摘要:

Abstract.Pharmacokinetic studies on the concentration of the beta1‐blocker metoprolol have been performed in maternal plasma, amniotic fluid, breast milk and the plasma of the newborn. The concentration of metoprolol in maternal plasma exceeded that in the amniotic fluid intially, but not later on. The quotient between the metoprolol concentration in the maternal venous blood and the mixed cord blood at the time of parturition is at about 1. In the maternal plasma the metoprolol concentration decreases rapidly after the latest dose, probably because of an increased clearance rate. Blood levels of metoprolol during the first postnatal hours increase almost fourfold and are generally followed by a decrease over the next 15 hours. Active metabolites of metoprolol (alfa‐OH‐metoprolol and O‐demethyl‐metoprolol) are found in the urine of the newborn. The breast milk concentration of metoprolol is three times as high as in the maternal plasma but the suckling newborn will only show very low or unmeasurable plasma levels between consecutive breast feeding periods, in the majority

ISSN:0001-6349    

DOI:10.3109/00016348409157125

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract.The transfer of atenolol and metoprolol to human breast milk was studied in 7 lactating women with hypertension. Concentrations of atenolol and metoprolol in maternal plasma and milk and in plasma of the nursed infants were determined. Blood samples were obtained from the women and from the infants during a dose interval. Milk was collected repeatedly from the left breast but only twice from the right breast. The ratio between the area under the milk concentration versus time curve (AUCm) and the area under the plasma concentration versus time curve (AUCp) in the mother varied between 2.0 and 3.1 for metoprolol and 1.1 and 3.1 for atenolol. The milk concentrations of metoprolol in the right breast were similar to those in the left breast, although the latter had been emptied more frequently. For atenolol the milk concentrations in the right breast were lower than in the left breast. The plasma concentrations of metoprolol and atenolol in the infants were negligible or below the limit of detection. Our results show that exposure of the infant to metoprolol can be minimized if nursing is not undertaken earlier than 3‐4 hours after dose intak

ISSN:0001-6349    

DOI:10.3109/00016348409157126

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract.Plasma levels of labetalol were measured in 7 hypertensive pregnant women who were given 200 mg three times daily orally. The plasma concentrations were usually lower than those reported in the non‐pregnant state at a comparative dose. In 5 women the ratio between fetal and maternal plasma labetalol concentrations could be calculated at parturition. The median value of this quotient was about 50%. The effect of labetalol 1 mg/kg body weight intravenously was registered with functional placental scintigraphy. Fifteen women participated. A computer‐linked gamma camera above the uterus registered the radioactivity in the placental region after two intravenous bolus injections of 18.5 MBq indium‐113m chloride. From the radioactivity uptake curves, uteroplacental blood flow indices could be calculated before and 30 minutes after the labetalol injection. Despite a significant reduction in maternal blood pressure, no change in uteroplacental blood flow index was found. This could indicate that the vascular resistance in the maternal placental circulation was reduced by labe

ISSN:0001-6349    

DOI:10.3109/00016348409157127

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract.Maternal and fetal β1‐adrenoceptor blockade was induced in sheep by infusing i.v. 11 pregnant ewes with metoprolol in doses producing maternal plasma concentrations of metoprolol comparable to those obtained in clinical use. Ten other ewes and their fetuses served as controls. Under acute anaesthesia the fetus was exteriorized and subjected to two levels of controlled asphyxia by intermittent, complete obstruction of the maternal placental blood flow. Fetal haemodynamic reactions were assessed by measuring fetal heart rate, cardiac contractility, cardiac output and cerebral blood flow. The metabolic reactions were evaluated from blood gases, pH, lactate and hypoxanthine concentrations, while the electrophysiological status of the brain was evaluated from the somatosensory evoked EEG potentials (SEP). Already during the period of moderate asphyxia the P‐blocked fetuses demonstrated a blunted haemodynamic response, in comparison with the control fetuses, resulting in an accelerating lactic acidosis, signs of a breakdown of intra‐cellular energy‐rich phosphates and an impaired cerebral function. During the period of severe asphyxia, both groups of fetuses exhibited signs of extensive cerebral deterioration. During the ensuing recovery phase, 80% of the control fetuses regained their brain function, as assessed by SEP, whereas this was true for only 30% of the β1‐blocked fetuses. It is concluded that the ovine fetus relies heavily on greatly increased sympathoadrenal activity to adapt itself to asphyxia and that blockade of the fetal β1‐adrenoreceptors by maternal medication is a hazard to the potentially a

ISSN:0001-6349    

DOI:10.3109/00016348409157128

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract.It is generally accepted that hypertensive cardiovascular complications can be prevented by treatment. However, during pregnancy, antihypertensive drugs might be hazardous in view of their influence on the fetus. Nevertheless, in spite of the diverging published results, even β‐blockers have been used in the pregnant patient. As our basic knowledge concerning the circulatory and fetal effects is minimal, we decided to elucidate the influence of the non‐selective β‐blocker, propranolol, on the haemodynamic circumstances in hypertensive pregnant rats. Renal hypertension was induced by clamping both renal arteries 4 weeks before pregnancy. Shortly before term, cardiac output was determined with the dye‐dilution technique and utero‐placental blood flow was determined with the microsphere technique, both before and after propranolol injection. Mean arterial pressure and heart rate were registered continuously. The acute propranolol injection reduced mean arterial pressure by 26%. This was due mainly to a 32% decrease in cardiac output, which in turn was due to a 24% decrease in stroke volume and a 6% decrease in heart rate. Both myometrial and placental blood flow decreased significantly, by 45 and 50%, respectively. It was furthermore of interest to observe the significant increase in blood flow resistance in both myometrium and placenta.In conclusion, it can be stated that the non‐selective β‐blocker propranolol, which lacks intrinsic stimulating activity, reduces mean arterial pressure mainly by a cardiac output decrease. The present results further indicate that the influence on peripheral blood flow might be caused by cardiac output changes as well as by direct effects on the utero‐plac

ISSN:0001-6349    

DOI:10.3109/00016348409157129

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract.Clinical as well as experimental studies have demonstrated a 70% reduction in utero‐placental blood flow in pregnancies affected by Severe hypertension (13, 19). In pregnant renal hypertensive rats, propranolol administration causes a further 50% reduction in utero‐placental blood flow (16). The present study on renal hypertensive rats was performed in order to explore the acute effects on central haemodynamics and utero‐placental blood flow of the non‐selective P‐blocker pindolol, which also has an intrinsic P‐stimulatory effect. Renal hypertension was induced by partial clamping of both renal arteries in female Wistar rats 4 weeks before pregnancy. Some 2‐4 days before expected parturition, cardiac output was determined with the dye‐dilution technique and blood flow to the reproductive organs with the microsphere technique, both before and after acute pindolol administration. Mean arterial pressure and heart rate were recorded continuously during the experiment. After pindolol injection, mean arterial pressure fell by 22% due to a 38% reduction in total peripheral resistance. No significant changes in cardiac output, stroke volume or heart rate were found. Placental blood flow was significantly reduced, by 30%, whereas myometrial and ovarian blood flows were reduced by only 18 and 9%, respectively.Thus, the reduction in blood supply to the reproductive organs in renal hypertensive rats after acute pindolol administration was most pronounced in the placenta. This reduction in placental flow was, however, only about half as pronounced as after propranolol, which lacks intrinsic β‐stimulatory effects. This may suggest that vasodilating β‐receptors may play an important role in the maternal p

ISSN:0001-6349    

DOI:10.3109/00016348409157130

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract.A review is presented as regards the neonatal effects of beta‐blocking agents in hypertension during pregnancy. Experience points to low fetal and neonatal risks, but firmly based data concerning the neonates are very scanty. An on‐going double‐blind study is presented in which pregnant women with hypertension are randomly allocated to either metoprolol or placebo treatment. One of the aims is to study the postnatal adaptation of the infants. The following measurements, recordings and examinations are performed: anthropometric measurements, Apgar score, blood gases and acid‐base status in umbilical (venous and arterial) blood, lactate and hypoxanthine in umbilical venous blood, catecholamines in umbilical arterial blood, pulse rate, blood glucose and a quantitative neurobehavioral assessment in the neonatal

ISSN:0001-6349    

DOI:10.3109/00016348409157131

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract.The effects of two different β‐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

ISSN:0001-6349    

DOI:10.3109/00016348409157132

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract.Forty term patients with pregnancy‐induced hypertension were treated with the β1‐adrenoceptor blocker atenolol (TenorminR; ICI) for at least 7 days prior to parturition. The antenatal cardiotocography (CTG) was visually analysed before and during treatment. The mean basal fetal heart rate (FHR) decreased from 143±7 beats per minute (bpm) to 13328 bpm. In 13.1% of the recordings in treated patients there was a decrease in long‐term variability for a period of more than 20 minutes; this was observed in only 2.3% prior to treatment. The amplitude of the accelerations was reduced from 23±6 bpm to 18±4 bpm. It was demonstrated that atenolol affected antenatal CTG, and this has to be taken into consideration when interpreting antenatal CTG as one parameter for evaluation of fetal w

ISSN:0001-6349    

DOI:10.3109/00016348409157133

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

Abstract.A one‐year population comprising 119 infants of 113 mothers with hypertension in pregnancy has been studied regarding fetal and neonatal mortality and morbidity. The overall incidence of hypertension in pregnancy was 3.7%, but was higher in preterm deliveries (from 16.6% in gestational weeks 25‐29 to 8.6% in gestational weeks 34‐36). Fetal loss with intra‐uterine death was related to hypertension in pregnancy in 23%.Auxological parameters in 16 SGA infants of hypertensive parturients showed growth recovery in all infants as regards head circumference and in all but 2 as regards body weight and body length.A controlled follow‐up study was performed in 104 infants of hypertensive mothers and 104 control infants of similar gestational age and birthweight but without pregnancy complications. There was a significantly higher rate of cesarean section, of low Apgar score at 1 minute, and SGA infants and neonatal morbidity requiring admittance to the neonatal intensive care unit. At 2 years of age the rate of neurodevelopmental handicaps was similar in the study population and in control infants. Stillborn infants all belonged to the group of mothers with hypertension starting before the 21st gestational week and with an increased serum urate level. Three of 4 infants with a handicap at 2 years also belonged to this group of mothers. With modern peri‐and neontal intensive care and appropriate fetal assessment, delivery after 26‐28 weeks of gestation seems to be associated with a slightly increased neonatal morbidity but no increase in long‐term handicaps at

ISSN:0001-6349    

DOI:10.3109/00016348409157134

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY