86 Uterine motility Flashcards
What are the 3 layers of the uterine wall?
- Perimetrium (serosa):
• Single thin outer layer of epithelium, not evident clinically - Myometrium:
• Thick middle layer of smooth muscle - Endometrium:
• Inner layer with glands, blood vessels, lymphatics and epithelial cells
Function of gap junctions in uterine motility?
- Uterine contractions depend on gap junctions for phasic propagation of depolarisation
- Gap junctions - functional connection between adjacent muscle cells
What makes up gas junctions?
Connexin 43
Hormones influence which 3 events in uterine motility?
- Menstrual cycle
- Pregnancy
- Labour
Minimal influence of autonomic innervation on contractions under physiological conditions
Intercalated discs
Provide structural support to adjacent cells
Connexin structure
- Transmembrane proteins
- 6 connexins = connexon
- Makes up the pore for a gap junction between the cytoplasm of two adjacent cells.
At which 3 sites in your body are gap junctions found?
- Cardiac muscle
- Vascular/ intestinal smooth muscle
- Uterine smooth muscle
Gap junctions in cardiac muscle?
• Constitutively expressed
• Arranged in intercalated discs
• Depolarisation starts from the sinoatrial (SA) node
(pacemaker)
Gap junctions in vascular/ intestine smooth muscle?
- Constitutively expressed
* Not concentrated in specialised areas (exception of myenteric interstitial cell of Cajal)
Gap junctions in uterine smooth muscle?
- Inducible (especially hormonally)
* Fundal dominance during labour may arise from anatomical arrangement of expressed gap junctions
Connexin 43 expression
(Uterus of pregnant rats)
• Immunofluoroescence is absent day 4
Evident day 14
Prominent day 20 (term in rat)
• Disappears postnatally
I.e. more gap junctions and connexins when they are physiologically needed, i.e. end of pregnancy
Innervation of the uterus?
• Sympathetic, parasympathetic and sensory
• Innervation of vascular smooth muscle and
myometrium
• Sympathetic outflow effect depends on receptor type:
- a-adrenoceptors: contraction
- b-adrenoceptors: relaxation
• Ratio of sympathetic receptor types influenced by hormonal status.
Posterior pituitary hormones?
- Antidiuretic hormone (ADH)/vasopressin (primarily acts on kidneys)
- Oxytocin
- Both 9 amino acid peptides, 2 amino acids different
- Both stimulate CONTRACTION of the uterus
- Oxytocin receptor numbers are influenced by sex hormone levels
Oxytocin
• Posterior pituitary hormone
• At term:
– Falling placental progesterone with sustained oestrogen levels.
–> Stimulates prostaglandin biosynthesis
–> Oxytocin receptor expression
- Uterine smooth muscle sensitive prior onset of labour
- Stimulates increasingly regular, co-ordinated contraction that travel from fundus to the cervix (fundal dominance)
- Uterus relaxes completely between contractions
Uterine stimulants (oxytocics) role?
• Induce abortion
• Induce and accelerate labour
• Contract the uterus after delivery to control postpartum
haemorrhage (PPH)
Uterine relaxants (tocolytics) role?
- (Treat menstrual cramps/dysmenorrhoea).
- Prevent or treat preterm labour
- Facilitate obstetric manoeuvres
- Counteract (iatrogenic) uterine hyperstimulation
What are drugs which stimulate uterine contractions called?
Oxytocics
Options for administrating uterine stimulants (oxytocics)
- Oxytocin:
• IV infusion to induce or accelerate labour
• IV or IM injection after delivery to control postpartum
haemorrhage (PPH) - Ergometrine
- E & F series prostaglandins
Name 3 alkaloids
- Ergotamine
- Dihydro-ergotamine
- Ergometrine
Ergometrine: • 5-HT receptor? • alpha-adrenoreceptor? • Dopamine receptor? • Uterine contraction? • Main uses?
- 5-HT receptor: Antagonist/partial agonist
- Alpha-adrenoreceptor: Weak antagonist/partial agonist
- Dopamine receptor: Weak
- Uterine contraction: +++
- Main uses: Obstetric haemorrhage
Uses of ergometrine in practice?
- Useful for bleeding related to early pregnancy complications e.g. miscarriage
- Causes sustained powerful uterine contractions
- Largely obsolete for postpartum haemorrhage (PPH) prophylaxis owing to stability, inadvisability in the presence of hypertension (vasoconstriction), adverse effect of nausea/vomiting
What is syntometrine?
- Combination of oxytocin + ergometrine
* For 3rd stage of labour
Prostaglandins’ role in pregnancy?
- Endometrium/ decidua and myometrium have significant prostaglandin synthesising capacity
- Membrane phospholipid substrate in late pregnancy
- Prostaglandin F2a (PGF2a) generated in large amounts
- Prostaglandin I2 (PGI2)/prostacyclin and prostaglandin E2 (PGE2) also occur naturally
- F series more vasoconstrictor, E series vasodilator, both act on cervical ripening and induce oxytocin receptors
Name 4 examples of prostaglandin drugs?
- Dinoprostone
• Equivalent to prostaglandin E2 (PGE2), naturally occurring - Carboprost
• Synthetic analogue of prostaglandin F2a (PGF2a) - Gemeprost
• Synthetic analogue of prostaglandin E1 (PGE1) - Misoprostol
• Synthetic analogue of prostaglandin E1 (PGE1)
What is misoprostol?
Uses?
Administration?
(PGE1 analogue)
• Room temperature storage
• Treatment/ prevention of peptic ulcers (initially)
• Medical abortion, myometrium sensitised by mifepristone
(progesterone receptor antagonist) then misoprostol
• Induction of labour
• Control of postpartum haemorrhage (PPH) secondary to uterine atony (not as effective as IV/IM oxytocin)
• Oral, vaginal, sublingual or rectal routes of administration
What are the 5 categories of uterine relaxants (tocolytics)?
- Beta 2-agonists
- Calcium channel blockers
- Nonsteroidal anti-inflammatory drugs (NSAIDs)
- Oxytocin receptor antagonist
- Nitrates
Beta 2-agonists as uterine relaxants (tocolytics):
• Name 3 examples
• Mechanism
• Side effects
- Ritodrine, terbutaline, salbutamol
- Increase cyclic AMP levels in smooth muscle
- Adverse effects of tachycardia, hypertension, hyperglycaemia
Calcium channel blockers as uterine relaxants (tocolytics):
• Name 2 examples
• Mechanism
- Nifedipine (current drug of choice for preterm labour)
- Magenisum sulphate
• Prevent intracellular calcium increase in smooth muscle
Which NSAIDs act as a uterine relaxant (tocolytics)? Action?
- Indomethacin
* Inhibit prostaglandin biosynthesis
Name an oxytocin receptor antagonist used as uterine relaxant (tocolytics)
Atosiban
How are nitrates used as uterine relaxants (tocolytics)?
- Nitric oxide (NO) donors
* Nitroglycerine patch
What is dysmenorrhoea?
Painful periods
What is menorrhagia?
Excessive blood loss
What is the cause for dysmenorrhoea and menorrhagia?
Prostaglandins
imbalance of prostaglandin E vs prostaglandins F in endometrium
Which NSAIDs are used to treat menstrual symptoms?
- Ibuprofen
- Naproxen
- Mefenamic acid
• Effective for pain relief, unclear whether via uterine relaxation or central analgesic effect
What reduces blood loss by ~ 10% in menstrual symptoms?
Antifibrinolytics
e.g. tranexamic acid
