Pharmacology of the uterus Flashcards

1
Q

what are the 3 layers of the uterus?

A

1)endometrium
2)myometrium
3)perimetrium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what muscle is the myometrium made of?

A

smooth muscle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what are the 3 fibres that make up the myometrium?

A

1)Outer=longitudinal
2)Middle= Figure-eight fibres
3)Inner= Circular fibres

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what occurs at all 3 layers of the fibres of the myometrium and what does this cause during labor?

A

They contract, causing an increase in the uterus pressure, increasing the pressure that’s put on the uterus, therefore pushing the baby out.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what is the mechanical property of the myometrium? and what does this mean?

A

Myogenic contractility- it can contract spontaneously without any external stimuli, contracting without any neuronal or hormonal input.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what his the role of Interstitial cells of Cajal (ICC’s)?

A

Act as pace maker cells in the myometrium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what do ICC’s look like?

A

brown line between smooth muscle cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

what are connexin proteins?

A

Gap junction proteins. They are a family of trans-membrane proteins that allow intracellular communication and the transfer of ions and small signalling molecules between cells.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Briefly describe what happens during sympathetic release of noradrenaline.

A

Sympathetic release of noradrenaline causes a contractile slow wave of electrical activity coming from the ICC to increase contractility. Gap junctions (ion channels) and connexion proteins expressed in adjacent cells form a gap junction for electrical coupling which you get after the ICC forms the electrical signal, coupled to gap junctions. Smooth muscle cells contract together

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

where do gap junctions occur? (4)

A

1)Between ICCs
2)Between ICCs and smooth muscle cells
3)Between smooth muscle cells
4)Function as a synctium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what do ICCs and smooth muscle cells work together as?

A

A synctium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what modulates the slow wave of ICC and smooth muscle responses?

A

Neurotransmitters and hormones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are ICC and smooth muscle responses sensitive to?

A

Sex hormones e.g Oestrogen and Progesterone.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe in detail the cellular mechanism of smooth muscle contraction.

A

1) You have G protein coupled receptors, which is coupled to phospholipase c enzyme
2)On binding of an agonist/ ligand, you have the PLC enzyme cleaving PIP into IP3 and DAG.
3)IP3 binds to its receptors on the sarcoplasmic reticulum, which causes calcium to be released from the sarcoplasmic reticulum
4)DAG binds to membrane receptors, which causes a a calcium influx into the cell
5)This causes depolarisation of the cell and causes activation of the voltage gated calcium channels, causing an influx of Ca2+
6)Ca2+ binds to calmodulin, which causes activation of the Myosin light chain kinase to phosphorylated light chain. This causes myosin to straighten and interact with actin
7)We get contraction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Does the increase in Ca2+ have a linear relationship with the force of contraction?

A

No

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what causes the contraction of smooth muscle?

A

Calcium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what are the 3 mechanisms of lowering the calcium lvls in extrusion?

A

1)Calcium pump to mitochondria
2) Calcium ATPase pump
3)Sodium Calcium exchanger

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what does low concentrations of stimulants on ICCs cause?

A

An increased slow wave frequency producing an increased frequency of contraction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what does higher concentrations of stimulants on ICCs cause?

A

Increased frequency of action potentials on top of slow waves (increased calcium conc peak), producing both an increased frequency and force of contraction.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what does a continued higher concentration of stimulants on ICCs cause?

A

An increased plateau of slow wave producing prolonged sustained contractions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What does a large concentration of stimulants on ICC cause?

A

1)Hypertonus (contraction occurs for a longer duration so relaxation period is shorter)
2)This occurs as a result of calcium extrusion processes not being effective

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what is the effect of large concentrations of stimulants on ICC in the myometrium to the infant?

A

This means that the duration of contrition is longer, which interferes with the blood flow, minimising blood loss resulting in foetal distress as the baby isn’t receiving enough O2 through the placenta.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Is there sympathetic or parasympathetic innervation in the myometrium?

A

Sympathetic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what causes the sympathetic innervation at the myometrium?

A

Neurotransmitters

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

expression of what adrenoreceptors are located at the myometrium? and what occurs here?

A

1)Alpha-1 adrenoreceptors= adrenaline/noradrenaline binds here to cause=Contraction
2)Beta-2 adrenoreceptors= Adrenaline/noradrenaline binds here to cause relaxation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What type of protein are alpha adrenoreceptos? and what occurs here that leads to contraction? (simple)

A

G protein coupled receptors-It is a Gq type
At the Gq type protein once agonist binds to the alpha adrenoreceptor= activation of Phospholipase C, increasing IP3 and DAG, ultimately increasing intracellular ca2+ conc, leading to smooth muscle contraction and glycogenolysis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what type of protein makes up the beta adrenoreceptors and what occurs here to result in relaxation? (CHECK THIS IDK IF CORRECT)

A

Beta adrenoreceptors made of Gs protein. When activated it unregulates adenyl cyclase, which converts ATP into cAMP. With an increase in the presence of cAMP, cAMP dependent protein kinase A phosphorylates calcium channels, increasing cellular calcium influx and in smooth muscle this cases relaxation.

28
Q

What are the 3 hormones that affect contractility of the smooth muscle?

A

1)Oestrogen
2)progesterone
3)oxytocin

29
Q

what type of hormone is oxytocin?

A

peptide

30
Q

Are oestrogen and progesterone steroid hormones. If so what does this mean?

A

Yes. This means they are made of cholesterol

31
Q

what does depolarisation mean and what does it result in?

A

An increase in the intracellular membrane potential, which results in further voltage-gated calcium channels opening, resulting in an action potential generation, which results in contraction.

32
Q

since the smooth muscle is innervated by the sympathetic nervous system. what neurotransmitter regulates it?

A

Noradrenaline- which then cause the release of adrenaline from adrenal gland (both noradrenaline and adrenaline act as agonists on adrenoreceptors in myometrium)

33
Q

sex hormones also regulate the myometrium.What 2 sex hormones and what do they cause?

A

1)oestrogen- increases contraction
2)Progesterone-inhibits contraction

34
Q

What type of receptors do Oestrogen and Progesterone work on?

A

Nuclear and membrane receptors

35
Q

Progesterone and Oestrogen work in a cycle as the cell work in syncytium. What occurs when oestrogen lvls increase and progesterone lvls decrease?

A

progesterone lvls decrease= menstruation
Oestrogen lvls increase= contraction of uterine smooth muscle

36
Q

Describe the changes in the steroid hormones on the pregnant uterus

A

1)Weak and uncoordinated contractions in the early pregnancy due to high progesterone
2)Strong and co-ordinated contractions at parturition/ labour due to increased oestrogen.
3)Ratio of oestrogen/progesterone ratio increases during childbirth. some may modulate the slow waves of icc

37
Q

Describe what happens because because the oestrogen/progestrone ration increases during parturition

A

1)Oestrogen increases increases gap junctions whilst progesterone decreases gap junctions expression in myometrium
2)Oestrogen/Progesterone receptors are also found on the ICCs

38
Q

Describe what happens in a non-pregnant uterus

A

1)Weak contractions early in cycle
2)Strong contractions during menstruation (decreased progesterone and increased prostaglandins)

39
Q

what are prostaglandins?

A

A group of lipids with hormone like actions that your body makes primarily at sites of tissue damage or infection.

40
Q

describe what happens in the non-pregnant uterus (progesterone and prostaglandins)

A

1)Weak contractions early in cycle
2)strong contractions during menstruation (decreased progesterone and increased prostaglandins)

41
Q

what are the roles of Prostoglandins? (PGE2 and PGF2 alpha)(list 4)

A

1)Induce myometrial contraction
2)role in dysmenorrhea (severe menstruation pain)
3)Menorrhagia (severe menstrual blood loss)
4)Pain after parturition

42
Q

what is a good treatment for contraction with pain?

A

NSAIDs

43
Q

what is the main function of prostaglandins?

A

Induce contractility

44
Q

what are the prostaglandins made from the myometrium and endometrium?

A

myometrium= PGE2
Endometrium=PGE2 alpha

45
Q

Are PGE2 and PGE2 alpha autocrine? and what does this mean?

A

they are autocrine and this means they act on the same cells they come from (endometrium and myometrium). They act together

46
Q

what happens to the oestrogen/progesterone ratio during parturition?

A

it increases
1)Oestrogen increases gap junctions, whilst progesterone decreases gap junction expression in myometrium
2)Oestrogen/progesterone receptors are also found on ICC

47
Q

PGE2 and PGE2 Alpha work together to achieve what?

A

1)Coordinate increased frequency/force of contraction
2)Increase gap junctions and soften the cervix

48
Q

what affect do PGE2 have on blood vessels and what affect do they have on the uterus

A

1)Binding to receptors on blood vessels causes them to dilate
2)Binding to receptors on the uterus causes contraction and therefore inducing labour

49
Q

what are 3 analogues of prostoglandins? and what are their functions?

A

1)Dinoprostone, PGE2
2)Carboprost, PGF2 alpha
3)Mistoprotol, PGE1

50
Q

what occurs In a non-pregnant uterus? (mention progesterone and prostaglandin lvls)

A

1)Weak contractions early in the cycle
2)Strong contractions during menstruation (due to decreased progesterone whilst increased prostaglandin’s which cause contraction)

51
Q

What are NSAIDs?

A

Non-steroidal anti-inflammatory drugs- these help to reduce the pain from contractions

52
Q

What are the problems of the analogues of prostaglandin (which are used to induce abortion).Give 3

A

1)Dinoprostone can cause systemic vasodilation
2)Potential for cardiovascular collapse (given as cervical gel/vaginal insert) so it doesn’t need to reach high systemic lvls to work, and can evade high lvls in the circulation
3)PGs-result in hypertonus and foetal distress

53
Q

what type of hormone is oxytocin?

A

Peptide

54
Q

where is oxytocin produced from and in response to what?

A

1) Oxytocin is released from the posterior pituitary gland after being synthesised in the hypothalamus
2)Released in response to suckling and cervical dilation and there is a role in parturition

55
Q

Is there a relationship between oxytocin and prostaglandins?Explain it

A

yes. Prostoglandins increase as oxytocin increases

56
Q

Describe the oxytocin to prostaglandin ratio, after late parturition stages as a result of release of oestrogen:

A

1)The oestrogen released from the late parturition stages results in
2)Increased oxytocin release, which means more binding at oxytocin receptors, which increases gap junctions
3)The oxytocin release also increases the synthesis of prostoglandinss
4)Oxytocin is only affective at term (require oestrogen-induced oxytocin receptor expression)

57
Q

what are the 2 synthetic versions/analogues of oxytocin? and what are their functions in low and high concentrations?

A

1)Syntocinon
2)Pictocin
In low concentrations of the analogues they increase the frequency and force of contraction
In high concentrations they cause hypertonous-may cause fetal distress

58
Q

give 3 uses of the analogues of oxytocin

A

1)Induction of labour at term-does not soften cervix
2)Treat/prevent postpartum haemorrhage
3)Syntometrine-oxytocin (rapid)/ergot (prolonged) combination

59
Q

Oxytocin alone causes rapid contraction but can be combined with ergot. What is ergot? and what does it cause when ingested?

A

1)Ergot is a fungus that grows on grasses and some cereals. It contains ergometrine (an ergot alkaloid).
2)when ingested It can result in ergotism, gangrene, convulsions and abortion.

60
Q

What are the actions, mechanism and uses of ergot?

A

Action-Powerful and prolonged uterine contractions but only when the myometrium is relaxed
Mechanism-Stimulation of alpha-adrenoreceptors, 5-HT receptors
Uses-Postpartum bleeding-not induction

61
Q

what are myometrial relaxants used for?

A

used in premature labour and can delay delivery by 48hrs so that the mother can be transferred to a specialist unit and can be given antenatal corticosteroids to aid foetal lung maturation and increase survival.

62
Q

what are the 4 types of myometrial relaxants?

A

1)Beta 2 adrenoreceptors e.g salbutamol
2)Calcium channel agonists e.g nifedipine (used in hypertension) or Mg Sulfate
3)Oxytocin receptor antagonists e.g retosiban
4)COX inhibitors e.g NSAIDs (decrease synthesis of prostaglandins)

63
Q

Describe the mechanism of action of myometrial relaxants

A

1)Stimulation of the B2 adrenoceptors on smooth muscle (vascular, airway and myometrial) produces relaxation.
2)You get PKA activity, which increases the calcium ATPase (SERCA) channel activity and you have an increased uptake into the SR and exclusion from the cell.
3)Increase in K+ channel activity which leads to hyperpolarisation and a lower calcium entry via the 4)voltage gated calcium channels.
5)You have a decrease in the myosin light chain kinase so therefore, you have the MLC not binding to actin and therefore not causing contraction.

64
Q

1)what hormone causes induction of labour at term?
2)what hormone causes induction of labour/ termination in early stages?
3)what causes postpartum bleeding?
4)What prevents premature birth

A

1)Induction of labour at term
Oxytocin
2)Induction of labour/termination in early term
Prostaglandins (not oxytocin – no oxytocin receptors)
3)Post-partum bleeding
Prostaglandins, oxytocin, ergots
4)Prevent premature birth
β2-adrenoreceptor agonists
Ca2+ channel blockers, Mg Sulfate
Oxytocin inhibitors

65
Q

what can be done to measure uterine contractions? and why is it used?

A

1)You can measure uterine contractions by doing an isometric recording and measure the tension generated with the diameter of the muscle ring, remains constant.
2)to investigate the functional properties of uterine, vascular, airway and bladder smooth muscle segments