Tocolytics and Uterotonics Flashcards
tocolytic drugs include (6)
magnesium sulfate CCB's beta agonists nitric oxide donors cyclooxyrgenase inhibitors oxytocin antagonists
tocolytics inhibit labor by
generation or alteration of intracellular messengers or inhibiting synthesis or block action of myometrial stimulant
magnesium sulfate MOA
alter calcium transport and availability for muscle contraction.
compete with intracellular calcium, reducing myometrial contractility.
hyper polarization of plasma membrane leads to inhibition of myosin light chain kinase activity as magnesium
also depression of motor endplate sensitivity and excitability
magnesium relaxes which 3 muscle groups
vascular, bronchial, and uterine smooth muscles
how does magnesium sulfate treat preeclampsia
relaxes vascular smooth muscle decreasing SVR and BP
anticonvulsant
decreases fibrin deposition, improving circulation to visceral organs
neonatal side effects for magnesium sulfate administration are rare but include (3)
hypotonia
respiratory depression
expect a lower APGAR
how to administer magnesium sulfate for the treatment of preeclampsia
loading dose of 4-6g IV over 20-30 minutes
infusion of 1-2 g/hour
continued through delivery and up to 24 hours post delivery
therapeutic level of magnesium sulfate and side effect to expect
4-9mEq/L, 4-8mg/dL
EKG changes: PQ lengthened, QRS widened
normal serum magnesium during pregnancy is
1.8-3mg/dL
at a serum level of 7-9mg/dL, magnesium has this effect
anticonvulsant
at a serum level of 10-12mg/dL, magnesium has this effect
tendon reflexes abolished
at a serum level of >12mg/dL, magnesium has this effect
respiratory depression
at a serum level of 15-20mg/dL, magnesium has this effect
SA and AV blocks, respiratory arrest
at a serum level of 18mg/dL, magnesium has this effect
apnea
at a serum level of 25mg/dL, magnesium has this effect
cardiac arrest
what does magnesium do to blood pressure
lowers it
what does magnesium do to NMB’s
potentiate them
what does magnesium do to alpha agonist drugs
antagonize them
side effects of magnesium sulfate (general list) includes (11)
flushing transient hypotension palpitations chest pain nausea blurred vision sedation pulmonary edema skeletal muscle weakness CNS depression vascular dilatation
treatment priorities for magnesium sulfate overdose include
discontinue infusion
secure airway
IV administration of calcium chloride
diuresis
anesthetic implications of magnesium sulfate includes (4)
exaggerated HoTN after administration of epidural or general anesthesia
succinylcholine dose not reduced for intubation but defasciculating doses are not required.
reduce maintenance doses of non depolarizing muscle relaxants
symptomatic hypocalcemia and respiratory compromise have occurred in cases of myotonic dystrophy
which CCB is most popular as a tocolytic and why
nifedipine because it can be given PO or SL
MOA of CCB’s as a tocolytic
block influx of calcium ions through cell membrane
block release of calcium from SR
inhibit calcium dependent myosin light chain kinase mediated phosphorylation. leads to myometrial relaxation
also acts on potassium channels
when calcium channel blockers are used as a tocolytic, birth is delayed for how long
2-7 days
side effects of calcium channel blockers include
HoTN dyspnea pedema tachycardia HA
avoid concomitant use of CCB’s with which drug and why
magnesium sulfate
enhance NMB effects affecting respiratory and cardiac function
anesthetic implications of calcium channel blockers (one having further implications)
expect HoTN with administration of neuraxial or GA
potential uterine atony that may be refractory to oxytocin and prostaglandins (which both act through calcium channels)
if uterine atony occurs on a CCB, what should you administer
methergine
MOA of B2 agonists as a tocolytic
stimulation of B2 receptors results in smooth muscle relaxation.
biochemical events lead to inhibition of myometrial contractility, increase in progesterone production.
MOA of progesterone
causes histologic changes in myometrial cells that limit spread of contractile impulsers
two common beta 2 agonists
terbutaline ritodrine (no longer marketed in US)
hazards of B2 stimulation includes
increased blood sugar and insulin levels in the mom
neonatal hypoglycemia
fetal tachycardia is common
hazards of B2 stimulation: increased BG and insulin levels in the mother timeline and electrolyte implication
increases within a few hours and returns to baseline within 72 hours
the same happens with potassium- it can reach 3mEq/L
hazards of B2 stimulation: neonatal hypoglycemia. side effects/expectations
increased insulin secretion in response to hyperglycemia
following delivery, glucose load from mother ceases leading to rebound hypoglycemia
side effects of the use of B2 agonists as a tocolytic include (general)
maternal and fetal tachycardia dysrhythmias ischemia HoTN pedema (rare) HA hyperglycemia hypokalemia increased plasma renin and vasopressin
anesthetic implications of beta 2 agonists
delay anesthesia for 60 minutes to allow the heart rate to decrease
if not possible, all drugs that increase heart rate should be avoided
monitor IV administration due to risk of fluid overload and pedema
treat HoTN with phenylephrine (>) or ephedrine
drugs that increase heart rate include (6)
ketamine atropine glycopyrrolate thiopental pancuronium etomidate
MOA of nitroglycerine
nitroglycerine is a nitric oxide donor with a short t1/2
its an endogenous substance necessary for smooth muscle tone
acts by increasing cyclic guanosine monophosphate (cGMP) and therefore inactivates myosin light chain kinases causing smooth muscle relaxation
are nitric oxide donors or magnesium sulfate more likely to delay delivery
magnesium sulfate
side effects of nitric oxide donors include
maternal HoTN and HA
MOA of cyclooxygenase
converts arachidonic acid to prostaglandin H2. substrate for tissue specific enzymes critical to giving birth
MOA of prostaglandins
enhance formation of myometrial gap junctions which increases available intracellular calcium by raising transmembrane influx and sarcolemmal release
MOA of cyclooxygenase inhibitors
reduce prostaglandin levels, inhibiting COX enzymes. results in decreased uterine contraction
2 cyclooxygenase inhibitors used as tocolytics and their selectivity
indomethacin (nonselective)
celecoxib (cox 2 selective)
efficacy of celecoxib as compared to magnesium sulfate for use as a tocolytic
equal efficacy in preventing preterm birth within 48 hours
anesthetic implications of cyclooxygenase inhibitors
platelet inhibition associated with nonselective cox inhibitors. transient and reversible, neuraxial anesthesia not contraindicated
atisoban class and MOA
class: oxytocin receptor antagonist
MOA: blocks normal effects of oxytocin in the uterus. the myometrium does remain sensitive to oxytocin
how does oxytocin stimulate contractions
by converting phosphatidylinositol triphosphate (PIP3) to inositol triphosphate (IP3).
IP3 binds to protein in SR causing calcium release into cytoplasm
why is atosiban not approved in US
reports of fetal death are associated with use of this drug before 28w gestation
anesthetic considerations for tocolytics in general
tocolytic PK and PD knowledge is essential (maternal and fetal physiology implications)
neuraxial preferred over GA (neonate APGAR scores are higher at 1 and 5 minutes)
patients on magnesium sulfate are candidates for neuraxial (careful attention is given to volume status)
since magnesium causes vasodilation, what complication is poorly tolerated in those women
maternal hemorrhage
leading and second leading cause of PPH
uterine atony
oxytocin admin (?)
(slide 29????)
where is oxytocin produced
posterior ptuitary
MOA of oxytocin
lowers threshold for depolarization of uterine smooth muscle. depolarization is enhanced by activation of calcium channels and increased prostaglandin production
synthetic oxytocin chemical makeup, side effects in relation to endogenous oxytocin
pitocin/syntocinon are octapeptides
cause fewer side effects than endogenous oxytocin (related to ADH and water intoxication)
oxytocin administration
20-40units/L of isotonic solution IV over 15-20 minutes
uses of oxytocin (2)
used prophylactically to reduce blood loss after delivery
infusion at a low controlled rate are used to induce labor
anesthetic considerations of oxytocin
causes a degree of vasodilation or decreased SVR which can result in significant HoTN and tachycardia.
associated with IV bolus of oxytocin so avoiding boluses is recommended
what is the second line treatment for uterine atony
ergot alkaloids
positive effects of ergot alkaloids in the treatment of uterine atony
effective for decreasing postpartum blood loss and PPH
produce tetanic uterine contractions restricting their use during the post delivery period
synthetic ergot alkaloid
methergine
semisynthetic ergot alkaloid
ergotrate
MOA of ergot alkaloids
not clear, thought to be an alpha adrenergic agonist effect
methergine dose
.2mg IM, contractions occur within minutes of administration
dose may be repeated in 15-20 minutes, total dose .8mg
IV administration of methergine can result in these side effects
profound HTN (have vasodilators avail)
severe n/v (effect on vomiting center)
cerebral hemorrhage
anesthetic implications of ergot alkaloids: do not use in women with
preexisting HTN: pregnancy induced or chronic
peripheral vascular disease or ischemic heart disease (MI’s have occurred in women treated with PO our IV ergot alkaloids)
second option when methergine is contraindicated (class, drug names)
prostaglandins
carboprost, hemabate (15 methylprostaglandin F2a)
how effective are prostaglandins in PPH refractory to oxytocin and ergot alkaloids?
80-90% effective
MOA of prostaglandins
increases myometrial calcium levels and subsequently increases myosin light chain kinase activity and uterine contraction
hemabate class and MOA
250mcg IM or directly into myometrium. repeat q15-30 minutes to a total dose of 2mg
prostaglandin
which drug has reduced blood loss at c section and is as effective as oxytocin
prostaglandin e1 analog misoprostol
misoprostol dose
800-10000mcg SL or buccal
misoprostol is not preferable to other uterotonics for the active management of
3rd stage labor
anesthetic implications of prostaglandins
all of these drugs have detrimental SE
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 which co morbidities
reactive airway disease and HTN
