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Reproduction > Pharmacology Of The Uterus > Flashcards

Pharmacology Of The Uterus Flashcards

1
Q

What are the three layers making up the smooth muscle of the uterus?

A

→ Outer longitudinal fibres
→ Middle figure eight fibres

→ Inner circular fibres

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2
Q

What do uterine contractions do?

A

→ Increase uterine pressure
→ Forces content towards the cervix

→ acts as a natural ligature to prevent blood loss

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3
Q

What is the activity of the myometrium like?

A

→ Spontaneously active basal electrical activity

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4
Q

What kind of contractions are there in parturition?

A

→ Rhythmic
→Contractions originate in the muscle itself
→Doesn’t require neuronal or hormonal input
→BUT highly sensitive to e.g. sex hormones

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5
Q

What is the myometrium sensitive to?

A

→ Neurotransmitters

→ Hormones

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6
Q

What type of cells are in the myometrium?

A

→ ICC pacemaker cells

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7
Q

How is synchronous contraction achieved?

A

→ Electrical communication between gap junctions

→ electrical activity is transmitted to adjacent cells

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8
Q

Where is electrical activity transmitted between in the myometrium?

A

→ Between ICCs
→ between ICC and smooth muscle

→ between smooth muscle cell

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9
Q

How do the myometrium cells function as?

A

→ A syncytium

→Different areas of uterus contract as one

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10
Q

Describe how contraction occurs

A

→ ICC periodic activation of inward currents
→ depolarisations

→ Ca2+ entry through VGCC
→ Intracellular calcium leads to contraction

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11
Q

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

A

→ Neurotransmitters and hormones

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12
Q

Describe how calcium is increased inside the cell

A

Slow wave of depolarisation
↓

Ca2+ channels get activated
↓
Ca2+ entry increases Ca2+
↓
Ca2+ binds to calmodulin
↓
This phosphorylates myosin light chain kinase
↓
actin interaction lead to contractions
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13
Q

Describe how oxytocin leads to increased Ca2+

A

Oxytocin is Gq couples
↓

Activation of phospholipase C
↓
PIP2 → DAG + IP3
↓
IP3 binds to IP3 receptors in the SR
↓
Causes Ca2+ from the store to be released into the cytosol
↓
Ca2+ increases
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14
Q

What are smooth muscle cells joined by?

A

→ Gap junctions

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15
Q

How can intracellular calcium be reduced?

A

→ Na+/Ca2+ exchanger
→ Ca2+ pump

→ some Ca2+ gets taken into the mitochondria

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16
Q

What is the effect of low concentrations of stimulants on ICCs?

A

→ Increase in slow wave frequency producing

→ Increase in frequency of contractions

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17
Q

How is the myometrium similar to other smooth muscle tissues?

A

→ There is a graded response - no threshold

→ increases in Ca2+ lead to increases in force of contraction

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18
Q

What is the effect of higher concentrations of stimulants on ICCs?

A

→ Increased frequency of action potentials on top of slow waves
→ Increased frequency and force of contractions

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19
Q

What is the effect of even higher concentrations of stimulants on ICCs?

A

→ plateau of slow wave producing prolonged sustained contractions

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20
Q

What is the effect of large concentrations of stimulants on ICCs?

A

→ hypertonus (incomplete relaxation)
→Ca2+ extrusion process is not as effective

→ interferes with blood flow - fetal distress

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21
Q

What innervation does the myometrium have?

A

→ Sympathetic

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22
Q

What receptors does the myometrium express?

A

→ alpha and beta adrenoceptors

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23
Q

What is the effect of alpha 1 adrenoceptor agonist?

A

→ contraction

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24
Q

What is the effect of beta 2 adrenoceptor agonist?

A

→ relaxation

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25
Q

What are alpha 1 adrenoceptors coupled with?

A

→ Gq

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26
Q

What are beta 2 adrenoceptors coupled with?

A

→ Gs

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27
Q

How does the Gs transduction mechanism work?

A

→ Stimulates the formation of cAMP
→ cAMP inhibits myosin light chain kinase

→ less contractile force

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28
Q

What effects do progesterone and estrogen have on contraction?

A

→ Progesterone - inhibits contraction

→ Estrogen - increases contraction

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29
Q

What contractions does a non-pregnant uterus have?

A

→ Weak contractions early in the cycle

→ Strong during menstruation (increased prostaglandins

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30
Q

Why does the myometrium contract during menstruation?

A

→ Increased prostaglandins and decreased progesterone

31
Q

What contractions does a pregnant uterus have?

A

→ Weak and uncoordinated in early pregnancy ( high progesterone)
→ strong and coordinated at parturition ( increased estrogen)

32
Q

What increases and decreases gap junction expression in the myometrium?

A

→ Increases - estrogen

→ Decreases - progesterone

33
Q

Where are estrogen and progesterone receptors also found?

A

→ ICCs

34
Q

What prostaglandins do the myometrium and endometrium synthesize?

A

→ synthesize PGE2 and PGF2alpha - promoted by estrogens

35
Q

What do prostaglandins induce?

A

→ Myometrial contractions
→ dysmenorrhoea

→ menorrhagia

36
Q

What helps with pain and contraction?

A

→ NSAIDs

37
Q

What is the function of prostaglandins?

A

→ Coordinate an increase and force of contractions
→ increase gap junctions

→ soften cervix

38
Q

What are 3 prostaglandin analogues?

A

→ Dinoprostone (PGE2)
→ Carboprost (PGF2a)

→ Misoprostol (PGE1)

39
Q

What is the function of PGE2?

A

→ Smooth muscle dilator around the body?

40
Q

What are the 4 uses of prostaglandin analogues?

A

→ Induction of labour - before term
→ induce abortion

→ postpartum bleeding
→ softening the cervix

41
Q

What is a side effect of dinoprostone?

A

→ Systemic vasodilation
→ cardiovascular collapse

→ hypertonus and fetal distress

42
Q

How is dinoprostone given to reduce side effects?

A

→ Gel

43
Q

What is oxytocin?

A

→ A non peptide hormone synthesised in the hypothalamus and released from the posterior pituitary gland

44
Q

When is oxytocin released?

A

→ In response to suckling

→ cervical dilatation

45
Q

Why is oxytocin not effective in earlier stages?

A

→ Receptors are not expressed pre term so they are not effective

46
Q

What does estrogen produce in the later stages of parturition?

A

→ Increased oxytocin release
→ Increased oxytocin receptors

→ increased gap junctions

47
Q

What is the function of oxytocin?

A

→ Increases the synthesis of prostaglandins

48
Q

What is ergot?

A

→ Fungus that grows on some cereals

49
Q

What happens when you ingest ergot?

A

→ Ergotism
→ Gangrene

→ convulsions
→ abortion

50
Q

What is the action of ergot on the myometrium?

A

→ Powerful and prolonged uterine contraction when myometrium is relaxed

51
Q

What is the mechanism of action of ergot?

A

→Stimulation of alpha adrenoceptors

→ 5-HT receptors

52
Q

What are the uses of ergot?

A

→ postpartum bleeding

→ not induction

53
Q

Why are myometrial relaxants given?

A

→ Delay delivery by 48h

→ mother can be given antenatal corticosteroids to help fetal lung maturation- surfactants

54
Q

What is an example of a b2 adrenoceptor stimulant?

A

→ Salbutamol

55
Q

How does salbutamol work?

A

→ relaxes uterine contractions by direct action on the myometrium
→ increases Ca2+ uptake into SR - Ca2+ not available for contraction

56
Q

What is salbutamol used for?

A

→ Reduce strength of contractions in premature labour

57
Q

What is an example of a Ca2+ channel antagonist?

A

→ Nifedipine

→ Mg sulfate

58
Q

What is an example of an oxytocin receptor antagonist?

A

→ Retosiban

59
Q

How do NSAIDs work?

A

→ Decrease prostaglandins

60
Q

What is an example of a COX inhibitor?

A

→ NSAIDs

61
Q

What is a side effect of NSAIDs?

A

→ Can cause fetal renal dysfunction

62
Q

What does stimulation of beta 2 adrenoceptors cause?

A

→ Smooth muscle relaxation

63
Q

How does beta 2 adrenoceptor stimulation work?

A

→ PKA activity
→ Increased Ca2+ activity which increases uptake into SR

→ Increases K+ channel activity → hyperpolarisation and decreased Ca2+ entry via VGCC
→ Downregulates MLCK

64
Q

What is used for induction of labour?

A

→ Oxytocin

65
Q

What is used for induction of labour/termination in early term?

A

→ Prostaglandins ( because no oxytocin receptors)

66
Q

What is used for postpartum bleeding?

A

→ Prostaglandins
→ Oxytocin

→ Ergots

67
Q

What is used to prevent premature birth?

A

→ Beta 2 adrenoceptor agonists
→ Ca2+ channel blockers

→ oxytocin inhibitors

68
Q

What are the 2 ways to measure uterine contractions?

A

→ Isometric tension recording

→ Measure tension generated with diameter of muscle ring remaining constant

69
Q

What happens 7 month till term?

A

→Oestrogen increases, progesterone stays constant

70
Q

What are prostaglandins?

A

→induce myometrial contraction (PGE and PGF)

71
Q

What happens to the oestrogen/progesterone ration in the last trimester?

A

→increases throughout last trimester

→culminating with strong, coordinated contractions for delivery

72
Q

What are myometrial contractility sensitive to?

A

→sex hormones, oxytocin and prostaglandins

73
Q

Why can’t oxytocin be given before term?

A

→oxytocin receptors increase as pregnancy increase.

→If given too early- no effect

Reproduction (12 decks)

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