In this article we will discuss about the drugs that stimulate uterine contractions.
Drug # 1. Prostaglandins (PG):
Prostaglandins (PG) are the only autacoids that are used in therapy because of their cytoprotective activity in the GIT mucosa, antiplatelet activity, and uterine stimulant and vasodilator actions. Out of the prostaglandins (D2, E2, F2a and I2) formed; PGE2 and PGI2 exert the broadest physiologic effects. PGE2 is synthesized by many tissues and causes contraction of the uterine muscle and is concerned with menstruation and child birth.
Therapeutic Uses:
Prostaglandins and its analogues are used in obstetrics for induction of abortion, labour and in severe postpartum hemorrhage. Gemeprost (PGE analogue) pessaries are preferred prostaglandin for the induction of therapeutic abortion during the first trimester. Gemeprost pessaries soften and dilate the cervix to facilitate trans-cervical operative procedures.
Misoprostol (PGE2) is given by mouth or vaginally to induce medical abortion. Dinoprostone (PGE2) is used as pessaries and vaginal gel for the induction of labour. Extra-amniotic injections are associated with more side effects and are rarely used. Mifepristone is a progesterone antagonist. It makes the uterus more sensitive to subsequent administration of a prostaglandin, thus facilitating the process of abortion with a lower dose of prostaglandin.
Carboprost (PGF2a) is given by deep intramuscular injection in postpartum hemorrhage due to uterine atony, when ergometrine and oxytocin have failed to control bleeding. It may cause hyperthermia and bronchospasm and is contraindicated in acute pelvic inflammatory, cardiac, renal, pulmonary or hepatic disease. The other uses of prostglandins are peptic ulcer, open angle glaucoma and ocular hypertension, congenital heart defects in infants to maintain patent ductus arteriosus prior to corrective surgery and to inhibit platelet aggregation during renal dialysis.
Drug # 2. Uterine Stimulants:
Apart from prostaglandin, the other drugs which stimulate uterine contractions are oxytocin and ergometrine. They are also termed as oxytocics or ecbolics.
i. Oxytocin:
Oxytocin and antidiuretic hormone (vasopressin) are the two hormones secreted by the posterior lobe of the pituitary gland. Oxytocin causes contraction of the uterine muscle. This effect is not marked until the later stages of pregnancy. At parturition, extremely small amounts of oxytocin cause powerful uterine contractions. Estrogens sensitise the uterus to the action of oxytocin and release of prostaglandin may be a contributing factor to its oxytocic action.
Oxytocin, in therapeutic doses, induces contractions in the fundus and body of the uterus only without affecting the lower segment and full relaxation occurs in between the contractions. Oxytocin contracts myoepithelium of mammary alveoli and facilitates the suckling of milk by the infant. Oxyocin is inactive orally.
Syntocinon (synthetic oxytocin) is used, since the natural oxytocin contains small amounts of vasopressin. It is given by intravenous infusion, total dose not exceeding 5 units for induction of labour for medical reasons (hypotonic uterine inertia) and in incomplete, inevitable or missed abortion. Syntometrine (a mixture of ergometrine 500 microgram and oxytocin 5 units) is used to prevent postpartum hemorrhage after delivery in high risk cases.
Oxytocin may cause uterine over stimulation leading to fetal distress, asphyxia, death and uterine rupture. Anaphylactic reactions are rare and large doses may cause placental abruption and amniotic fluid embolism. It should not usually be combined with prostaglandin to induce labour. Oxytocin is contraindicated in conditions where vaginal delivery is inadvisable including the presence of uterine scar from major surgery, fetal distress, severe pre-eclamptic toxemia and severe CVS disease.
ii. Ergot Alkaloids:
Ergot, a fungus that grows on rye, contains a large number of bioactive substances, of which alkaloids are of clinical importance.
Ergot alkaloids are divided into:
Amine alkaloids- Ergometrine (ergonovine).
Aminoacid alkaloids- Ergotamine and ergotoxine.
Bromocriptine, dihydroergotoxine and methysergide are semi synthetic ergot alkaloids.
Aminoacid alkaloids have alpha adrenergic blocking and vasoconstrictor properties and are used in migraine.
Ergometrine and methylergometrine are oxytocics. Small doses cause rhythmic contractions of uterus,but with larger doses they become more or less continuous. They have little effect on other smooth muscles.
Ergometrine and methylergometrine in a dose of 500 (orally) or 250 (intramuscularly) micrograms are used in the routine management of the third stage of labour after child birth to cause the uterus to contract and thus prevent postpartum hemorrhage and to stop bleeding due to incomplete abortion.
Common side effects of ergometrine are GIT disorders, chest pain, vasoconstriction and transient hypertension.
Ergometrine is contraindicated for induction and first and second stages of labour, as powerful contraction caused by ergometrine may rupture the uterus or cause fetal asphyxia. It is not used in severe cardiovascular diseases, impaired pulmonary, hepatic and renal functions, sepsis and eclampsia.
Bromocriptine, a semi-synthetic ergot alkaloid, acts as a stimulant of dopamine receptors in the brain. It inhibits both basal and stimulated prolactin and growth hormone secretion from the pituitary. It has less specific dopamine like actions in other areas of the central nervous system (basal ganglia and vomiting centra) and on blood vessels.
Bromocriptine is well absorbed and almost completely metabolized in the liver and is excreted in the bile. Hyperprolactinemia (increased production of prolactin by the pituitary) can cause impotence in men and an ovulatory infertility in women.
Bromocriptine restores prolactin concentrations to normal and ovulatory menstruation returns to normal. It is used in infertility or impotence due to hyper-prolactinemia, cyclical benign breast disease (danazol more effective), acromegaly (octreotide more effective), and inhibition of lactation (more effective than estrogen) and Parkinsonism in patients intolerant to levodopa.
Nausea and vomiting are common side effects. Others include dizziness, postural hypotension and constipation. Neuropsychiatry side effects are uncommon except in patients with Parkinson’s disease. Cabergoline and quinagolide are similar and can be used in patients intolerant to bromocriptine.
Drug # 3. Tocolytic Agents:
These are the drugs that inhibit uterine contractions. β2 agonists salbutamoi, terbutaline and ritodrine diminish uterine activity and are used sometimes in the management of premature labour between 24 and 33 weeks of pregnancy.