Pharmacology of the Uterus Flashcards
what are the three layers of the myometrium?
all smooth muscle
outer longditudinal layer
middle figure of 8 layer
inner circular layer
what is the purpose of having multiple muscle configurations?
allows contraction of the in a 3D twisting motion
increases intrauterine pressure so the contents are pushed towards to cervix
the contraction acts as a ligature to prevent post partum blood loss
how is the myometrium innervated?
it is myogenic
it is modulated by the ANS - which is responsive to changes in oestrogen and progesterone
it is innervated by alpha and beta2 adrenoreceptors
what is the role of oestrogen in myometrial contraction?
increases contractions by increasing the number of gap junctions between the muscle cells
also increases oxytocin production and receptor number
what is the role of progesterone in myometrial contractions?
decreases contraction
how does alpha-adrenoreceptor activation effect contraction?
increases contraction
how does beta2-adrenoreceptor activation effect contraction? how is this used in pregnancy?
decrease contraction
used in delaying premature birth for 48 hours to allow the administration of corticosteroids to aid lung growth, and allow transfer to a specialist facility
what is the mechanism of action for beta2 stimulants?
activate Gs
increase PKA
which inhibits MLCK - no Ca2+ influx and so no contractions
also cause the reuptake of Ca2+ into stores
what are the contraindications for beta 2 stimulants?
asthma
how do the uterine contractions change across the cycle in a non-pregnant person?
there is low progesterone in the early cycle - allows oestrogen to act causing weak contractions
as progesterone increases - contractions stop
then oestrogen rises in the menstruation phase - causing strong and coordinated contractions
how are contractions initiated?
spontaneous depolarisation of the interstitial cells of Cajal
increases the mechanical activity of SM
conducted to neighbouring SM cells via gap junctions
depolarisation and AP firing of the SM cells
causes VDCC channels to open
Calcium release causes contraction
how does calcium cause contraction in SMC?
Calcium forms a complex with calmodulin (calcium calmodulin complex)
myosin light chain kinase causes interaction between this and actin
leads to contraction
how is contraction terminated?
Na/Ca exhanger in the ER
Na/Ca ATPase in the cell membrane
other than beta2-adrenoreceptor stimulants, what other uterine relaxants can be used?
Ca2+ antagonists
oxytonin receptor antagonists
COX inhibitors
what is the role of Ergometrine?
potent agent causing prologued and powerful contraction of the myometrium - when it is relaxed
used in post-partum haemorrhage prevention
what is oxytocin?
neurotransmitter released from the posterior pituitary in response to suckling and cervical dilation - along with increased oestrogen production
how does oxytocin work?
binds to Gq - increased PLC - causes PIP formation:
- IP3 -increased intracellular calcium release
- DAG - increases extracellular calcium release
it is only effective when oestrogen is present - as this causes production of the oxytocin receptors
what is the difference in action of low concentration of oxytocin vs high concentration?
low concentration causes increased force and frequency of contractions through increases slow wave frequency
high concentrations causes a plateau in slow waves - lading to hypertonus and incomplete relaxation – leads to reduced blood flow and foetal distress
when in oxytocin used?
in induction of labour at term
in prevention of postpartum haemorrage
what is the effect of prostaglandins on the myometrium
both cause prolongs and powerful contraction with cervical softening
PGE2 causes vasodilation
PGF2 causes vasoconstriction
when are prostaglandins used?
in abortion - early or mid terms as does not rely on E2
what are some of the side effects of PGEs?
cause dysmennohia and menorrhagia
cause foetal distress and hypertonus
why can NSAIDS be used to treat period pain?
block COX - meaning decreased PGE release
means there is a reduced chance of mennorrhagia
