Search PubMed⌕ Search

Biomedical subjects

H Wesseling

Publications and source records attributed to H Wesseling.

At least 127 records · Page 7Linked to original sources
PubMed1981

Sublingual and oral isoxsuprine in patients with Raynaud's phenomenon.

Oral and sublingual isoxsuprine 20 mg were compared with placebo in double blind randomised cross over trial in 7 patients with Raynaud's phenomenon. Skin thermography, plethysmography of the finger tips and direct temperature measurements showed that sublingual isoxsuprine was slightly but consistently superior to the oral form and to placebo; no significant difference was observed between the latter two treatments. It is concluded that sublingual administration of isoxsuprine has advantages over their routes of administration, and that thermography is a suitable technique for qualitative, but less appropriate for quantitative, measurement of drug effects in patients with Raynaud's phenomenon.

Administration, Oral↗
PubMed1981

Hepatic and renal disposition of pancuronium and gallamine in patients with extrahepatic cholestasis.

The plasma clearance of pancuronium in patients with extrahepatic cholestasis was 16% lower than in a control group (1.47 +/- 0.11 ml min-1 kg-1 v. 1.76 +/- 0.21 ml min-1 kg-1), but the difference was not significant. A significant increase in the elimination half-life T 1/2 beta of pancuronium (from 141 to 224 min) and a significant increase in the volume of the peripheral compartment (V2) was found in patients with extrahepatic cholestasis when compared with control patients. There was a significantly lower cumulative biliary excretion of pancuronium (0.3 +/- 0.3% v. 10.9 +/- 3.2% in the controls) during the 48-h period of observation. The biotransformation and cumulative urinary excretion patterns of pancuronium revealed no significant differences between the two groups of patients. The increase of T 1/2 beta pancuronium in patients with extrahepatic cholestasis was mainly a consequence of the increase in the volume of distribution. No significant differences in the plasma clearance, T 1/2 beta or in the volume of distribution were observed with gallamine in the patients with extrahepatic cholestasis when compared with the control group. The cumulative urinary excretion of gallamine during 48 h in both groups of patients was approximately 100%. We concluded that in patients with cholestasis and normal glomerular filtration, gallamine is probably more reliable than pancuronium for neuromuscular blockade.

Adult↗
PubMed1981

Bile salts and neuromuscular blocking agents.

The influence of the primary bile salts taurocholate and chenodeoxycholate on the neuromuscular blockade of the non-depolarizing drugs Org 6368, pancuronium, Org NC 45 and hexafluorenium was studied in cats. An increase in the effects of these agents, all possessing widely varying molecular structures, was found following administration of the bile salts. The bile salt concentrations in plasma were similar to those obtained after 9-10 days of extrahepatic cholestasis in cats. The effect of Org NC 45, a new monoquaternary analogue of pancuronium, was increased more than that of pancuronium. This increase in effect is probably a result of inhibition of the hepatic uptake of the neuromuscular blocking drugs. The neuromuscular blocking effect of gallamine was not influenced significantly by the administration of bile salts.

Animals↗
PubMed1981

The effect of dantrolene sodium in relation to blood levels in spastic patients after prolonged administration.

In 25 patients with spasticity, pharmacokinetics and effects of dantrolene sodium were investigated after prolonged administration. A beneficial effect occurred in seven patients. The results were better on 100 mg daily than on a higher daily dose. An increase of the daily dose from 200 to 400 mg was not associated with higher blood levels. Many side effects were noted such as: anorexia, nausea, drowsiness, depression and muscle weakness. From this study we conclude that dantrolene sodium is a muscle relaxant with a weak to moderate effect in patients with spasticity; the effect at doses higher than 200 mg daily is probably poor.

Adult↗
PubMed1979

The effect of dantrolene sodium on rat skeletal muscle in relation to the plasma concentration.

Dantrolene sodium is a muscle relaxant used in the treatment of spasticity. It has been shown to interfere with calcium release from the sarcoplasmic reticulum and thus to inhibit excitation--contraction coupling. The effect of dantrolene sodium on the twitch tension of the tibialis anterior muscle of the rat was measured after 2 mg/kg i.v. or 25 mg/kg orally. Plasma concentrations were estimated at maximum twitch depression and during recovery from the block. In a separate series of experiments the half-life of labelled dantrolene sodium was measured in blood plasma, skeletal muscle and heart muscle of rats. Dantrolene sodium 2 mg/kg i.v. gave a maximal block of approximately 47%, the mean dantrolene sodium concentration was then 5.8 microgram/ml. A half-life for distribution of 1.1 min and an elimination half-life of 31 min after intravenous administration were observed, elimination rate constants in skeletal and heart muscle were comparable. Recovery from the block went much slower, the half-time of the process being approximately 80 min. Dantrolene sodium 25 mg/kg orally gave a maximal block of approximately 38% at a mean plasma concentration of 3.6 microgram/ml after 14 min. The recovery was again very slow. These experiments demonstrated that dantrolene sodium acts according to a two-compartment pharmacokinetic model. There was a discrepancy between duration of effect and plasma concentration of dantrolene sodium in the rat. This suggests that the receptor for dantrolene sodium is not located in the central compartment.

Animals↗
PubMed1979

Relationship between plasma concentration and effect of dantrolene sodium in man.

Dantrolen sodium is a muscle relaxant, which is used in the treatment of spasticity. Although it is given chronically, little is known about its pharmacokinetic behaviour. The relationship between the effect of a single oral dose of dantrolene sodium and its plasma concentration in healthy volunteers was studied by measuring the effect on the twitch tension, and in spastic patients on the decrease in muscle hypertonia. On the twitch tension dantrolene gave a depression of 49.1 +/- 9.4% (+/- DS) within 1.15 and 3.45 h after ingestion of 100 mg. The mean maximal plasma concentration was 1.24 +/- 0.32 microgram/ml (+/- SD). The effect and the plasma concentration were correlated. No relationship between the plasma concentration of dantrolene sodium and its effect could be established in patients, although definite activity in 6 out of 7 patients was observed after a single oral dose of 100 mg, and plasma concentration of dantrolene sodium greater than 0.3 microgram/ml were consistenly associated with better results than placebo treatment in 6 out of 7 patients.

Adult↗
PubMed1977

Human experience of cetiedil, a new vasodilator with anticholinergic properties.

Cetiedil, a new vasodilating drug with anticholinergic properties, was shown to be metabolised very rapidly in man after intravenous and oral administration of the 14C-compound. Higher concentrations of labelled compound after oral than after intravenous administration at the same sampling time, and proportional differences in urinary excretion, suggest that metabolic handling of the drug differs depending on the route of administration. Experiments in which inhibition of saliva secretion was measured indicated that (an) active metabolite(s) probably was (were) responsible for the action of the drug. As an anticholinergic drug, cetiedil is at least 400 times weaker than atropine.

Administration, Oral↗
PubMed1976

The effects of dantrolene sodium on cardiac and skeletal muscle in rats.

Dantrolene sodium in different concentrations was administered to the spontaneously beating heart placed in a modified Langendorff apparatus. Heart frequency and contractility were recorded. Dantrolene sodium was also administered to the rat diaphragm. Twitch tension after indirect supramaximal stimulation was recorded. Dantrolene sodium produced a long lasting dose-dependent reduction of the contractility of the isolated rat heart up to 75% of control values. It had no effect on the heart frequency. The drug also decreased the force of contraction of the rat skeletal muscle in vitro to the same extent. The diaphragm appeared to be more sensitive to low concentrations of dantrolene sodium than was heart muscle i.e. the dose-response curve on rat diaphragm was flatter. It may be concluded however that higher concentrations of dantrolene sodium may effect the contractility of heart muscle as well and that this may have clinical implications.

Animals↗
PubMed1975

Effect of premedication on stress and plasma cortisol in patients bronchoscoped under local anaesthesia.

Four groups of 8 patients undergoing bronchoscopy were premedicated with either pentobarbitone 1 mg/kg i.m. followed by i.v. saline, or diazepam 10 mg and saline i.v., or diazepam 10 mg i.m. followed by diazepam 20 mg i.v. and, diazepam 20 mg i.m. and then saline i.v. Both the patients and the bronchoscopist were asked to score the premedication as excellent, satisfactory, unsatisfactory or bad. Plasma cortisol was measured before premedication and before and after bronchoscopy. Preoperatively plasma cortisol increased in every group except that given diazepam 20 mg i.m., and during bronchoscopy it rose in all except the group who received 20 mg diazepam i.v. In patients who considered the premedication unsatisfactory, the rise in plasma cortisol from before premedication until after bronchoscopy was significantly higher than in satisfied subjects. It appears that in patients undergoing bronchoscopy higher doses of diazepam (20-30 mg) gave better suppression of stress than 10 mg diazepam, or 1 mg/kg pentobarbitone.

Adult↗
PubMed1975

Interaction of diphenylhydantoin (DPH) and tolbutamide in man.

The influence of tolbutamide administration on the plasma concentrations of diphenylhydantoin (DPH) was investigated in seventeen long-stay patients with epilepsy. Tolbutamide, 0.5 g 2-3x daily, considerably increased the proportion of non-protein-bound DPH in plasma (mean: 44.6% of control values). The increase was transient, unlike the decrease found in total plasma DPH-concentration (approx. 10% of control values). In vitro experiments confirmed that the interaction between DPH and tolbutamide was due to displacement of DPH from plasma proteins. Some factors that limit the capacity to metabolise DPH in the liver are discussed; they may increase the risk of DPH-intoxication in patients who take sulphonyl-ureas.

Adult↗