Uncomplicated premature labour
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
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.
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
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.