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PubMed1959

The biological activity of a new analogue of oxytocin in which the tyrosyl group is replaced by phenylalanyl.

A new synthetic analogue of oxytocin with a phenylalanyl group instead of a tyrosyl group has been investigated. The most prominent biological properties of this peptide were its oxytocic activity on the rat or cat uterus in vivo and on milk-ejection pressure in the rabbit. Another remarkable feature was the striking difference in pressor activity measured in spinal cats and in anaesthetized rats. The presence of the phenylalanyl group in the molecule in the above-mentioned position did not increase the antidiuretic potency in unanaesthetized rats. The authors propose a nomenclature for the peptides related to oxytocin and vasopressin.

Animals↗
PubMed1964

QUANTITATIVE COMPARISON BETWEEN OXYTOCIN AND FOUR RELATED NEUROHYPOPSIAL PEPTIDES ON THE HUMAN UTERUS IN SITU.

Quantitative assays of four synthetic peptides related to oxytocin were carried out on the post partum human uterus in vivo by means of external tocography. The following activities (U/mg, means and standard errors) were found: isoleucine(8)-oxytocin 365+/-70, asparagine(4)-oxytocin 150+/-40, desamino(1)-oxytocin 1,030+/-300, serine(4)-isoleucine(8)-oxytocin 335+/-95. None of the conventional bioassay procedures proved to be fully reliable for predicting the oxytocic activity in man of peptides related to oxytocin. If the tocographically recorded effects of equipotent doses of the compounds are compared with those of oxytocin no qualitative differences can be observed.

Asparagine↗
PubMed1990

Does cord drainage of placental blood facilitate delivery of the placenta?

A series of 1,908 women delivering vaginally, and actively managed in stage 3 of labour, were randomly assigned to 2 groups to study if cord drainage of placental blood facilitated delivery of the placenta. Prophylactic oxytocics were given with the birth of the anterior shoulder. In both groups, early cord clamping was practised, timing being at the midwives' discretion. In the control group the cord remained clamped; in the drainage group the cord was unclamped and the volume of placental blood measured. Controlled cord traction completed active management at evidence of separation/descent of the placenta. Rates for retained placenta, postpartum haemorrhage and transfusion were similar. It was concluded that when the third stage of labour is actively managed, placental drainage of cord blood confers no extra benefits. Pre- and post-delivery Kleihauer tests were performed on blood from 20 women in each group. All tests were negative. Contrary to previous work, this does not suggest that cord drainage reduces the fetomaternal transfusion rate. The well known association of prolonged duration of stage 3 of labour and the risk of haemorrhage was strongly confirmed.

Drainage↗
PubMed1976

Kallikreinlike activity in perfusates and urine of isolated rat kidneys.

In the perfusate and the urine produced during perfusion of isolated rat kidneys a kallikreinlike enzyme similar to that found in the kidney was detectable by bioassay 15-25 min after the beginning of the perfusion. The source of the kallikrein activity was the kidney itself, since before the perfusion was started the blood remaining in the kidneys was washed out and the perfusion medium was free of kallikrein and its precursors and substrates. The kallikreinlike activity of the perfusate was characterized by a) an oxytocic effect on isolated rat uterus, b) a kininogenase activity on kininogen II, c) an esterase activity on N-benozyl-L-arginine ethyl ester, and d) a hypotensive effect on anethetized rats. These properties were inhibited by diisopropyl activity in the perfused kidney was lower than that in the nonperfused organ, but the total amount of kallikrein activity released to the excreted urine and the perfusate was significantly greater than the corresponding activity that disappeared in the kidney. This result is in keeping with the concept that the renal tissue is able to synthesize kallikrein.

Animals↗
PubMed2006

A double-blind randomized controlled trial of oral misoprostol and intramuscular syntometrine in the management of the third stage of labor.

BACKGROUND: The aim of this study was to compare the efficacy and safety of oral misoprostol 400 mug with intramuscular syntometrine in the management of the third stage of labor. MATERIAL AND METHODS: This was a double-blind randomized controlled trial conducted in a tertiary care hospital. Three hundred and fifty-five women randomized to receive either oral misoprostol 400 mug or intramuscular syntometrine in the third stage of labor were studied. The change in hemoglobin level from before to 48 h after delivery, use of additional oxytocics and treatment related side effects were the main outcome measures. RESULTS: There were no significant differences between the two groups in terms of the change in hemoglobin level and mean blood loss. The incidence of shivering was significantly higher in the misoprostol group whilst that of vomiting was significantly higher in the syntometrine group. There were no differences in the incidence of nausea, headache, diarrhea and pyrexia between the two groups. CONCLUSION: Orally administered misoprostol at a dose of 400 mug is an acceptable alternative in preventing post-partum blood loss, as measured by the peri-partum change in hemoglobin level and was not associated with an increased incidence of side effects.

Administration, Oral↗
PubMed1978

Historical view on ergot alkaloids.

A short survey of the history of ergot, of the original and, for a long time, only source of ergot alkaloids, is given. Once a dreaded poison, ergot has changed its role over the centuries to become a rich treasure house of valuable pharmaceuticals. In the Middle Ages it was the cause of epidemics of ergotism, which cost tens of thousands of people their lives. Ergot was first mentioned by the German physician Lonitzer in 1582 as a remedy used by midwives for quickening childbirth. The isolation of pharmacologically useful alkaloids started in 1906 with the discovery of ergotoxine and its adrenolytic activity by Barger, Carr and Dale. In 1918, Stoll isolated ergotamine, the first chemically pure ergot alkaloid, which found widespread therapeutic use in obstetrics and internal medicine. In 1935 the specific oxytocic principle of ergot, ergonovine, was discovered simultaneously in four separate laboratories. Since then, worldwide investigations on ergot alkaloids resulted in the elucidation of their structures and total syntheses and preparation of valuable therapeutics such as Methergine, Hydergine, Dihydergot, and others.

Chemistry↗
PubMed1990

Induction of labor in intrauterine fetal death with 16-phenoxy-prostaglandin-E2-methylsulfonylamide (sulprostone)--effects on uterine contractility, coagulation and kallikrein-kinin systems.

Thirty-two patients with intrauterine fetal death after the 20th week of pregnancy were treated with 1-3 intramuscular injections of 500 mg of 16-phenoxy-PGE2-methylsulfonylamide (sulprostone). Intrauterine pressure records demonstrated onset of contractions within 20 min of injection and all women aborted-delivered after in mean 11 h (4-31 h). No effect on routine hematologic and plasma parameters, kallikrein-kinin and factor XII systems was observed. It is concluded that 16-phenoxy-PGE2-methylsulfonylamide is an effective and safe oxytocic agent for the induction of labor in case of intrauterine fetal death with minimal effects on the coagulation system.

Adult↗
PubMed1988

Changes in plasma cyclic AMP and cyclic GMP during spontaneous labor and labor induced by oxytocin, prostaglandin F2 alpha and prostaglandin E2.

To investigate the response of cyclic nucleotides to the oxytocic agents administered for induction of labor, plasma concentrations of cyclic AMP (cAMP) and cyclic GMP (cGMP) were determined by radioimmunoassay during spontaneous labor and labor induced by oxytocin (OT), prostaglandin F2 alpha (PGF2 alpha), or PGE2 (PGE2). Subjects were 7 Japanese women in each labor group. Plasma cAMP levels significantly rose at the time of crowning of the fetal head in all 4 groups. They did not increase until that time in the 3 labor groups (spontaneous, OT-induced, and PGF2 alpha-induced labor groups). In the PGE2-induced labor group, plasma cAMP levels were significantly higher at labor onset (mean +/- SEM = 16.5 +/- 1.3 pg/ml) when compared to the pretreatment values (13.7 +/- 1.0 pg/ml), and increased thereafter gradually toward the time of crowning of the head (26.3 +/- 2.0 pg/ml). Plasma cGMP levels in the OT-induced group significantly rose after the onset of labor and remained at a high level until expulsion of the fetus. Plasma cGMP levels in the other groups did not change significantly throughout labor. These results suggest that cAMP may be involved in the labor process induced by PGE2, and that cGMP may be in that induced by OT.

Cyclic AMP↗
PubMed1976

Effects of adrenalectomy and hypophysectomy on water and electrolyte metabolism in male and female rats with inherited hypothalamic diabetes insipidus (Brattleboro strain).

Observations on water and electrolyte metabolism after hypophysectomy or adrenalectomy, in male and female rats with hereditary hypothalamic diabetes insipidus (Brattleboro strain) are confirmed and extended. The diabetic (homozygous, DI) state relative to the non-diabetic (heterozygous, non-DI) state was characterized by (1) water intake of 55-120% body weight; (2) copious urine hypo-osmotic to plasma; (3) greater excretory rates of total solute, Na, Ca and Mg; (4) similar plasma composition except that in male DI rats, K concentration was less, and in female DI rats osmolarity was higher; (5) glomerular filtration rates (GFR) were similar with close correlations between: food and water intakes, water intake and output, urinary Na and K, Na and Cl, K and Cl, and Ca and Mg; (6) both female DI and non-DI rats had lower urinary Na:K ratios and lower plasma Na concentrations than males; (7) female DI rats excreted relatively larger amounts of K and Cl, and had higher plasma Ca concentrations than other groups. Hypophysectomized DI rats had decreased water intake and urine output, decreased solute excretion, decreased loss of osmotically free water, lower excretory rates of Na, K and Cl, and increased urinary osmolarity and K concentrations. Hypophysectomized non-DI rats had increased urinary excretory rates, decreased solute excretion (by 60-70%), decreased osmotically free water absorption, decreased urinary osmolarity, Na and K concentrations, and increased excretory rates of Ca and Mg. Hypophysectomized DI and non-DI rats had increased plasma osmolarity and Na concentration. Plasma renin activities (PRA) were higher in DI than in non-DI rats with female values lower than those of males; values for both sexes of DI and non-DI rats were reduced after hypophysectomy. Adrenalectomized DI rats had about a 50% reduction in water intake, urine output and free water clearance, increased urinary concentration of electrolytes and total solute by day 4 after operation; their Na balance (dietary:urine) did not change significantly in contrast to adrenalectomized non-DI rats in which a greater percentage of dietary Na appeared in the urine. GFR was similarly reduced in adrenalectomized DI and non-DI rats. Plasma osmolarity increased in adrenalectomized male DI, decreased in female DI and non-DI, and did not change in male non-DI rats. Plasma K concentrations increased after adrenalectomy in all groups, only non-DI rats had a significantly decreased plasma Na concentration. There was no sex difference in pituitary oxytocic activity but it was consistently reduced in DI rats; there was little change after adrenalectomy in male DI and non-DI rats; but there was an increase in DI and non-DI females. Pituitaries of DI rats had no measurable ADH activity (except the inherent activity of oxytocin). Pituitary ADH values for male and female non-DI rats were similar and were unaffected by adrenalectomy.

Adrenal Glands↗
PubMed1977

The obstetric performance of the grand multipara.

The computerized records of all women delivered between July, 1974, and June, 1975, at the Mater Mothers' Hospital were analysed, and the obstetric complications associated with grand multiparity were examined. Hypertension, preeclampsia, unstable lie, malpresentation and retained placenta are found to be more common in women of high parity. The low morbidity associated with these conditions in the data may have been related to the close supervision and active management carried out. Anaemia remained more frequent in the grand multiparous women despite modern antenatal care. Hypertension in the grand multiparous women could not be explained by age in the data presented. The cause for hypertension in this group of women remains obscure. Newborn babies of grand multiparas developed neonatal jaundice more frequently. The association between jaundice and oxytocic usage in the data only partially accounted for this observation.

Adult↗
PubMed1975

Effect of prostaglandin F2 alpha on the neurohypophysis. A histochemical study.

Ten micrograms of PG F2 alpha in distilled water were injected intraperitoneally into thirty non-pregnant female rats and their hypophysis was studied after aldehyde-fuchsin and performic acid-alcian blue staining. A definite depletion of posterior pituitary principle was observed in the hypophysis. The role of oxytocin in relation to the oxytocic effect of prostaglandin F2 alpha is discussed.

Animals↗
PubMed2005

Women's perceptions of pain and discomfort after childbirth in Angola.

Prophylactic treatment against postpartum haemorrhage is a widely investigated area and injection of Oxytocics has been considered as the best choice. The occurrence of postpartum pain and discomfort was studied in a population of birthing women in an overcrowded labour ward in Angola where the oxytocin-filled device Uniject was used. This study indicates that birthing women's perceived postpartum pain increases with parity and during breastfeeding, but does not confirm that injection of oxytocin increases pain and discomfort. This is an important finding, since it might facilitate the introduction of a management practice, likely to reduce haemorrhage-related maternal morbidity and mortality after delivery in underprivileged populations. The birthing women were, by and large, satisfied with the care and treatment provided, but the encounters with midwives seem to vary in quality. Further investigation is needed to elucidate parturient women's experience of postpartum pain and their perceptions of the quality of care and treatment.

Adult↗
PubMed2006

[Effects of methylergometrine and oxytocin on blood loss and uterine contraction during cesarean section].

BACKGROUND: The effects of intravenous oxytocics on blood loss and uterine contraction during cesarean section were studied in 136 parturients. METHODS: The subjects were randomized to receive either methylergometrine 0.2 mg bolus (MEM group; n = 34), oxytocin 10 IU over 30 seconds (OX 30 s group; n = 34), oxytocin 10 IU over 5 minutes (OX 5 m group; n = 34) or oxytocin 10 IU over 15 minutes (OX 15 m group; n = 34). The subjects received spinal anesthesia with 11-12 mg of intrathecal isobaric bupivacaine (0.5%). Additional intramyometrial prostaglandin F2alpha (PGF2alpha) was administered when obstetrician diagnosed uterine atony. We analyzed total amount of blood loss including amniotic fluid and number of parturients that received additional intramyometrial PGF2alpha to evaluate uterine contraction. RESULTS: The amounts of blood loss in the OX 30 s and OX 5 m groups were significantly lower than in the MEM group, and the numbers of parturients received additional PGF2alpha in all the oxytocin treat ment groups were significantly lower than in the MEM group (P < 0.05). There were no significant differences in blood loss and uterine contractior among the oxytocin treatment groups. CONCLUSIONS: Intravenous oxytocin 10 IU over 30 seconds to 15 minutes was effective to decrease blood loss and uterine contraction than intravenous methylergometrine 0.2 mg bolus.

Adult↗
PubMed1991

[Two cases of pulmonary edema during and after cesarean section].

Pulmonary edema occurred during and after Cesarean section under general anesthesia in two pregnant women. They had no preoperative complication. After delivery, anesthesia was maintained with 66% N2O in oxygen and intravenous injection of pentazocine and diazepam. At the same time, 0.2 mg of methylergometrin was injected intramuscularly and 2,000 micrograms of prostaglandin F2 alpha was injected to the muscle of the uterus in order to induce uterine contraction. In one case, SpO2 dropped and airway pressure increased immediately after the administration. In another case, chest rale was auscultated on postoperative round at 2 hours after operation. The cases suggest that pulmonary edema was caused by a large quantity of oxytocics, which increased volume load on systemic circulation.

Adult↗
PubMed1991

Anaesthesia for caesarean section in a patient with Wolff-Parkinson-White syndrome.

The anaesthetic management is described of a patient with Wolff-Parkinson-White syndrome who had to undergo caesarean section due to failed induction of labour. Spinal anaesthesia with hyperbaric nupercaine was given. The main problem encountered during anaesthetic management was repeated attacks of supraventricular tachycardia which were primarily due to anxiety or occurred during pharmacological intervention with oxytocics.

Adult↗
PubMed1986

Prescribing for labour.

Prostaglandins, particularly PGE2 vaginally, can be valuable for cervical ripening or induction of labour in some women. Ease of use must not be allowed to result in unjustified intervention. Amniotomy followed by oxytocin infusion are the methods of choice for induction of labour. Careful monitoring of the maternal and fetal condition are vital, especially if an epidural block is in place. Augmentation of labour is only appropriate for inefficient primigravid labour. Failure to progress in a multiparous woman is more likely to be due to obstruction. Low residue, easily digested foodstuffs are not necessarily contraindicated during normal labour. When properly used, Entonox can provide analgesia equivalent to 75-100 mg pethidine. Sodium citrate is the antacid of choice during labour and should be combined with an H2-receptor blocking agent for caesarean section, or other procedure involving anaesthesia. The routine injection of Syntometrine at delivery of the anterior shoulder to prevent PPH is widespread in the UK but has not been properly tested. Oxytocics are invaluable in the treatment of PPH.

Anesthesia, General↗
PubMed1995

[Is drug use in maternity wards baby-friendly enough?].

Quality assurance in the care of breast-feeding women and their nursing infants also applies to drugs administered during delivery and puerperium. Large variations among hospitals may indicate that drug use is irrational. A survey comparing the extent of drug sales from the hospital pharmacy to maternity wards in eight Norwegian hospitals was performed in 1992 and the results were compared with data from 1988. The purpose was to examine whether the drug use was "baby-friendly" with regard to the following criteria; proven efficacy for the indication; no effect on milk ejection, milk production and interaction with infant; minimal transfer of drug to milk. Large variations were found among hospitals in the case of some oxytocic drugs. High use of oxytocin as nasal spray and metylergometrine as tablets may indicate unnecessary use of drugs. A large decrease (89%) in the use of hypnotics was found from 1988 to 1992, which may indicate previous irrational use of these drugs. Pethidine as pain relief during delivery remained stable during this period, and was received by 40-60% of women giving birth. None of the drugs given to the mothers was assessed to represent a risk to the breast-fed infant. In general, drug use in maternity wards had decreased during the last four years and, with some exceptions, appeared to be more baby-friendly.

Adult↗
PubMed1993

[The effect of peridural analgesia on uterine contractions].

OBJECTIVE: To study the impact of 0.25% bupivacaine on the frequency and intensity of uterine contractions. METHODOLOGY: 52 patients in labour. Continuous internal tokographic measurement of uterine activity at 10 minutes before instilling the bupivacaine and at 30 minutes after doing so. The true frequency and intensity of the uterine contractions were the two parameters that were studied. RESULTS: There was a significant variation (matched Student's test) between the two parameters that were studied: there was transitory hypokinesia (p = 0.003) and intense prolonged hyperkinesia (p < 0.001). CONCLUSION: 0.25% bupivacaine produces hyperkinetic increases in intensity of the contractions of which the mechanism has not been elucidated; therefore it is inadvisable to add oxytocics in the minutes after instilling bupivacaine.

Analgesia, Epidural↗