• 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.

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.

• 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.

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.

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.

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.

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.

• 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 ).

• 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

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.

Prostaglandin inhibitors

Indomethacin• Trials of indomethacin versus ritodrine

show that both treatment are equally effective in postponing delivery

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.

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.

• 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.

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.

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.

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)