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Biomedical subjects

W Kirch

Publications and source records attributed to W Kirch.

At least 271 records · Page 15Linked to original sources
PubMed1983

Bopindolol, a new long-acting beta-adrenoceptor antagonist--a randomized comparison against propranolol in hypertensive patients.

In a randomized parallel-group trial the blood-pressure lowering effect of a new beta-adrenoceptor blocker bopindolol (LT 31-200) in a dose of 1-4 mg once daily (eight patients) was compared with that of propranolol in a dose of 40-120 mg t.i.d. (nine patients). The average blood pressure fell in the bopindolol group from 185/113 mmHg to 135/90 mmHg and in the propranolol group from 183/120 mmHg to 147/102 mmHg. Both changes were statistically significant. This was achieved during a nine week treatment period at the end of which the average dose of bopindolol was 3 mg per day and of propranolol 330 mg per day. One patient receiving bopindolol interrupted the trial because of restlessness and insomnia, and one receiving propranolol because of bronchospasm. Side-effects were, otherwise, mild in both groups. During a one-year treatment period following the comparative trial, the seven patients who had received bopindolol showed no evidence of tachyphylaxia, the blood-pressure remaining well controlled while the dosage was slightly reduced. No new side-effects were reported and the ANA and AMA tests remained negative in all patients.

Adrenergic beta-Antagonists↗
PubMed1982

Interaction of metoprolol, propranolol and atenolol with concurrent administration of cimetidine.

Pharmacokinetics of metoprolol, propranolol, and atenolol were investigated in six healthy volunteers following 7 days of oral monotherapy with these drugs, and after 7 days concurrent administration of each of these betareceptor antagonists with cimetidine. Application of cimetidine did not lead to any interaction with atenolol, whereas mean peak plasma levels of metoprolol were increased by 70%, and those of propranolol by 95% due to concurrent administration of cimetidine (P less than 0.05). The plasma level time curve (AUC) of the two above-mentioned beta blockers behaved similarly (P less than 0.05). Other kinetic parameters of these two drugs were not influenced to a statistically significant extent by cimetidine, despite the tendency for the elimination half-life of metoprolol and propranolol to be prolonged when cimetidine is added. Measurement of exercise-induced tachycardia on the sixth day of administration showed no differences between monotherapy with the beta blockers and combined treatment with each of them together with cimetidine. Apart from one volunteer who complained of anxiety, weakness, and sweating on the sixth day of cimetidine/metoprolol administration, no adverse effects could be observed during the combination therapy with cimetidine and the beta blockers, nor during monotherapy with beta blockers.

Adult↗
PubMed1982

Clinical pharmacokinetics of atenolol--a review.

Atenolol is a hydrophilic betareceptor blocking drug, which is predominantly eliminated via the kidneys, only about 5% of the atenolol is metabolised by the liver. After oral administration atenolol is incompletely absorbed from the intestine, so about 50% of the beta blocker are finally biovailable. In plasma only 3% of atenolol are protein-bound. There exists a linear relationship between the atenolol plasma levels and the degree of beta blocking effect measured by inhibition of the exercise-induced tachycardia. No correlation was found between plasma levels of atenolol and blood pressure lowering activity of the drug. After oral administration elimination half life of atenolol is calculated from 6 to 9 h by different authors. In patients with impaired renal function elimination half life of atenolol gradually increases to values of 36 h in uraemic patients (glomerular filtration rate (GFR) less than 10 ml/min). Between GFR and atenolol plasma clearance as well as renal clearance a close significant correlation is described. Prolongation of elimination half life requires a dosage adjustment of atenolol in patients with renal failure. A marked interaction of atenolol is found when calcium or aluminium hydroxide are concurrently administered with the beta blocker whereas cimetidine does not influence atenolol kinetics.

Administration, Oral↗
PubMed1982

The influence of renal function on plasma levels and urinary excretion of acebutolol and its main N-acetyl metabolite.

The pharmacokinetics of acebutolol and its major N-acetyl metabolite diacetolol were determined following acute intravenous and chronic oral administration to 22 subjects with glomerular filtration rate (GFR) between 3 and 127 ml/min. Following chronic oral administration the mean terminal elimination half-life of unchanged acebutolol was about 10 hours independent of renal function, whereas the hall-life of the N-acetyl metabolite increased from 12.8 hr in subjects with normal renal function (GFR greater than 90 ml/min) to 24.0 hr in preuremic patients (GFR less than 10 ml/min). The mean area of the plasma level-time curve (AUC) of the metabolite was 14.2 mg 1-1 hr in patients with normal renal function and rose to a value of 81.4 mg 1-1 hr in preuremic patients. The mean AUC of the parent drug was not influenced by changes in renal function. The considerable accumulation of the acetyl metabolite, which has about the same beta blocking activity as the unchanged drug, necessitates dose reduction of acebutolol in the presence of different degrees of renal impairment (reduction by half of the normal daily dose in patients with GFR between 30 and 10 ml/min and by three quarters when GFR less than 10 ml/min). In subjects with normal renal function, the ratio between the AUC of the parent drug and that of its major N-acetyl metabolite was 3:1 after intravenous injection of the drug, while it was 1:2.5 following chronic oral administration, indicating a marked first pass metabolism of acebutolol.

Acebutolol↗
PubMed1981

Pharmacokinetics of atenolol in relation to renal function.

The pharmacokinetics of atenolol were determined following acute intravenous and chronic oral administration to 20 subjects with a glomerular filtration rate (GFR) between 5 and 113 ml/min. Plasma levels in a further 5 patients on haemodialysis were measured after intravenous treatment. The mean half life of elimination increased from 5.9 h in patients with normal renal function to 42.1 h in preuraemic patients (GFR less than 10 ml/min) following a single i.v. dose. The half life of elimination following chronic oral administration was not significantly different. Mean peak plasma concentrations increased from 540 ng/ml in patients with normal renal function to 1493 ng/ml in preuraemic patients following chronic oral treatment with 100 mg/day. The mean half life of elimination during a single haemodialysis treatment was 4.3 h. In patients with a GFR greater than 10 ml/min the normal daily dose of atenolol should be employed, in patients with a GFR between 10 and 30 ml/min the dose should be reduced by half, and in patients with a GFR less than 30 ml/min a reduction by three quarters of the normal dose is recommended.

Administration, Oral↗
PubMed1981

Interaction of atenolol with furosemide and calcium and aluminum salts.

Six healthy subjects were treated with 100 mg atenolol. After a therapy-free interval of 4 wk the same subjects received the same dose of atenolol with furosemide, 40 mg, with calcium (as the lactate gluconate and carbonate), 500 mg, or with aluminum hydroxide, 5.6 gm. Atenolol alone and in combination was administered first as a single oral dose; a long-term 6-day treatment began 48 hr later. Addition of furosemide did not influence atenolol kinetics, but aluminum hydroxide led to an insignificant reduction (P greater than 0.05) of mean peak plasma levels of about 20% and of the area under the plasma concentration-time curve (AUC -infinity) from 5818 to 4353 ng ml-1 hr (P greater than 0.05). Calcium altered atenolol kinetics distinctly mean peak plasma levels of atenolol fell 51% (P less than 0.001), AUC0-infinity fell from 5818 to 3935 ng ml-1 hr (P less than 0.01) and elimination half-life (t1/2) increased to a mean of 11.0 hr (compared to 6.2 hr with atenolol alone). The prolongation of t1/2 induced by calcium coadministration led to atenolol cumulation during the long-term dosage. Twelve hours after atenolol, 100 mg, and calcium, 500 mg, exercise tachycardia was lower than with atenolol alone (P less than 0.001). During the 4-wk treatment in six hypertensive patients, blood pressure values of those on atenolol alone were not different from those on the combination therapies (P greater than 0.05).

Adult↗
PubMed1980

[Renal function in therapeutic starvation (author's transl)].

There are many publications on various complications of therapeutic starvation, but only few cases and of renal complications have been described. During starvation two characteristic changes in kidney function occur: a reduction in glomerular filtration rate by about 50% and a decrease in renal uric acid clearance by impairment of tubular uric acid secretion with consequent hyperuricaemia. During fasting ketone bodies compete with uric acid for a common tubular secretion site. The development of some of the renal complications described in the literature so far can be explained bal failure with uric acid nephropathy, renal ischaemia and pre-existing kidney disease have been published. Furthermore reversible salt-losing nephropathies were observed. It is essential in the prophylaxis of renal complications during fasting to ensure that a sufficient fluid intake is maintained and the urinary output is controlled. Before therapeutic starvation is commenced parameters of renal function (urinalysis, blood urea, serum creatine, serum uric acid) must be determined and then monitored at regular intervals. After starvation has commenced the administration of uricosuric agents must be avoided and intravenous pyelography is contraindicated.

Acidosis↗
PubMed1980

Single intravenous dose kinetics accumulation of atenolol in patients with impaired renal function and on hemodialysis.

The concentration of atenolol in plasma and urine was determined following an intravenous (i.v.) dose given to 17 hypertensive patients with a glomerular filtration rate (GFR) between 5 and 105 ml/min and in 4 patients on hemodialysis. In patients with normal renal function the mean half life of elimination was calculated to be 6.8 h. This value increased to a mean of 50.1 h in patients with a GFR below 10 ml/min. In patients on hemodialysis the half life of elimination was about 4 h. The elimination rate constants as well as the body and renal clearances of atenolol have a significant correlation with the GFR. Although accumulation of atenolol was observed, especially after multiple oral doses and in patients with a GFR below 30 ml/min, no toxic side effects occurred.

Adult↗
PubMed1980

Elimination of guanfacine in patients with normal and impaired renal function.

1. Total body clearance and renal clearance after single intravenous doses of guanfacine were 360 +/- 262 (mean +/- s.d.) and 233 +/- 245 ml/min, respectively, in patients with normal renal function (glomerular filtration rate (GFR) > 90 ml/min), 308 +/- 274 and 34 +/- 22 ml/min, respectively, in patients with moderately impaired renal function (GFR 30-10 ml/min), and 257 +/- 187 and 18 +/- 15 ml/min, respectively, in preuremic patients (GFR < 10 ml/min). 2. The cumulative urinary excretion up to 48 h after a single intravenous injection of guanfacine was 57.0 +/- 32.0% in patients with GFR > 90 ml/min, 14.0 +/- 9.0% in patients with GFR 30-10 ml/min and 7.5 +/- 2.4% in preuremic patients. 3. In normal as well as impaired renal function the elimination rate constant of guanfacine was 0.05 h-1, which corresponds to an elimination half-life of 14 h, independent of renal function. 4. These results suggest that non-renal elimination of guanfacine plays an important role in patients with renal failure. 5. Intestinal absorption of guanfacine was calculated to be 59 +/- 19% in patients with GFR > 90 ml/min, to 68 +/- 16% in patients with GFR 30-10 ml/min, and to 73 +/- 36% in preuremic patients.

Absorption↗
PubMed1980

Antihypertensive effect of guanfacine: a double-blind cross-over trial compared with clonidine.

1. Sixteen patients with essential hypertension were treated with guanfacine and with clonidine for 5 weeks each in a double-blind, placebo-controlled, cross-over trial. Dosage ranged from 2 to 6 mg guanfacine and from 0.3 to 0.9 mg clonidine daily in two or three divided doses. 2. Both compounds caused a significant and comparable decrease in blood pressure. Patients whose blood pressure was not reduced to normal by 2 to 3 mg guanfacine daily did not respond better to an increase in the dose. 3. Dryness of the mouth and constipation occurred with about equal frequency with both agents, but sedation and orthostatic circulatory effects were considerably more frequent with clonidine. 4. A withdrawal syndrome was observed on discontinuation of clonidine in one patient as opposed to no rebound hypertension on stopping guanfacine treatment. 5. Guanfacine caused a significant decrease in plasma noradrenaline and adrenaline, suggesting a decrease in sympatho-adrenal activity.

Adolescent↗
PubMed1978

[Second increase in plasma volume after single infusion of hydroxyethyl starch (author's transl)].

6 patients without evidence for renal, hepatic or pancreatic disease were treated with intravenous infusions of 500 ml hydroxyethyl starch (6%) over a period of 60 min. In the course of the infusion we observed an increase in plasma volume from 2.72 +/- 0.101 to 3.36 +/- 0.141. After 2 h plasma volume decreased to 3.02 +/- 0.101 but showed a second peak of 3.23 +/- 0.121 after 4 h (p less than 0.01). 24 h following infusion an increase in plasma volume of 4,8% was found as compared to preinfusion values. The second increase in plasma volume cannot be explained by the total concentration of hydroxyethyl starch since the latter decreased continuously. The increase in plasma volume was accompanied by a decrease in average molecular weight (-Mw and -Mn). It is suggested that serum amylase produces small osmotic active molecules by degradation of hydroxyethyl starch, thus leading to an increase in plasma volume. 12--24 h after the infusion of hydroxyethyl starch serum amylase was more than twice as high basal values. This is caused by the formation of a high molecular hydroxyethyl starch-amylase-complex which cannot be eliminated easily. When hydroxyethyl starch is given repeatedly to normovolemic patients, the second increase in plasma volume should be considered as a possible cause for acute hypervolemia. This is especially true for patients with myocardial insufficiency.

Adult↗
PubMed1978

Antihypertensive effect of N-amidino-2-(2,6-dichlorophenyl) acetamide hydrochloride. A double-blind cross-over trial versus clonidine.

Sixteen patients with essential hypertension were treated with N-Amidino-2-(2,6-dichlorophenyl) acetamide hydrochloride (BS 100--141) and clonidine for five weeks each in a double-blind cross-over trial. Dosage ranged from 2 to 6 mg BS 100--141 and from 0.3 to 0.9 mg clonidine daily in two or three divided doses. Both compounds caused a significant and comparable fall in blood pressure. Patients whose blood pressure was not reduced to normal levels by 2 to 3 mg BS 100--141 daily did not respond better to an increase in the dose. Dry mouth and constipation occurred about equally frequently with both agents, but sedation and orthostatic circulatory effects were considerably more frequent with clonidine. Rebound hypertension likewise occurred in five patients following clonidine withdrawal as opposed to no patient after BS 100-141.

Adolescent↗