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Reproductive system > Pharmacology of the uterus > Flashcards

Pharmacology of the uterus Flashcards

1
Q

What is the smooth muscle layer of the uterus called?

A

Myometrium

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2
Q

Describe the structure of the Myometrial layers.

A
  • inner layer of circular fibres
  • middle layer with figure of 8 spiral fibres
  • outer layer of longitudinal fibres
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3
Q

How does the myometrium contract?

A

It is myogenic, providing rhythmic contractions

*doesn’t need activation of neuronal pathways or hormonal input, but still highly sensitive to neurotransmitters and hormones

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4
Q

How is the myometrium myogenic?

A

due to interstitial cells of Cajal (ICCs) which initiate and coordinate myometrial contractions by creating electrical signals via gap junctions

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5
Q

What are gap junctions made of?

A

connexion proteins

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6
Q

What do gap junctions allow for?

A

communication between cells via movement of molecules, ions and electrical impulses (electrical coupling)

the gap junctions therefore function as a syncytium to achieve synchronous contraction of the myometrium

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7
Q

Where are gap junctions located?

A

between ICCs
between ICCs and myometrial smooth muscle cells
between myometrial smooth muscle cells

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8
Q

Describe the process of Myometrium transduction.

A

1) ICC periodic activation of inward current
2) Causes depolarisation of smooth muscle cells (electrical coupling via gap junctions) which then opens VGCCs
3) Ca2+ influx through VGCCs
4) Increase in [Ca2+]i
5) Contraction of myometrial smooth muscles

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9
Q

What causes more sustained myometrial contractions?

A

slow waves of ICCs and smooth muscle responses mediated by neurotransmitters & hormones

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10
Q

Describe the Methods by which [Ca2+]i increases.

A
  • Ca2+ entry via VGCCs

- Ca2+ release from sarcoplasmic reticulum after IP3 binds IP3 receptors on SR

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11
Q

How does an increase in [Ca2+]i cause contraction?

A

1) Calmodulin (calcium sensor) binds Ca2+
2) Calmodulin activates myosin light chain kinase
3) Myosin light chain kinase phosphorylates myosin, allowing for myosin to interact with actin and increases ATPase activity of myosin, altering myosin structure and increasing its affinity for ATP, allowing it to be primed for contraction

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12
Q

How is depolarisation transmitted to adjacent cells?

A

via gap junctions

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13
Q

What must happen for rhythmic contractions of the myometrium?

A

A subsequent decrease in Ca2+ after the initial increase so the myometrial smooth muscle cells don’t stay contracted all the time

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14
Q

Give some Methods by which [Ca2+]i decreases.

A
  • Ca2+ pumped out of the cell via Ca2+ ATPase
  • Ca2+ taken up by sarcoplasmic reticulum via SERCA pumps to be stored
  • Ca2+ extruded via Na+/Ca2+ exchanger
  • small amount of Ca2+ stored in mitochondria
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15
Q

What is the Effect of ICC stimulant concentration on contraction?

A

Low concentration of stimulants on ICCs

  • increase in slow wave frequency
  • increased frequency of contractions

High concentration of stimulants on ICCs

  • increase in action potential frequency on top of slow waves
  • increase in frequency & force of contraction

Higher concentrations
-increase in plateau of slow wave producing sustained contractions

Large concentrations

  • hypertonus (incomplete relaxation) and Ca2+ extrusion processes not effective
  • interferes with foetal blood flow and causes foetal distress
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16
Q

Describe the innervation of the uterine.

A

Mostly sympathetic innervation

  • alpha adrenoceptor (aGq) causes contraction
  • beta 2 adrenoceptor (aGs) causes relaxation
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17
Q

What is the Effect of progesterone on uterine contraction?

A

inhibits uterine contraction

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18
Q

What is the Effect of oestrogen on uterine contraction?

A

increases uterine contraction

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19
Q

Describe the differences between Contractions in non-pregnant and pregnant uterus.

A

Non-pregnant

  • weak contractions in early cycle
  • strong contractions during menstruation (high prostaglandins, low progesterone)

Pregnant

  • weak and uncoordinated in early pregnancy (high progesterone)
  • strong and coordinated and parturition (high oestrogen)
20
Q

What is the Effect of oestrogen and progesterone on gap junctions?

A

Oestrogen increases expression of gap junctions

Progesterone decreases expression of gap junctions

*causes contraction/relaxation of myometrium at parturition

21
Q

What is the Effect of prostaglandins on uterus contraction?

A

Prostaglandins (PGE2 & PGF2a) induce myometrial contraction

  • coordinate increased frequency & force of contractions
  • increase gap junctions
  • soften cervix
22
Q

What promotes the synthesis of uterine prostaglandins and where are they produced?

A

Oestrogen promotes the synthesis of PGE2 & PGF2a either in the:

  • myometrium (autocrine)
  • endometrium (paracrine)

*oxytocin also increases synthesis of PGs to induce contraction

23
Q

What are the Side effects of uterine prostaglandins after parturition?

A

dysmenorrhoea (painful menstruation)
menorrhagia (prolonged bleeding)
pain

*treat using NSAIDs which reduce contractions and pain by inhibiting cyclo-oxygenase enzyme (which normally produces PGs)

24
Q

Name the Prostaglandin Analogues.

A

Dinoprostone (PGE2)
Carboprost (PGF2a)
Mistoprotol (PGE1)

25
Q

What are the Uses of prostaglandin analogues?

A

Induction of labour (pre term)
Induce abortion
Postpartum bleeding
Softening the cervix

26
Q

What are the Concerns of prostaglandin analogues?

A

Dinoprostone (PGE2) cause cause systemic vasodilation, resulting in acute hypotension and cardiovascular collapse

PGs can cause hypertonus causing foetal distress, however this is not a problem is inducing abortion

27
Q

Why do oxytocin levels increase during parturition?

A

Oestrogen released at later stages in parturition causes an increase in:

  • oxytocin and oxytocin receptors
  • gap junctions
28
Q

Why is oxytocin only effective at term?

A

because it requires oestrogen-induced oxytocin receptor expression, which is only available at later stages of parturition due to high oestrogen levels

29
Q

What are Oxytocin analogues?

A

Syntocinon & Pitocin

  • need high oestrogen levels to express oxytocin receptors
  • induce labour
  • treat/prevent post-partum haemorrhage
30
Q

Low concentrations of oxytocin analogue causes…

A

increased frequency & force of contractions

31
Q

High concentrations of oxytocin analogue causes…

A

hypertonus which may cause foetal distress

32
Q

What is Syntometrine?

A

combination of oxytocin (rapid) and ergot (prolonged) to cause contractions and prevent bleeding at the same time

33
Q

What is Ergot?

A

exogenous fungus that grows on some cereal (e.g. rye) and grasses

  • contains potent agents including ergot alkaloids (e.g. ergometrine, ergotamine), histamine, tyramine and ACh
  • when ingested it can cause ergotism, gangrene, convulsions and abortion
34
Q

What is Effect of ergot on uterine contractions?

A

causes prolonged uterine contractions- but only when myometrium is relaxed
-stimulates alpha adrenoceptors & 5-HT receptors

also used to treat post-partum bleeding (but not to induce abortion)

35
Q

When are Myometrial relaxants used?

A

used in pre-term labour

36
Q

Why are myometrial relaxants important in pre-term labour?

A

important to delay delivery by 48 hours so mother is transferred to specialist unit and given antenatal corticosteroids to aid foetal lung maturation and increase survival

37
Q

Give some Types of myometrial relaxants.

A

Beta 2 (aGs) adrenoceptor agonists

Ca2+ Channel antagonists

Oxytocin receptor antagonists

COX-inhibitors

*all used to prevent premature birth

38
Q

What is the use of Beta 2 (aGs) adrenoceptor agonists?

A

Salbutamol

  • relax uterine contractions by a direct action on myometrium
  • used to reduce strength of contractions in premature labour
39
Q

What is the use of Ca2+ Channel antagonists?

A

Nifedipine- used in hypertension

Mg Sulphate- used for pre-eclampsia, eclampsia and foetal neuroprotection

40
Q

Give a Oxytocin receptor antagonist.

A

Retosiban

41
Q

What is the use of COX inhibitors?

A

NSAIDs

  • decrease in PGs, decreasing contractions
  • may cause foetal renal dysfunction
42
Q

Name the Drugs to induce labour at term.

A

oxytocin (due to high oestrogen> oxytocin receptor expression)

43
Q

Name the Drugs to induce labour/termination in early term.

A

prostaglandins (because no oxytocin receptor expression)

44
Q

Name the Drugs used to treat/prevent post-partum bleeding.

A

prostaglandins, oxytocin, ergot

45
Q

Name the Drugs to prevent premature birth.

A

Myometrial relaxants:

  • B2 adrenoceptor agonists
  • Ca2+ channel antagonists
  • Oxytocin receptor antagonists
  • COX inhibitors
46
Q

What are the Methods of measuring uterine contraction?

A

Isometric Tension Reading
-measuring tension while diameter of muscle ring remains constant

Large Organ Baths
-e.g. aortic ring experiment

*these are widely used techniques to investigate the functional properties of uterine, vascular, airway and bladder smooth muscle segments

Reproductive system (12 decks)

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