Tocolytics & Uterotonics Flashcards
Why are tocolytics given?
The goal of tocolytics is to allow the uterine to relax so we can delay delivery long enough, give corticosteroids, and optimize the parturient
What is the onset of tocolytics?
onset is 18 hours, maximum benefit at 48 hours
Why are tocolytics given for a neonate?
to reduce neonatal risk including respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, perinatal death
List the 6 tocolytic drugs:
magnesium sulfate calcium channel blockers B-adrenergic agonists Nitric oxide donors Cyclooxygenase inhibitors Oxytocin antagonists
Tocolytics inhibit labor by
generation or alteration of intracellular message
inhibiting synthesis or block action of a myometrial stimulant
-they are considered to have a marginal effect
What is the mechanism of action of magnesium sulfate?
- 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
What muscles does magnesium sulfate relax?
vascular, bronchial, and uterine smooth muscle
What are two additional effects magnesium sulfate has?
depress motor endplate sensitivity
muscle membrane excitability
What does magnesium sulfate treat?
treatment of preeclampsia
relaxes vascular smooth muscle decreasing SVR &
BP
anticonvulsant (raises seizure threshold)
Decreases fibrin deposition, improving circulation
to visceral organs
What are the neonatal side effects of magnesium sulfate?
hypotonia
respiratory depression
What is the loading dose of magnesium sulfate?
4 to 6 grams IV over 20-30 minutes
What is the infusion dose of magnesium sulfate?
1 to 2 gm/hour
What is the therapeutic level of magnesium sulfate?
4 to 9 mEq/L
How long is magnesium sulfate given?
continued through delivery and up to 24 hours post delivery
What is the normal level of serum magnesium during pregnancy?
1.8 to 3 mg/dL
What is the tocolytic range of magnesium sulfate?
4 to 8 mg/dL
What EKG changes will we see with magnesium sulfate & at what range?
at 4 to 8 mg/dL we will have prolonged p to q and QRS is widened
At what range of serum magnesium is it an anticonvulsant effect?
7 to 9 mg/dL
What range of serum magnesium are tendon reflexes abolished?
10 to 12 mg/dL
What range of serum magnesium does respiratory depression occr?
> 12 mg/dL
At what range of serum magnesium does SA and AV blocks and respiratory arrest occur?
15-20 mg/dL
At what range of serum magnesium does apnea occur?
18 mg/dL
At what range of serum magnesium do we see cardiac arrest?
25 mg/dL
What are the most concerning side effects of magnesium sulfate?
CNS depression, hypotension, sedation, skeletal muscle weakness
Magnesium sulfate antagonizes
alpha agonist
Magnesium sulfate potentiates
neuromuscular blocking drugs
Other side effects of magnesium sulfate include:
flushing, palpitations, chest pain, nausea, blurred vision, pulmonary edema, and vascular dilation
How do we treat a magnesium sulfate overdose?
stop the infusion
secure airway- support breathing
administer calcium chloride
diuretics
What are the important anesthetic implications of magnesium sulfate?
-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
What is the most commonly used calcium channel blocker?
nifedipine because it can be taken PO or sublingually
What is the mechanism of action of calcium channel blockers?
- 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
How long is birth delayed with calcium channel blockers?
2-7 days
What are the side effects of calcium channel blockers?
hypotension, dyspnea, pulmonary edema, tachycardia, headache
What should be avoided when giving calcium channel blockers?
Avoid concomitant use with magnesium sulfate because it enhances neuromuscular blocking effects causing affecting respiratory and cardiac function
What are the anesthetic implications of calcium channel blockers?
-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
What do you give if uterine atony occurs when giving calcium channel blockers?
make sure to have adequate IV access and use methergine (IM)
What beta 2 agonist do we use?
Terbutaline
What is an additional reason to administer terbutaline?
Can be given to asthmatics
What is the mechanism of action of beta 2 agonist?
results in smooth muscle relaxation
Biochemical events lead to:
inhibition of myometrial contractility
increase in progesterone production
What does progesterone do?
progesterone causes histologic changes in myometrial cells that limit the spread contractile impulses
What are the side effects of beta 2 agonists?
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
What are the most common hazards of beta 2 agonists?
fetal tachycardia is common
- neonatal hypoglycemia
- increased blood sugar and insulin levels in the mother
Why does beta 2 agonist cause neonatal hypoglycemia?
increased insulin secretion in response to hyperglycemia
following delivery, glucose load from the mother
ceases leading to rebound hypoglycemia
What course does blood sugar and insulin levels take in the mother with beta 2 agonists?
increases within a few hours and returns to baseline within 72 hours without treatment
Why do we get hypokalemia in patients receiving beta 2 agonists?
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
How should we treat hypotension when giving beta 2 agonists?
phenylephrine and ephedrine
but always think about why they may be hypotensive… are they dehydrated, etc?
What drugs should be avoided when giving beta 2 agonists?
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
What are the side effects of nitric oxide donors?
maternal hypotension
headache
What is the order of tocolytics we would give?
magnesium, calcium channel blocker, beta 2 agonists, nitric oxide donors
What is the mechanism of action for nitric oxide doonors?
acts by increasing cyclic guanosine monophosphate (cGMP)
inactivates myosin light-chain kinases causing
smooth muscle relaxation
What is an example of a nitric oxide donor?
nitroglycerine
What kind of substance is nitric oxide?
nitric oxide is an endogenous substance necessary for smooth muscle tone
What is the mechanism of action of cylcooxygenase?
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
Prostaglandins enhance formation of
myometrial gap junctions
What is the mechanism of action of cylooxygenase inhibitors?
reduce prostaglandin levels
inhibiting cyclooxygenase enzymes
results in decreased uterine contraction
What is the given example of nonselective and selective COX inhibitors?
indomethacin-non-selective
celecoxib (celebrex)- cox-2 selective inhibitor
tocolytic efficacy equal to magnesium sulfate in
preventing preterm birth within 48 hours
What are the anesthetic implications of cyclooxygenase inhibitors?
platelet inhibition is associated with non-selective COX inhibitors
Transient and reversible
Neuraxial anesthesia is not contraindicated
What is the muscle relaxant of choice for a rapid sequence induction in mothers?
succinylcholine
magnesium sulfate potentiates both types of
muscle relaxants
defasiculation and priming are not
recommended
What is the preferred method of drug administration for laboring mothers?
neuraxial is preferred over general anesthesia because it is safer
neonate apgar scores are higher at 1 & 5 minutes
What is the leading cause of postpartum hemorrhage?
uterine atony
What is the first line of hemorrhage prevention for women?
fundal massage
What is the first uterotonic we would administer?
oxytocin- we give synthetic oxytocin (pitocin, syntocinon)
causes fewer side effects than endogenous
oxytocin
What is the dosage of oxytocin?
20-40 units/L of isotonic solution IV over 15 to 20 minutes
Where is endogenous oxytocin produced?
posterior pituitary gland
What is the mechanism of action of oxytocin?
lowers threshold for depolarization of uterine smooth muscle
depolarization is enhanced by activation of calcium
channels and increased prostaglandin production
When and why is oxytocin used?
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
What are the anesthetic considerations of oxytocin?
can cause a degree of vasodilation or decreased SVR which results in hypotension and tachycardia
DO NOT BOLUS oxytocin
What is the second line of utertonics used?
ergot alkaloids
What is the mechanism of action of ergot alkaloids?
unclear but thought to have an alpha-adrenergic agonist effect
When do we give ergot alkaloids?
give during the post-delivery period because it produces tetanic uterine contractions
What ergot alkaloids do we give?
methergine- synthetic
ergotrate- semisynthetic
What is the dosage of methergine?
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
IV administration of methergine can result in:
profound hypotension, severe N/V, and cerebral hemorrhage
When should ergot alkaloids not be used?
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
What are anesthetic implications of ergot alkaloids?
monitor BP carefully and have vasodilating drugs available
nausea and vomiting occur in 10-20% of women
What is the mechanism of action of prostaglandins?
increases myometrial calcium levels and subsequently increases MLCK activity and uterine contraction
When should prostaglandin be used?
80-90% effective in PPH refractory to oxytocin and ergot alkaloids
What prostaglandin is typically used?
15-methylprostaglandin F2A (Carboprost, Hemabate)
What are the anesthetic implications of prostaglandins?
-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
What is the dose of hemabate?
250 mcg IM or directly into the myometrium
repeat every 15 to 30 minutes to a total dose of 2
mg
Misoprostol is not preferable to other utertonics for
the active management of 3rd stage labor
What is as effective as oxytocin in reducing blood loss at cesarean section?
misoprostol
dose: 800-1000 mcg administered sublingual or buccal
