Uterus Pharmacology Flashcards
name an important property of the myometrium
it is myogenic, self stimulating, produces regular contractions without the need for hormonal or nervous input
what is the importance of the myometrium producing rhythmic contractions over sustained contractions?
sustained contractions are more dangerous as they can restrict blood flow, leading to foetal distress
what is a contraction and its role?
it is an an increase in uterine pressure
- forces content towards the cervix
- also acts as a prevention for blood loss
how does these synchronous contractions come about?
pacemaker cells in the myometrium intimate and coordinate contractions
-these cells are called the Interstitial Cells of Cajal (ICC’s)
how does electrical communication occur?
via gap junctions made of connexion proteins
Between ICCs
Between ICCs and SM cells
Between SM cells
how do the gap junctions function and what do they allow?
as a syncytium, integrated and functioning as a whole
depolarisations can be transmitted to neighbouring cells via gap junctions
-allow electrical coupling between the ICC and SM cells
the electrical activity of ICC’s leads to activation of what?
- inward currents that pass the threshold
- causes depolarisation and Ca2+ entry via VGCC’s and contraction
what are slow waves of ICCs and smooth muscle responses modulated by?
neurotransmitters and hormones
explain the cellular mechanisms of SM contractions?
depolarisation of cells, VGCC’s, ca2+ levels increase, binds to IP3 receptors on intracellular calcium store. release of calcium into cytosol, binds to calmodulin and activates MLCK. Myosin light chain/actin interactions and contraction
-oxytocin acts this way, increasing calcium and therefore causing contractions
relationship between calcium levels and contraction
Graded response
increases in intracellular ca2+ concentration = increases in force of contraction
mechanisms for lowering Ca2+
increase Ca2+ into SR, increase ca2+ out of cell via Na+/Ca2+ channel and Ca2+ ATPase channel
too high concentrations of calcium can produce what?
prolonged sustained contractions
-useful for preventing blood loss, but can cause foetal distress
what is hypertonus?
incomplete relaxation, occurs with large concentrations of calcium
how can myometrial contractions be regulated?
- neurotransmitters
- sex hormones
- prostaglandins
- oxytocin
explain how contractions can be regulated by neurotransmitters?
- sympathetic innvervation
- alpha receptors and beta 2 receptors
alpha adrenoceptor agonist binding causes what?
contraction
beta-2 adrenoceptor agonist binding causes what?
relaxation
explain how contractions can be regulated by sex hormones?
- progesterone inhibits contraction
- oestrogen increases contraction
why is the ratio of oestrogen and progesterone carefully controlled?
imbalance could lead to early labour
what is a non-pregnant uterus like?
- weak contractions early in cycle
- strong contractions during menstruation due to progesterone and prostaglandins
what is a pregnant uterus like?
- weak and uncoordinated in early pregnancy due to high progesterone
- strong and co-ordinated at parturition due to oestrogen
how does the oestrogen / progesterone ratio change during parturition?
increases
-oestrogen increases
where are oestrogen and progesterone receptors also found
on ICCs
what can oestrogen modulate?
- activate the oxytocin receptors
- modulate prostaglandin and oxytocin levels at uterine SM cells
- increase gap junctions in myometrium
explain how contractions can be regulated by prostaglandins?
- contractile agents
- oestrogen promotes the synthesis of PGE2 and PGF2α from the endometrium and myometrium
- both of these induce myometrial contraction
- increase expression of gap junctions
- coordinate increased frequency/force of contractions
- soften cervix
does PGE2 have the same function in every past of the body?
no, PGE2 is a relaxant in other types of SM – dilates blood vessels
what role do prostaglandins play in menstrual pain?
- dysmenorrhoea (severe menstrual pain)
- menorrhagia (severe menstrual blood loss)
- pain after parturition
what can be used to reduce contraction and pain?
NSAIDs
when are prostaglandins effective?
early and middle pregnancy
why do prostaglandins soften the cervix?
so its easier to push out the baby
name some prostaglandin analogues
Dinoprostone (PGE2), Carboprost (PGF2α), Mistoprotol (PGE1) analogues
uses of prostaglandin analogues
- Induction of labour – before term
- Induce abortion
- Postpartum bleeding
- Softening the cervix
concerns of prostaglandin analogues
- Dinoprostone can cause systemic vasodilatation
- Potential for cardiovascular collapse (given as cervical gel/vaginal insert)
- PGs – hypertonus and foetal distress
where is oxytocin synthesised and released from?
synthesised in hypothalamus, released from posterior pituitary gland
what causes oxytocin release?
- suckling and cervical dilatation
- oestrogen
how does oestrogen, released at later stages of parturition, affect oxytocin?
- increased oxytocin release and oxytocin receptor expression
- increased gap junctions
why is oxytocin only effective at term?
requires oestrogen-induced oxytocin receptor expression
uses of oxytocin?
- Induction of labour at term – does not soften cervix
- Treat / prevent post-partum haemorrhage
low vs high oxytocin concentrations
Low concentrations of oxytocin increase frequency and force of contractions
High concentrations cause hypertonus – may cause fetal distress
name 2 synthetic versions of oxytocin
Syntocinon and Pitocin
Ergot to ergometrine
- fungus that grows on some cereals
- powerful and prolonged uterine contraction, only when myometrium is relaxed
- stimulation of alpha adrenoceptors
- use in stopping post-partum bleeding - NOT induction
when might myometrial relaxants be used?
in premature labour
-Important: Delay delivery by 48 hrs, so mother can be transferred to specialist unit, and given antenatal corticosteroids to aid foetal lung maturation and increase survival
name some myometrial relaxants
beta 2-adrenoceptor stimulants e.g. Salbutamol
- relax uterine contractions by a direct action on the myometrium
- reduce strength of contractions in premature labour
- may occur as a side effect of drugs used in asthma
Ca2+ channel antagonists e.g. Mg sulphate
Oxytocin receptor antagonists e.g. Retosiban
COX inhibitors e.g. NSAIDs, decrease prostaglandin levels, but may cause fetal renal dysfunction
Stimulation of beta 2-adrenoceptors on SM (vascular, airway, myometrial) produces relaxation - explain the mechanism
agonist eg. adrenaline binds to beta-2 receptor, activates PKA
- increase in Ca2+ ATPase activity, so Ca2+ enters SR or leaves the SM cell
- increase in K+ channel activity, causing hyperpolarisation and decreased Ca2+ entry via VGCCs
- decreased MLCK
