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Duke Pharmacology- Hannah > Tocolytics & Uterotonics > Flashcards

Tocolytics & Uterotonics Flashcards

1
Q

Why are tocolytics given?

A

The goal of tocolytics is to allow the uterine to relax so we can delay delivery long enough, give corticosteroids, and optimize the parturient

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2
Q

What is the onset of tocolytics?

A

onset is 18 hours, maximum benefit at 48 hours

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3
Q

Why are tocolytics given for a neonate?

A

to reduce neonatal risk including respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, perinatal death

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4
Q

List the 6 tocolytic drugs:

A 
magnesium sulfate
calcium channel blockers
B-adrenergic agonists
Nitric oxide donors
Cyclooxygenase inhibitors
Oxytocin antagonists
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5
Q

Tocolytics inhibit labor by

A

generation or alteration of intracellular message
inhibiting synthesis or block action of a myometrial stimulant
-they are considered to have a marginal effect

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6
Q

What is the mechanism of action of magnesium sulfate?

A
  • alter calcium transport and availability for muscle contraction
  • compete with intracellular calcium reducing myometrial contractility
  • Hyperpolarization of the plasma membrane leads to inhibition of the myosin light-chain kinase activity as magnesium
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7
Q

What muscles does magnesium sulfate relax?

A

vascular, bronchial, and uterine smooth muscle

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8
Q

What are two additional effects magnesium sulfate has?

A

depress motor endplate sensitivity

muscle membrane excitability

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9
Q

What does magnesium sulfate treat?

A

treatment of preeclampsia
relaxes vascular smooth muscle decreasing SVR &
BP
anticonvulsant (raises seizure threshold)
Decreases fibrin deposition, improving circulation
to visceral organs

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10
Q

What are the neonatal side effects of magnesium sulfate?

A

hypotonia

respiratory depression

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11
Q

What is the loading dose of magnesium sulfate?

A

4 to 6 grams IV over 20-30 minutes

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12
Q

What is the infusion dose of magnesium sulfate?

A

1 to 2 gm/hour

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13
Q

What is the therapeutic level of magnesium sulfate?

A

4 to 9 mEq/L

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14
Q

How long is magnesium sulfate given?

A

continued through delivery and up to 24 hours post delivery

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15
Q

What is the normal level of serum magnesium during pregnancy?

A

1.8 to 3 mg/dL

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16
Q

What is the tocolytic range of magnesium sulfate?

A

4 to 8 mg/dL

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17
Q

What EKG changes will we see with magnesium sulfate & at what range?

A

at 4 to 8 mg/dL we will have prolonged p to q and QRS is widened

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18
Q

At what range of serum magnesium is it an anticonvulsant effect?

A

7 to 9 mg/dL

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19
Q

What range of serum magnesium are tendon reflexes abolished?

A

10 to 12 mg/dL

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20
Q

What range of serum magnesium does respiratory depression occr?

A

> 12 mg/dL

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21
Q

At what range of serum magnesium does SA and AV blocks and respiratory arrest occur?

A

15-20 mg/dL

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22
Q

At what range of serum magnesium does apnea occur?

A

18 mg/dL

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23
Q

At what range of serum magnesium do we see cardiac arrest?

A

25 mg/dL

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24
Q

What are the most concerning side effects of magnesium sulfate?

A

CNS depression, hypotension, sedation, skeletal muscle weakness

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25
Q

Magnesium sulfate antagonizes

A

alpha agonist

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26
Q

Magnesium sulfate potentiates

A

neuromuscular blocking drugs

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27
Q

Other side effects of magnesium sulfate include:

A

flushing, palpitations, chest pain, nausea, blurred vision, pulmonary edema, and vascular dilation

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28
Q

How do we treat a magnesium sulfate overdose?

A

stop the infusion
secure airway- support breathing
administer calcium chloride
diuretics

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29
Q

What are the important anesthetic implications of magnesium sulfate?

A

-exaggerated hypotension after administration of epidural or general anesthesia
- succinylcholine dose is not reduced for intubation
defasiculating doses are not required
reduce maintenance doses of nondepolarizing
muscle relaxants
-symptomatic hypocalcemia and respiratory compromise have occurred in cases of myotonic dystrophy

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30
Q

What is the most commonly used calcium channel blocker?

A

nifedipine because it can be taken PO or sublingually

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31
Q

What is the mechanism of action of calcium channel blockers?

A
  • blocks the influx of calcium ions through the cell membrane
  • block release of calcium ions from the SR
  • inhibit calcium-dependent myosin light chain kinase-mediated phosphorylation
  • acts on potassium channels
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32
Q

How long is birth delayed with calcium channel blockers?

A

2-7 days

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33
Q

What are the side effects of calcium channel blockers?

A

hypotension, dyspnea, pulmonary edema, tachycardia, headache

34
Q

What should be avoided when giving calcium channel blockers?

A

Avoid concomitant use with magnesium sulfate because it enhances neuromuscular blocking effects causing affecting respiratory and cardiac function

35
Q

What are the anesthetic implications of calcium channel blockers?

A

-hypotension with administration of neuraxial or general anesthesia
-potential uterine atony that may be refractory to oxytocin and prostaglandins
Both act through calcium channel blockers

36
Q

What do you give if uterine atony occurs when giving calcium channel blockers?

A

make sure to have adequate IV access and use methergine (IM)

37
Q

What beta 2 agonist do we use?

A

Terbutaline

38
Q

What is an additional reason to administer terbutaline?

A

Can be given to asthmatics

39
Q

What is the mechanism of action of beta 2 agonist?

A

results in smooth muscle relaxation
Biochemical events lead to:
inhibition of myometrial contractility
increase in progesterone production

40
Q

What does progesterone do?

A

progesterone causes histologic changes in myometrial cells that limit the spread contractile impulses

41
Q

What are the side effects of beta 2 agonists?

A

increased incidence of adverse side-effects in the mother and fetus: maternal and fetal tachycardia, dysrhythmias, ischemia, hypotension, pulmonary edema (rarely), headache, hyperglycemia, hypokalemia, increased plasma renin and vasopressin

42
Q

What are the most common hazards of beta 2 agonists?

A

fetal tachycardia is common

  • neonatal hypoglycemia
  • increased blood sugar and insulin levels in the mother
43
Q

Why does beta 2 agonist cause neonatal hypoglycemia?

A

increased insulin secretion in response to hyperglycemia
following delivery, glucose load from the mother
ceases leading to rebound hypoglycemia

44
Q

What course does blood sugar and insulin levels take in the mother with beta 2 agonists?

A

increases within a few hours and returns to baseline within 72 hours without treatment

45
Q

Why do we get hypokalemia in patients receiving beta 2 agonists?

A

potassium is redistributed to the intracellular compartment lowering levels
can reach as low as 3 mEq/L
Returns to normal in 72 hours without treatment

46
Q

How should we treat hypotension when giving beta 2 agonists?

A

phenylephrine and ephedrine

but always think about why they may be hypotensive… are they dehydrated, etc?

47
Q

What drugs should be avoided when giving beta 2 agonists?

A

anesthesia should be delayed for 60 minutes to allow the heart rate to decrease, if not possible all drugs that increase HR should be avoided
ketamine, atropine, glycopyrrolate, thiopental, pancuronium, etomidate

48
Q

What are the side effects of nitric oxide donors?

A

maternal hypotension

headache

49
Q

What is the order of tocolytics we would give?

A

magnesium, calcium channel blocker, beta 2 agonists, nitric oxide donors

50
Q

What is the mechanism of action for nitric oxide doonors?

A

acts by increasing cyclic guanosine monophosphate (cGMP)
inactivates myosin light-chain kinases causing
smooth muscle relaxation

51
Q

What is an example of a nitric oxide donor?

A

nitroglycerine

52
Q

What kind of substance is nitric oxide?

A

nitric oxide is an endogenous substance necessary for smooth muscle tone

53
Q

What is the mechanism of action of cylcooxygenase?

A

cyclooxygenase converts arachidonic acid to prostaglandin H2
substrate for tissue-specific enzymes critical to
giving birth
increase available intracellular calcium
raise influx and SR release

54
Q

Prostaglandins enhance formation of

A

myometrial gap junctions

55
Q

What is the mechanism of action of cylooxygenase inhibitors?

A

reduce prostaglandin levels
inhibiting cyclooxygenase enzymes
results in decreased uterine contraction

56
Q

What is the given example of nonselective and selective COX inhibitors?

A

indomethacin-non-selective
celecoxib (celebrex)- cox-2 selective inhibitor
tocolytic efficacy equal to magnesium sulfate in
preventing preterm birth within 48 hours

57
Q

What are the anesthetic implications of cyclooxygenase inhibitors?

A

platelet inhibition is associated with non-selective COX inhibitors
Transient and reversible
Neuraxial anesthesia is not contraindicated

58
Q

What is the muscle relaxant of choice for a rapid sequence induction in mothers?

A

succinylcholine
magnesium sulfate potentiates both types of
muscle relaxants
defasiculation and priming are not
recommended

59
Q

What is the preferred method of drug administration for laboring mothers?

A

neuraxial is preferred over general anesthesia because it is safer
neonate apgar scores are higher at 1 & 5 minutes

60
Q

What is the leading cause of postpartum hemorrhage?

A

uterine atony

61
Q

What is the first line of hemorrhage prevention for women?

A

fundal massage

62
Q

What is the first uterotonic we would administer?

A

oxytocin- we give synthetic oxytocin (pitocin, syntocinon)
causes fewer side effects than endogenous
oxytocin

63
Q

What is the dosage of oxytocin?

A

20-40 units/L of isotonic solution IV over 15 to 20 minutes

64
Q

Where is endogenous oxytocin produced?

A

posterior pituitary gland

65
Q

What is the mechanism of action of oxytocin?

A

lowers threshold for depolarization of uterine smooth muscle
depolarization is enhanced by activation of calcium
channels and increased prostaglandin production

66
Q

When and why is oxytocin used?

A

as soon as the cord is cut because we are reducing blood loss after delivery
-can also be used at low controlled rate to induce labor

67
Q

What are the anesthetic considerations of oxytocin?

A

can cause a degree of vasodilation or decreased SVR which results in hypotension and tachycardia
DO NOT BOLUS oxytocin

68
Q

What is the second line of utertonics used?

A

ergot alkaloids

69
Q

What is the mechanism of action of ergot alkaloids?

A

unclear but thought to have an alpha-adrenergic agonist effect

70
Q

When do we give ergot alkaloids?

A

give during the post-delivery period because it produces tetanic uterine contractions

71
Q

What ergot alkaloids do we give?

A

methergine- synthetic

ergotrate- semisynthetic

72
Q

What is the dosage of methergine?

A

0.2 mg IM- contractions occur within minutes of administration
dose may be repeated in 15 to 20 minutes for a
total dose of 0.8 mg

73
Q

IV administration of methergine can result in:

A

profound hypotension, severe N/V, and cerebral hemorrhage

74
Q

When should ergot alkaloids not be used?

A

pre-existing hypertension; pregnancy induced or chronic
peripheral vascular disease or ischemic heart disease
MIs have occured in woman treated with oral or IV
ergot alkaloids

75
Q

What are anesthetic implications of ergot alkaloids?

A

monitor BP carefully and have vasodilating drugs available

nausea and vomiting occur in 10-20% of women

76
Q

What is the mechanism of action of prostaglandins?

A

increases myometrial calcium levels and subsequently increases MLCK activity and uterine contraction

77
Q

When should prostaglandin be used?

A

80-90% effective in PPH refractory to oxytocin and ergot alkaloids

78
Q

What prostaglandin is typically used?

A

15-methylprostaglandin F2A (Carboprost, Hemabate)

79
Q

What are the anesthetic implications of prostaglandins?

A

-use of carboprost in women with reactive airway disease can result in bronchospasm, ventilation perfusion mismatch and hypoxemia
monitor oxygen saturation and lung sounds
-misoprostol can be used in patients with reactive airway disease or pulmonary hypertension

80
Q

What is the dose of hemabate?

A

250 mcg IM or directly into the myometrium
repeat every 15 to 30 minutes to a total dose of 2
mg

81
Q

Misoprostol is not preferable to other utertonics for

A

the active management of 3rd stage labor

82
Q

What is as effective as oxytocin in reducing blood loss at cesarean section?

A

misoprostol

dose: 800-1000 mcg administered sublingual or buccal

Duke Pharmacology- Hannah (14 decks)

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