Pharmacology of the uterus Flashcards
(41 cards)
What is the structure of the myometrium?
It’s the smooth muscle of the uterus
- Outer longitudinal fibres
- Middle figure of 8 fibres
- Inner circular fibres
What does contraction of the myometrium mean?
Contraction means increase in uterine pressure forcing content towards the cervix and acts as a natural ligature to prevent blood loss
What are the mechanical properties of the myometrium?
- Spontaneously active
- Produce regular contractions without neuronal or hormonal input
- Highly sensitive to neurotransmitters and hormones
- Rhythmic contractions for parturition
How is synchronous contraction achieved?
Pacemaker cells present in myometrium(ICCs)
-These initiate and coordinate contractions
Electrical communications in myometrium via gap junctions made of connection proteins
What are gap junctions present between?
Between:
- ICCs
- ICCs and smooth muscle cells
- Smooth muscle cells
What do the gap junctions function as in the myometrium?
Function as a syncytium
How do the waves of electrical activity lead to contraction?
ICC periodic activation of inwards currents –> Depolarisations –>Ca2+ entry through VGCCs –>increase {ca2+]i –> Contraction
What are slow waves of ICCs and smooth muscle responses modulated by?
Slow waves of ICCs and smooth muscle responses are . modulated by neurotransmitters and hormones
What is the cellular mechanism of smooth muscle contraction?
- Substrate binds to receptor
- Galphaq subunuit stimulates PIP2–>IP3+DAG
- IP3 binds to the SR causing a release of Ca2+
- DAG increases membrane permeability excitability increasing depolarization and activating VGCCs
- [Ca2+]i increases and allows binding of Ca2+ calmodulin to MLCK increasing myosin light chain/actin interactions
What mechanisms are there for lowering [Ca2+] (Ca2+ extrusion)?
- ATP Ca2+ pump on sarcoplasmic reticulum causes active uptake of Ca2+ into the SR
- ATP Ca2+ pump on membrane causes active release of Ca2+ out of cell
- Na+/K+ ATP pump drives the Ca2+/Na+ pump to release Ca2+ out of cell
What do low concentrations of stimulants on ICCs cause?
Cause increase in slow wave frequency, increasing frequency of contractions
What does a higher concentration of stimulants on ICC cause?
Causes increase in frequency of action potentials on top of slow waves leading to increased frequency and force of contractions
What does a higher concentration still of stimulants on ICC cause?
Cause increased plateau of slow waves, producing prolonged sustained contractions
What does a large concentration of stimulant on ICC cause?
Causes:
- Hypertonus(Incomplete relaxation)
- The Ca2+ extrusion becomes ineffective
- Interference with blood flow
- Fetal distress
What type of innervation does the myometrium have?
Sympathetic innervation
What does an alpha adrenoceptor agonist cause in the myometrium?
Causes contraction
What does a beta2 adrenoceptor agonist cause in the myometrium?
Causes relaxation
What do oestrogen and progesterone do to contraction?
Progesterone inhibits contraction
Oestrogen increases contraction
When do weak and strong contractions occur in a non-pregnant uterus?
- Weak contraction occurs early in the cycle(high progesterone)
- Strong contraction during menstruation (decreased progesterone and increased prostaglandins)
When do weak and strong contractions occur in a pregnant uterus?
- Weak contractions occur early in the cycle
- Strong and coordinated at parturition(increased oestrogen)
What happens to the estrogen/progesterone ratio during parturition?
Ratio increases
-Oestrogen increases while progesterone decreases gap junction expression in myometrium
Are oestrogen and progesterone receptors found on ICCs?
Oestrogen and progesterone receptors found on ICCs
What prostaglandins to the myometrium and endometrium synthesise and what do they induce?
Myometrium and endometrium synthesise PGE2 and PGF2alpha
-both these prostaglandins induce myometrial contraction
What do prostaglandins have a role in?
Have a role in dysmenorrhoea, menorrhagia, pain after parturitions
