Pharmacology Of The Uterus Flashcards
What are the three layers making up the smooth muscle of the uterus?
→ Outer longitudinal fibres
→ Middle figure eight fibres
→ Inner circular fibres
What do uterine contractions do?
→ Increase uterine pressure
→ Forces content towards the cervix
→ acts as a natural ligature to prevent blood loss
What is the activity of the myometrium like?
→ Spontaneously active basal electrical activity
What kind of contractions are there in parturition?
→ Rhythmic
→Contractions originate in the muscle itself
→Doesn’t require neuronal or hormonal input
→BUT highly sensitive to e.g. sex hormones
What is the myometrium sensitive to?
→ Neurotransmitters
→ Hormones
What type of cells are in the myometrium?
→ ICC pacemaker cells
How is synchronous contraction achieved?
→ Electrical communication between gap junctions
→ electrical activity is transmitted to adjacent cells
Where is electrical activity transmitted between in the myometrium?
→ Between ICCs
→ between ICC and smooth muscle
→ between smooth muscle cell
How do the myometrium cells function as?
→ A syncytium
→Different areas of uterus contract as one
Describe how contraction occurs
→ ICC periodic activation of inward currents
→ depolarisations
→ Ca2+ entry through VGCC
→ Intracellular calcium leads to contraction
What are the slow waves of ICCs and smooth muscle responses modulated by?
→ Neurotransmitters and hormones
Describe how calcium is increased inside the cell
Slow wave of depolarisation
↓
Ca2+ channels get activated ↓ Ca2+ entry increases Ca2+ ↓ Ca2+ binds to calmodulin ↓ This phosphorylates myosin light chain kinase ↓ actin interaction lead to contractions
Describe how oxytocin leads to increased Ca2+
Oxytocin is Gq couples
↓
Activation of phospholipase C ↓ PIP2 → DAG + IP3 ↓ IP3 binds to IP3 receptors in the SR ↓ Causes Ca2+ from the store to be released into the cytosol ↓ Ca2+ increases
What are smooth muscle cells joined by?
→ Gap junctions
How can intracellular calcium be reduced?
→ Na+/Ca2+ exchanger
→ Ca2+ pump
→ some Ca2+ gets taken into the mitochondria
What is the effect of low concentrations of stimulants on ICCs?
→ Increase in slow wave frequency producing
→ Increase in frequency of contractions
How is the myometrium similar to other smooth muscle tissues?
→ There is a graded response - no threshold
→ increases in Ca2+ lead to increases in force of contraction
What is the effect of higher concentrations of stimulants on ICCs?
→ Increased frequency of action potentials on top of slow waves
→ Increased frequency and force of contractions
What is the effect of even higher concentrations of stimulants on ICCs?
→ plateau of slow wave producing prolonged sustained contractions
What is the effect of large concentrations of stimulants on ICCs?
→ hypertonus (incomplete relaxation)
→Ca2+ extrusion process is not as effective
→ interferes with blood flow - fetal distress
What innervation does the myometrium have?
→ Sympathetic
What receptors does the myometrium express?
→ alpha and beta adrenoceptors
What is the effect of alpha 1 adrenoceptor agonist?
→ contraction
What is the effect of beta 2 adrenoceptor agonist?
→ relaxation
