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Repro > Pharmacology of the Uterus > Flashcards

Pharmacology of the Uterus Flashcards

1
Q

Describe the structure of the myometrium

A
  • Outer longitudinal fibres
  • Middle figure-eight fibres
  • Inner circular fibres
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2
Q

What does contraction of the myometrium do?

A

Increase in uterine pressure, forcing content towards the cervix and acts as a natural ligature to prevent blood lost.

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3
Q

What type of muscle is the myometrium?

A

Spontaneously active - myogenic

Produces regular contractions without neuronal or hormonal input

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4
Q

What is the myometrium sensitive to?

A

It is highly sensitive to neurotransmitters and hormones

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5
Q

Why does the myometrium contract rhythmically?

A

It contractions rhythmically for parturition

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6
Q

How is synchronous contraction achieved?

A

By pacemaker cells in the myomterium - the interstitial cells of cajal (ICCs) that initiate and coordinate contractions
- Electrical communication via gap junctions made of connexion proteins

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7
Q

Where are the gap junctions located and what do they do?

A
  • Between ICCs
  • Between ICCs and smooth muscle cells
  • Between smooth muscle cells
  • Function as a syncytium
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8
Q

Describe the electrical activity of the myometrium

A

ICC periodic activation of inward currents which causes depolarisation. Calcium enters via VGCCs and increases intracellular calcium levels and causes contraction.

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9
Q

What modulates the slow waves of ICCs and smooth muscle responses?

A

Neurotransmitters and hormones

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10
Q

Briefly describe the mechanism of smooth muscle contractions

A
  • Oxytocin or another substance binds to a GCPR q/11.
  • IP3 binds to SR and causes release of Calcium and increases intracellular calcium
  • DAG activates ion channels.
  • Action of ion channels increases membrane excitability
  • Causes depolarisation
  • Activates VGCCs which induces Ca2+ influx
  • Increase of intracellular calcium
  • Activates calmodulin, activates myosin light chain kinase that cause the reaction between the myosin head and the actin.
  • This causes contraction
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11
Q

What is the graded response of calcium?

A

Incremental increases in calcium -> incremental increases in force of contraction

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12
Q

What is excitation - contraction coupling?

A
  • Increase in slow wave frequency producing high frequency of contractions
  • Increase in frequency of action potentials on top of slow waves producing both high frequency and force of contractions
  • Increase plateau of slow wave producing prolonged sustained contractions
  • Hypertonus
  • Ca2+ extrusion processes not effective
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13
Q

What is hypertonus?

A

It is incomplete relaxation

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14
Q

What type of innervation does the myometrium receive?

A

Sympathetic innervation

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15
Q

What receptors does the myometrium express?

A

Express:

  • Alpha-adrenoreceptors
  • Beta adrenoreceptors
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16
Q

What do alpha adrenoreceptor agonists cause?

A

Contraction

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17
Q

What does beta adrenoreceptors cause?

A

Relaxation

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18
Q

What does progesterone do on the myometrium?

A

It inhibits contraction

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19
Q

What does oestrogen do on the myometrium?

A

It increases contraction

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20
Q

Describe the regulation of the myometrium via sex hormones during non-pregnancy

A

Weak contractions early in the cycle

Strong contractions during menstruation (low progesterone, high prostaglandins)

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21
Q

Describe the regulation of the myometrium via sex hormones during pregnancy

A

Weak and uncoordinated in early pregnancy (high progesterone)
Strong and co-ordinated at parturition (high oestrogen)

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22
Q

What increases during parturition?

A

Oestrogen/Progesterone ratio increases
Oestrogen increases while progesterone decreases gap junction expression in myometrium
Oestrogen/Progesterone receptors are also found on ICCs

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23
Q

What does the myometrium and endometrium synthesise?

A

They synthesise prostaglandins: PGE2 and PGF2a - promoted by oestrogens.

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24
Q

What do the prostaglandins do?

A

They induce myometrial contraction

25
Q

What is dysmenorrhoea?

A

Severe menstrual pain

26
Q

What is menorrhagia?

A

Severe menstrual blood loss

27
Q

What drugs can reduce contraction and pain?

A

NSAIDs

28
Q

What do NSAIDs and Prostaglandins do?

A

They act together to:

  • Coordinate high frequency/force of contractions
  • High gap junctions
  • Soften cervix
29
Q

When are prostaglandins effective?

A

In early and middle pregnancy

30
Q

What are analogues?

A

Compounds with a molecular structure closely similar to that of another

31
Q

Give examples of prostaglandin analogues

A
  • Dinoprostone (PGE2)
  • Carboprost (PGF2a)
  • Mistoprotol (PGE1)
32
Q

What are the uses of prostaglandin analogues?

A
  • Induction of labour; before term
  • Induce abortion
  • Postpartum bleeding
  • Softening the cervix
33
Q

What are the concerns of the use of prostaglandin analogues?

A
  • Dinoprostone can cause systemic vasodilatation
  • Potential for cardiovascular collapse
  • Cause hypertonus and foetal distress
34
Q

What is oxytocin?

A

It is a non-peptide hormone synthesised in the hypothalamus and released from the posterior pituitary gland

35
Q

What is oxytocin released in response to?

A

In response to suckling and cervical dilatation

36
Q

What does oestrogen do in parturition?

A

Increases oxytocin release
Increases oxytocin receptors
Increased gap junctions

37
Q

What does oxytocin increase?

A

It increases synthesis of prostaglandins

38
Q

What time is oxytocin only effective?

A

It is only effective at term - requires oestrogen-induced oxytocin receptor expression.

39
Q

Name 2 synthetic oxytocin drugs

A

Syntocinon

Pitocin

40
Q

What are the pharamcological actions of oxytocin analogues?

A
  • Low concentrations increase frequency and force of contractions
  • High concentrations cause hypertonus and may cause fetal distress
41
Q

What are the uses of oxytocin analogues?

A
  • Induce labour at term - does not soften cervix
  • Treat/prevent post-partum haemorrhage
  • Syntometrine - oxytocine (rapid) / ergot (prolonged) combination
42
Q

What is ergot?

A

Fungus that goes on some cereals (e.g. Rye) and grasses

43
Q

What does ergot contain?

A

It contains array of potent agents inc. ergot alkaloids (e.g. ergometrine, ergotamine; both based on LSD moiety), histamine, tyramine and acetylcholine

44
Q

What happens when ergot is ingested?

A
  • Ergotism
  • Gangrene
  • Convulsions
  • Abortion
45
Q

What is the action of ergot?

A
  • Powerful and prolonged uterine contraction, but only when the myometrium is relaxed
46
Q

What does ergot act on?

A

It stimulates alpha adrenoreceptors and 5-HT receptors

47
Q

What are the uses of ergot?

A

Post-partum bleeding - Not induction

48
Q

Why are relaxants used in premature labour?

A

They can delay delivery by 48 hours, so the mother can be transferred to specialist unit, and given antenatal corticosteroids to aid foetal lung maturation and increase survival.

49
Q

What are beta2 adrenoreceptor stimulants used for?

A
  • Relax uterine contractions by a direct action on the myometrium
  • Used to reduce strength of contractions in premature labour
  • May occur as a side effect of drugs used in asthma
50
Q

Give an example of beta 2 adrenoreceptors

A

salbutamol

51
Q

Give examples of calcium channel antagonists

A

Nifedipine (used in hypertension)

Mg Sulfate

52
Q

Give an example of oxytocin receptor antagonists

A

Retosiban

53
Q

Give an example of COX inhibitors

A

NSAIDs

54
Q

What does the stimulation of beta2 adrenoreceptors on smooth muscle do?

A

It causes the adenylyl cyclase to change ATP to cAMP activates PkA. This increases Ca2+ ATPase (SERCA) to increase uptake into SR/exculsion from the cell. It also increases K+ channel activity, causing hyperpolarisation decreasing in Ca2+ entry via VGCCs.
PkA also dereases the action of MLCK.
All of these produce relaxation

55
Q

What induces labour at term?

A

Oxytocin

56
Q

What induces labour/termination in early term?

A

Prostaglandins

57
Q

What causes post-partum bleeding?

A

Prostaglandins
Oxytocin
Ergots

58
Q

What prevents premature birth?

A

Beta2 adrenoreceptor agonists
Ca2+ channel blockers, Mg Sulfate
Oxytocin inhibitors

59
Q

How is uterine contraction measured?

A

Isometric tension recording

- Measure tension generated with diameter of the muscle ring remains constant

Repro (11 decks)

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