Uterus Pharmacology

Question 1

name an important property of the myometrium

Answer 1

it is myogenic, self stimulating, produces regular contractions without the need for hormonal or nervous input

Question 2

what is the importance of the myometrium producing rhythmic contractions over sustained contractions?

Answer 2

sustained contractions are more dangerous as they can restrict blood flow, leading to foetal distress

Question 3

what is a contraction and its role?

Answer 3

it is an an increase in uterine pressure

• forces content towards the cervix
• also acts as a prevention for blood loss

Question 4

how does these synchronous contractions come about?

Answer 4

pacemaker cells in the myometrium intimate and coordinate contractions
-these cells are called the Interstitial Cells of Cajal (ICC’s)

Question 5

how does electrical communication occur?

Answer 5

via gap junctions made of connexion proteins

Between ICCs
Between ICCs and SM cells
Between SM cells

Question 6

how do the gap junctions function and what do they allow?

Answer 6

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

Question 7

the electrical activity of ICC’s leads to activation of what?

Answer 7

• inward currents that pass the threshold

- causes depolarisation and Ca2+ entry via VGCC’s and contraction

Question 8

what are slow waves of ICCs and smooth muscle responses modulated by?

Answer 8

neurotransmitters and hormones

Question 9

explain the cellular mechanisms of SM contractions?

Answer 9

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

Question 10

relationship between calcium levels and contraction

Answer 10

Graded response

increases in intracellular ca2+ concentration = increases in force of contraction

Question 11

mechanisms for lowering Ca2+

Answer 11

increase Ca2+ into SR, increase ca2+ out of cell via Na+/Ca2+ channel and Ca2+ ATPase channel

Question 12

too high concentrations of calcium can produce what?

Answer 12

prolonged sustained contractions

-useful for preventing blood loss, but can cause foetal distress

Question 13

what is hypertonus?

Answer 13

incomplete relaxation, occurs with large concentrations of calcium

Question 14

how can myometrial contractions be regulated?

Answer 14

• neurotransmitters
• sex hormones
• prostaglandins
• oxytocin

Question 15

explain how contractions can be regulated by neurotransmitters?

Answer 15

• sympathetic innvervation

- alpha receptors and beta 2 receptors

Question 16

alpha adrenoceptor agonist binding causes what?

Answer 16

contraction

Question 17

beta-2 adrenoceptor agonist binding causes what?

Answer 17

relaxation

Question 18

explain how contractions can be regulated by sex hormones?

Answer 18

• progesterone inhibits contraction

- oestrogen increases contraction

Question 19

why is the ratio of oestrogen and progesterone carefully controlled?

Answer 19

imbalance could lead to early labour

Question 20

what is a non-pregnant uterus like?

Answer 20

• weak contractions early in cycle

- strong contractions during menstruation due to progesterone and prostaglandins

Question 21

what is a pregnant uterus like?

Answer 21

• weak and uncoordinated in early pregnancy due to high progesterone
• strong and co-ordinated at parturition due to oestrogen

Question 22

how does the oestrogen / progesterone ratio change during parturition?

Answer 22

increases

-oestrogen increases

Question 23

where are oestrogen and progesterone receptors also found

Answer 23

on ICCs

Question 24

what can oestrogen modulate?

Answer 24

• activate the oxytocin receptors
• modulate prostaglandin and oxytocin levels at uterine SM cells
• increase gap junctions in myometrium

Question 25

explain how contractions can be regulated by prostaglandins?

Answer 25

- 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

Question 26

does PGE2 have the same function in every past of the body?

Answer 26

no, PGE2 is a relaxant in other types of SM – dilates blood vessels

Question 27

what role do prostaglandins play in menstrual pain?

Answer 27

- dysmenorrhoea (severe menstrual pain) - menorrhagia (severe menstrual blood loss) - pain after parturition

Question 28

what can be used to reduce contraction and pain?

Answer 28

NSAIDs

Question 29

when are prostaglandins effective?

Answer 29

early and middle pregnancy

Question 30

why do prostaglandins soften the cervix?

Answer 30

so its easier to push out the baby

Question 31

name some prostaglandin analogues

Answer 31

Dinoprostone (PGE2), Carboprost (PGF2α), Mistoprotol (PGE1) analogues

Question 32

uses of prostaglandin analogues

Answer 32

- Induction of labour – before term - Induce abortion - Postpartum bleeding - Softening the cervix

Question 33

concerns of prostaglandin analogues

Answer 33

- Dinoprostone can cause systemic vasodilatation - Potential for cardiovascular collapse (given as cervical gel/vaginal insert) - PGs – hypertonus and foetal distress

Question 34

where is oxytocin synthesised and released from?

Answer 34

synthesised in hypothalamus, released from posterior pituitary gland

Question 35

what causes oxytocin release?

Answer 35

- suckling and cervical dilatation | - oestrogen

Question 36

how does oestrogen, released at later stages of parturition, affect oxytocin?

Answer 36

- increased oxytocin release and oxytocin receptor expression - increased gap junctions

Question 37

why is oxytocin only effective at term?

Answer 37

requires oestrogen-induced oxytocin receptor expression

Question 38

uses of oxytocin?

Answer 38

- Induction of labour at term – does not soften cervix | - Treat / prevent post-partum haemorrhage

Question 39

low vs high oxytocin concentrations

Answer 39

Low concentrations of oxytocin increase frequency and force of contractions High concentrations cause hypertonus – may cause fetal distress

Question 40

name 2 synthetic versions of oxytocin

Answer 40

Syntocinon and Pitocin

Question 41

Ergot to ergometrine

Answer 41

- 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

Question 42

when might myometrial relaxants be used?

Answer 42

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

Question 43

name some myometrial relaxants

Answer 43

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

Question 44

Stimulation of beta 2-adrenoceptors on SM (vascular, airway, myometrial) produces relaxation - explain the mechanism

Answer 44

agonist eg. adrenaline binds to beta-2 receptor, activates PKA 1. increase in Ca2+ ATPase activity, so Ca2+ enters SR or leaves the SM cell 2. increase in K+ channel activity, causing hyperpolarisation and decreased Ca2+ entry via VGCCs 3. decreased MLCK