Practical Pharmacology-3rd Class
Dosing Schedule of Oxytocin, Ergometrine & Prostaglandine in Obebstetricد.شذى هاني 16-3- 2017
Drugs that producing uterine contraction (Oxytocic Drugs)
In clinical practice the following drugs are of importance:
1- Oxytocin: Syntocinon, Pitocin.
2- Ergometrine: Ergonovine
3- Prostaglandins:
a) PGE2
b) PGF2α
Oxytocin, Pitocin, Syntocinone
It is an octapeptide hormone released from the posterior lobe of the pituitary gland. It stimulates contraction of myometrium of pregnant uterus particularly at term. Stimulates both the frequency and force of uterine contractility particularly of the fundus segment of the uterus.
These contractions resemble the normal physiological contractions of uterus (contractions followed by relaxation)
Clinically oxytocin is given only when uterine cervix is soft and dilated.
SHAPE \* MERGEFORMAT
*NOTE: The nerve supply to the uterus includes both excitatory and inhibitory sympathetic components: adrenaline, acting on β2-adrenoceptors, inhibits uterine contraction, whereas noradrenaline, acting on α- adrenoceptors, stimulates contraction.Oxytocin also stimulates contraction of myoephhelial cells of breast particularly after sucking and cause release of milk.
It also has a vasodilator action and a weak antidiuretic that can result in water retention, which can be problematic in patients with cardiac or renal disease, or preeclampsia.
SHAPE \* MERGEFORMAT
Mechanism of action
The interaction of endogenous or administered oxytocin , with myometrial cell membrane receptor promotes the influx of ca ++ from extra cellular fluid in to the cell , this increase in cytoplasmic calcium ,stimulates uterine contraction .Clinical uses of Oxytocin:
1- Induction of Labor.
2- Augmentation of slow Labor.
3- Prevention and treatment of post - partum hemorrhage (combined with ergometrine).
4- Use as nasal spray to induce lactation.
Contraindication of Oxytocin:
1- Women of high parity (more than 5).2- Mechanical obstruction to safe normal vaginal delivery such as contracted pelvis or abnormal fetal presentation.
3- Previous uterine scar such as caesarean section and myomectorny.
4- Placenta Previa.
Administration & Dosage of Oxytocin;
- It is given by IV infusion, but it is also given as buccal tablet or nasal spray but these two routes show irregular absorption which lead to less contractility.Dose of oxytocin is measured in units
500 USP (united state pitocin) units = 1 mg. So each unit = 2 ug.
- Usually oxytocin preparations (Syntocinon, Pitocin) contain 10 units/ ml.
- For induction of labor or to augment slow labor, the common method is to mix 1-2 units of oxytocin in 500 ml of 5 % glucose water solution and start running this at 1 ml (15 drops) / minute, This dose is increased gradually at 30 minutes interval according to strength and frequency of uterine contraction . This procedure can be done by manual control or infusion pump.
For Impaired milk ejection ,one puff in each nostril 2-3 min before nursing.
Unwanted effects of oxytocin
●Dose-related hypotension (arising from its vasodilator action), with associated reflex tachycardia.
●Its antidiuretic hormone-like effect on water excretion by the kidney causes water retention and, consequent hyponatraemia
●Inappropriate use of oxytocin can lead to utrine repture.
● Prolonged stimulation of uterus may cause fetal arrhythmias.
Ergot Alkaloids
Ergometrine (Ergonovine)
It is one of ergot derivatives which act by stimulation of uterine activity. It differs from oxytocin by:
1- Alkaloid derivatives induce TETANIC CONTRACTION of uterus without relaxation in between(not like normal physiological contractions)
SHAPE \* MERGEFORMAT
Ergometrine causes contractions of uterus as a whole i.e. fundus and cervix (tend to compress rather than to expel the fetus)
2- Oxytocin is given parenterally only while ergometrine given parenterally and orally.
3- Duration of action of oxytocin is few seconds while ergometrine reach one hour.
4- Ergometrine causes vasoconstriction leading to increase in BP. particularly in already hypertensive patient, patient with peripheral vascular disease and with heart disease.
Clinical uses of Ergometrine
1- Prophylaxis and treatment of post - partum hemorrhage in normal labour and in caesarean section.2- Treatment of bleeding in abortion.
3- In puerperium if bleeding is heavy.
Administration & Dosage of Ergometrine
1- Orally: 0.5 - 1 mg, action begin after 8 minutes and last for one hour. 2- I M: 200-500 ug, action begins within 2-6 minute.
3- Slow I V: 100 - 500 ug, action, begins within one minute.
- In the treatment of Post - partum hemorrhage, 500 ug is give I V , if uterus is still flaccid with bleeding give another same dose (but must be the last dose). If bleeding continues give oxytocin by I V infusion which give quick action but brief.
For this reason oxytocin is usually mixed with ergometrine in a preparation called syntometrine which contains.
500 ug Ergometrine
5 I U oxytocin
This preparation have the advantages of quick onset of action (due to oxytocin) and prolonged effect (due to ergometrine).
Prostaglandines:
They are modified fatty acids results from enzymatic synthesis from arachidonic acid. It has been suggested that it may play physiological rule during labor:
1- Induction of labor when there is fetal or maternal contra - indication to oxytocin.
2- In case of fetal death in the uterus.
3- When vaginal delivery is desired for safety of mother or child in cases such as Rh. incompatibility or maternal diabetes mellitus.
4-Postpartum hemorrhage
NOTE: Prostaglandins also play a part in two of the main disorders of menstruation: dysmenorrhoea (painful menstruation) and menorrhagia (excessive blood loss). Dysmenorrhoea is associated with increased production of PGE2 and PGF2α; non-steroidal anti-inflammatory drugs, which inhibit prostaglandin biosynthesis, are used to treat dysmenorrhea.
Administration & Dosage of PGs:
PGF2α available in 5mg / ml sterile solution called Dinoprost. They are given I V, extra- amniotically, intra- amniotically, vaginal gel or vaginal pessary.
1- I V Route:
a- 5 ug / ml of PGF2α is used for induction of labour when PG is not contra indicated. For I V drips, Add 1 ml from ampoule to 1000 ml or 0.5 ml to 500 ml of sterile normal saline or 5 % glucose water, start with 2.5 ug / minute, maintained at least 30 minutes, if good contraction obtained, maintain the rate. If contraction is weak increase the dose to 5 ug / min. b- In therapeutic termination of pregnancy, missed abortion or vesicular mole. The dose is 50 ug / ml solution.
2- Extra-Amniotic:
- It is used for therapeutic termination of pregnancy in a dose of 250 ug / ml solution.
- Take 1 ml from ampoule of PGF2 α, add it to 19 ml normal saline or 5 % glucose water to get 20 ml diluted solution containing 250 ug / ml.
- Insert Foley Catheter (self retaining) through cervix (into space between fetal membrane and uterine wall). PGF2 solution is inserted; through the catheter with initial dose 1 ml then 1 or 2 ml every 1 or 2 hours.
3- Intra Amniotic
It is use for therapeutic termination of pregnancy in a dose of 5 mg / ml, here the solution is used from ampoule without dilution.-Transabdominal tap of amniotic sac with drawn at least one ml of amniotic fluid, then 40 mg (8 ml) of PGF2 α slowly injected in the amniotic sac. If after 24 hours abortions not occur, we can give a dose of 2-8 ml of PGF2 α.
7