There are many groups of tocolytics, like:
1.Beta adrenergic receptor agonists: React with beta adrenergic receptors to reduce intracellular ionized calcium and prevent activation of myometrial contractile proteins.
Ritodrine and terbutaline has been used but only ritodrine has been approved.
a.Ritodrine:
Neonates whose mothers were treated with ritodrine had less mortality and respiratory distress, they achieved a gestational age of 36wks or birth wt of 2500g or more.
The tocolytic effects of ritodrine may be transient due to beta adrenergic receptor desensitization.
Ritodrine infusion is started at a dose of 50 micrograms/ min and increased in every 20 min until uterus is quiescent or side effects limit escalation of dose.
The maximum recommended infusion rate is 350 micrograms/ min.
If pulse rate is more than 120/min infusion rate should not be increased.
Potential side effects of beta agonists are palpitations, tremors.
Serious complications are pulmonary edema, hyperglycemia, hypokalemia, hypotension, arrhythmias, myocardial ischemia.
Tocolytics are the third most common cause of acute respiratory distress and death of pregnant women.
Beta agonists cause retention of sodium and water with time usually 24hrs to 48hrs, they can lead to volume overload.
Increased capillary permeability, disturbance of cardiac rhythm and myocardial ischemia can occur.
Myocardial sepsis appreciably increases this risk.
Ritodrine was withdrawn voluntarily in 2003 from US.
Contraindications for the use of Ritodrine: diabetes mellitus, cardiac disease, digitalis use, severe anemia, hyperthyroidism and hypertension.
b.Terbutaline:
It is not been used as much as ritodrine, but is effective in temporarily arresting contractions when given parenterally.
Dose is 5 to 10 micrograms/min, increased every 10 to 15 min to a maximum of 80 micrograms/min.
Can cause hyperglycaemia and side effects are similar to ritodrine.
2 . Magnesium sulphate :
Ionic magnesium in a sufficiently high concentration can alter myometrial contractility by acting as a calcium antagonists.
Following a loading dose of 4g, infusion is started at 2g/hr and infusion rate carefully titrated according to uterine response and toxicity.
Once uterus is relaxed, the infusion rate is maintained at its lowest effective rate for 12 to 24 hrs and then weaned off.
Monitor for evidence of hypermagnesemia, which may present as flushing, nausea, headache, drowsiness, blurred vision, respiratory depression, weakness diplopia, muscular paralysis or cardiac arrest.
Contraindications :
myasthenia gravis, heart block, renal disease, recent myocardial infarction.
3.Prostaglandin inhibitors:
Prostaglandins are involved in the establishment of contractions of normal labor.
Group of enzymes collectively termed PG synthase is responsible for the conversion of free arachidonic acid to PGs.
Antagonists act by blocking this system.
Eg.Indomethasin: Oral loading dose 50 to 100 mg, rectal loading dose100 to 200mg.
Followed by 25 to 50 mg every 4 to 6 hrs.
Serum concentration usually peaks 1 to 2hrs after oral administration.
Rectal administration peaks sightly sooner.
Oligohydramnios can develop if used for more than 24 to 48 hrs .
If detected early have to discontinue.
Fetal complications:
Premature closure of patent ductus arterioses, oligohydromnios, necrotising enterocolitis etc.
To mother:
Headache, dizziness, gastritis, vomiting, diarrhea etc. Contraindications:
Allergy, drug induced asthma, peptic ulcer, hepatic and renal dysfunction.
4.Calcium channel blockers:
Myometrial activity is directly related to cytoplasmic free calcium, and a reduction in its concentration inhibits contraction.
These are safer and more effective tocolytics than beta mimetics.
Nifedipine is the most commonly used .
Nifedipine: Dosage 20 mg followed by 10 to 20 mg every 6 to 8 hr.
Nifedipine does not significantly prolong pregnancy if treated with IV Mg so4 for pre term labor initially.
Nifedipine enhances the neuromuscular blocking effects of Mg that can interfere with pulmonary and cardiac function.
Side effects – dizziness, flushing, headache, peripheral edema.
It decreases vascular resistance leading to hypotention and decrease in uteroplacental perfusion.
Fetus can have hypercapnea, acidosis, hypothermia etc.
Contraindications :
CCF(congestive cardiac failure), aortic stenosis.
5.Atosiban:
This nona peptide oxytocine analogue is a competitive antagonist of oxytocin, decreases oxytocin induced contractions.
Dose – 6.75 mg bolus over 1min followed by infusion at 18mg per hr for 3hrs and then 6mg per hr for up to 45 hrs.
Side effects:
Nausea, chest pain, vomiting, dyspnoea.
6.Nitric oxide donors:
Example: Nitroglycerine.
Though these potent smooth muscle relaxants affect the vasculature of gut and uterus are not showed to be superior to other tocolytics.
If tocolytics are given they should be given concomitantly with corticosteroids.
As perinatal outcomes in preterm neonates are generally good after 34wks, most practitioners do not recommend tocolytics at or after 34wks.
Preterm labor-etiologicalfactors
Preterm labor-pathogenesis and diagnosis
Preterm labor-investigations
Preterm labor-prediction
Preterm labor-complications
Preterm labor -prevention
Preterm labor-bacterialvaginosis
Preterm labor-progesterone.html
Preterm labor-cervical circlage
Pretem labor-management
Preterm labor-tocolytics
Preterm labor-with premature rupture of membranes
1.Beta adrenergic receptor agonists: React with beta adrenergic receptors to reduce intracellular ionized calcium and prevent activation of myometrial contractile proteins.
Ritodrine and terbutaline has been used but only ritodrine has been approved.
a.Ritodrine:
Neonates whose mothers were treated with ritodrine had less mortality and respiratory distress, they achieved a gestational age of 36wks or birth wt of 2500g or more.
The tocolytic effects of ritodrine may be transient due to beta adrenergic receptor desensitization.
Ritodrine infusion is started at a dose of 50 micrograms/ min and increased in every 20 min until uterus is quiescent or side effects limit escalation of dose.
The maximum recommended infusion rate is 350 micrograms/ min.
If pulse rate is more than 120/min infusion rate should not be increased.
Potential side effects of beta agonists are palpitations, tremors.
Serious complications are pulmonary edema, hyperglycemia, hypokalemia, hypotension, arrhythmias, myocardial ischemia.
Tocolytics are the third most common cause of acute respiratory distress and death of pregnant women.
Beta agonists cause retention of sodium and water with time usually 24hrs to 48hrs, they can lead to volume overload.
Increased capillary permeability, disturbance of cardiac rhythm and myocardial ischemia can occur.
Myocardial sepsis appreciably increases this risk.
Ritodrine was withdrawn voluntarily in 2003 from US.
Contraindications for the use of Ritodrine: diabetes mellitus, cardiac disease, digitalis use, severe anemia, hyperthyroidism and hypertension.
b.Terbutaline:
It is not been used as much as ritodrine, but is effective in temporarily arresting contractions when given parenterally.
Dose is 5 to 10 micrograms/min, increased every 10 to 15 min to a maximum of 80 micrograms/min.
Can cause hyperglycaemia and side effects are similar to ritodrine.
2 . Magnesium sulphate :
Ionic magnesium in a sufficiently high concentration can alter myometrial contractility by acting as a calcium antagonists.
Following a loading dose of 4g, infusion is started at 2g/hr and infusion rate carefully titrated according to uterine response and toxicity.
Once uterus is relaxed, the infusion rate is maintained at its lowest effective rate for 12 to 24 hrs and then weaned off.
Monitor for evidence of hypermagnesemia, which may present as flushing, nausea, headache, drowsiness, blurred vision, respiratory depression, weakness diplopia, muscular paralysis or cardiac arrest.
Contraindications :
myasthenia gravis, heart block, renal disease, recent myocardial infarction.
3.Prostaglandin inhibitors:
Prostaglandins are involved in the establishment of contractions of normal labor.
Group of enzymes collectively termed PG synthase is responsible for the conversion of free arachidonic acid to PGs.
Antagonists act by blocking this system.
Eg.Indomethasin: Oral loading dose 50 to 100 mg, rectal loading dose100 to 200mg.
Followed by 25 to 50 mg every 4 to 6 hrs.
Serum concentration usually peaks 1 to 2hrs after oral administration.
Rectal administration peaks sightly sooner.
Oligohydramnios can develop if used for more than 24 to 48 hrs .
If detected early have to discontinue.
Fetal complications:
Premature closure of patent ductus arterioses, oligohydromnios, necrotising enterocolitis etc.
To mother:
Headache, dizziness, gastritis, vomiting, diarrhea etc. Contraindications:
Allergy, drug induced asthma, peptic ulcer, hepatic and renal dysfunction.
4.Calcium channel blockers:
Myometrial activity is directly related to cytoplasmic free calcium, and a reduction in its concentration inhibits contraction.
These are safer and more effective tocolytics than beta mimetics.
Nifedipine is the most commonly used .
Nifedipine: Dosage 20 mg followed by 10 to 20 mg every 6 to 8 hr.
Nifedipine does not significantly prolong pregnancy if treated with IV Mg so4 for pre term labor initially.
Nifedipine enhances the neuromuscular blocking effects of Mg that can interfere with pulmonary and cardiac function.
Side effects – dizziness, flushing, headache, peripheral edema.
It decreases vascular resistance leading to hypotention and decrease in uteroplacental perfusion.
Fetus can have hypercapnea, acidosis, hypothermia etc.
Contraindications :
CCF(congestive cardiac failure), aortic stenosis.
5.Atosiban:
This nona peptide oxytocine analogue is a competitive antagonist of oxytocin, decreases oxytocin induced contractions.
Dose – 6.75 mg bolus over 1min followed by infusion at 18mg per hr for 3hrs and then 6mg per hr for up to 45 hrs.
Side effects:
Nausea, chest pain, vomiting, dyspnoea.
6.Nitric oxide donors:
Example: Nitroglycerine.
Though these potent smooth muscle relaxants affect the vasculature of gut and uterus are not showed to be superior to other tocolytics.
If tocolytics are given they should be given concomitantly with corticosteroids.
As perinatal outcomes in preterm neonates are generally good after 34wks, most practitioners do not recommend tocolytics at or after 34wks.
Preterm labor-etiologicalfactors
Preterm labor-pathogenesis and diagnosis
Preterm labor-investigations
Preterm labor-prediction
Preterm labor-complications
Preterm labor -prevention
Preterm labor-bacterialvaginosis
Preterm labor-progesterone.html
Preterm labor-cervical circlage
Pretem labor-management
Preterm labor-tocolytics
Preterm labor-with premature rupture of membranes
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