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Biomedical subjects

A Melander

Publications and source records attributed to A Melander.

At least 127 records · Page 7Linked to original sources
PubMed1985

Comparison of a narcotic (oxicone) and a non-narcotic anti-inflammatory analgesic (indoprofen) in the treatment of renal colic.

Intravenous indoprofen (400 mg), a cyclooxygenase inhibitor, was compared with intramuscular oxicodone hydrochloride (= oxicone 10 mg), a narcotic analgesic agent, in regard to efficacy and side effects in the treatment of renal colic. Oxicone was combined with papaverine (20 mg). Patients were randomized to either treatment, and the drugs were given in double-dummy fashion, i.e. one injection of active drug plus one placebo injection. Pain intensity before and after treatment was registered by the patient (visual analog scale) and by a nurse, who also registered side effects. Oxicone was given to 46 patients and indoprofen to 48. The groups did not differ in body weight, age, sex distribution, or pretreatment intensity of pain. More patients required additional treatment in the oxicone than in the indoprofen group (19 v. 10). At 2-5 min after injection, pain reduction was greater with indoprofen, and more patients in this group had pain relief after 3-5 hours. Side effects were less frequent with indoprofen than with oxicone (1 v. 20 patients), in particular from the central nervous system. This difference probably was related to indoprofen's slow and poor penetration of the blood-brain barrier. The study affirmed that non-narcotic cyclooxygenase inhibitors can replace narcotic analgesics for acute pain alleviation in renal colic. Indoprofen seems to be a useful alternative, with low risk of central nervous side effects.

Adult↗
PubMed1985

Pharmacokinetics of dixyrazine: low bioavailability, improved by food intake.

The single-dose kinetics of the psychotropic phenothiazine dixyrazine was assessed in eight young healthy volunteers given the drug at three occasions: 10 mg intravenously, 25 mg orally in the fasting state, and 25 mg orally together with a standardized breakfast of 1,840 kJ. The plasma concentrations of dixyrazine were measured by high-pressure liquid chromatography. Like some other lipophilic weakly basic drugs, dixyrazine showed a rapid disappearance from plasma, having an elimination half-life of 3.4 h, a clearance of about 1,200 ml/min, and an apparent volume of distribution of 5.9 l/kg. Dixyrazine was found to have a very low and interindividually varying bioavailability; in the fasting state, dixyrazine bioavailability was only 1% in one subject, 3-6% in five others, and 11 and 24% in the remaining two subjects. The mean fasting bioavailability was 7.4%. After intake with breakfast, the mean bioavailability was increased to 12.4% (p less than 0.01), with a range of 2-29%. Probably, the low oral bioavailability is due to extensive presystemic (hepatic) degradation, and the food effect to a reduction of this process.

Administration, Oral↗
PubMed1985

Different effects of different nutrients on theophylline absorption in man.

The influence of concomitant intake of a standardized breakfast (1,840 kJ) and of carbohydrate (830 kJ), fat (645 kJ), and protein (365 kJ) on the absorption of theophylline (400 mg) from a modern formulation of choline theophylline (4 X 135 mg) was examined in 18 healthy volunteers. After fasting overnight, they ingested the drug both immediately after the meal/nutrient and on an empty stomach, fasting being continued for another 4 h. Theophylline concentrations in serum were analyzed by high-pressure liquid chromatography. The results indicate that carbohydrate and the complete breakfast, but not fat or protein, delayed the absorption of theophylline. This is of particular interest as previous animal studies suggest that theophylline may be partially absorbed by an active transport mechanism operating in glucose uptake, and as carbohydrate has been found to increase the absorption rate of phenytoin, another acidic drug with a pKa similar to that of theophylline. This emphasizes the complexity of factors regulating the absorption of drugs and their interactions with food and dietary components.

Adult↗
PubMed1984

Chlorpropamide-alcohol flush: significance of body weight, sex and serum chlorpropamide level.

Chlorpropamide-alcohol flush (CPAF) tests were carried out in 15 male and 15 female Type 2 diabetics. Twelve subjects were CPAF-positive and 18 were -negative. The two groups did not differ in age or duration of diabetes, but the CPAF-positive subjects weighed less (mean difference 13 kg) and had higher plasma chlorpropamide levels. There was a negative correlation between plasma chlorpropamide and body weight, and a positive correlation between plasma chlorpropamide and the increase in facial skin temperature. Females had higher plasma chlorpropamide, a greater skin temperature increase and lower body weight than males; there were 11 females and only 1 male amongst the 12 CPAF-positive subjects. The findings confirm that plasma chlorpropamide is a major determinant of the CPAF reaction and also show that body weight strongly influences the chlorpropamide level and, consequently, the outcome of the CPAF test. The sex difference in body weight probably accounts for most, if not all, of the sex difference in the incidence of the CPAF.

Body Weight↗
PubMed1984

Platelet aggregation and plasma levels of acetylsalicylic acid in stroke patients on long-term treatment with an enteric-coated aspirin formulation.

Enteric-coated formulations of acetylsalicylic acid (ASA) should be advantageous in prophylaxis after stroke because they cause fewer gastrointestinal side effects. However, the absorption of unchanged ASA and the effectiveness of these formulations have been questioned, which prompted the present investigation. Fourteen elderly stroke patients on long-term medication with enteric-coated ASA 1.5 g daily and four patients on placebo were studied. When tested with arachidonic acid platelet aggregation was completely inhibited in all ASA subjects whereas it was normal in the controls. Plasma samples, drawn every 1/2 h for 6 h after tablet intake, were analyzed by HPLC. The presence of ASA was short lasting with a mean peak concentration of 55 mumol/l reached after 2-3.5 h. Salicylic acid (SA) appeared later, having a mean peak value of 591 mumol/l after 2.5-6 h. Thus, absorption of ASA as well as inhibition of platelet aggregation were confirmed during long-term medication with enteric-coated ASA.

Aged↗
PubMed1984

Actions and interactions of acetylsalicylic acid, salicylic acid and diflunisal on platelet aggregation.

Acetylsalicylic acid (ASA) is increasingly employed in the secondary prophylaxis of thromboembolic diseases, due to its capacity to inhibit platelet aggregation. The anti-aggregatory effect of ASA on platelets can be inhibited in vitro by a high concentration of salicylic acid (SA). SA is generated in vivo upon ASA administration, and the SA thus formed might impair the antiplatelet effect of ASA. To assess this possibility, the platelet response to ASA was tested in healthy volunteers before and after medication for 1 week with ASA 1 g t.i.d., with SA 1 g t.i.d., and with the SA derivative diflunisal 0.5 g b.i.d. Pre-medication test doses of 1 g ASA always inhibited platelet aggregation in vivo. Neither treatment with SA nor diflunisal, producing plasma steady-state concentrations of about 1.0 and 0.35 mmol/l, respectively, inhibited platelet aggregation. Nor did administration of SA, diflunisal or ASA itself impair the anti-aggregatory effect of a fresh test dose of ASA. ASA inhibited platelet aggregation in vitro at 0.03 mmol/l, whereas SA and diflunisal failed to impair platelet aggregation until concentrations exceeding 2.0 and 0.5 mmol/l, respectively, were reached. These findings make it unlikely that SA formed upon administration of ASA would impair the anti-aggregating capacity of ASA.

Adult↗
PubMed1984

Indobufen interacts with the sulphonylurea, glipizide, but not with the beta-adrenergic receptor antagonists, propranolol and atenolol.

This study assessed the possible interactions of the cyclooxygenase inhibitor indobufen with one sulphonylurea, glipizide, and with two beta-adrenoceptor antagonists, one of which is extensively metabolised already in the first passage through the liver (propranolol) while the other essentially escapes biotransformation (atenolol). Indobufen was first given as a single 200 mg dose and then for a 5 day period in a dosage of 200 mg twice daily, to six healthy volunteers. Glipizide (5 mg), propranolol (80 mg) and atenolol (100 mg) were given as single doses before and during indobufen medication. The drug concentrations were measured by selective and sensitive h.p.l.c. methods. The findings suggest that the lipophilic acid indobufen can inhibit the metabolic inactivation of another lipophilic acid, glipizide, but does not interfere with the disposal of the two basic drugs, propranolol and atenolol. The increased glipizide concentrations following indobufen were associated with an enhanced blood glucose reduction. Hence, this interaction may be clinically relevant.

Adult↗
PubMed1984

In vivo absorption of theophylline and salicylic acid from rat small intestine.

In vivo absorption of theophylline and salicylic acid from the rat small intestine was studied by a closed segment technique. The drugs were administered at 1 and 4 mM in dissolved form, both in the presence and absence of phlorizin (0.01 mM). Drug concentrations were measured by high-pressure liquid chromatography. Phlorizin inhibited the absorption of theophylline (pKa = 8.6) at 4 mM but not at 1 mM. In contrast, the absorption of salicylic acid (pKa = 3) both at 1 and 4 mM was unaffected by phlorizin. This suggests that an active transport system, sensitive to phlorizin, is involved in the rat intestinal absorption of theophylline, but not in that of salicylic acid. Apart from differences in drug structure, differences in the degree of ionization may influence the access of acidic drugs to this transport system.

Animals↗
PubMed1984

Vasoactive intestinal peptide stimulation of human thyroid cell function.

Neurons containing vasoactive intestinal peptide (VIP) have been found to reach thyroid follicular cells in man and other mammals. Human thyroid cells in culture were exposed to different concentrations of VIP and TSH, and thyroid cell activation was assessed by measurements of cAMP accumulation. VIP exerted a dose-dependent activation, and this thyroid-stimulating effect was more rapid and short-acting than that of TSH. At low concentrations of the two agents, their effects were additive, but they seemed to initiate their effects via different receptors, since polyphloretin phosphate inhibited the effect of TSH but not that of VIP. Moreover, antiadrenergic and anticholinergic agents did not influence thyroid activation by VIP. In addition to cAMP activation in cell cultures, VIP stimulated T4 release from human thyroid slices. It is possible that, in addition to sympathetic-adrenergic and parasympathetic-cholinergic nerves, VIPergic nerves may participate in the autonomic nervous control of thyroid function.

Adult↗
PubMed1984

Influence of cigarette smoking on goiter formation, thyroglobulin, and thyroid hormone levels in women.

The possible influence of cigarette smoking on goiter formation, thyroglobulin (Tg) secretion, and thyroid hormone production was assessed by estimations of the presence of palpable goiter and by RIAs of Tg, T3, rT3, T4, and TSH in sera from 441 women (48-53 yr old), representing a normal population included in a study on the prevalence of thyroid disease. Smoking habits were evaluated by a questionnaire, and the women were then classified as never smokers (n = 192), smokers (n = 169), and exsmokers (n = 80). Smokers were subdivided as moderate (1-19 cigarettes/day) and heavy (greater than or equal to 20 cigarettes/day). Palpable goiter was found in 15% of the smokers, in contrast to only 4% of the exsmokers and 9% of the never smokers. Among smokers, 37% had serum Tg values over 30 micrograms/liter (third quartile), while such values were found in only 16% of the exsmokers and 18% of the never smokers. In addition, smokers were found to have higher serum T3 and lower rT3 concentrations than never smokers; this difference was most pronounced in heavy smokers. Serum T4 was not different, while TSH was insignificantly lower in smokers than in nonsmokers. Exsmokers did not differ significantly from never smokers in any of these parameters. It seems possible that cigarette smoking may have two, calorigenically opposed, effects on thyroid hormone production; it may be goitrogenic (possibly due to inhaled thiocyanate), but it may also enhance the formation of T3 at the expense of rT3 formation.

Body Weight↗
PubMed1984

Local anaesthesia and immunomodulatory effects of antithyroid drugs.

Propylthiouracil (PTU) and propranolol can suppress, while methimazole (MMI) can enhance, mitogenic activation of lymphocytes. The present study investigated whether this effect of PTU, as has been shown for propranolol, relates to local anaesthetic activity. MMI (1 mM) but not PTU (1 mM) reduced the action potential in rat skeletal muscle. Thus, PTU seems to lack local anaesthetic activity. Moreover, the recorded local anaesthetic capacity of MMI hardly explains the stimulatory influence of MMI on lymphocyte activation. Apparently, the interference of MMI and PTU with lymphocyte activation seems to be due to another mechanism than local anaesthetic activity.

Action Potentials↗
PubMed1984

Drug selection in the treatment of pregnancy hypertension. A survey.

Effective blood pressure treatment has only been available during the last 20-25 years. Most antihypertensive drugs employed for other hypertensive conditions have also been used in hypertensive states of pregnancy. In this survey, most of the drugs already in use and some new ones are discussed. No special emphasis is placed on the use of drugs in emergency situations. As beta-adrenoceptor blocking drugs are widely used nowadays, the principal differences between some beta-blockers are discussed in detail. A discussion of future requirements in order to get a better picture of the value of antihypertensive drugs completes this survey.

Adrenal Glands↗
PubMed1984

Fetal heart rate during treatment of maternal hypertension with beta-adrenergic antagonists. A preliminary report.

The effects of two different beta-adrenergic antagonists on maternal arterial pressure and fetal heart rate were studied in 8 pregnant women with pregnancy hypertension. The fetal heart rate was monitored by abdominal ECG recording under standardized conditions. Basal heart rate, long-term variability and short-term variability were calculated in a computer. Four patients received 50-100 mg atenolol once daily; the other 4 received pindolol 10 mg b.i.d. Reduction in mean arterial blood pressure was seen in both groups of patients. The basal fetal heart rate was decreased in atenolol-exposed fetuses but not in pindolol-exposed fetuses. In this preliminary study there was no apparent effect on the fetal heart rate variability.

Adrenergic beta-Antagonists↗
PubMed1983

Clinical pharmacology of glipizide.

The clinical pharmacology of glipizide and other sulfonylureas is briefly reviewed. Reevaluation of the University Group Diabetes Program data suggests that sulfonylureas do not increase cardiovascular mortality. Instead, a long-term study of subjects with impaired glucose tolerance indicates that sulfonylureas reduce the frequency of cardiovascular morbidity and can postpone or even prevent the development of impaired glucose tolerance to manifest diabetes. It is likely that all sulfonylureas have the same principal mechanism(s) of action but that they differ in potency and pharmacokinetics, resulting in considerable clinical differences. Thus, glipizide and glibenclamide (glyburide) are much more potent than tolbutamide and chlorpropamide. Glipizide has the most rapid absorption and onset of action, as well as the shortest half-life and effect-duration; hence the risk of long-lasting hypoglycemia is minute. Glipizide has complete bioavailability, and its blood glucose-lowering effect is improved when it is given before breakfast. Glipizide may be administered once daily without loss of therapeutic efficacy.

Biological Availability↗
PubMed1983

Plasma chlorpropamide: a critical factor in chlorpropamide-alcohol flush.

The chlorpropamide-alcohol flush (CPAF) phenomenon was quantitatively related to blood levels of acetaldehyde and chlorpropamide in 105 Type II diabetics, of whom 74 had not previously taken the drug and 31 were on chronic treatment. Standardized skin temperature recordings were made with a sensitive probe. Plasma ethanol and acetaldehyde concentrations were determined by gas chromatography, and those of chlorpropamide by high-pressure liquid chromatography. There were significant positive correlations between plasma acetaldehyde and the skin temperature increase, between plasma chlorpropamide and plasma acetaldehyde, and between plasma chlorpropamide and the skin temperature increase. CPAF-positive patients became CPAF-negative and vice versa following reduction and increase, respectively, in the dose of chlorpropamide. Thus, the CPAF reaction is a consequence of chlorpropamide inhibition of the oxidation of ethanol-generated acetaldehyde, and it appears that the plasma concentration of chlorpropamide is critical. It remains an open question whether the CPAF test has any prognostic value.

Acetaldehyde↗
PubMed1983

Serum and saliva concentrations of sulfamethoxazole and trimethoprim in adults and children: relation between saliva concentrations and in vitro activity against nasopharyngeal pathogens.

The combination sulfamethoxazole/trimethoprim (SMX/TMP) was given orally to 4 healthy adult volunteers in mean daily doses of 23.0/4.6 mg/kg body weight for 6 days. The serum and saliva concentrations of the drugs were assayed on days 1, 3 and 6. On the first day (0-12 h) there was no measurable concentration of SMX in the saliva. On days 3 and 6 the mean peak levels of SMX in saliva were 7.8 and 9.8 micrograms/ml, i.e. 8-9% of the corresponding mean peak serum levels. In contrast, the concentrations of TMP in saliva were more than twice as high as those in serum. The mean SMX/TMP ratios in saliva days 3 and 6 were 1.3 and 1.4, respectively, i.e. approximately one-twentieth of the mean SMX/TMP ratios in serum. SMX/TMP was also administered to children with serous otitis media. The drug concentrations in saliva were assayed 2-3 h after administration on days 6 and 9 of a 10-day course, with a mean daily dose of 34.5/6.9 mg/kg body weight. The mean saliva concentration of SMX in the children was slightly higher than in adults and the mean TMP concentration about half of that in adults. The mean SMX/TMP ratio in the children's saliva was 4.2. The in vitro activity of SMX/TMP 20:1 and 4:1 was determined against H. influenzae, D. pneumoniae, B. catarrhalis and group A streptococci. H. influenzae, D. pneumoniae and group A streptococci were found more susceptible to TMP than to SMX, while the reverse was true for B. catarrhalis. In the 3 former, the potentiation of SMX by TMP was more pronounced than was the potentiation of TMP by SMX, while the opposite was recorded for B. catarrhalis. The most beneficial effect of the SMX/TMP combination against nasopharyngeal pathogens was recorded for B. catarrhalis and the weakest effect for H. influenzae and group A streptococci. With the exception of B. catarrhalis, the administration of TMP alone to adults may be just as effective against nasopharyngeal pathogens as is the SMX/TMP combination in children.

Adult↗