Pharmacology Of The Uterus Flashcards
Describe the structure of the Myometrium
Has 3 different layers of smooth muscles
- An outer layer with Longitudinal fibres
- Middle figure eight fibres (mesh like)
- Inner circular fibres
What are some mechanical properties of the Myometrium?
Rhythmic contractions
- Spontaneously active
- Vary during menstrual cycle and pregnancy
- Force content towards the cervix
Where do these rhythmic contractions originate from?
- Contractions originate in the muscle itself
- doesn’t require neuronal or hormonal input
- But highly sensitive to sex hormones
What initiates the contractions?
- Spontaneous depolarisation of pacemaker cells
- These give rise to action potentials
- Electrical communication between cells
- Gap junctions spread depolarisation
- Myometrium can function as a syncytium
Describe the excitation contraction coupling mechanism
- Mechanical activity of smooth muscle causes an increase in tension
- Membrane potential of pacemakers
- This causes electrical activity being conducted by syncytium to SMCs
How are pacemakers and smooth muscle responses controlled?
Slow waves of pacemakers and smooth muscle responses are modulated by neurotransmitters and hormones
Describe the steps in which a contraction is caused by hormones/neurotransmitters
- Ca2+ Calmodulin
- Forms myosin Light chain Kinase
- Myosin light chain/actin interactions
- Contractions
Describe some properties of the uterus
- Has strong contractile properties due to smooth muscle content of the Myometrium
- Spontaneously contractile
- Pacemaker cells initiate depolarisation which can spread from cell to cell
- Depolarisation results in calcium entry = contraction
What are the 2 hormones used in sex regulation?
Progesterone
Oestrogen
State some similarities and differences between progesterone and oestrogen
- Oestrogen increases contraction
- Progesterone inhibits contraction
- Both act at nuclear and membrane receptors
How are neurotransmitters used in regulation?
Sympathetic innervation
- Expression of alpha and beta adrenoreceptors
- A adrenoceptor agonist: Contraction
- B2 adrenoceptor agonist: Relaxation
Describe the hormonal changes of the uterus during pregnancy
- Weak and uncoordinated contractions in early pregnancy (high progesterone)
- 7 month til term: Oestrogen increases, Progesterone stays constant
- Oestrogen/Progesterone ratio increases throughout last trimester culminating with strong coordinated contractions for delivery
Where are non peptide hormones synthesised and released into?
- Non peptide hormone synthesised in hypothalamus
- It is then released from the posterior pituitary gland
- Released in response to suckling and cervical dilatation
What does Oestrogen release?
Oxytocin
What does Oxytocin do?
- Increases the expression of oxytocin receptors
- Also increases the synthesis of prostaglandins
- Oxytocin stimulates the release of prostaglandins
What does Prostaglandins induce?
Myometrial contraction (PGE and PGF)
What does prostaglandins have a role in?
Role in:
- Dysmenorrhea
- Menorrhagia
- Pain after parturition
What are NSAIDs? What do they do?
- NSAIDs are effective
- Reduce contraction and pain
Provide a summary of this part
- 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: act in concert for delivery
State the contractile agents of the Myometrium
- Ergots
- Oxytocin
- Prostaglandins
What is an Ergot?
- A fungus that grows on some cereals and grasses
- Contains Ergometrine
What action does an Ergot carry out?
Powerful and prolonged uterine contraction
What is the neuro mechanism of the Ergot?
Stimulation of the ã adrenoceptors, 5 HT receptors
Describe what Oxytocin is used for
- Used to induce/augment labour
- Dose dependent increases in contraction
- But too much can cause sustained contraction and fetal distress
- Also used in postpartum haemorrhage
Describe what prostaglandins are used for
- Induction of labour
- Induce abortion
- Postpartum bleeding
Describe Myometrial relaxants
- Relaxants May be used in premature labour
- Delay delivery by 48 hours so mother can be transferred to specialist unit and given antenatal corticosteroids to aid foetal lung maturation and increase survival
- Progesterone can be used in preterm labour or to prevent miscarriage
What are some Myometrial relaxants?
- Ca2+ channel antagonists e.g nifedipine
- Oxytocin receptor antagonists e.g Retosiban
- Ā2 adrenoceptor stimulants e.g terbutaline sulfate
- Relax uterine contractions by a direct action on the Myometrium
- Used to reduce strength of contractions in premature labour
- No longer recommended in uncomplicated preterm labour
