UTERINE STIMULANTS - Abortifacients & UTERINE RELAXANTS - tocolytics

UTERINE STIMULANTS — Abortifacients

These drugs increase uterine contractions and are known as oxytocics or ecbolics.

Oxytocin

secreted by posterior pituitary along with ADH.
Both oxytocin and ADH are synthesized within the nerve cell bodies in supraoptic and paraventricular nuclei of hypothalamus;
Stored in the nerve endings within the neurohypophysis.
Stimuli for release à coitus, parturition, suckling
It increases the uterine contractions with complete relaxation in between. It increases the contraction of upper segment (fundus and body) of uterus whereas lower segment is relaxed facilitating the expulsion of the fetus.
Non-pregnant uterus is resistant to oxytocin.
Estrogen increases whereas progesterone decreases the sensitivity of uterus to oxytocin.

Mechanism of action

Action of oxytocin on myometrium is independent of innervation.
There are specific G-protein coupled oxytocin receptors which mediate the response mainly by depolarization of muscle fibres and influx of Ca2+ ions
Oxytocin increases PG synthesis and release by the endometrium which may contribute to the contractile response
number of oxytocin receptors increases markedly during later part of pregnancy

Oxytocin is involved in milk ejection reflex whereas prolactin causes milk secretion.
High doses of oxytocin cause fall in BP (due to vasodilation) resulting in reflex tachycardia.
It also has ADH like action in high dose and can result in fluid retention.
Being a peptide, oxytocin is inactive orally and is generally administered by i.m. or i.v. routes,
plasma t½ 6–12 min

Uses

used for the induction of labor in post-maturity and uterine inertia.
slow i.v. infusion: 5 IU is diluted in 500 ml of glucose or saline solution (10 milli IU/ml

Before starting infusion, confirm that:
- • presentation is correct
- • foetal lungs are adequately mature
- • there is no cephalopelvic disproportion
- • no placenta previa
- • no foetal distress and
- • no uterine scar

can also be used for the treatment of postpartum hemorrhage. – DOC
Carbetocin à long-acting analogue of oxytocin à for prevention of uterine atony after caesarean section and to control PPH.

Oxytocin challenge test is performed to know the adequacy of uteroplacental circulation in high risk pregnancies.

Adverse effects

Injudicious use may result in rupture of uterus due to powerful uterine contractions.
also cause water intoxication due to ADH like action.
should not be used in cases of contracted pelvis, obstructed labour, malpresentation, history of LSCS, hypovolemic states and cardiac disease.

Ergot Derivatives

Ergometrine is derived from Claviceps purpura and is used as an oxytocic agent.
Produces uterine contractions in the upper as well as lower segment and is used to control postpartum hemorrhage.
Its derivative, methylergometrine is more potent oxytocic and is preferred for this indication.
Latter is administered at the delivery of anterior shoulder. These drugs are preferred over oxytocin for this indication.
Hypertension and sepsis are contraindications for their use.

Oxytocin	Ergot
*contraction of upper segment* (fundus and body) of uterus whereas lower segment is relaxed facilitating the expulsion of the fetus.	contractions in the upper as well as lower segment
Normal relaxation in between — *fetal oxygenation does not suffer.*
PPH – DOC	alternative
Preferred over ergometrine/PGs: Because of its short t½ and slow i.v. infusion, intensity of action can be controlled and action can be quickly terminated.
	They can decrease milk secretion if higher doses are used for many days postpartum – due to inhibition of prolactin.

Prostaglandins à PGE2, PGF2α, 15-methyl PGF2α, Misoprostol

UTERINE RELAXANTS à tocolytics

These drugs decrease uterine contractions
Mainly used to delay labour when premature contractions are present.
Suppression of premature labour may be needed to allow the foetus to mature, to allow time for initiating glucocorticoid therapy for foetal lung maturation or
to transfer the mother in labour to a centre with proper facilities.
However, no clearly satisfactory drug is available since none of them has been shown to improve foetal outcome.
An attempt to delay premature labour is likely to succeed only if cervical dilatation is < 4 cm.

Measures to delay labour should not be undertaken if

membranes have ruptured, antepartum haemorrhage is occurring, in severe toxaemia of pregnancy, intrauterine infection or foetal death

BETA AGONISTS

Ritodrine, isoxsuprine and terbutaline, salbutamol
selective β2 agonists useful as tocolytic agents.
Delivery can be postponed in about 70% cases by few hours to few weeks
should not be used in mother having heart disease or diabetes mellitus.
Fetal Pulmonary edema is a serious complication of these drugs at high doses.
Neonate may develop hypoglycemia and ileus.
β2 agonists can also produce tachycardia, palpitations, tremors, hyperglycemia and hypokalemia.

MAGNESIUM SULPHATE

mainly used to control convulsions in eclampsia.
also possesses tocolytic activity and can be used.
competing with Ca2+ ions for entry into myometrium
preferred over β2 agonists in patients with cardiac problems, diabetes, hyperthyroidism and hypertension.
Toxicity is manifested initially as loss of patellar reflex followed by respiratory depression and finally cardiac arrhythmias and arrest.
Magnesium sulphate by i.v. or inhalational route has also been utilized in the treatment of acute severe asthma.

OTHER DRUGS

oxytocin antagonist ‘atosiban’ can also be used to delay premature labour. – available in UK and Europe

Ethyl alcohol (i.v. infusion), NSAIDs and progesterone also suppress uterine contractions but are rarely used for this indication.
‘Halothane’ is an efficacious tocolytic agent and is the anaesthetic of choice for version (external or internal).
Hydroxyprogesterone has been used prophylactically to prevent pre–term labour; however, teratogenic potential limits its use.
Calcium channel blockers and atosiban provides the best balance of successful delayed delivery with lesser risk to mother and baby.

UTERINE STIMULANTS – Abortifacients & UTERINE RELAXANTS – tocolytics