hypokalemia unless the patient is a known diabetic or requires
immediate surgery 36.In pregnant women with autoimmune
disease, ritodrine should be used with caution because it may
induce vasculitis 37. There are also concern that terbutaline
may act as a developmental neurotoxicant and in-utero
exposure to it may create a subpopulation that is sensitized
to adverse neural effects of a subsequent exposure to
organophosphorous insecticides 38. A large multicenter study
comparing these three beta-agonsists with oxytocin antagonist
(atosiban) concluded that there was little difference in their
effectiveness in delaying delivery between these groups.
However, atosiban was associated with fewer maternal side
effects 39. The RCOG recommends that if a tocolytic drug is
used, ritodrine is no longer first choice. Atosiban and nifedipine
appear to be preferable as they have fewer adverse effects
and seem to have comparable effectiveness 34.
Calcium channel blockers
Interest in calcium channel blockers arose to reduce the
cardiovascular complications of beta-agonists. Use of
nifedipine in preterm labor was associated with a lower
incidence of adverse hemodynamic and metabolic changes
compared to ritodrine after 24 and 48 hours of tocolysis 40.
Nifedipine and nicardepine have been used in this regard and
they are especially useful in women with twin pregnancy,
diabetes mellitus, heart disease and cardiomyopathies, all of
which are adversely affected by beta-agonists. A systemic
review of 12 randomized controlled trials concluded that
calcium channel blockers (nifedipine) are safer and more
effective than betamimetics 41. Nicardepine was also found
to be more effective and safer than salbutamol in another
prospective randomized controlled trial 42. A recent Cochrane
Reivew on preterm labor concluded that when tocolysis is
indicated for preterm labor, calcium channel blockers are
preferable to other tocolytic agents especially compared with
betamimetics 43. They have been shown to reduce the number
of women delivering within the next 7 days and the incidence
of respiratory distress syndrome (RDS), necrotising
enterocolitis, intraventricular hemorrhage and neonatal
jaundice 43. A recommendation has been made by the Royal
College of Obstetricians and Gynecologists (RCOG) to use
nifedipine (or atosiban) as the first line treatment in preference
to betamimetics 34. However, a recent meta-analysis concluded
that when indirectly compared (delay in delivery by 48 hours
and reduction in RDS) to atosiban, nifedepine tocolysis is
more effective 44. Commonly used regimen is 20 mg initial
dose followed by 10-20 mg every 4-6 hours until the uterine
contractions subside, and in-utero transfer and/or steroid
administration was completed 45. Though rare, serious side
effects including myocardial infarction 46 and deaths 47 have
been reported with the use of nifidepine, especially in women
with cardiovascular disorders. Limited data is available
regarding the use and safety of nicardepine in preterm labor.