TOCOLYTICS

Tocolytics
Agents that inhibit uterine contractions
Decreases the uterine motility

Uses
 To delay or prevent the premature labor.
 The primary goal is to maintain pregnancy for at least
48hrs to enable administration of corticosteroids for
lung maturity
 More recently magnesium sulfate for neuroprotection
 Possibly maternal transport to tertiary care facility
Contraindications
 ruptured membranes
 fetus older than 34 WOG
 has IUGR
 antepartum hemorrhage
 eclampsia or severe pre eclampsia
 chorioamnionitis
 IUFD
 CLASSIFICATION
1. Adrenergic Agonists
Salbutamol
Terbutaline
Ritodrine

2. Calcium Channel Blockers

Nifedipine
Nicadipine
Verapamil

3. Magnesium Sulphate

4. Cyclo-oxygenase Inhibitors
Indomethacin

5. Oxytocin Antagonists
Atosiban
 ADRENERGIC AGONISTS

• Terbutaline
• Salbutamol
• Ritodrine
 Mechanism of action

- Selective beta 2 agonists

Stimulate the beta 2 receptors in myometrium

Rise in cyclic AMP

Reduce intracellular Calcium

Inhibit activation of MLCK

Inhibit the interaction of actin and myosin

Smooth muscle relaxation
 Terbutaline

Category C drug

Pharmacokinetic

 Onset: immediately(iv), 6-15 min (sc)

 Duration : 90 min - 4 hr
 Has longer half life and has fewer side effect than other
adrenergic drugs
 Dose:

•Subcutaneous injection
of 0.25mg every 3 to 4 hrs

•Intravenous: Initial dose

10mcg/min increase by
5mcg per min every 10
minutes until labor stops.
Salbutamol

Category C drug

Used primarily to delay labor for 24-72 hrs in premature labor

Dose
Oral 2mg
Maximum dose upto 10mg
 Isoxsuprine

Effective for 48hrs to allow time for steroids and

antibiotics to work.
Dose:
Oral or IM 5-10mg 4-6
hourly
 Ritodrine

Category B drug
Dose
Given by IV infusion, 50 mcg/min and is
increased by 50 mcg every 10 min until
contractions cease
Infusion continued for about 12 hrs after contraction
cease.
 10mg per oral 30min prior to stopping IV
medication followed by 10mg per oral every 2hour
or 20mg per oral every 4hour for 24hours.
If stable reduce dose to 10-20mg every 4-6hours
Maximum dose 120mg/day
 Adverse Effects of Adrenergic
Agonists

Maternal
 headache,
 palpitation, tachycardia,
 pulmonary edema, cardiac failure,
 hyperglycemia, hyperinsulinemia,
 lactic acidemia ,
 hypokalemia and even death
Fetal
Tachycardia,
Heart failure,
Intra uterine fetal death

Neonatal
Hypoglycemia and
Intraventricular hemorrhage,
 Contraindication

Diabetic Mother
Heart Disease
Receiving beta blockers
 Calcium Channel Blockers

Nifedipine
Category B drug

As effective as beta 2 agonists and fewer side effects

than ritodrine.
 Mechanism of action

Blocks the entry of calcium inside the cell

Inhibits the interaction of actin and myosin

Uterine relaxation
Dose
 Oral 20 mg followed by 20 mg after half an hour.
Once the contraction stop, it is given in a dose of
10-20mg TID/QID for 48 hours.
 Adverse Effects

Maternal
 Hypotension
 Tachycardia
 Headache
 Flushing
 Nausea
GI reflux

Sub lingual nifedipine should not be used during pregnancy.

Fetal
 Fetal hypoxia due to reduced placental perfusion
 Magnesium Sulphate

Category A drug

Pharmacokinetics
- Onset : Immediately IV
- Duration of action : 30 min
- Elimination : urine
 Mechanism of action

Acts by competitive inhibition to calcium ion at

motor end plate or at the cell membrane and reduces
calcium influx
 Also decreases acetylcholine release and its
sensitivity at motor end plate
Direct depressant action on uterine muscles
Dosing
 Loading dose at 4-6 gm IV 10-20% over 20 mins
(slow)
 Maintenance dose 2-4 gm/hr for 12-24 hrs as
tolerated following cessation of contractions
Monitoring
Suspend or postpone using if:
 Respiratory rate<16/min (respiratory depression)
 Absent knee jerk (muscle paresis)
 Urine output<30ml/hour in preceding 4 hours (impaired renal function)
Therapeutic level : 4-7
mEq/L

Antidote
Injection Calcium Gluconate 10% 10
ml IV in 10mins.
 Adverse Effects
Maternal
 Flushing,
 perspiration,
 headache,
 Muscle weakness and
 Pulmonary edema (rare)
Fetal
 Skeletal Demineralization,
 Hypocalcemia and
 Hyper magnesia

Neonates
 Lethargy,
 Hypotonia,
 Skeletal abnormalities
 Contraindications

Myasthenia Gravis and

Impaired Renal Function
 Cyclo Oxygenase Inhibitors

Indomethacin
Category C Drug
 Mechanism of action

 Reduces the synthesis of Prostaglandin and thereby

reduces the intracellular free calcium
 Uterine relaxation
 Dosing
Loading dose 50 mg PO or
PR followed by 25 mg
every 6 hrs
for 48 hrs
 Adverse Effects
Maternal
Heart burn,
GI bleeding,
Thrombocytopenia,
renal injury
platelet dysfunction,
asthma
Fetal
 Constriction of ductus arteriosus
 Oligohydraminos

Contraindications
 Active peptic ulcer,
 Hepatic disease,
 Coagulation disorders
 Oxytocin
AtosibanAntagonists
Mechanism of action
 Blocks the myometrial oxytocin receptors
 Inhibits intracellular calcium release, (release of
PG)
 Inhibits myometrial contraction
 Maternal side effects

nausea,
vomiting,
headache,
allergic reaction.
Dosing
IV infusion 300 mcg/min (Initial bolus may
be needed)
Thank You