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REPRODUCTION > Pharmacology of the Uterus > Flashcards

Pharmacology of the Uterus Flashcards

1
Q

What is the structure of the myometrium?

A
  • Outer longitudinal fibres
  • Middle figure of 8 fibres
  • Inner circular fibres
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2
Q

What does contraction of the myometrium cause?

A

Increases uterine content towards the cervix and acts as a natural ligature to prevent blood loss

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3
Q

What type of muscle is in 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

Highly sensitive to neurotransmitters and hormones

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5
Q

Why does the myometrium need to contract rhythmically?

A

For parturition (childbirth)

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6
Q

How is synchronous activity achieved?

A
  • Pacemaker cells called interstitial cells of Cajal (ICCs)
    • Initiate and coordinate contractions
    • Electrical communication via gap junctions made of connexion proteins
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7
Q

Where are gap junctions located?

What do they function as?

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 current = depolarisation

Ca2+ enters via VGCCs = increase of intracellular calcium = contraction

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9
Q

What modulates slow waves of ICCs and smooth muscle responses?

A

Slow waves of ICCs and smooth muscle responses are modulated by neurotransmitters and hormones

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10
Q

Describe the mechanism of smooth muscle contractions

A
  • Oxytocin or another substance binds to GCPR q/11
  • IP3 binds to SR and causes release of Ca2+ increasing intracellular Ca2+
  • DAG activates ion channels
  • Action of ion channels increase membrane excitabillity
  • = depolarisation
  • Activates VGCC’s induce Ca2+ influx
  • Increase intracellular calcium
  • Ca2+/calmodulin complex will activate MLCK
  • This phosphorylates myosin at a regulatory area caled myosin light chain at ser 19
  • Increases ATPase activity of myosin head x1000 fld
  • Allows myosin II to interact with actin forming actomyosin
  • A molecule of ATP will come along and cause contraction of smooth muscle
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11
Q

What does a graded response of calcium mean?

A

Incremental increases in calcium = incremental increases in force of contraction

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12
Q

What is a mechanism for lowering Ca2+?

A
  • This accounts for the relaxing phase of the wave of contraction
  • Removing calcium removes the contractile tone
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13
Q

Describe excitation contraction coupling

A

Distinctive pattern of electrical activity - Ca2+ changes - contraction

  • Low concentrations of stimulants on ICCs
    • slow wave frequency producing ­ frequency of contractions
  • Higher concentrations
    • frequency of action potentials on top of slow waves (i.e. ­peak [Ca2+]i) producing both ­ frequency and force of contractions
  • Higher concentrations still
    • plateau of slow wave producing prolonged sustained contractions
  • Large concentrations
    • Hypertonus (incomplete relaxation)
    • Ca2+ extrusion processes not effective
    • Important: Interfere with blood flow – foetal distress
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14
Q

What is hypertonus?

A

Incomplete relaxation

(Ca2+ processes are not effective - this is important as it interferes with blood flow = foetal distress)

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15
Q

What type of innervation does the myometrium recieve?

A

Sympathetic innervation

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16
Q

What receptors does the myometrium express?

A

α-adrenoceptor agonist – CONTRACTION coupled to Gq/11

β2-adrenoceptor agonist – RELAXATION coupled to Gas

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17
Q

What do alpha adrenoreceptor agonists cause?

A

Contraction - coupled to Gq/11

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18
Q

What do beta adrenoreceptor agonists cause?

A

Relaxation coupled to Gas

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19
Q

What does progesterone do on to the myometrium?

A

Inhibits contraction

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20
Q

What does oestrogen do on the myometrium?

A

Increases contraction

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21
Q

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

A
  • Weak contractions early in cycle
  • Strong contractions during menstruation - low progesterone, high prostaglandins
22
Q

Describe the regulation of the myometrium via sex hormones during pregnancy

A
  • Weak + uncoordinated in early pregnancy = high progesteronoe
  • Strong and co-ordinated at parturition = high oestrogen
23
Q

How doe the sex hormones increase during parturition?

A
  • Oestrogen/progesterone ratio increases during parturition
    • Oestrogen increases while progesterone decreases gap junction expression in myometrium
    • Oestrogen/ progesterone receptors are also found on ICCs
24
Q

What does the myometrium and endoemetrium synthesise?

A

They synthesise prostaglandins: PGE2 and PGF2a - promoted by oestrogens

25
Q

What do prostaglandins do?

A

induce myometrial contraction

26
Q

What do prostaglandins play a role in?

A
  • Dysmenorrhoea (severe menstrual pain)
  • Menorrhagia (severe menstrual blood loss)
    • Pain after parturition
27
Q

What drugs can reduce contraction and pain?

A

NSAIDs are effective reduce contracion and pain, inhibit the COX enzyme = reducing prostaglandin levels

28
Q

When are prostaglandins effective?

A

In early and middle pregnancy

29
Q

Give examples of prostaglandin analogues?

A
  • Dinoprostone (PGE2)
  • Carboprost (PGF2a)
  • Mistoprotol (PGE1)
30
Q

What are the uses of prostaglandin analogues?

A
  • Induction of labour - before term
  • Induce abortion
  • Postpartum bleeding
  • Softening the cervix
31
Q

What are the concerns of using prostaglandin analogues?

A
  • Dinoprostone can cause systemic vasodilatation
  • Potential for cardiovascular collapse (given as cervical gel/vaginal insert)
  • PGs – hypertonus and foetal distress (if used to induce labour however okay to induce abortion)
32
Q

What is the role of the hormone oxytocin?

A

Peptide hormone synthesised by the posterior pituitary gland

*

33
Q

What is oxytocin released in response to?

A

Suckling and cervical dilation

34
Q

What does oestrogen do in parturition?

A
  • Increases oxytocin release
  • Increases oxytocin receptors
  • Increased gap junctions
  • Oxytocin also increases synthesis of prostaglandins
35
Q

What time is oxytocin effective?

A

Only effective at term - requires oestrogen induced oxytocin expression

36
Q

What are two synthetic versions of oxytocin?

A

Syntocinon and pitocin

37
Q

What are the pharmacological actions of oxytocin analogues?

A
  • Low concentrations increase frequency and force of contractions
  • High concentrations cause hypertonus and may cause fetal distress
38
Q

Uses of oxytocin analogues?

A
  • Induction of labour at term – does not soften cervix
  • Treat / prevent post-partum haemorrhage
  • Syntometrine – oxytocin (rapid)/ergot (prolonged) combination
39
Q

What is ergot? how it it used for uterine contractions?

A

ERGOT = fungus which grows on some cereals

Contains array of potent agents inc. ergot alkaloids, histamine, tyramine and acetylcholine

When ingested can cause gangrene, convulsions and abortion

ACTION = powerful and prolonged uterine contraction - however only when myometrium is relaxed

40
Q

What does ergot act on?

A

Alpha adrenoreceptors and 5-HT receptors

41
Q

What are the uses of ergot?

A

Post-partum bleeding - not induction

(as myometrium also acts as a natural ligature for bleeding)

42
Q

Why are relaxants used in premature labour?

A
  • They will delay the delivery by 48 hours, this allows the mother to be transferred to a specialist unit and given antenatal corticosteroids to air foetal lung maturation and increase survival
43
Q

Give examples of myometrial relaxants

A
  • b2-adrenoceptor stimulants e.g. Salbutamol
  • Ca2+ channel antagonists e.g. nifedipine (used in hypertension) or Mg Sulfate
  • Oxytocin receptor antagonists e.g. Retosiban
  • COX inhibitors e.g. NSAIDs (decrease PG levels can treat dysmenorrhea and menorrhagia)
44
Q

What is the action of beta-2 adrenoceptor stimulants?

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
45
Q

What does stimulation of beta2 adrenoreceptors on smooth muscle do?

A
  • Causes adenylyl cyclase to change ATP to cAMP activating PkA
  • Increases Ca2+ ATPase to increase uptake into SR from the cell
  • Also increased K+ channel activity = hyperpolarisation decreasing in Ca2+ entry via VGCC’s
  • PkA also decreases the action of MLCK
    • All of these produce relaxation
46
Q

What induces labour at term?

A

Oxytocin

47
Q

What induces labour in early term and at term?

A

Early term: Prostaglandins (not oxytocin - no oxytocin receptors)

Induction of labour at term: Oxytocin

48
Q

What causes post-partum bleeding?

A

Prostaglandins, oxytocin, ergots

49
Q

What prevents premature birth?

A
  • b2-adrenoreceptor agonists
  • Ca2+ channel blockers, Mg Sulfate
  • Oxytocin inhibitors
50
Q

How is uterine contraction measured?

A

Using Isometric tension recording

= measure tension generated with diameter of the muscle ring remains constant

REPRODUCTION (11 decks)

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