Tocolytics & Uterotonics Flashcards
purpose of tocolytics
- delay delivery
- can be administered concomitantly with corticosteroids –> prior to 33 weeks gestation to reduce neonatal risk
- onset approximately 18 hours, max benefit at 48 hours
corticosteroids prevent what risks to the neonate?
- RDS
- IVH
- NEC
- perinatal death
what are the tocolytic drugs?
- magnesium sulfate
- calcium channel blockers
- beta adrenergic agonists
- nitric oxide donors
- cox inhibitors
- oxytocin antagonists
how do tocolytics inhibit labor?
- generation or alteration of intracellular messengers
- inhibiting synthesis of block action of a myometrial stimulant
MOA of magnesium sulfate
- alters calcium transport and availability of Ca2+ for muscle contraction
- competes with intracellular calcium to reduce myometrial contractility
- hyperpolarization of plasma membrane leads to inhibition of myosin light chain kinase activity as magnesium
- RELAXATION of vascular, bronchial and uterine smooth muscles
mag for treatment of preeclampsia
- relaxes vascular smooth muscle to decrease SVR and BP
- anticonvulsant
- decreases fibrin deposition, improving circulation to visceral organs
neonatal side effects of mag
- hypotonia
- respiratory depression
mag dose/admin directions
- loading dose 4-6 g IV over 20-30 min
- followed by infusion of 1-2 g/hr
- continue through delivery and up to 24 hours post delivery
normal serum mag level
1.8-3 mg/dL
tocolytic range for magnesium
4-8 mg/dL
-can have EKG changes here like P-Q elongation and widened QRS
anticonvulsant range for mag
7-9 mg/dL
at what level does magnesium cause cardiac arrest?
25 mg/dL
side effects mag sulfate
- decreased BP (transient)
- antagonism of alpha agonist
- potentiation of NDMRs/skeletal muscle weakness
- flushing
- palpitations
- chest pain
- nausea
- blurred vision
- sedation
- CNS depression
mag sulfate OD treatment priorities
- d/c mag infusion
- secure airway
- IV admin of calcium chloride or gluconate
- diuresis
mag sulfate anesthetic implications
- exaggerated HoTN after epidural or admin of GA
- succ does not reduced and defasciculating doses not required
- reduce maintenance dose of NDMR
- symptomatic hypocalcemia and respiratory compromise have occurred in cases of myotonic dystrophy
common calcium channel blocker for tocolytic use
nifedipine because can be given PO or sublingual
Ca2+ channel blockers MOA
- block influx of calcium ions through cell membrane
- block release of calcium from the SR
- inhibit calcium dependent MLCK-mediated phosphorlyation which leads to myometrial relaxation
- also act on potassium channels
- when used as tocolytic, birth delayed between 2-7 days
side effects of calcium channel blockers
- hypotension
- dyspnea
- pulmonary edema
- tachycardia
- HA
- avoid concomitant use with mag sulfate (bc will enhance NMB effects and affect cardiac and resp function)
calcium channel blocker anesthetic implications
- expect HoTN with admin of neuraxial or GA
- potential uterine atony that may be refractory to oxytocin and prostaglandins
- methergine if atony occurs
Beta 2 agonist MOA
- stimulation of beta 2 receptors results in smooth muscle relaxation
- inhibition of myometrial contractility
- increase progesterone production which causes changes in myometrial cells to limit contractile impulses
common B2 agonists used as tocolytics
terbutaline
main hazards of B2 agonist as tocolytic
- increased blood sugar and insulin levels in mom (increases w/in few hours and returns to normal at 72 hours)
- potassium redistributed to intracellular compartment; low level can reach 3 mEq/L
- neonatal hypoglycemia due to increased insulin secretion in response to hyperglycemia
- fetal tachycardia also common
beta 2 agonists side effects
- maternal/fetal tachycardia
- dysrhythmias
- ischemia
- hypotension
- pulmonary edema
- HA
- hyperglycemia
- hypokalemia
- increased plasma renin and vasopressin
anesthetic implications of beta2 agonist as tocolytic
- delay anesthesia for 60 min to allow HR to decrease
- avoid drugs that increase HR - ketamine, atropine, glyco, thiopental, pancuronium, etomidate
- monitor IV admin due to risk of fluid overload and pulmonary edema
- treat hypotension with phenylephrine and/or ephedrine
nitric oxide donor tocolytic MOA
- endogenous substance necessary for smooth muscle tone
- acts by increased cyclic guanosine monophosphate (cGMP)
- cGMP inactivates MLCK causing smooth muscle relaxation
nitric oxide donor side effects
- maternal HoTN common
- HA
COX inhibitors as tocolytic MOA
- COX converts arachidonic acid to prostaglandin H2 (which is a substrate for tissue specific enzymes critical to giving birth)
- prostaglandins enhance formation of myometrial gap junctions and increase avail intracellular calcium
- so COX inhibitors reduce prostaglandin levels which inhibit COX enzymes and result is decreased uterine contraction
COX-inhibitors used for tocolytics
- indomethacin (non-selective)
- celebrex (COX-2 selective), tocolytic efficacy equal to Mg in preventing preterm birth within 48 hours
COX inhibitors anesthetic implications
- plt inhibition associated with non-selective COX (transient and reversible; neuraxial NOT contraindicated)
- other maternal side effects are MINIMAL
oxytocin receptor antagonist
atosiban
atosiban MOA
- blocks normal effects of oxytocin in uterus
- stimulates contractions by converting phosphatidylinositol triphosphate to inositol triphosphate
- IP3 binds to protein in SR causing calcium release in cytoplasm
atosiban facts
- not approved for use in US
- reports of fetal death associated with use of drug before 28 weeks gestation
- myometrium DOES remain sensitive to oxytocin
uterotonics
-stimulate uterine contraction
PPH leading cause
- uterine atony
- admin of oxytocin
oxytocin
- endogenous hormone produced by post pit gland
- lowers threshold of depolarization of uterine smooth muscle
- synthetic oxytocin = octapeptide; fewer S/E than endogenous oxytocin
- routinely administered after delivery
dose post-delivery of oxytocin
20-40 units/L if isontonic solution IV over 15-20 min
oxytocin uses in obstetrics
- used prophylactically to reduce blood loss after delivery
- infusions at low controlled rate are used to induce labor
oxytocin anesthetic implications
- causes a degree of vasodilation or decreased SVR which can result in significant hypotension and tachycardia
- associated with IV bolus of oxytocin normally so AVOID bolus
Ergot Alkaloids as uterotonic
- second line treatment for uterine atony
- effective for decreasing postpartum blood loss and PPH
- produce tetanic uterine contractions restricting their use during postdelivery period
examples of ergot alkaloids
- methergine = synthetic
- ergotrate = semisynthetic
Ergot alkaloids MOA
-not clear but thought to be an alpha adrenergic agonist effect
methergine dose
- 0.2 mg IM
- contractions occur within minutes of admin
- dose may be repeated in 15-20 min
- total max dose 0.8 mg
IV admin of methergine causes what?
- profound hypertension
- severe N/V
- cerebral hemorrhage
ergot alkaloids anesthetic implications
- do not use in women with HTN; pregnancy induced or chronic; do not use in those with PVD or ischemic heart disease
- monitor BP carefully and have vasodilating drugs available
- N/V occurs in 10-20% of women
prostaglandins
- 80-90% effective in PPH refractory to oxytocin and ergot alkaloids
- drug = hemabate, carboprost
prostaglandins MOA
-increases myometrial calcium levels and subsequently increases MLCK activity and uterine contraction
hemabate dose
- 0.25 mg IM or directly into myometrium
- repeat Q15-30 min to a total dose of 2 mg
misoprostol
- prostaglandin E1 analog
- reduced blood loss at C-section and is as effective as oxytocin
- dose = 0.8-1 mg (administered sublingual or buccal)
prostaglandins anesthetic implications
- all of these drugs have detrimental side effects
- use of carboprost in women with RAD can result in bronchospasm, V/Q mismatch and hypoxemia
- monitor O2 sats and lung sounds
- misoprostol can be used in patients with RAD or pulm HTN
