A comparative study of the relative enzyme inducing properties of anticonvulsant drugs in epileptic patients. 1984.
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Anticonvulsants↗
Biomedical subjects
A Hedges
Publications and source records attributed to A Hedges.
The comparative inhibitory and bactericidal activities of meropenem and imipenem against Acinetobacter spp. and Enterobacteriaceae resistant to second generation cephalosporins.
The inhibitory and bactericidal activities of meropenem and imipenem were compared using Acinetobacter spp. and Enterobacteriaceae resistant to second generation cephalosporins. The inhibitory activity of both agents was similar for Acinetobacter spp. but meropenem was more active against the Enterobacteriaceae. Bactericidal activities were compared employing time-kill curves which indicated meropenem was more bactericidal than imipenem against Enterobacteriaceae at pharmacologically achievable concentrations while imipenem was more bactericidal than meropenem against Acinetobacter spp.
Acinetobacter↗
Skin disinfection in preterm infants.
Greater care and a more thorough approach to intravenous catheter site disinfection may be important for the prevention of catheter related sepsis, especially with coagulase negative staphylocci in preterm infants. The efficacy of skin disinfection was evaluated in preterm infants using a skin swabbing technique after disinfectant exposure. In the first part of the study, 25 peripheral intravascular catheter sites were quantitatively sampled immediately after routine cannula insertion. Bacterial counts greater than 100 colony forming units/cm2 were observed from 10 (40%) sites. In the second part, sampling for bacterial colony counts was done after skin cleansing with various durations of exposure of chlorhexidine/alcohol swabs or povidone iodine. The overall mean reduction in bacterial colony counts after skin cleansing ranged from 90-99%. Skin sterilisation was achieved in 33-92% of cases. The use of two consecutive 10 second exposures resulted in a significantly improved reduction in colony counts compared with a single 10 second wipe. A longer 30 second exposure also resulted in a greater reduction of bacterial numbers compared with a shorter duration of 5 or 10 seconds. Repopulation of disinfected sites occurred within 48 hours. This effect was delayed by occluding the cleansed site with a semipermeable dressing. There were no significant differences between povidone iodine and the chlorhexidine swabs in reducing bacterial numbers. This study has demonstrated that a brief exposure with a premoistened disinfectant swab is not sufficient for complete elimination of resident skin flora of newborn infants. The use of two consecutive cleanings, or a longer duration of cleansing is recommended for more effective skin sterilisation.
Catheterization↗
Antagonism by domperidone of the ocular hypotensive effect of pergolide.
1. The effect of pre-dosing with 15 mg domperidone, a relatively selective dopamine 2-receptor antagonist, on the ocular hypotensive action of a single oral dose of 25 micrograms pergolide, a dopamine 2-receptor agonist, was studied in 9 normal human volunteers, using a non-invasive method. 2. Compared with domperidone followed after 1 h by placebo, placebo followed after 1 h by pergolide had an ocular hypotensive effect in both eyes. Domperidone followed after 1 h by pergolide had no effect on intraocular pressure in both eyes. 3. The results of this study showed that domperidone inhibited the ocular hypotensive action of pergolide, suggesting that pergolide reduces intraocular pressure by the stimulation of the peripheral dopamine 2-receptors.
Adult↗
The influence of changes in buccal potential difference on the buccal absorption of propranolol.
A buccal potential difference (b.p.d.) exists across the mucous membrane of the mouth, which can be made less negative by contact with aspirin. The influence of changing the b.p.d. with aspirin on the buccal absorption of propranolol from a series of buffers of pH5-10 has been studied in eight volunteers. The study confirmed that the buccal absorption of propranolol was markedly pH dependent, but pretreatment of the buccal membrane with aspirin had no influence on the absorption of propranolol.
Absorption↗
Pharmacokinetic interaction between indoramin and ethanol.
1. The effect of ethanol consumption (0.5 g/kg) on the pharmacokinetics of the alpha adrenoceptor antagonist indoramin, administered orally (50 mg) or intravenously (0.175 mg/kg) has been investigated in young volunteers. Sedation was also assessed using a visual analogue scale. 2. After oral indoramin administration, ethanol caused increases of 58% (P less than 0.01) in Cpmax, and 25% (P less than 0.05) in AUC. There was no effect of alcohol on elimination half-life. The combination of ethanol and indoramin was more sedative than indoramin alone. 3. Ethanol did not alter the pharmacokinetics of an intravenous dose of indoramin. However indoramin caused a small but statistically significant increase (26%) in blood ethanol concentrations during the first 1.25 h after dosing. Both indoramin and ethanol caused sedation. 4. The increased bioavailability of oral indoramin in the presence of ethanol may reflect some enhanced absorption, but it is also consistent with inhibition of first-pass metabolism of a flow-limited drug. The clinical implications are discussed.
Administration, Oral↗
Is there a central nervous withdrawal syndrome associated with discontinuing long-term treatment with propranolol?
Thirty healthy volunteers were treated with beta-adrenoceptor blocking doses of long-acting propranolol for at least 28 days before being randomized to continue propranolol treatment, receive identical placebo under double-blind conditions, or discontinue all treatment. No evidence of a central nervous withdrawal syndrome occurred during the next 28 days as assessed by changes in psychomotor tests, rating scales, visual analogue scales, tremor recordings and melatonin excretion. Three subjects in the placebo withdrawal group but none in the propranolol group complained of insomnia for up to 14 days of the withdrawal period.
Adult↗
A study of the interaction between oxytetracycline and pyridostigmine.
1. Oxytetracycline and pyridostigmine were given alone and in combination for 4 days to 12 normal male volunteers in a double-blind, randomised cross-over study. On the fifth day, the pharmacokinetic profiles of the two drugs were examined, and blood and plasma cholinesterase activity was measured. 2. No significant interaction on absorption or pharmacokinetics of either drugs was detected when they were given in combination. 3. There was a small but statistically significant increase in erythrocyte cholinesterase when oxytetracycline was given in combination with pyridostigmine, the pharmacological significance of which is not clear.
Adult↗
Flupirtine maleate and antipyrine half-life.
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Adult↗
Comparison of effects of lysine aspirin, soluble aspirin and conventional aspirin on buccal potential difference in healthy volunteer subjects.
The effects of aspirin, soluble aspirin and lysine aspirin on buccal mucosal potential difference (p.d.) were compared in a double-blind trial. Placebo and three doses of each preparation containing 150, 300 and 600 mg of aspirin were allocated according to a latin square design. Six volunteer subjects were studied; each received a total of 10 treatments at least 24 h apart. All doses of each preparation considered, a significant treatment effect was seen [F (d.f. = 2,306) = 6.2, P less than 0.003]. Lysine aspirin showed the least effect of the active treatments on buccal p.d. with a change from baseline of +8.5 mV compared with +13.3 for soluble aspirin +14.4 for conventional aspirin and -5.2 mV for placebo.
Aspirin↗
Effect of a hydantoin prostaglandin analogue, BW245C, during oral dosing in man.
Following an open pilot study, the effects of repeated oral doses of BW245C, a hydantoin prostaglandin analogue, were studied in man. Six healthy volunteers received 150 micrograms BW245C or placebo 6-hourly for 5 days according to a double blind randomised balanced design with 7 days interval between treatments. Measurements of headache, facial flushing, heart rate, blood pressure, systolic time intervals, ECG, platelet aggregation responses to ADP and of subjective effects were made before and 1 and 3 h after the first dose of BW245C/placebo on days 1, 3 and 5 of dosing. BW245C produced significantly (p less than 0.05) higher headache scores than placebo on days 3 and 5; facial flushing, nasal stuffiness and abdominal discomfort were more frequent on BW245C than placebo. Heart rate, derived from the ECG, was significantly (p less than 0.05) higher and pre-ejection period significantly (p less than 0.05) shorter on BW245C at 1 h after dosing on each day. Left ventricular ejection time index, QS2 index, PR interval, QRS duration and T wave height were unchanged. Heart rate, counted at the radial pulse, and systolic and diastolic blood pressure, all measured lying and standing, were similar for BW245C and placebo. Platelet aggregation responses were not significantly different between the two treatments. The results indicate that repeated oral doses of BW245C, sufficient to cause moderately uncomfortable subjective effects, do not inhibit platelet aggregation.
Adenosine Diphosphate↗
The use of intravenous meptazinol for analgesia in colonoscopy.
A double blind study comparing intravenous pethidine and meptazinol has been performed to establish the efficacy and safety of meptazinol as an analgesic agent in colonoscopy. Twenty two patients received pethidine and 23 patients received meptazinol and no difference in analgesic effect or sedative effect could be demonstrated either by observer or patient assessment using a visual analogue scale. A group of 10 patients in the pethidine group and 9 in the meptazinol group had continuous recording of electrocardiogram, pulse rate and blood pressure throughout the procedure. Significant falls in both systolic and diastolic blood pressure were recorded in the pethidine group but not the meptazinol group. Benign cardiac arrhythmias were recorded in both groups before and after the administration of premedicant drug and 1 patient in each group had transient ST depression. Side effects were recorded with equal frequency in each group except for vomiting which occurred in 5 of 23 meptazinol patients but none of the pethidine patients. Meptazinol is an effective analgesic drug in colonoscopy which produces less cardiovascular depression than pethidine and thus may be useful in selected patients especially the elderly or those with known cardiovascular disease.
Azepines↗
A comparative study of the relative enzyme inducing properties of anticonvulsant drugs in epileptic patients.
The antipyrine clearance and the urinary excretion of D-glucaric acid (D-GA) were determined in 122 patients receiving chronic anticonvulsant drug treatment and in 21 drug-free control subjects. Patients treated with carbamazepine (CBZ), phenytoin (DPH), primidone (PMD) and phenobarbitone (PB), either alone or in combination, showed higher values of antipyrine clearance and excreted larger amounts of D-GA as compared to controls. While antipyrine clearance values did not differ significantly from one drug group to another, D-GA excretion was significantly higher in patients treated with CBZ than in those treated with DPH. In patients treated with sodium valproate antipyrine clearance did not differ from control values. There was a trend for D-GA excretion to be higher in these patients but the difference was not statistically significant. Significant positive correlations were found between the dosage of CBZ, DPH, PMD and PB and both indices of enzyme induction. These data demonstrate a dose-dependent degree of enzyme induction in patients receiving therapeutic doses of these anticonvulsants. The relative potency at average dose levels for antipyrine clearance was PB (1), DPH (0.92), CBZ (0.84), PMD (0.82) and for log D-GA excretion was PB (1), CBZ (0.96), PMD (0.95), DPH (0.90).
Anticonvulsants↗
A chemically stable analogue, 9 beta-methyl carbacyclin, with similar effects to epoprostenol (prostacyclin, PGI2) in man.
The effects of 9 beta-methyl carbacyclin, a chemically stable analogue of epoprostenol (prostacyclin, PGI2) were studied, in comparison with epoprostenol, both in vitro and in vivo in man. In vitro 9 beta-methyl carbacyclin and epoprostenol inhibited platelet aggregation induced by ADP, collagen, the endoperoxide analogue U46619 and arachidonic acid. The potency of 9 beta-methyl carbacyclin relative to epoprostenol was comparable in ADP and collagen-aggregated platelet rich plasma (PRP), 9 beta-methyl carbacyclin being 0.01 times as active as epoprostenol. The anti-aggregatory potencies of the two compounds were comparable in PRP and whole blood. The phosphodiesterase inhibitor isobutyl methyl xanthine enhanced the anti-aggregatory activity of both compounds in vitro. 9 beta-methyl carbacyclin and epoprostenol elevated platelet cyclic AMP, 9 beta-methyl carbacyclin being 0.04 times as active as epoprostenol. In a placebo controlled trial both drugs produces significant headache and facial flushing when compared with placebo. Nasal stuffiness, abdominal discomfort and nausea were reported on all three treatments. Both drugs caused significant and comparable increase in heart rate and decrease in pre-ejection (PEP) and PEP/left ventricular ejection time (LVET) ratio compared with placebo. Systolic and diastolic blood pressure, LVET and QS2 index were unchanged. Platelet aggregation responses to ADP were significantly inhibited by all three doses of both drugs compared with placebo. Bleeding time was significantly longer during epoprostenol infusion than either placebo or 9 beta-methyl carbacyclin infusion. Neither drug had significant effect, compared with placebo, on kaolin activated clotting time in PPP, PRP or in PRP in the presence of heparin, prothrombin time, partial thromboplastin time, thrombin clotting time, fibrinogen, fibrinogen degradation products or euglobulin clot lysis time. The pharmacodynamic effects and duration of action of 9 beta-methyl carbacyclin and of epoprostenol are similar; 9 beta-methyl carbacyclin is approximately 100 times less potent than epoprostenol in man.
1-Methyl-3-isobutylxanthine↗
The effects of cimetidine and ranitidine on psychomotor function in healthy volunteers.
Single oral doses of cimetidine (400 mg), ranitidine (150 mg), promethazine (25 mg) or placebo were administered to 8 healthy volunteers in a double-blind study. Cimetidine and ranitidine did not cause any significant change in critical flicker frequency (c.f.f.), reaction time, pursuit rotor of the visual analogue scale scores for sedation. Promethazine significantly lowered c.f.f., prolonged reaction time and increased sedation when compared with placebo. It is concluded that in this study cimetidine and ranitidine had little, if any, effect on psychomotor function.
Adult↗
Dipyridamole increases red cell deformability.
The effects of dipyridamole on red cell filterability both in vitro and ex vivo were measured. In a balanced, randomised and double-blind trial, six healthy male and female volunteers (22-37 years) were given dipyridamole 400 mg/day or matching placebo in four divided doses for 3 days, and heparinised venous blood samples were taken 1 h after the ingestion of the last dose. Filterability of red cells was increased significantly (P less than 0.05 paired t-test) when the subjects were on dipyridamole compared with placebo. In separate experiments, 15 min incubation with 2 or 20 micrograms/ml dipyridamole in vitro was found to have no effect on the filterability of freshly prepared red cell suspensions. After 24 h storage at 4 degrees C, the filterability of red cells was significantly decreased (P less than 0.01) and this could be partially prevented by adding dipyridamole to the stored cells (P less than 0.05). These results suggest that dipyridamole has an effect on the behaviour of the red cell membrane to increase the deformability of the cells. This may contribute to its therapeutic effect.
Adult↗
The pharmacokinetics of lysine theophylline, a new soluble theophylline, in human volunteers.
A comparative study of the pharmacokinetics of lysine theophylline and aminophylline in normal subjects reveals no significant difference. If lysine theophylline is shown to have the same clinical efficacy as aminophylline, the hypersensitivity reactions associated with the latter could be avoided.
Adult↗
The use of intramuscular meptazinol in the relief of post-operative pain after abdominal hysterectomy--a review.
In previously published studies of post-abdominal hysterectomy pain control reviewed here, meptazinol in doses of 50, 75 and 100 mg intramuscularly (i.m.) caused significant dose-related pain relief. Meptazinol 100 mg i.m. was equipotent as an analgesic when compared with either Omnopon 20 mg i.m., pentazocine 60 mg i.m. or pethidine 100 mg i.m. Meptazinol in doses of 60, 75 and 100 mg i.m. was not significantly different from pethidine 100 mg in relieving pain when assessed by the pain relief score.
Azepines↗