evaluating the pooled data from both runs, a significant inverse correlation was observed between delta G and delta IRG. This relationship between delta G and delta IRG suggests that glucagon plays a role in maintaining normal blood glucose levels during strenuous exercise.

Adult↗
PubMed1980

Prazosin kinetics and effectiveness in renal failure.

Single and repeated doses of prazosin were given to 17 hypertensive patients, 5 with normal renal function and 12 with impaired renal function. Blood for prazosin assay was drawn after a 1-mg single dose and after patients reached steady-state levels with their long-term maintenance dose. As blood was drawn blood pressure was recorded. Prazosin absorption was not altered in patients with impaired renal function, and there is no cumulation of the drug when given repeatedly to patients with impaired renal function. Elimination kinetics were virtually identical regardless of degree of renal function. Effect on blood pressure was significantly better at the dosage range of 3 to 8 mg/day than at higher doses of 9 to 20 mg/day. There does not appear to be a direct relationship between the peak plasma prazosin level and the nadir of antihypertensive response. This would seem to indicate that the drug leaves the plasma and goes to the vascular smooth muscle receptor site of action. There appears to be no impairment in prazosin elimination in patients with impaired renal function, and its effectiveness (with diuretic or dialysis) is optimum at 3 to 8 mg/day.

Adult↗
PubMed1980

Dynamics and kinetics of ophthalmic timolol.

Timolol is a beta adrenergic antagonist in 0.25% or 0.5% eyedrop solution for glaucoma. In a double-blind crossover study in healthy males we measured systemic beta blockade, intraocular pressure, and timolol kinetics after the first and ninth 12-hourly dose of a 0.5% ophthalmic solution. Timolol ophthalmic and placebo were each given as 2 drops to each eye with precautions to prevent the normal loss of drug in tears and overflow (high dose) and as 1 drop to each eye with no special precautions (standard therapeutic dose). Exercise tachycardia, measured at 70 and 255 min after administration of drug, was lower at both levels. Postexercise 1-sec forced expiratory volume (FEV1) was not affected. Intraocular pressure measured at 3 and 8 hr after drug was lower at both dose levels. Timolol was consistently present in urine but was not detectable in most plasma samples. Dynamic effects were not greater after the ninth than after the first dose, and the urinary excretion data provided no evidence of drug cumulation.

Blood Pressure↗
PubMed1980

Effects of amiloride on oral glucose loading, serum potassium, renin, and aldosterone in diet-controlled diabetes.

The effects of amiloride on oral glucose loading, serum potassium, renin, and aldosterone were evaluated in 10 patients with diet-controlled diabetes. Eight had mild hypertension, and 2 had normal blood pressure. Prior to receiving amiloride all were studied for renin and aldosterone responses while supine and after 2 hr ambulation. All had a normal response to change in position in the renin and aldosterone systems. Before administration of amiloride glucose tolerance tests were carried out, with simultaneous determinations for potassium and insulin. Amiloride 5 to 10 mg was given orally for 6 wk. Blood glucose and serum potassium levels were monitored weekly. After 6 wk renin and aldosterone responses were again determined, as were oral glucose tolerance and serum potassium and serum insulin levels. Amiloride did not induce hyperkalemia in these diabetic patients and did not alter the postamiloride relationship. It is concluded that amiloride is safe for patients with an intact renin aldosterone system, more especially those with normal renal function and diet-controlled diabetes mellitus.

Aldosterone↗
PubMed1980

Pharmacology and pharmacokinetics of minoxidil.

Minoxidil is a potent oral vasodilator acting on the arteriolar side of the circulation. Reflex tachycardia and sodium retention are consequences of increased sympathetic activity. Its biotransformation is 90% hepatic, with no evidence of accumulation of minoxidil when it is given chronically in patients with either normal renal function. The half-life is approximately 3 hr, regardless of whether the dose is given singly or on a multiple-dose basis. It is widely distributed throughout the body, and hence its volume of distribution is greater than 200 liters. There appears to be a dissociation between the peak plasma concentration and the antihypertensive response owing to the fact that minoxidil rapidly leaves the plasma on its way to the principal site of action, that is, the vascular smooth-muscle receptor site. No tolerance or refractoriness appears to develop with long-term minoxidil administration.

Absorption↗
PubMed1980

Protein binding of bilirubin in plasma of anephric patients.

The protein binding of bilirubin was determined in the plasma of seven adult surgically anephric patients, eight adult physiologically anephric patients (creatinine clearance < 5 ml/min) and 13 adult normal volunteers. The determinations were carried out with undiluted plasma to which bilirubin, about 10 mg/100 ml, had been added. The free fraction of bilirubin in plasma (ratio of free to total concentration was (19.8 +/- 8.1) X 10(-5) in the surgically anephric, (10.4 +/- 4.0) X 10(-5) in the physiologically anephric, and (1.81 +/- 0.34) X 10(-5) in the normal subjects (mean +/- standard deviation). Based on this difference in plasma protein binding, patients in renal failure may be expected to have lower steady state plasma concentrations of total (free plus bound) bilirubin than do patients with normal renal function if the formation rate and intrinsic metabolic clearance of the pigment are the same as in normal subjects. This conclusion is consistent with available clinical evidence.

Adult↗
PubMed1980

Dynamic exercise response in hypertensive adolescent on clonidine therapy: clonidine therapy in adolescent hypertension.

The cardiovascular response to dynamic exercise is compared in 16 normotensive control adolescents (C), 15 untreated hypertensive (H) adolescents, and 14 hypertensive adolescents on clonidine therapy (HRx) for blood pressure control. All subjects exercised to exhaustion (heart rate (HR) = 200) on a treadmill by Bruce protocol. Blood pressure and HR were monitored during exercise and recovery. Systolic pressure was greater in H and HRx and than C at baseline, exercise, and recovery (P less than 0.01) as was the product of systolic blood pressure times heart rate (SBP X HR). Diastolic blood pressure (DBP) was greater in H and HRx at base line but decreased in all subjects (C, H, and HRx) during vigorous exercise. Our results indicate that H and HRx adolescents have higher SBP and HR at rest and exercise consistent with a hyperkinetic circulatory state; DBP response to exercise is normal in H adolescents; and, clonidine in HRx lowered baseline HR and blood pressure but did not alter a normal exercise response.

Adolescent↗
PubMed1979

The effect of renal transplantation on plasma protein binding.

The in vitro plasma protein binding was determined in nine maintenance hemodialysis patients who later underwent renal transplantation. The organic acid fluorescein (10 micrograms/ml) or the organic base quinidine (5 micrograms/ml) was added to the pre and post transplant serum of these patients. Drug concentrations were measured spectrophotofluorometrically after equilibrium dialysis. The results were compared with the plasma protein binding of eight normal volunteers. The patients on maintenance hemodialysis had lower plasma protein binding of fluorescein than normals (78 +/- 5% vs 89 +/- 4, p less than 0.001). Plasma protein binding improved significantly after renal transplantation (85 +/- 3, p less than 0.01) but was still lower than in normals (p 0.05). Plasma protein binding of quinidine was not significantly different than in normal volunteers (77 +/- 8%) either prior to (72 +/- 10%) or after (73 +/- 12%) kidney transplantation. Plasma protein binding of quinidine remains unaffected by renal transplantation. However, the abnormal plasma protein binding or organic acids in chronic renal failure may be significantly improved by renal transplantation.

Adult↗
PubMed1978

Timolol kinetics in chronic renal insufficiency.

A single-dose kinetic study of oral timolol, 20 mg, was undertaken in 3 groups of volunteers with varying degrees of renal function--(1) 10 normal subjects (N); (2) 9 patients with moderate chronic renal insufficiency (MCRI; C cr, 20 to 50 ml/min); (3) 4 patients with end-stage renal disease (ESRD)--to assess the need for dosage modification as renal function diminishes. There were borderline statistical differences in absorption between groups. The mean peak concentration (C max) was 84.3 +/- 44.8 ng/ml at 0.8 +/- 0.4 hr for N and 87.1 +/- 22.8 ng/ml at 1.7 +/- 1.2 hr (p, NS) for MCRI. N and MCRI mean half-lives (5.2 +/- 2.6 hr and 4.0 +/- 1.2 hr) were not statistically different. Salivary levels correlated with plasma levels in 3 N and 1 MCRI patient. Group differences in blood pressure and pulse response to timolol seems to reflect differences present at baseline with percent change from baseline identical for the two groups except at 12 to 24 hr. Administration of timolol on an interdialysis day revealed similar kinetic and physiologic response in the normal and the MCRI group. During dialysis, timolol, 20 mg, induced significant hypotension and bradycardia.

Adult↗
PubMed1978

Steady-state serum levels of quinidine and active metabolites in cardiac patients with varying degrees of renal function.

The concentrations of quinidine, (3S)-3-hydroxyquinidine (3-OH), and 2'-oxoquinidinone (2'-OXO) in serum samples from 25 patients on long-term quinidine therapy were determined by a high-pressure liquid chromatography assay. Large individual variation in the levels of each of the compounds measured was observed. After correcting for differences in protein binding, the ratio of 3-OH/quinidine in serum water is 0.61 +/- 0.31 (SD) and the ratio of 2'-OXO/quinidine is 0.39 +/- 0.44. Seven of the 25 patients had serum water levels of one of these metabolites similar to or greater than that of quinidine. The quinidine levels, after normalizing for dose, are significantly higher in hemodialysis patients (about twice) than in nonazotemic patients; azotemic patients have mean values intermediate between them. Quinidine, 3-OH, and 2'-OXO are equally potent antiarrhythmic drugs (ED50 = 0.18, 0.17, and 0.21 mmoles/kg, respectively) when tested against chloroform- and hypoxia-induced ventricular fibrillation in mice. O-Desmethylquinidine, a new metabolite detected in urine of quinidine-treated patients, is less active. Quinidine and 2'-OXO are equally potent (ED50 = 0.010 mmoles/kg), while 3-OH seems less potent and more toxic when tested against BaCl2-induced ventricular arrhythmias in rabbits. Thus, these metabolites appear to contribute to the effects of quinidine and may make a significant contribution in some cases.

Adult↗
PubMed1978

Long-term clinical effects, bioavailability, and kinetics of minoxidil in relation to renal function.

Minoxidil was used to treat 26 patients (17 to 67 years old) with severe hypertension and varying degrees of renal function. Our object was to assess long-term clinical efficacy, kinetics (acute and chronic), and bioavailability of minoxidil in chronic renal insufficiency. Minoxidil, 27 to 30 mg per day, decreased systolic and diastolic blood pressure during the first three months of therapy. Between the third and 24th months (30 months in one patient) there was no further change. Propranolol or clonidine was needed to control heart rate, and furosemide or dialysis was needed to control edema induced by minoxidil. Renal function improved in some of the mildy azotemic patients. Minoxidil kinetics after the customary dose did not differ whether the drug was taken as tablet or solution. Kinetic parameters during chronic administration of minoxidil did not differ from those after acute administration. The kinetics in chronic renal insufficiency do not differ from these in subjects with normal renal function.

Adolescent↗
PubMed1977

Cumulation of N-acetylprocainamide, an active metabolite of procainamide, in patients with impaired renal function.

N-Acetylprocainamide (NAPA) accumulated in the plasma of 6 cardiac patients with renal failure taking procainamide chronically for therapy (4 were undergoing hemodialysis) and contributed to the therapeutic and toxic effects of the procainamide. NAPA plasma levels ranged from 14.0 to 28.0 microgram/ml 3 hr after a dose of procainamide which is well above the 3-hr NAPA plasma levels of nonazotemic cardiac patients (range 1.9 to 6.3 microgram/ml; p = 0.002) on larger doses of procainamide. There was almost no decline in NAPA plasma levels on interdialysis days. In one of the patients with renal failure NAPA was still present 15 days (13.8 microgram/ml) and 38 days (0.9 microgram/ml) after procainamide was stopped, indicating a half-life of several days. Measurement of procainamide plasma concentrations by the usual fluorometric or colorimetric methods does not detect NAPA. Since NAPA accumulates in patients with impaired renal function, the concentrations of both this active metabolite and procainamide should be determined in these patients if drug level monitoring is to be helpful.

Acetylation↗