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Biomedical subjects

I Livingstone

Publications and source records attributed to I Livingstone.

10 recordsLinked to original sources
PubMed2004

A randomised comparison of oral misoprostol and vaginal prostaglandin E2 tablets in labour induction at term.

OBJECTIVE: To compare the efficacy of 100 microg of oral misoprostol with 3 mg prostaglandin E2 vaginal tablets in term labour induction. DESIGN: A non-blinded, randomised, controlled trial. SETTING: A tertiary level, teaching Scottish Hospital. POPULATION: Two hundred women at term with indications for labour induction and modified Bishop's cervical score of less than 8. METHODS: The women were randomly allocated to receive either 100 microg of misoprostol orally (which could be repeated 4 hourly to a maximum of five doses if indicated), or a 3 mg tablet of prostaglandin E2 vaginally (which could be repeated in 6 hours, according to routine departmental protocol). MAIN OUTCOME MEASURE: The number delivering vaginally within 24 hours of the induction. RESULTS: Seventy-five women delivered vaginally in the misoprostol group and 73 in the PGE2 group. Of these, 50.7% in the misoprostol group and 54.8% in the PGE2 group delivered within 24 hours of the induction (RR 0.92, 95% CI 0.7 to 1.3). More women in the misoprostol group were given oxytocin, but this was not statistically significant (60%vs 47%, RR 1.3, 95% CI 0.98 to 1.7). Two women in the misoprostol group had uterine hyperstimulation. The neonatal outcomes were not significantly different in the two groups. There was a pound 1100 saving on direct drug costs in the misoprostol group. CONCLUSIONS: Oral misoprostol (100 microg) has similar efficacy to vaginal PGE2 tablets, and may be an option to consider for term labour induction.

Administration, Intravaginal↗
PubMed1984

Bioavailability and pharmacokinetics of phenytoin during pregnancy.

Five epileptic women needing to commence phenytoin therapy during pregnancy received a single intravenous and a single oral dose of phenytoin several days apart before starting regular intake of the drug. Plasma phenytoin concentration - time data were analysed by three different pharmacokinetic techniques. However assessed, the mean oral bioavailability of the drug proved to be about 90% of the intravenous bioavailability. This finding makes it unlikely that impaired bioavailability accounts for the increase in oral phenytoin dosage necessary in pregnancy to maintain plasma phenytoin concentrations at pre-pregnancy values. Phenytoin clearance in the pregnant subjects was approximately double the published values for phenytoin clearance in non-pregnant persons. This suggests that increased (metabolic) clearance accounts for the increased phenytoin dosage requirement of pregnancy.

Aging↗
PubMed1983

Chronic propranolol administration during pregnancy. Maternal pharmacokinetics.

The pharmacokinetics of propranolol (P) and its major metabolites, propranolol glucuronide (PGLUC), 4-hydroxypropranolol (4OHP), 4-hydroxypropranolol glucuronide (4OHPGLUC) and naphthoxylactic acid (NLA), (Walle et al. 1972) were determined, whenever possible, in the first, second and third trimesters of pregnancy in thirteen patients and also when these patients were at least three months post-partum. No correlations were found between the mean arterial blood pressure (post-therapy) or the fall in blood pressure as a result of the P therapy (p much greater than 0.05) and P dose, peak P plasma concentrations, peak 4-hydroxypropranolol (4OHP) plasma concentrations or peak (P plus 4OHP) plasma concentrations. However, a positive nonlinear relationship was found between the daily P dose (independent variable) and peak P plasma concentrations over the daily dose range 30-160 mg/day. The elimination half-lives of NLA for patients in the third trimester of pregnancy were significantly shorter (p = 0.072, df = 13) than those when the patients were at least three months post-partum. Also, the areas under the plasma level-time curves of NLA were significantly less (p less than 0.05, df = 13) for patients in the third trimester of pregnancy than when these patients were at least three months post-partum. The results of this study indicate that the pharmacokinetics of P, PGLUC, 4OHP and 4OHPGLUC are not significantly altered by pregnancy. However, the kinetics of NLA do appear to be altered. The formation of NLA by N-dealkylation of P and further oxidation, appears to be competitively inhibited by unidentified substances, perhaps endogenous steroids, especially in the third trimester when compared to at least three months post-partum.

Adult↗
PubMed1983

Metabolism of propranolol in the human maternal-placental-foetal unit.

Propranolol (P) and all of its major known metabolites were found in maternal plasma, cord plasma and neonatal plasma in 10 women at term, irrespective of the P doses administered and the time elapsed (up to 15 h) between administration of the last P dose and delivery. The ratios of cord plasma to simultaneous maternal plasma levels for propranolol and its major metabolites (mean +/- SD) were: propranolol 0.32 +/- 0.17, propranolol glucuronide 0.86 +/- 0.36, 4-hydroxypropranolol 1.4 +/- 1.0, 4-hydroxypropranolol glucuronide 0.71 +/- 0.45 and naphthoxylactic acid 3.0 +/- 1.6. P binding in cord plasma at delivery was 67.2 +/- 3.9% (mean +/- SD) which was significantly less ('t' = 13.4, df = 13, p less than 0.001) than the P binding in maternal plasma at delivery (87.5 +/- 1.6%, mean +/- SD). The plasma protein binding (mean +/- SD) of naphthoxylactic acid in cord plasma (98.6 +/- 0.2%) was significantly greater ('t' = 3.808, df = 4, p less than 0.02) than the naphthoxylactic acid binding in maternal plasma at delivery (97.6 +/- 0.4%). When the simultaneous concentrations of P and naphthoxylactic acid in maternal and cord plasma are compared in conjunction with protein binding and ionic effects, it would seem that metabolism of P does occur in the placental/foetal unit.

Blood Proteins↗
PubMed1983

Propranolol, propranolol glucuronide, and naphthoxylactic acid in breast milk and plasma.

High-performance liquid chromatographic assays for propranolol and its major metabolites in plasma and breast milk are described. The breast milk/whole plasma ratios of propranolol in three lactating women were in the range of 0.33 to 1.65. The half-life of elimination of propranolol from breast milk was 6.5 +/- 3.4 h (mean +/- SD), which was significantly longer (t = 1.844, df = 4, p less than 0.01) than the half-life of elimination of propranolol from plasma, which was 2.6 +/- 1.2 h (mean +/- SD). The half-life of elimination of the propranolol metabolite naphthoxylactic acid from breast milk was 4.2 +/- 0.9 h (mean +/- SD), which was not significantly different (t = 0.042, df = 4, p greater than 0.05) from the mean half-life of elimination from plasma, which was 4.2 +/- 1.2 h (mean +/- SD). The penetration of propranolol glucuronide into breast milk was slower and to a lesser extent than that of propranolol and naphthoxylactic acid. The maximum dose, calculated from the results presented in this paper, ingested as either propranolol or as propranolol glucuronide in breast milk by the neonate would be less than 0.1% of the maternal dose.

Female↗
PubMed1983

Propranolol in pregnancy three year prospective study.

We compared propranolol with methyldopa in a randomized prospective study of 28 women with pregnancy associated hypertension. Both drugs were equally effective in controlling maternal hypertension. There was no significant difference in the birthweights of the babies in each group. However one infant born to a mother receiving propranolol had symptomatic hypoglycaemia. The mean peak levels of propranolol, propranolol glucuronide, 4-hydroxypropranolol, and 4-hydroxypropranolol glucuronide were not significantly different in the first, second, third trimesters and at least 3 months post partum. The mean peak plasma level of naphthoxylactic acid however was significantly less in the third trimester compared with post partum levels. Propranolol and its metabolites were found to cross into breast milk with the maximum dose likely to be ingested by the infant as either propranolol or propranolol glucuronide being 7 micrograms of propranolol per 100 g of breast milk, being approximately 0.1% of the maternal dose.

Blood Pressure↗
PubMed1981

The clearance of anticonvulsant drugs in pregnancy.

30 epileptic patients taking one or more of the anticonvulsants phenytoin, carbamazepine, phenobarbitone, methylphenobarbitone and ethosuximide have been studied during the courses of 34 pregnancies. In all cases the drug dosage requirement to maintain therapeutic range plasma anticonvulsant levels increased during pregnancy and fell again during the puerperium. Calculated plasma drug clearances showed a marked increase during pregnancy, reaching a peak in the third trimester, and declined again in the 3 months following pregnancy to pre-pregnancy values. For the more extensively used drugs the mean ratios of the plasma clearances in the third trimester to those in the pre- or post-pregnancy state were phenytoin 2.5:1 (p less than .001), carbamazepine 1.9:1 (p less than .005), phenobarbitone 1.6:1 (p less than .001). The limitations of the plasma clearance approach for phenytoin, a drug which is eliminated largely by Michaelis-Menten kinetic mechanisms, are discussed.

Adult↗
PubMed1979

Acute intoxication with sodium valproate.

Two epileptic patients developed an acute toxic encephalopathy consisting of altered behavior, deteriorating seizure control, and confusion while taking sodium valproate alone. Serum valproate levels were greater than 100 microgram/ml in both. Toxic symptoms resolved when the dose of valproate was reduced, with a consequent fall in serum concentration of the drug.

Acute Disease↗
PubMedDate not supplied

Effects of dexamethasone on fibre subtypes in rat muscle.

The extent to which dexamethasone treatment produced atrophy of fast-twitch (EDL) and slow-twitch (SOL) muscles in rat was investigated. The mean weight of steroid-treated EDL muscles was decreased as compared to normal, whereas SOL muscles from normal and dexamethasone-treated animals showed no significant difference. Muscle fibre diameters also showed comparatively minor changes in SOL, which consists of Type 1 (slow oxidative) and Type 2A (fast oxidative/glycolytic) fibres. Rat EDL contains, in addition to Type 1 and Type 2A fibres, two sub-populations of fast glycolytic fibres (Types 2B and 2B'). These fibre types showed the most severe degree of atrophy both after dexamethasone treatment and after denervation. The mean ratio of the weights of denervated to innervated EDL muscles was lower in steroid-treated rats than in normal animals suggesting that the atrophy produced by steroid treatment in conjunction with denervation was more than simply additive. Analysis of the proportions of histochemical fibre types in SOL and EDL showed that dexamethasone treatment produced no major alterations in the fibre type constitution of these muscles. However, further histochemical studies showed that there was relatively severe impairment of myophosphorylase activity in Type 2B' (fast glycolytic) fibres as compared to other fibre types; conversely Type 1 fibres frequently contained increased myophosphorylase. Levels of beta-hydroxybutyrate dehydrogenase were low in both normal and steroid-treated EDL but high in SOL which also showed higher general oxidative activity. It is suggested that the particular susceptibility of fast glycolytic fibres to atrophy as a result of steroid treatment may be linked to: 1 the relatively severe reduction of myophosphorylase activity in these fibres and 2 their comparative inability to utilize alternative energy sources, especially substrates derived from free fatty acids.

Adenosine Triphosphatases↗