PubMed Health⌕ Search

Biomedical subjects

R Huupponen

Publications and source records attributed to R Huupponen.

At least 109 records · Page 6Linked to original sources
PubMed1985

The effect of ocular pigmentation on intraocular pressure response to timolol.

The one-hour intraocular pressure (IOP) response to topical ocularly applied timolol was studied in darkly and lightly pigmented eyes. One drop of 0.25% 1-timolol was applied to one eye of ten subjects with brown and ten subjects with blue iris color. In the treated and untreated eyes with blue iris color the IOP fell significantly from the baseline value, whereas no pressure reduction was obtained either in the treated or untreated eyes with brown iris color. Beta-blocking agents are known to accumulate in pigment-containing ocular structures. The lack of a one-hour pressure response to timolol in darkly pigmented eyes observed in our study may refer to the reduction of 1-timolol in the biophase due to excessive pigment binding.

Adult↗
PubMed1984

Roles of chlorpropamide, alcohol and acetaldehyde in determining the chlorpropamide-alcohol flush.

The value and reproducibility of the chlorpropamide-alcohol flush (CPAF) have been questioned, and objective measures of the test are required. Recording of facial skin temperature, measurement of chlorpropamide, ethanol and acetaldehyde concentrations have been proposed for this purpose. The present study was designed to evaluate the relative contributions of these variables in determining CPAF. Twenty-one Type 2 (non-insulin-dependent) diabetic patients (11 CPAF-positive and 10 CPAF-negative according to previous tests with standard amounts of alcohol and chlorpropamide) were investigated in a random fashion with either chlorpropamide or placebo given on three subsequent evenings before a two-step alcohol challenge with increasing body-weight-matched amounts of alcohol. Higher rises in facial skin temperature and heart rate, higher flush-score and higher acetaldehyde levels resulted from chlorpropamide therapy than followed placebo. After smaller alcohol challenges (with chlorpropamide pretreatment) there were positive intercorrelations between flush-score, rise in facial skin temperature, and plasma concentrations of chlorpropamide and blood acetaldehyde. The increased alcohol dose abolished most of these correlations and a minimum temperature rise of 1.8 degrees C appeared in all but two subjects regardless of previous CPAF classification. During the current experimental conditions, the previously-classified CPAF-positive and CPAF-negative patients did not differ with respect to flush-score, rise in skin temperature, heart rate, blood acetaldehyde or ethanol concentrations, whereas they differed with respect to chlorpropamide concentrations. The present results support the view that CPAF is associated with elevated blood acetaldehyde levels due to inhibition of aldehyde dehydrogenase by chlorpropamide.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗
PubMed1984

Effect of guar gum, a fibre preparation, on digoxin and penicillin absorption in man.

The effect of guar gum on the absorption of digoxin and phenoxymethyl penicillin was studied in a double blind study in 10 healthy volunteers. Guar gum reduced serum digoxin concentration during the early absorption period, but a similar amount of digoxin was found in 24 h urine whether given with or without guar gum. Both the peak penicillin concentration and the area under the serum curve were significantly reduced by the gum.

Adult↗
PubMed1984

Effect of the short-term beta-adrenoceptor blockade on exercise metabolism in cold weather.

Carbohydrate and lipid metabolism at rest and after 1 h submaximal physical exercise in cold weather (between -1 and -6 C) were studied in ten healthy male subjects treated in a randomized double-blind fashion for 2 days with either placebo, the non-selective beta-adrenoceptor antagonist with high ISA pindolol (10 mg), or the cardioselective drug atenolol (100 mg). Four subjects, on both atenolol and pindolol, complained of muscular fatigue during exercise on beta blockade; four other subjects perceived some fatigue. There were no significant differences in blood glucose or insulin levels between treatments and placebo period. Post-exercise growth hormone levels increased on placebo (p less than 0.01), on pindolol (p less than 0.01), and on atenolol (p less than 0.05), but the alteration was more prominent on pindolol than on placebo (p less than 0.05). The plasma free fatty acid concentrations increased during exercise on placebo and pindolol (p less than 0.05) and on atenolol (p less than 0.01). Serum triglyceride concentrations decreased significantly during exercise on placebo or pindolol (p less than 0.01). Triglyceride levels before exercise were significantly higher on beta blockade than on placebo (p less than 0.05). The metabolic parameters taken before and after exercise did not explain the muscle fatigue experienced by many subjects during exercise.

Adrenergic beta-Antagonists↗
PubMed1984

Blood glucose and serum C-peptide after a single chlorpropamide dose.

A single chlorpropamide dose, when compared to placebo, reduced blood glucose in volunteers during fasting and glucagon stimulation without increase in pancreatic beta cell secretion. The finding suggests that extrapancreatic mechanisms may play a substantial role in the chlorpropamide action also after a single drug dose.

Adult↗
PubMed1983

Effect of the benzodiazepine derivative, diazepam, on the clonidine-stimulated human growth hormone secretion.

gamma-Aminobutyric acid (GABA) has both stimulatory and inhibitory effect on human GH secretion. We previously reported that the benzodiazepine derivative diazepam, which exerts its main pharmacological effect by facilitating GABA-mediated transmission, is able to reduce the GH response to L-dopa and apomorphine. To establish whether diazepam affects the alpha-adrenergic regulation of GH secretion, the GH response to clonidine (an alpha-agonist) was investigated in seven volunteers after placebo and diazepam premedications. After placebo pretreatment, clonidine (0.15 mg iv infused over 20 min) significantly stimulated GH secretion: the mean serum GH level rose from a basal level of 4.7 +/- 1.1 (+/- SEM) ng/ml to a maximum of 10.8 +/- 1.6 ng/ml (P less than 0.025). After 3 days of diazepam treatment, a similar GH response to clonidine was observed; the mean serum GH level rose from a basal value of 2.3 +/- 0.3 ng/ml to a maximum of 9.4 +/- 1.3 ng/ml. It is concluded that the inhibitory effect of diazepam on human GH secretion is mediated via inhibition of dopaminergic transmission, whereas the alpha-adrenergic control of GH release is not affected. Since diazepam potentiates GABAergic transmission, its effect may reflect the role of endogenous GABA in human GH secretion.

Adult↗
PubMed1982

Glipizide pharmacokinetics and response in diabetics.

The pharmacokinetics of and response to glipizide were studied in six insulin-independent diabetics by radioimmunoassay for glipizide and insulin. Blood glucose was also monitored. Beside control (off glipizide) the patients were studied when given 10 mg glipizide either as a single daily dose or divided into two doses. The peak drug concentration was reached on an average within 1.8-2.3 h. The AUCs did not differ between the two dosage regimens. The mean elimination half-life was 4.7 +/- 0.4 h, Vd 17.0 +/- 2.6 l, and the calculated total clearance 41.6 +/- 4.3 ml/min (mean +/- s.e.m.). In one patient a more than two-compartment pharmacokinetic model was obvious. The once or twice daily dosage regimens did not differ significantly in their ability to reduce blood glucose, but the overall efficacy of the therapy was poor in these patients. The maximal efficacy of a single 10-mg dose of glipizide to reduce blood glucose was maintained at the same level between 1.5 and 8 h despite the continued rapid falling of serum glipizide concentration over this period.

Adult↗
PubMed1982

Chlorpropamide and glibenclamide serum concentrations in hospitalized patients.

The relationships between the daily doses of the drugs and the steady state serum concentration was studied in 51 patients on chlorpropamide and in 27 patients on glibenclamide. All the patients were hospitalized during the study. A wide interindividual variation in chlorpropamide levels was observed and thus, the prediction of drug concentration was difficult from the dosage alone, despite a statistically significant correlation between the dose per body weight and the serum drug level. The differences could not be explained on the serum creatinine levels, age, sex, liver diseases or other drugs used concomitantly. In the case of glibenclamide, a wide interindividual variation in serum concentration of the drug also occurred.

Aged↗
PubMed1981

Plasma AVP after intravenous chlorpropamide.

The proposed ADH-releasing capacity of chlorpropamide was tested after intravenous administration of the drug to nine healthy fasted volunteers. When compared with the placebo experiment, no evidence for increased ADH release was found. On the contrary, the AVP values measured after chlorpropamide injection were slightly lower during the first 2 h than after the saline injection. Serum chlorpropamide concentration was also measured. After a rapid distribution phase, a slow elimination phase followed. The calculated t 1/2 for distribution phase was 1.00 +/- 0.26 hrs (mean +/- s.e.m.).

Arginine Vasopressin↗
PubMed1981

Chlorpropamide bioavailability and pharmacokinetics.

The pharmacokinetics of chlorproamide was studied in eight healthy volunteers after intravenous and oral dosage. A long elimination half-life with considerable variations between subjects was recorded. The normalized areas under the curve were in close agreement between the subjects, suggesting that they had all absorbed the same magnitude of chlorpropamide. The AUCs after i.v. and p.o. administration did not differ significantly from each other. Thus, the differences in the bioavailability do not seem to be a critical factor in the previously reported large interindividual variations in chlorpropamide steady-state concentrations.

Administration, Oral↗
PubMedDate not supplied

Kinetics of propiverine as assessed by radioreceptor assay in poor and extensive metabolizers of debrisoquine.

A pharmacokinetic study with 30 mg propiverine p.o. was performed in healthy volunteers (10 males, 6 females, age 36-56 years, body weight 55-100 kg, body height 162-184 cm, Broca index 0.96-1.19). 8 of them were poor and 8 extensive metabolizers of the debrisoquine type hydroxylation polymorphism. The total anticholinergic activity of the parent compound and active metabolites was measured with a radioreceptor assay calibrated with the metabolite M2. The affinity of this metabolite to the muscarinic receptors was similar to that of atropine. The urinary excretion of 3 major metabolites was determined with TLC and densitometry. Arterial blood pressure, heart rate, diameter of pupils, accommodation and parotic salivary flow were also measured. The concentrations of anticholinergic equivalents of propiverine were below 1 ng/ml of M2. 1.4-6.0% of the dose were excreted as N-oxidized metabolites into the urine. The poor and extensive metabolizers of debrisoquine did not differ significantly with regard to the concentration time behaviour of the active drug components, pattern of major metabolites, adverse drug reactions or any pharmacodynamic parameters measured.

Adult↗
PubMedDate not supplied

Adverse cardiovascular effects of sulphonylurea drugs. Clinical significance.

Sulphonylureas are widely used in the treatment of diabetes mellitus. Since the publication of the University Groups Diabetes Program (UGDP) results the discussion on their possible cardiovascular side effects has been lively and sometimes even passionate. The initial UGDP findings about the adverse effects of tolbutamide on the cardiovascular system have been criticised, particularly for shortcomings in the study design. The results of other epidemiological studies of the sulphonylurea effects on cardiovascular morbidity and mortality published this far have been contradictory. This is understandable because the factors involved are very complex. Most of these studies have used tolbutamide only, and the findings cannot necessarily be directly extrapolated to other sulphonylureas. Only properly performed prospective studies may provide further information on this issue. High concentrations of several sulphonylureas may have inotropic effects on heart muscle in in vitro animal models, but human studies performed in vivo do not support the view of clinically significant inotropy for sulphonylureas. High concentrations of tolbutamide or glibenclamide (glyburide) may affect the myocardial metabolism in isolated organs, but the possible clinical significance of these findings remains unknown. Some epidemiological and experimental studies have associated oral antidiabetic treatment with the occurrence of cardiac arrhythmias or increased digitalis toxicity. Only a few results are available, and there may be differences between the sulphonylureas in this respect. Antiaggregatory properties have been postulated for some sulphonylureas. Gliclazide, in particular, has been studied, but some other compounds of this class have also been effective in short term studies. If confirmed, these effects on haemostasis would be noteworthy. The sulphonylurea effects on serum lipids, especially on HDL-cholesterol, have been discussed widely during the last few years. Decreases in HDL-cholesterol concentrations were suggested to be associated with sulphonylurea therapy. However, these findings were not confirmed in recent cross-sectional and longitudinal studies performed with different sulphonylureas. Chlorpropamide, and to a lesser extent tolbutamide, may cause dilutional hyponatraemia and aggravate existing heart failure. Glibenclamide may increase the clearance of water in the kidney.

Cardiovascular Diseases↗
PubMedDate not supplied

Multiple-dose pharmacokinetics of selegiline and desmethylselegiline suggest saturable tissue binding.

The goal of this study was to examine the multiple-dose pharmacokinetics of selegiline and its metabolites desmethylselegiline, 1-methamphetamine, and 1-amphetamine after oral administration of selegiline HCl. Twelve healthy volunteers received 10 mg of selegiline HCl once daily for 8 days. The pharmacokinetic profiles of selegiline and the metabolites were examined from serum samples for 24 hours (i.e., the dosing interval, tau) on days 1, 4, and 8. The results indicated significant apparent accumulation of selegiline and desmethylselegiline during the 8-day period of selegiline administration. The AUC tau S of selegiline and desmethylselegiline were increased 2.7 fold (p < 0.001) and 1.5 fold (p < 0.001), respectively, from day 1 to day 8. However, the half-lives of selegiline (range, 1.5-3.5 h) and desmethylselegiline (range, 3.4-5.3 h) were found to be relatively short. Accordingly, the short half-lives of these compounds failed to predict the apparent accumulation. With both of the 1-amphetamine metabolites of selegiline, steady state was reached by day 4. We suggest that the most likely explanation for the apparent accumulation of selegiline and desmethylselegiline was the saturation of the MAO-B binding sites in tissues, although decreased first-pass metabolism of selegiline cannot be ruled out. The observed increase in selegiline and desmethylselegiline concentrations on multiple dosing is not likely to significantly increase the pharmacodynamic effect or adverse effects of selegiline compared with what has been found after a single 10-mg dose.

Administration, Oral↗
PubMedDate not supplied

Effect of subchronic metformin treatment on macronutrient selection in genetically obese Zucker rats.

Metformin has been particularly recommended to be used in obese type 2 diabetic patients because of its weight decreasing and serum lipid profile normalizing effects. In the present study the effects of subchronic metformin treatment on macronutrient selection, weight gain and plasma insulin and glucose were investigated in 20 genetically obese male Zucker rats which were maintained on a free-feeding self-selection paradigm with three pure macronutrient diets of carbohydrate, fat and protein. Half of the rats were given metformin hydrochloride 320 mg/kg/day up to 18 days in drinking water. The other half of the animals received normal drinking water as a control. Metformin treatment significantly reduced 24 hr carbohydrate (P < 0.01), fat (P < 0.001) and protein (P < 0.01) intake. The proportion of fat of the total consumed energy was significantly increased by metformin (P < 0.01) while the proportion of protein was decreased (P < 0.05). In hunger stimulated feeding experiment metformin decreased selectively protein intake (P < 0.01). Changes in macronutrient selection were associated with reduced body weight gain in metformin treated rats (P < 0.001). Metformin markedly reduced the hyperinsulinaemia (P < 0.01) and plasma glucose levels (P < 0.05), which suggests improved glucose tolerance after metformin treatment. It is concluded that subchronic metformin treatment can modify the composition of energy intake in a macronutrient selective manner.

Animals↗
PubMedDate not supplied

Effect of chronic treatment with ICI D7114, a selective beta 3-adrenoceptor agonist, on macronutrient selection and brown adipose tissue thermogenesis in Sprague-Dawley rats.

ICI D7114 is a selective beta 3-agonist which stimulates brown adipose tissue thermogenesis. In the present study the effects of 18 days treatment with ICI D7114 (2 mg/kg/day orally) on macronutrient selection and brown adipose tissue thermogenesis were investigated in Sprague-Dawley rats. The rats were maintained on a free-feeding self-selection paradigm with three pure macronutrient diets of carbohydrate, fat and protein. Treatment with ICI D7114 did not change the macronutrient selection or total calories consumed by the rats. To monitor the thermogenic activation of brown adipose tissue the binding of [3H]GDP to brown adipose tissue mitochondria was measured. The treatment with ICI D7114 increased the binding of GDP both when expressed as total binding per lobe (P < 0.001) and per mg of protein (P < 0.01). It is concluded that ICI D7114, used in doses affecting brown adipose tissue thermogenesis, does not change the macronutrient selection or total energy intake in Sprague-Dawley rats.

Adipose Tissue, Brown↗