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Physiology 2 > Pharmacology of the Uterus (repro) > Flashcards

Pharmacology of the Uterus (repro) Flashcards

1
Q

Structure of Myometrium

A

Smooth muscle of uterus (3 layers):

  • outer longitudinal fibres
  • middle figure-eight fibres
  • inner circular fibres
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2
Q

Mechanical properties of myometrium

A

Rhythmic contractions:

  • spontaneously active
  • vary during menstrual cycle and pregnancy
  • force content towards cervix

Contractions originate in muscle itself:

  • doesn’t require neuronal or hormonal input
  • but highly sensitive eg to sex hormones
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3
Q

What initiates contraception?

A
  • spontaneous depolarisation of pacemaker cells (give rise to action potentials)
  • electrical communication between cells
  • gap junctions spread depolarisation
  • myometrium can function as a syncytium
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4
Q

Excitation-contraction coupling

A
  • mechanical activity of smooth muscle (increase in tension)
  • membrane potential of pacemakers (action potentials and slow waves)
  • electrical activity is conducted by syncytium to SMCs
  • slow waves of pacemakers and smooth muscle responses are modulated by neurotransmitters and hormones
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5
Q

Basal and Elevated Ca2+

A
  • similar to other smooth muscle tissues
  • increased Ca2+ leads to contraction
  • graded response: incremental increase in Ca2+ leads to incremental increases in force of contraction
  • mechanisms for lowering Ca2+ (eg Ca2+ extrusion
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6
Q

Contractions modulated by hormones and neurotransmitters

A

eg Oxytocin:

  • action of ion channels increase membrane excitability
  • causes depolarisation
  • activation of VGCCs induces Ca2+ influx
  • increased Ca2_ leads to it binding to calmodulin
  • myosin light chain kinase is produced
  • causes myosin light chain/actin interactions
  • this causes contractions
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7
Q

How to measure uterine contraction?

A
  • isometric tension recording:
  • measure tension generated with diameter of the muscle ring remains constant
  • large organ baths (aortic ring experiments)
  • widely used techniques to investigate the functional properties of uterine, vascular, airway and bladder smooth muscle segments
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8
Q

Summary of pharmacology of uterus

A
  • uterus has strong contractile properties due to smooth muscle content the myometrium
  • spontaneously contractile
  • pacemaker cells initiate depolarisation which can spread from cell to cell
  • depolarisation results in calcium entry and contractions
  • contractile activity can be modulated by hormones or neurotransmitters
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9
Q

Regulation of myometrial contractility by neurotransmitters

A
  • sympathetic innervation
  • expression of alpha and beta adrenoceptors
  • alpha-adrenoceptor agonist causes contraction
  • beta2-adrenoceptot agonist causes relaxation
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10
Q

Regulation of myometrial contractility by sex hormones

A
  • progesterone inhibits contraction
  • oestrogen increases contraction
  • both act at nuclear and membrane receptors

non pregnant uterus:
- weak contractions early in cycle
- strong contractions during menstruation (progesterone low)
pregnant uterus:
- weak and uncoordinated contractions early in pregnancy (high progesterone)
- 7 month till term, oestrogen increases, progesterone stays constant
- oestrogen: progesterone ratio increases throughout last trimester culminating with strong, coordinated contractions for delivery

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11
Q

Regulation of myometrial contractility by oxytocin

A
  • non-peptide hormone synthesised in hypothalamus and released from posterior pituitary gland
  • released in response to suckling and cervical dilatation
  • oestrogen (released at later stages of pregnancy) causes:
  • oxytocin release, increase expression of oxytocin receptors
  • oxytocin also increases synthesis of prostaglandins
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12
Q

Regulation of myometrial contractility by prostaglandins

A
  • prostaglandins induce myocetrial contraction (PGE and PGF)
  • role in dysmenorrhoea (severe menstrual pain), menorrhagia (severe menstrual blood loss), pain after parturition
  • NSAIDs are effective which reduce contraction and pain
  • oxytocin stimulates release of prostaglandins
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13
Q

Summary of myometrial contractility

A
  • myometrial contractility is sensitive to sex hormones, oxytocin and prostaglandins
  • progesterone and oestrogen have opposite effects which links to contractility during menstrual cycle or in pregnancy
  • oxytocin and prostaglandins increase contractility
  • oestrogen can stimulate oxytocin release, oxytocin stimulates PG synthesis - acts in concert for delivery
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14
Q

Ergot to ergometrine

A
  • Ergot: fungus that grows on some cereals (eg rye) and grasses
  • contains ergometrine
  • action: powerful and prolonged uterine contraction
  • mechanism: stimulation of alpha-adrenoreceptors and 5-HT receptors
  • uses: postpartum bleeding (not induction)
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15
Q

Oxytocin and Prostaglandins

A

Oxytocin:

  • used. to induce/ augment labour at term
  • dose dependant increases in contraction but too much can cause sustained contraction and foetal distress
  • also used in postpartum haemorrhage

Prostaglandins:

  • induction of labour (before term)
  • induce abortion
  • postpartum bleeding
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16
Q

Myometrial relaxants

A
  • relaxants may be used in premature labour
  • delay delivery by 48hrs so mother can be transferred to specialist unit and given antenatal corticosteroids to aid foetal lung maturation and increase survival

Types of relaxants:

Beta2-adrenoreceptor stimulants:
- eg ritodrine
- relax uterine contractions by a direct action on myometrium
- used to reduce strength of contractions in premature labour
- may occur as a side effect of drugs used in asthma
Ca2+ channel antagonists:
- eg nifedipine (used in hypertension) or Mg sulphate
Oxytocin receptor antagonists:
- eg Retosiban
COX inhibitors:
- eg NSAIDs
- lower level of prostaglandin means NSAIDS are useful to treat dismenorrhoea and menorrhagia

17
Q

Summary of hormones in uterus

A 
Induction of labour:
- oxytocin 
Induction of labour/ termination in early term:
- prostaglandins (not oxytocin - no oxytocin receptors)
Post-partum bleeding:
- prostaglandins, oxytocin, ergots 
Prevent premature birth:
- beta2-adrenoreceptor agonists
- Ca2+ channel blockers, Mg sulphate 
- oxytocin inhibitors
18
Q

Glossary

A
  • Myometrium – smooth muscle layer(s) of the uterus
  • Gap junctions – connections between cells that allow - transfer of (electrical) signal
  • VGCC – voltage-gated calcium channels
  • Parturition – childbirth
  • Ergometrine – a potent contractor of the uterus found in ergot
  • Functional syncytium – a mass of cells that function as one

Physiology 2 (38 decks)

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