Indications
- Uncomplicated premature labour
Administration/AbsorptionDosage
- By intravenous infusion
- initially 50 micrograms/minute
- increased gradually according to response by 50 micrograms/minute
every 10 minutes until contractions stop or maternal heart rate reaches
140 beats per minute
- continue for 12–48 hours after contractions
cease (usual rate 150–350 micrograms/minute)
- max. rate 350 micrograms/minute
- By intramuscular injection
- 10 mg every 3–8 hours
continued for 12–48 hours after contractions have ceased
- then by mouth, 10 mg 30 minutes before termination
of intravenous infusion, repeated every 2 hours for 24 hours, followed
by 10–20 mg every 4–6 hours
- max. oral dose 120 mg daily
DistributionMechanism- Tocolytic
- Uterine smooth muscle
(myometrium) has beta-receptors on its membrane.
- As with airway smooth
muscle, treatment with beta-agonists relaxes its tone and inhibits its
contractions.
- Stimulation of beta-receptors activates the enzyme adenyl
cyclase which converts ATP to cyclic-AMP.
- Cyclic AMP, in turn,
activates another enzyme, protein kinase A, that phosphorlyates K+ channels in the myometrial membrane and so opens them
- Increased K+
permeability stabilises the membrane potential, thereby preventing
action potentials and uterine contraction.
- Selectivity
- Has a bulky N-substituent => high β2-selectivity
- Also, the 4'-hydroxy on the benzene ring is important for activity as
it is needed to form hydrogen bonds
- However, the 4'-hydroxy makes it
susceptible to metabolism by catechol-O-methyl transferase (COMT)
- Since it is β2-selective it is used
for premature labor
ExcretionSide effects- Concurrent beta-1 activity
- => increase in heart rate, rise in
systolic pressure, decrease in diastolic pressure, chest pain secondary
to MI, and arrhythmia.
- May also cause fluid retention
secondary to decrease in water clearance
- when added to the tachycardia and increased myocardial work may result in cardiac failure
- In addition, they increase gluconeogenesis
in the liver and muscle resulting in hyperglycemia, which increases
insulin requirements in diabetic patients
- The passage of beta-agonists
through the placenta does occur and may be responsible for fetal
tachycardia, as well as hypoglycemia or hyperglycemia at birth.
Interactions
Contraindications
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