Pharmacology Of The Uterus Flashcards
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
STRUCTURE OF MYOMETRIUM
diagrams Smooth muscle of the uterus •Outer longitudinal fibres •Middle figure-eight fibres •Inner circular fibres
MECHANICAL PROPERTIES OF
MYOMETRIUM
Rhythmic contractions Spontaneously active Vary during menstrual cycle and pregnancy Force content towards the cervix Contractions originate in the muscle itself Doesn’t require neuronal or hormonal input BUT highly sensitive to e.g. sex hormones
SO WHAT INITIATES THE
CONTRACTION?
Spontaneous depolarisation of ‘pacemaker’ cells Give rise to action potentials Electrical communication between cells Gap junctions spread depolarisation Myometrium can function as a syncytium
EXCITATION-CONTRACTION
COUPLING
Slow waves of pacemakers and smooth muscle responses are modulated
by neurotransmitters and hormones
diagrams
BASAL AND ELEVATED [CA2+]I
Similar to other smooth muscle tissues
• [Ca2+]i contraction
•Graded response: incremental increases in [Ca2+]i incremental
increases in force of contraction
•Mechanisms for lowering [Ca2+]i: e.g. Ca2+ extrusion
diagram
CONTRACTION MODULATED BY
HORMONES AND NEUROTRANSMITTERS
diagram
HOW TO MEASURE UTERINE
CONTRACTION?
• E.g. Isometric tension recording
Measure tension generated with diameter of the muscle ring remains constant
• Y1 practicals: Large organ baths – aortic ring experiments
• Widely used techniques to investigate the functional properties of uterine, vascular, airway and bladder smooth muscle segments
OXYTOCIN-INDUCED CONTRACTIONS
diagrams
ION CHANNEL MODULATORS
diagram
REGULATION BY NEUROTRANSMITTERS
Sympathetic (not parasympathetic) innervation
Expression of α- and β- adrenoceptors
α-adrenoceptor agonist – contraction
β2-adrenoceptor agonist – relaxation
REGULATION BY SEX HORMONES
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 contactions in early 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
diagrams
REGULATION BY OXYTOCIN
Non-peptide hormone synthesised in hypothalamus and released from the 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
REGULATION BY PROSTAGLANDINS
Prostaglandins induce myometrial contraction (PGE and PGF)
Role in dysmenorrhoea (severe menstrual pain), menorrhagia (severe menstrual blood loss), pain after parturition
NSAIDs are effective – reduce contraction and pain
Oxytocin stimulates release of prostaglandins
Contractile Agents
diagram
Ergot to ergometrine
• Ergot - fungus that grows on some cereals (e.g. rye) and grasses
• Contains ergometrine
Action• Powerful and prolonged uterine contractionMechanism• Stimulation of -adrenoceptors, 5-HT receptors?
Uses• Post-partum bleeding - NOT induction
Oxytocin and Prostaglandins
Oxytocin Used to induce/augment labour at term Dose dependent increases in contraction – but too much can cause sustained contraction and fetal distress Also used in postpartum haemorrhage
Prostaglandins
Induction of labour – before term
Induce abortion
Postpartum bleeding
Myometrial Relaxants
Relaxants may be used in premature labour
• Important: Delay delivery by 48 hrs, so Mother can be transferred to specialist unit, and given antenatal corticosteroids to aid foetal lung maturation and increase survival
- 2-adrenoceptor stimulants e.g. ritodrine
- 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
- Ca2+ channel antagonists e.g. nifedipine (used in hypertension) or Mg Sulfate
- Oxytocin receptor antagonists e.g. Retosiban
- COX inhibitors e.g. NSAIDs
- ( prostaglandin) – why NSAIDS are useful to treat dysmenorrhoea and menorrhagia
