Uterine Motility Flashcards
Briefly identify and describe the main layers of the uterus.
1) Perimetrium (serosa)
– Single thin outer layer of epithelium, not evident clinically
2) Myometrium
– Thick middle layer of smooth muscle
3) Endometrium
– Inner layer with glands, blood vessels, lymphatics and epithelial cells
Describe the physiological control of uterine motility.
1) Uterine contractions depend on gap junctions for phasic propagation of depolarisation
– Connexin 43
2) Hormonally influenced
– Menstrual cycle
– Pregnancy
– Labour
3) Minimal influence of autonomic innervation on contractions under physiological conditions.
Define connexin 43.
“Component of gap junctions, which allow for gap junction intercellular communication (GJIC) between cells.” (important for function of uterus including muscle contraction)
Distinguish between the junctions found in the heart, in vascular/intestinal smooth muscle, and in uterine muscle.
Gap junctions:
1) Cardiac muscle
– Constitutively expressed
– Arranged in intercalated discs
2) Vascular/intestinal smooth muscle
– Constitutively expressed
– Not concentrated in specialised areas (exception of myenteric interstitial cell of Cajal)
3) Uterine smooth muscle
– Inducible (especially hormonally).
– Fundal dominance during labour may arise from anatomical arrangement of expressed gap junctions.
Describe the expression of connexin 43 in rates during pregnancy.
- Uterus of pregnant rats.
- Immunofluorescence is absent day 4, evident day 14 and prominent day 20 (term).
- Disappears postnatally.
Describe 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.
Identify the main posterior pituitary hormones. Where are they produced ? secreted ?
Oxytocin and ADH/vasopressin (both created in the hypothalamus and secreted from the posterior pituitary into the circulation)
Compare the structure of ADH, and Oxytocin.
ADH and oxytocin are both 9 amino acid peptides, 2 amino acids different.
What are the main actions of ADH and Oxytocin ?
Both stimulate contraction of the uterus
ADH primarily acts on kidneys
Oxytocin also acts on mammary glands
What is the primary factor influencing number of Oxytocin receptors ?
Oxytocin receptor numbers and effect on uterine contraction are influenced by sex hormone levels.
Describe the number of oxytocin receptors in pregnancy.
At the start, few oxytocin receptors. At term, much increased (need oxytocin to trigger uterine contractions)
Describe the nature of uterine contractions in labour.
Increasingly regular, co-ordinated contractions that travel from the fundus to the cervix (fundal dominance) (stimulated by oxytocin)
Uterus relaxes completely between contractions.
Why are uterine relaxations in between contractions important ?
Because otherwise fetus would not receive enough blood
Identify groups of drugs which may modulate physiological control of uterine motility.
1) Uterine stimulants (oxytocics) (stimulate uterine contractions)
2) Uterine relaxants (tocolytics)
Identify the main clinical uses of oxytocics.
– Induce abortion.
– Induce and accelerate labour.
– Contract the uterus after delivery to control postpartum
haemorrhage (PPH).
Identify the main clinical uses of toxolytics.
– (Treat menstrual cramps/dysmenorrhoea).
– Prevent or treat preterm labour.
– Facilitate obstetric manoeuvres.
– Counteract (iatrogenic) uterine hyperstimulation.
Identify the main groups of oxytocics, and the main clinical uses of each.
– Oxytocin (induce or accelerate labour + after delivery to control postpartum haemorrhage)
– Ergometrine (for bleeding related to early pregnancy complications such as miscarriage (oxytocin is not effective)
– Syntometrine (combination of oxytocin and ergometrine for the third stage of labour)
– E and F series prostaglandins
How is therapeutic Oxytocin administered ?
• IV infusion to induce or accelerate labour
• IV or IM injection after delivery to control postpartum
haemorrhage (PPH)
Briefly state the mechanism of action of Ergometrine.
Causes sustained powerful uterine contractions.
To what extent can Ergometrine be used for prophylaxis PPH ?
Largely obsolete for postpartum haemorrhage (PPH) prophylaxis owing to stability, inadvisability in the presence of hypertension (vasoconstriction), adverse effect of nausea/vomiting.
Which parts of the uterus produce prostaglandins ?
- Endometrium/deciduaand myometrium have significant prostaglandin synthesising capacity
- Amniotic fluid also contains prostaglandins (so can break membranes to release these)
Identify the main prostaglandins which occur naturally.
Prostaglandin F2a (PGF2a) generated in large amounts. Prostaglandin I2 (PGI2)/prostacyclin and prostaglandin E2 (PGE2) also occur naturally.
State the main effects of E and F series Prostaglandins.
F series more vasoconstrictor, E series vasodilator, both act on cervical ripening and induce oxytocin receptors.
Identify the main medicinal Prostaglandins, stating which naturally occurring Prostaglandin each is equivalent to.
• 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)
Identify the main clinical uses + administration of Misoprostol.
USES
– 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).
ADMIN
– Oral, vaginal, sublingual or rectal routes of administration (room temperature storage)
Identify the main groups of tocolytics.
1) b2-agonists
2) Calcium channel blockers and Magnesium Sulphate
3) Non-steroidal anti-inflammatory drugs (NSAIDs)
4) Oxytocin receptor antagonist
5) Nitrates
b2-agonists
- Examples
- Mode of action
- Side effects
• b2-agonists
– Ritodrine, terbutaline, salbutamol.
– Increase cyclic AMP levels in smooth muscle.
– Adverse effects of tachycardia, hypertension, hyperglycaemia.
• Calcium channel blockers (and Magnesium Sulphate)
- Examples
- Mode of action
• Calcium channel blockers (and Magnesium Sulphate)
– Nifedipine (the current drug of choice for preterm labour)
– ^ Prevents intracellular calcium increase in smooth muscle
• NSAIDs
- Examples
- Mode of action
• Non-steroidal anti-inflammatory drugs (NSAIDs)
– Indomethacin
– Inhibit prostaglandin biosynthesis
• Oxytocin receptor antagonist
-Example
• Oxytocin receptor antagonist
-Example: Atosiban
• Nitrates
- Example
- Mode of action
• Nitrates
– Nitric oxide (NO) donors
– Nitroglycerine patch
Identify a potential cause of Dysmenorrhoea and Menorrhagia.
Prostaglandins may play a role
– Imbalance of prostaglandin E vs prostaglandin F in endometrium.
Identify possible treatment options for Dysmenorrhoea and Menorrhagia.
• NSAIDs are effective for pain relief (unclear whether via uterine relaxation or central analgesic effect)
– Ibruprofen, naproxen, mefenamic acid
• Antifibrinolytics, i.e. tranexamic acid can help reduce blood loss by 50%
