Pharmacology of the Uterus

Question 1

what are the three layers of the myometrium?

Answer 1

all smooth muscle

outer longditudinal layer
middle figure of 8 layer
inner circular layer

Question 2

what is the purpose of having multiple muscle configurations?

Answer 2

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

Question 3

how is the myometrium innervated?

Answer 3

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

Question 4

what is the role of oestrogen in myometrial contraction?

Answer 4

increases contractions by increasing the number of gap junctions between the muscle cells
also increases oxytocin production and receptor number

Question 5

what is the role of progesterone in myometrial contractions?

Answer 5

decreases contraction

Question 6

how does alpha-adrenoreceptor activation effect contraction?

Answer 6

increases contraction

Question 7

how does beta2-adrenoreceptor activation effect contraction? how is this used in pregnancy?

Answer 7

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

Question 8

what is the mechanism of action for beta2 stimulants?

Answer 8

activate Gs
increase PKA
which inhibits MLCK - no Ca2+ influx and so no contractions

also cause the reuptake of Ca2+ into stores

Question 9

what are the contraindications for beta 2 stimulants?

Answer 9

asthma

Question 10

how do the uterine contractions change across the cycle in a non-pregnant person?

Answer 10

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

Question 11

how are contractions initiated?

Answer 11

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

Question 12

how does calcium cause contraction in SMC?

Answer 12

Calcium forms a complex with calmodulin (calcium calmodulin complex)
myosin light chain kinase causes interaction between this and actin
leads to contraction

Question 13

how is contraction terminated?

Answer 13

Na/Ca exhanger in the ER

Na/Ca ATPase in the cell membrane

Question 14

other than beta2-adrenoreceptor stimulants, what other uterine relaxants can be used?

Answer 14

Ca2+ antagonists
oxytonin receptor antagonists
COX inhibitors

Question 15

what is the role of Ergometrine?

Answer 15

potent agent causing prologued and powerful contraction of the myometrium - when it is relaxed

used in post-partum haemorrhage prevention

Question 16

what is oxytocin?

Answer 16

neurotransmitter released from the posterior pituitary in response to suckling and cervical dilation - along with increased oestrogen production

Question 17

how does oxytocin work?

Answer 17

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

Question 18

what is the difference in action of low concentration of oxytocin vs high concentration?

Answer 18

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

Question 19

when in oxytocin used?

Answer 19

in induction of labour at term

in prevention of postpartum haemorrage

Question 20

what is the effect of prostaglandins on the myometrium

Answer 20

both cause prolongs and powerful contraction with cervical softening
PGE2 causes vasodilation
PGF2 causes vasoconstriction

Question 21

when are prostaglandins used?

Answer 21

in abortion - early or mid terms as does not rely on E2

Question 22

what are some of the side effects of PGEs?

Answer 22

cause dysmennohia and menorrhagia

cause foetal distress and hypertonus

Question 23

why can NSAIDS be used to treat period pain?

Answer 23

block COX - meaning decreased PGE release

means there is a reduced chance of mennorrhagia