Stimulus for contraction
- Oxytocin
- High oestrogen:progesterone ratio
- Prostaglandins
- Mechanical stretch of uterus/cervix
Uterine smooth muscle modifications
- Numerous gap junctions \(\to\) forms functional syncytium
- Unstable membrane potential \(\to\) spontaneous depolarizations
- Exhibits baseline tone
Steps of contraction
- Depolarization opens L-type calcium channels \(\to\) calcium influx
- Calcium binds to calmodulin and MLCK \(\to\) phosphorylates light chain of myosin
- Myosin-actin cross-bridge cycling occurs, consuming ATP \(\to\) contraction
Tocolytics (class, dose, MOA, AEs)
Salbutamol
- Beta-2 agonist (some beta-1 activity)
- 10mcg/min infusion
- \(\uparrow\)cAMP \(\to\) \(\uparrow\)PKA \(\to \ \uparrow\)phosphorylation (inactivation) of MLCK \(\to\) relaxation
- Causes maternal + foetal tachycardia. Maternal hypokalaemia, lactic acidosis, hyperglycaemia
Magnesium
- Divalent cation
- 16mmol load \(\to\) 8mmol/hr IV
- Blocks L-type calcium channels \(\to\) lower intracellular Ca \(\to\) less Ca-calmodulin-MLCK complex activity
- Causes hypotension, maternal AV blocks \(\to\) cardiac arrest, muscle weakness \(\to\) resp arrest, sedation
Nifedipine
- Dihydropyridine CCB
- 20mg PO \(to\) 20mg QID
- Blocks L-type calcium channels \(\to\) lower intracellular Ca \(\to\) less Ca-calmodulin-MLCK complex activity
- Causes headache, flushing, dizziness, hypotension. Impairs HPV \(\to\) maternal V/Q mismatch.