Pharmacology of the Uterus

Question 1

MYOMETRIUM:
What are the 3 muscular layers it consists of?

How does its contraction aid in labour?

What’s it described to be?

How does Oestrogen and Progesterone affect it?

What are the contractions like in a Non-pregnant uterus? What’s it due to?

What are the contractions like in a Pregnant uterus? What’s it due to?

What is it innervated by? What do the receptor types cause?

Answer 1

• Inner Circular, Middle “Figure-of-8”, Outer Longitudinal fibres
• Leads to increased Intrauterine pressure, which forces its contents down towards the cervix
• Myogenic
• • Oestrogen - INCREASES contraction
  • Progesterone - INHIBITS contraction
• • Weak contractions early in cycle
  • Strong contractions during menstruation - ↓Progesterone, ↑Prostaglandins
• • Weak, uncoordinated contractions in early pregnancy
  • Strong, coordinated contractions during labour (↑Oestrogen)
• Sympathetics (ANS)
  o α adrenoceptors = CONTRACTION
  o β2 adrenoceptors = RELAXATION

Question 2

SYNCHRONOUS CONTRACTION:
What cell type causes the contractions?

What is Electrical coupling in the myometrium?

What does the Uterus act as when it has electrically connected cells?

How does Oestrogen affect this coupling system?

Answer 2

• Interstitial Cells of Cajal (ICCs), which initiate and coordinate contraction
• Electrical activity moves from ICC to SMCs through Gap junctions, made of Connexin proteins
• SYNCYTIUM
• Increases expression of gap junctions to promote contraction

Question 3

SLOW WAVES AND ACTION POTENTIALS:
What are the Slow waves?

How do Action potentials lead to a contraction?

What type of receptor is an Oxytocin receptor? How does its activation lead to contraction?

CONTRACTILITY:
What occurs when there’s a LOW concentration of stimulants on ICC/SMCs?

What occurs when there’s a HIGHER concentration of stimulants on ICC/SMCs?

What occurs when there’s a VERY HIGH concentration of stimulants on ICC/SMCs?
→ What can this lead to?

Answer 3

• Slow depolarisations produced by ICCs
• Causes Opening of VGCCs = ↑[Ca2+] =
  Formation of Ca-Calmodulin complex = Activation of MLCK = Contraction
• GPCRs, which cause ↑DAG/IP3 = ↑[Ca2+] = Contraction

• ↑Slow wave frequency leads to ↑SMC contraction
• ↑Action potential frequency on top of the slow waves, leading to Prolonged and Sustained SMC contractions
• HYPERTONUS - Single contraction lasting longer than 2 minutes; Incomplete relaxation due to Ca-raising mechanisms being much greater than the Ca-lowering mechanisms
  → Hypertonus can interfere with blood flow = Foetal distress, Prevent bleed

Question 4

OXYTOCIN:
What is it? Where is it produced and released? What stimulates its release?

What are its synthetic forms?

What is its action dependant on? How?

When is it only effective?

What occurs when there are LOW and HIGH concentrations of it?

What are its uses?

Answer 4

• Nonpeptide hormone produced in Hypothalamus and released from Posterior Pituitary
  o Released in response to Suckling and Cervical dilatation
• Pitocin/Syntocinon
• OESTROGEN - its released at later stages of labour causing ↑Oxytocin release, ↑Oxytocin receptors and ↑Gap junctions
• AT TERM
• • Low = ↑Frequency/Force of contraction
  • High = Hypertonus
• • INDUCTION of labour AT TERM
  • Treat/prevent Post-partum Haemorrhage

Question 5

PROSTAGLANDINS:
What are 2 types? What do they cause? Where are they produced?

What stimulates its production?

What is involved in? How? What is therefore effective to use here?

What does it do?

When is it effective?

What are its uses?

What are its side-effects?

Answer 5

• PGE2 (Vasodilator) and PGF2α (Vasoconstrictor) produced in Myometrium and Endometrium
• OESTROGEN
• • Dysmenorrhoea (severe pain due to uterine contractions)
  • Menorrhagia (severe blood loss due to excess vasodilation)
  o NSAIDs effective here
• ↑Frequency/Force of contractions, ↑Gap junctions, Softens cervix, ↑Oxytocin
• EARLY AND MIDDLE PREGNANCY
• INDUCTION of labour BEFORE TERM, ABORTION, Treat Post-partum Haemorrhage, Softening the cervix
• Systemic vasodilation, Hypertonus

Question 6

ERGOMETRINE:
What are Ergots? What do they contain?

What does the Ingestion of ergots lead to?

What does this drug do?

What is it used to treat?

Answer 6

• Fungus that grows on some cereals and grasses
  o Contains potent agents, like Ergometrine, Histamine, Tyramine, Ach
• Ergotism, Gangrene, Convulsions, and Abortion
• Causes powerful and prolonged uterine contractions when myometrium is relaxed
• POST-PARTUM HAEMORRHAGE

Question 7

MYOMETRIAL RELAXANTS:
What are they used in? Why?

What do β2 agonists do?

What do COX Inhibitors do? What can it cause?

What other relaxants can be used?

Answer 7

• Premature labour - Delays delivery by 48hrs
• Relaxes uterus, Reduces strength of contractions e.g. Salbutamol
• ↓PG production e.g. NSAIDs
  o Can cause Foetal renal dysfunction due to reduction of its blood flow
• • CCBs e.g. Magnesium Sulfate
  • Oxytocin Receptor antagonists e.g. Retosiban