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πš™πš‘πš’πšœπš’πš˜πš•πš˜πšπš’ 𝟸 : πš›πšŽπš™πš›πš˜πšπšžπšŒπšπš’πš˜πš— > Pharmacology of the Uterus > Flashcards

Pharmacology of the Uterus Flashcards

(69 cards)

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1
Q

What are the three layers making up the smooth muscle of the uterus?

A

β†’ Outer longitudinal fibres
β†’ Middle figure eight fibres
β†’ Inner circular fibres

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2
Q

What are the three layers of the uterus?

A

β†’ endometrium
β†’ Myometrium
β†’ perimetrium

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3
Q

What do uterine contractions do?

A

β†’ Increase uterine pressure
β†’ Forces content towards the cervix
β†’ acts as a natural ligature to prevent blood loss

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4
Q

What is the activity of the myometrium like?

A

β†’ Spontaneously active basal electrical activity

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5
Q

What kind of contractions are there in parturition?

A

β†’ Rhythmic

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6
Q

What is the myometrium sensitive to?

A

β†’ Neurotransmitters

β†’ Hormones

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7
Q

What type of cells are in the myometrium?

A

β†’ ICC pacemaker cells

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8
Q

How is synchronous contraction achieved?

A

β†’ Electrical communication between gap junctions

β†’ electrical activity is transmitted to adjacent cells

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9
Q

Where is electrical activity transmitted between in the myometrium?

A

β†’ Between ICCs
β†’ between ICC and smooth muscle
β†’ between smooth muscle cell

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10
Q

How do the myometrium cells function as?

A

β†’ A syncytium

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11
Q

Describe how contraction occurs?

A

β†’ ICC periodic activation of inward currents
β†’ depolarisations
β†’ Ca2+ entry through VGCC
β†’ Intracellular calcium leads to contraction

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12
Q

What are the slow waves of ICCs and smooth muscle responses modulated by?

A

β†’ Neurotransmitters and hormones

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13
Q

Describe how calcium is increased inside the cell?

A 
Slow wave of depolarisation 
                      ↓
Ca2+ channels get activated
                       ↓
Ca2+ entry increases Ca2+ 
                     ↓
Ca2+ binds to calmodulin
                     ↓
This phosphorylates myosin light chain kinase 
                       ↓ 
actin interaction lead to contractions
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14
Q

Describe how oxytocin leads to increased Ca2+?

A 
Oxytocin is Gq couples 
                    ↓
Activation of phospholipase C 
                     ↓
PIP2 β†’ DAG + IP3 
                    ↓
IP3 binds to IP3 receptors in the SR 
                     ↓ 
Causes Ca2+ from the store to be released into the cytosol 
                      ↓ 
Ca2+ increases
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15
Q

What are smooth muscle cells joined by?

A

β†’ Gap junctions

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16
Q

How can intracellular calcium be reduced?

A

β†’ Na+/Ca2+ exchanger
β†’ Ca2+ pump
β†’ some Ca2+ gets taken into the mitochondria

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17
Q

What is the effect of low concentrations of stimulants on ICCs?

A

β†’ Increase in slow wave frequency producing

β†’ Increase in frequency of contractions

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18
Q

How is the myometrium similar to other smooth muscle tissues?

A

β†’ There is a graded response - no threshold

β†’ increases in Ca2+ lead to increases in force of contraction

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19
Q

What is the effect of higher concentrations of stimulants on ICCs?

A

β†’ Increased frequency of action potentials on top of slow waves
β†’ Increased frequency and force of contractions

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20
Q

What is the effect of even higher concentrations of stimulants on ICCs?

A

β†’ plateau of slow wave producing prolonged sustained contractions

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21
Q

What is the effect of large concentrations of stimulants on ICCs?

A

β†’ hypertonus (incomplete relaxation)
β†’Ca2+ extrusion process is not as effective
β†’ interferes with blood flow - fetal distress

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22
Q

What innervation does the myometrium have?

A

β†’ Sympathetic

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23
Q

What receptors does the myometrium express?

A

β†’ alpha and beta adrenoceptors

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24
Q

What is the effect of alpha 1 adrenoceptor agonist?

A

β†’ contraction

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25
What is the effect of beta 2 adrenoceptor agonist?
β†’ relaxation
26
What are alpha 1 adrenoceptors coupled with?
β†’ Gq
27
What are beta 2 adrenoceptors coupled with?
β†’ Gs
28
How does the Gs transduction mechanism work?
β†’ Stimulates the formation of cAMP β†’ cAMP inhibits myosin light chain kinase β†’ less contractile force
29
What effects do progesterone and estrogen have on contraction?
β†’ Progesterone - inhibits contraction | β†’ Estrogen - increases contraction
30
What contractions does a non-pregnant uterus have?
β†’ Weak contractions early in the cycle | β†’ Strong during menstruation (increased prostaglandins
31
Why does the myometrium contract during menstruation?
β†’ Increased prostaglandins and decreased progesterone
32
What contractions does a pregnant uterus have?
β†’ Weak and uncoordinated in early pregnancy ( high progesterone) β†’ strong and coordinated at parturition ( increased estrogen)
33
What increases and decreases gap junction expression in the myometrium?
β†’ Increases - estrogen | β†’ Decreases - progesterone
34
Where are estrogen and progesterone receptors also found?
β†’ ICCs
35
What prostaglandins do the myometrium and endometrium synthesize?
β†’ synthesize PGE2 and PGF2alpha - promoted by estrogens
36
What do prostaglandins induce?
β†’ Myometrial contractions β†’ dysmenorrhoea β†’ menorrhagia
37
What helps with pain and contraction?
β†’ NSAIDs
38
What is the function of prostaglandins?
β†’ Coordinate an increase and force of contractions β†’ increase gap junctions β†’ soften cervix
39
What are 3 prostaglandin analogues?
β†’ Dinoprostone (PGE2) β†’ Carboprost (PGF2a) β†’ Misoprostol (PGE1)
40
What is the function of PGE2?
β†’ Smooth muscle dilator around the body?
41
What are the 4 uses of prostaglandin analogues?
β†’ Induction of labour - before term β†’ induce abortion β†’ postpartum bleeding β†’ softening the cervix
42
What is a side effect of dinoprostone?
β†’ Systemic vasodilation β†’ cardiovascular collapse β†’ hypertonus and fetal distress
43
How is dinoprostone given to reduce side effects?
β†’ Gel
44
What is oxytocin?
β†’ A non peptide hormone synthesised in the hypothalamus and released from the posterior pituitary gland
45
When is oxytocin released?
β†’ In response to suckling | β†’ cervical dilatation
46
Why is oxytocin not effective in earlier stages?
β†’ Receptors are not expressed pre term so they are not effective
47
What does estrogen produce in the later stages of parturition?
β†’ Increased oxytocin release β†’ Increased oxytocin receptors β†’ increased gap junctions
48
What is the function of oxytocin?
β†’ Increases the synthesis of prostaglandins
49
What is ergot?
β†’ Fungus that grows on some cereals
50
What happens when you ingest ergot?
β†’ Ergotism β†’ Gangrene β†’ convulsions β†’ abortion
51
What is the action of ergot on the myometrium?
β†’ Powerful and prolonged uterine contraction when myometrium is relaxed
52
What is the mechanism of action of ergot?
β†’Stimulation of alpha adrenoceptors | β†’ 5-HT receptors
53
What are the uses of ergot?
β†’ postpartum bleeding | β†’ not induction
54
Why are myometrial relaxants given?
β†’ Delay delivery by 48h | β†’ mother can be given antenatal corticosteroids to help fetal lung maturation
55
What is an example of a b2 adrenoceptor stimulant?
β†’ Salbutamol
56
How does salbutamol work?
β†’ relaxes uterine contractions by direct action on the myometrium β†’ increases Ca2+ uptake into SR - Ca2+ not available for contraction
57
What is salbutamol used for?
β†’ Reduce strength of contractions in premature labour
58
What is an example of a Ca2+ channel antagonist?
β†’ Nifedipine | β†’ Mg sulfate
59
What is an example of an oxytocin receptor antagonist?
β†’ Retosiban
60
What is an example of a COX inhibitor?
β†’ NSAIDs
61
How do NSAIDs work?
β†’ Decrease prostaglandins
62
What is a side effect of NSAIDs?
β†’ Can cause fetal renal dysfunction
63
What doest stimulation of beta 2 adrenoceptors cause?
β†’ Smooth muscle relaxation
64
How does beta 2 adrenoceptor stimulation work?
β†’ PKA activity β†’ Increased Ca2+ activity which increases uptake into SR β†’ Increases K+ channel activity β†’ hyperpolarisation and decreased Ca2+ entry via VGCC β†’ Downregulates MLCK
65
What is used for induction of labour?
β†’ Oxytocin
66
What is used for induction of labour/termination in early term?
β†’ Prostaglandins ( because no oxytocin receptors)
67
What is used for postpartum bleeding?
β†’ Prostaglandins β†’ Oxytocin β†’ Ergots
68
What is used to prevent premature birth?
β†’ Beta 2 adrenoceptor agonists β†’ Ca2+ channel blockers β†’ oxytocin inhibitors
69
What are the 2 ways to measure uterine contractions?
β†’ Isometric tension recording | β†’ Measure tension generated with diameter of muscle ring remaining constant

πš™πš‘πš’πšœπš’πš˜πš•πš˜πšπš’ 𝟸 : πš›πšŽπš™πš›πš˜πšπšžπšŒπšπš’πš˜πš— (12 decks)

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