This document discusses various tocolytic agents used to delay preterm labor, including beta-sympathomimetics like ritodrine, magnesium sulfate, prostaglandin inhibitors like indomethacin, calcium channel blockers like nifedipine, nitric oxide donors, atosiban, and progesterone. Each work by different mechanisms of action but generally aim to relax the uterus and delay delivery. The document outlines dosages, effectiveness, side effects, and contraindications of these various tocolytic agents.

2. • Preterm delivery is a major cause of
perinatal morbidity and mortality.
• Tocolytic agents are effective in reducing
the likelihood of delivery within 48 hours to
permit in-utero transfer to a tertiary
perinatal center & to allow the
administration of corticosteroids to
enhance pulmonary maturity.

3. Beta sympathomimetics
There are three known types of beta-
adrenergic receptors in humans:
– B1 receptors occur primarily in the heart,
small intestine, and adipose tissue.
– B2 receptors are found in the uterus, blood
vessels, bronchioles, and liver.
– B3 receptors are found predominantly on
white and brown adipocytes.

4. • Although some B-sympathomimetic
agents have been proposed as B2-
selective agents, at the dosages used
pharmacologically, stimulation of all
receptor types often occurs.
• Such stimulation results in many of the
side effects associated with the B-
sympathomimetic agents.

5. Ritodrine Hydrochloride
• the effect of ritodrine in prolonging the
gestational age of preterm labour is
definite but limited to only two days.
• Ritodrine can cause more side effects if it
given for a long period.

6. Dosage
• Dissolve 3 ampoules of ritodrine ( 150 mg ) in
500 ml solution, the preparation contains 300 ug
of ritodrine per milliliter.
• Start intravenous infusion at a rate of 100 ug/
min ( 5-6 drops/min ). Increase every 10 minutes
by 50 ug/ min ( 2-3 drops )until contraction stop,
the pulse rate exceeds 120 bpm, toxicity
appears or maximal rate of 350 ug/ min.
• Once adequate dose is reached , it should be
maintained for 12 hours after contractions stop.

7. Contraindication
– cardiac disease especially ventricular outflow
obstruction.
– Hyperthyroidism
– Uncontrolled insulin-dependent diabetes.
– Chorioamnionitis.
– Multifetal gestation.
– Severe obstetrical bleeding.
– Severe anemia.
– Asthmatic patient already taking beta-adrenergic
agents.

8. Magnesium Sulfate
• Magnesium sulphate is used mainly for patients
who have contraindications to beta-adrenergic
agents.
• Magnesium sulfate is usually administered
intravenously as an initial bolus of 4–6 g over 30
minutes, followed by a maintenance infusion of
1–2 g per hour.
• Serum magnesium levels of 4–7 mEq/L are
considered therapeutic for inhibiting myometrial
activity.

9. • Several observational reports have
suggested that antenatal magnesium
sulfate treatment for preterm labor or
preeclampsia is associated with a
decreased risk for cerebral palsy in very
low birth weight infants (Grether JK. Et al
2000 ).

10. • Once cessation of uterine activity is achieved, the patient
is generally maintained at the lowest effective infusion
rate for 12–24 hours and then weaned.
• Affection deep tendon reflexes occurs when serum
magnesium levels above 10 mEq/L.
• Significant respiratory depression can occur as serum
levels reach 12–14 mEq/L, and cardiac arrest may occur
with levels greater than 15 mEq/L.
• In general, respiratory depression does not occur before
loss of deep tendon reflexes. The toxic effects of high
magnesium levels can be rapidly reversed with the
infusion of 1 g of calcium gluconate

11. Contraindications
• Absolute contraindications to the use of
magnesium sulfate include myasthenia gravis
and heart block.
• Relative contraindications include underlying
renal disease and recent myocardial infarction.
• Concurrent use of calcium channel blockers and
magnesium sulfate can theoretically result in
profound hypotension and probably should be
avoided.

12. Prostaglandin inhibitors
Indomethacin
• Trials of indomethacin versus ritodrine
show that both treatment are equally
effective in postponing delivery

13. Side effects
• There is increase rate of oligohydramnious &
intraventricular haemorrhage and necrotizing
enterocolitis has been found in association of
antenatal indomethacin use.
• There is also worries about the effect of
indomethacin on the ductus arteriosus and
isolated reports of premature closure.
• However Doppler studies of the ductus
arteriosus suggest that there is less effect at
earlier gestations before 32 weeks gestation.

14. Calcium channel blocker
• Calcium channel blockers such as nifidipine
appear to be powerful uterine relaxant. The
mechanism of action appears to be derived from
blockade of voltage-dependent calcium
channels in myometrial cells.
• Nifidipine can be given by the sublingual or oral
routes. A standard dosage regimens of 20 mg
every 6 hours produces therapeutic levels with a
mean half-life of 81 minutes.

15. • Nifedipine was successful or better than ritodrine
in stopping preterm contractions with less
maternal side effects than ritodrine ( childress
and kate, 1994 ).
• The major side effect in pregnant women is
reflex tachycardia due to nifedipine induced
decreased vascular resistance and systemic
hypotention, reduced atrio-ventricular conduction
is also observed. Other side effects such as
maternal palpitations, headache.

16. Nitric Oxide donor
• Nitroderm patch ( 10-20 mg)
• The maternal side effect profile and treatment
discontinuation rates were fewer for nitroderm,
suggesting it was a safer alternative to ritodrine
with equal efficacy. ( Lees CC et al 1999 )
• In systematic review of randomized control
trials. Nitroglycerin was more effective for
arresting preterm labour than placebo but not
more effective when compared to ritodrine or
magnesium. (Morgan PJ et al., 2002 )
• Side effects: Headache, Hypotention.

17. Atosiban
• The safety and efficacy of atosiban and
ritodrine were compared in a trial of 247
women. The efficacy was similar in those
who received atosiban or ritodrine.
Atosiban was better tolerated and had less
maternal and fetal adverse effects ( J.M.
Moutquin et al 2000 ).
• The reported side-effects of atosiban are
nausea & headache.

18. Progesterone
• The mechanism of action of progesterone
is complex and there remains debate
regarding the relationship of its withdrawal
to the onset of labour in women.
• Two studies showed that the incidence of
preterm delivery was reduced in women
given progesterone in comparison to
placebo. (E.B. da Fonseca et al 2003, MF
green et al 2003)