Quick review over oxytocics & tocolytics medications

1. Oxytocics &
Tocolytics

2. Oxytocics (Uterine
Stimulants)
Posterior Pituitary hormones
 Oxytocin
 Carbetocin
 Vasopressin
Ergot alkaloids
 Ergometrine (Ergonovie)
 Methergine (Methylergometrine)
Prostaglandins
 PGE2 (Dinoprostone)
 Carboprost (analog of PGF2α)
 Misoprostol (Synthetic replacement of
PGE1)
Miscellaneous
 Quinine, Emetine, Alcohol, Ethacridine
Tocolytics ( Uterine
Relaxants)
 β2 adrenergic receptor agonists
 Terbutaline
 Retodrine
 Isoxsuprine
Magnesium Sulphate
Calcium channel blockers
 Nifedipine
 Nicardipine
Oxytocin receptor antagonist
 Atosiban
 Prostaglandin synthetase inhibitors
 Indomethacin
 Aspirin
 Ibuprofen
 sulindac
Nitric oxide donors
 Nitroglycerine
Halothane
OXYTOCICS & TOCOLYTICS

3. *
* Oxytocics are the drugs that have the power to stimulate the contraction of uterine
muscles
* First-line agent to prevent and treat Postpartum Hemohrrage (PPH)
M.O.A: Acts through oxytocin receptors present in smooth muscles of Uterine wall
(myometrium) by increasing intracellular calcium levels. Also increases local
prostaglandin production.
* Oxytocin may be administered by slow IV bolus, IV infusion, or IM injection.
* Onset of action: Uterine contractions: IM: 3 to 5 minutes; IV: ~1 minute
* Duration: IM: 2 to 3 hours; IV: 1 hour
* Half-life elimination: 1 to 6 minutes
* Excretion: Urine (small amount unchanged)
 DOSE: Induction or stimulation of labor: IV
• Initial 0.5 to 2 milliunits/minute, incrementally increase by 1 to 2 milliunits/minute
every 15 to 40 minutes
• Infusion rates up to 6 milliunits/minute provide oxytocin levels similar to those with
spontaneous labor; rates >9 to 10 milliunits/minute are rarely required.
* Postpartum uterine bleeding
• IM: 10 units after delivery of the placenta.
• 5 or 10 initially and can be followed by a maintenance infusion of 10 units/hour.
Maximum cumulative dose: 40 units

4. *
• A newer analogue of Oxytocin
• much rapid onset, longer duration of action & half life much longer than Oxytocin.
• Onset of action: IV: <1 minute
• Duration: IV: ~60 minutes; IM: ~120 minutes.
• Half-life elimination: Terminal: IV: 33 minutes; IM: 55 minutes.
 M.O.A: Binds oxytocin receptors located in uterine smooth muscle producing
rhythmic uterine contractions characteristic to deliver, as well as increasing both
the frequency of existing contractions and uterine tone. Enhances uterine
involution early in postpartum.
 DOSE :Postpartum hemorrhage, prevention:
• Following cesarean section/vaginal delivery: IV, IM: 100 mcg (single dose only).
• IV: Administer undiluted as bolus IV injection over 1 minute

5. *
• Available in Oral dosage form also.
• Onset of action: Oxytocic: IM: 2-5 minutes; IV: Immediately
• Duration: IM: ~3 hours; IV: 45 minutes
• Half-life elimination: ~3 hours
 M.O.A : Increases the tone, rate and amplitude of contractions on the smooth
muscles of the uterus, producing sustained contractions which shortens the third
stage of labor and reduces blood loss.
 Dose: Prevention of hemorrhage:
• IM, IV: 0.2 mg after delivery of placenta, may be repeated every 2 to 4 hours as
needed.
• IV administer over at least 1 minute
• Note: IV administration should only be considered during life-threatening
situations.

6. *
• Onset of action (uterine contractions): Vaginal suppository: Within 10 minutes.
• Duration: Vaginal suppository: Up to 2 to 3 hours.
• Half-life elimination: 2.5 to 5 minutes.
 M.O.A : It induces contraction of uterine smooth muscle at any stage of pregnancy
and is reported to act predominantly as a vasodilator on blood vessels and as a
bronchodilator on bronchial muscle.
 Dose : One tablet 3mg to be inserted. A second tablet may be inserted after six to
eight hours if labour is not established. Maximum dose 6 mg.
• Note: Failure to induce regular contractions after 8 hours indicates failed induction
and alternative management of patient should be considered.
• Remove 30 minutes prior to administering an oxytocic agent.
• THE TOTAL TREATMENT PERIOD WITH PROSTIN E2 SHOULD NOT, IN ANY INSTANCE,
EXCEED 18 HOURS.
•
• Insert high into vagina after removal from its foil package. Bring to room
temperature just prior to use. Patient should remain supine for 10 minutes
following insertion.

7. *
• Carboprost is an analog of naturally occurring prostaglandin F2 alpha (dinoprost)
 M.O.A : Hemostasis at the placentation site is achieved through the myometrial
contractions , it stimulates uterine contractility which usually results in expulsion of
the products of conception
• It also stimulates the gastrointestinal tract smooth muscles
• Dose : Postpartum uterine bleeding: IM: Initial: 250 mcg; if needed, may repeat at
15- to 90-minute intervals; maximum total dose: 2 mg (8 doses)
• Administer deep IM , rotate site if repeat injections are required.
• Do not inject IV
• Time to peak, serum: IM: 30 minutes

8. *
• induce uterine contractions.
• Use for cervical ripening
• Can be given Oral, Rectal, Vaginal
 Dose : Missed abortion (treatment) :
• Intravaginal : 800 mcg; may repeat every 3 hours for 2 additional doses if needed
• Postpartum hemorrhage: 600 to 1,000 mcg as a single dose

9. *
• Preterm labour & delivery (<34 weeks pregnancy) can be delayed by drugs in order
to improve the perinatal outcome
• Decrease uterine contractility/motility
• Used to delay/postpone labour, arrest threatened abortion
• Allow the fetus to mature
• Initiate glucocorticoid therapy (Dexamethasone) for fetal lung maturation
• Transfer the woman in labour to proper facilities
• They are likely to succeed only if cervical dilatation is < 4 cms, effective in
reducing the risk of delivery within 24 to 48 hours atleast (2-7 days).
• Tocolytics Contraindications:• Pre-eclampsia or eclampsia
• Rupture of membranes• Placenta previa, abruption placenta• Severe toxemia of
pregnancy• Intra uterine infection• Intra uterine death of the fetus.

10. *
• M.O.A : Relaxes bronchial and uterine smooth muscle by action on beta2-receptors with less
effect on heart rate
• β 2 adrenergic receptor agonists
Dose : Premature labor (acute; short-term [≤72 hours] tocolysis)
• IV infusion: 2.5 to 5 mcg/minute; increased gradually up to a maximum of 25 mcg/minute
• SubQ: 0.25 mg every 20 minutes to 3 hours for upto 4 doses or until tocolysis achieved ; hold
for pulse >120 beats per minute.
• Glucose & Potassium monitored (risk of hyperglycemia & hypokalemia/arrhythmia)
• Terbutaline has not been approved for and should not be used for prolonged tocolysis (>72
hours)
• Oral not recommended.

11. *
M.O.A : Mg competes with calcium at the level of the plasma membrane voltage-gated
channels to reduce myometrial contractility.
• Diaphoresis (sweating) & flushing are common side effects.
• Contraindicated in women with Myasthenia gravis (Muscle weakness)
• Predelivery administration ( <24 hours) of Mg is neuroprotective for neonate.
• Infusions suggested for 2 days for 24-34 weeks gestation, not recommended to use more than
5-7 days for tocolysis.
Dose : IV Loading 6 gm over 20 mins then 1-2 gm/hr continuos infusion.
• Infusion continued for 12 hours after cessation of contractions.
• Mg toxicity treated by Calcium gluconate ( 1 gm IV in 10 mins)

12. *
• Nifedipine as First line for 32-34 weeks or 24-32 weeks if Indomethacin contraindicated.
• Discontinue tocolysis after 48 hours of Corticosteroid dose.
• Reduce the risk of delivery with in 48 hours of treatment initiation.
M.O.A : It blocks the entry of calcium inside the cell.
• reduces the tone of myometrium & opposes the contraction
Dose : Tocolysis (off-label use):
• Oral: Immediate release: Initial: 20 to 30 mg as a loading dose, followed by 10 to 20 mg every
3 to 8 hours for up to 48 hours; maximum dose: 180 mg/day
• There may be marked hypotension, especially if the patient is volume depleted, dehydrated or
in CHF
• Reduced placental perfusion may cause fetal hypoxia.

13. *
• Less effective tocolytic drug, theoretically it can be more effective at later gestational ages
since oxytocin receptor conc increases with gestation.
• Not recommended to use in <28 week gestation
• Less side effects than any other tocolytic drug, but Very expensive
• Selective oxytocin-vasopressin receptor antagonist.
M.O.A : Atosiban is a peptide analogue of oxytocin, acts as an antagonist at oxytocin
receptors.
• Effects are elicited via competition with oxytocin at myometrial cell membrane receptors.
• Also inhibit oxytocin-induced PGF2alpha, but not PGE2.
Dose : IV: Initial: 6.75 mg bolus injection, followed by continuous infusion of 300 mcg/minute
for 3 hours. Then decrease infusion rate to 100 mcg/minute for up to 45 hours; maximum:
330.75 mg/48 hours.

14. *
• Cox inhibitors (Cox 1 in gestational tissues)/Prostaglandin Synthetase inhibitors
M.O.A : Decreases synthesis of PGs thereby reduces intracellular free Calcium & uterine contractions
• Best therapy on the basis of 4 outcomes :
oDelayed delivery >48hrs
oReduce neonatal mortality
oReduce neonatal respiratory distress syndrome
oReduce maternal side effects
• First line therapy for most women with 24-32 weeks gestation, due to favourable side effects profile
at this stage.
• Do not use >72hrs because of concern about premature constriction of the ductus arteriosus,
necrotizing enterocolitits and oligohydramnios(via reducing fetal urine output).
Dose : Tocolysis (off-label use):
• Initial: 50 to 100 mg orally or rectally, followed by 25 mg every 4 to 6 hours orally in women between
24 and 32 weeks' gestation. Duration of treatment is generally limited to 48 to 72 hours

15. *
• M.O.A: Nitroglycerin forms free radical nitric oxide
• Nitric oxide donor (N.O essential for maintenance of normal smooth muscle tone).
• Contraindicated in hypotension
Dose : IV: 50 mcg once; may repeat at 1-minute intervals as needed to sufficiently relax the
uterus; maximum total dose: 250 mcg
• If urgent uterine relaxation is required (eg, for fetal extraction), may use initial bolus of 100
to 200 mcg
• IV infusion rate of 20 mcg/min until contractions stop.
• Transdermal patches also used . 10mg GTN patch to the skin of abdomen ( no more than 2
patches applied simultaneously).

16. *