Tocolytics & Uterotonics Flashcards
Tocolytics
Relax uterus to delay delivery
Inhibit labor via generation or alteration intracellular messengers and/or inhibit synthesis or block action of myometrial stimulant
Administer concomitantly w/ corticosteroids
Onset ≈ 18hrs
Maximum effect at 48hrs
Magnesium Sulfate
1st choice tocolytic
Vascular, bronchial, & uterine smooth muscle relaxation ↓BP
Depresses motor endplate sensitivity; potentiates NMBDs
Antagonizes α agonists
Magnesium Sulfate
Preeclampsia Treatment
Relaxes VSMC, ↓SVR/BP, anticonvulsant, ↓fibrin deposition improving circulation to visceral organs
Magnesium Sulfate
Neonatal SE
Hypotonia & respiratory depression
Magnesium Sulfate MOA
Alter Ca2+ transport & availability for muscle contraction
Complete w/ intracellular Ca2+ → reducing myometrial contractility
Hyperpolarization plasma membrane leads to inhibition myosin light-chain kinase activity
Depress motor endplate sensitivity
Muscle membrane excitability
Magnesium Sulfate Dose
Loading dose 4-6g IV over 20-30min
Infusion 1-2g/hr
Therapeutic level 4-9mEq/L
Continue through delivery & 24hrs post-delivery
Normal Serum Magnesium
1.8-3 mg/dL Tocolytic range 4-8mg/dL Anticonvulsant 7-9mg/dL Tendon reflexes abolished 10-12mg/dL Respiratory depression >12mg/dL SA/AV blocks (respiratory arrest) 15-20mg/dL Apnea 18mg/dL Cardiac arrest 25mg/dL
MAGNESIUM
Tocolytic Range
Serum Mg2+ 4-8mg/dL
EKG changes: ↑PQ & QRS
MAGNESIUM
Anticonvulsant
7-9mg-dL
MAGNESIUM
Tendon Reflexes Abolished
10-12mg/dL
MAGNESIUM
Respiratory Depression
> 12mg/dL
MAGNESIUM
SA & AV Block
Respiratory Arrest
15-20mg/dL
MAGNESIUM
Apnea
18mg/dL
MAGNESIUM
Cardiac Arrest
25mg/dL
Magnesium Sulfate SE
Transient HoTN* Sedation* Skeletal muscle weakness* CNS depression* Flushing Palpitations Chest pain Nausea Blurred vision Pulmonary edema Vascular dilatation
Magnesium Sulfate Overdose
TREATMENT
- Discontinue infusion
- Secure airway
- IV calcium chloride admin
- Diuresis (Mg2+ excretion)
Magnesium Sulfate Anesthetic Implications
HoTN after epidural or general anesthesia administration
Succinylcholine dose NOT reduced for intubation; de-fasciculating doses not required
Reduce non-depolarizing muscle relaxant maintenance doses d/t upregulation
Symptomatic hypocalcemia and respiratory compromise have occurred in myotonic dystrophy cases
Calcium Channel Blockers
2nd choice tocolytic
Nifedipine commonly used PO or sublingually
Delays birth b/w 2-7 days when used as tocolytic
Ca2+ Channel Blockers MOA
Block calcium ions influx through cell membrane
Block calcium release from SR (impairs Ca2+ ability to work on the vascular smooth muscle cells)
Inhibit calcium-dependent myosin light chain kinase mediated phosphorylation → myometrial relaxation
Acts on potassium channels
Ca2+ Channel Blockers SE
Hypotension exaggerated w/ neuraxial or general anesthesia Dyspnea Pulmonary edema Tachycardia Headache
Ca2+ Channel Blockers Anesthetic Implications
Expect hypotension w/ neuraxial or general anesthesia
Avoid concomitant use w/ Mg2+ sulfate
Potential uterine atony refractory to oxytocin and prostaglandins
- Both act through Ca2+ channels
- Adequate IV access and Methergine to treat uterine atony
β2 Agonists
3rd choice tocolytic
β2 receptors result in smooth muscle relaxation
Myometrial contractility inhibition
↑progesterone production - progesterone causes histologic changes in myometrial cells that limit contractile impulse spread
Ex: Terbutaline
β2 Stimulation Causes
↑maternal blood sugar & insulin levels
K+ redistributed to intracellular compartment lowering levels (as low as 3mEq/L)
Returns to baseline w/in 72hrs
Neonatal hypoglycemia
↑ insulin secretion in response to hyperglycemia
Following delivery glucose load from the mother ceases leading to rebound hypoglycemia
Fetal tachycardia common
β2 Agonists SE
Maternal & fetal tachycardia Dysrhythmias Ischemia Hypotension d/t vasodilation Pulmonary edema Headache Hyperglycemia Hypokalemia ↑ plasma renin & vasopressin
β2 Agonists Anesthetic Implications
Delay anesthesia for 60min to allow heart rate to decrease
Avoid drugs that increase heart rate - Ketamine, Atropine, Glycopyrrolate, Thiopental, Pancuronium, Etomidate
Monitor IV administration d/t fluid overload & pulmonary edema risk
Treat hypotension w/ Phenylephrine or Ephedrine
Nitric Oxide Donors MOA
Nitric oxide - endogenous substance necessary for smooth muscle tone
↑cyclic guanosine monophosphate (cGMP)
Inactivates MLCK causing smooth muscle relaxation
Example: Nitroglycerin
Nitric Oxide Donors SE
Maternal HoTN
Headache
Cyclooxygenase Inhibitors
NSAIDs
COX inhibitors prevent arachidonic acid conversion to prostaglandin H2
↓prostaglandin levels ↓uterine contraction
Non-selective: Indomethacin
COX-2 selective: Celecoxib
Cyclooxygenase MOA
COX converts arachidonic acid → prostaglandin H2
Prostaglandins enhance myometrial gap junction formation
↑available intracellular Ca2+
COX Inhibitors Anesthetic Implications
Platelet inhibition associated w/ non-selective COX inhibitors
- Transient & reversible
Neuroaxial anesthesia not contraindicated
Other maternal side effects minimal and have little concern for anesthesia
Tocolytics Anesthetic Implications
Neuraxial preferred over general anesthesia
Know baseline BP & fluid-volume status
Magnesium causes vasodilation; maternal hemorrhage poorly tolerated
Succinylcholine muscle relaxant choice for rapid sequence induction
Magnesium sulfate potentiates muscle relaxants; no de-fasciculating dose
Uterotonics
Uterine atony leading postpartum hemorrhage cause
- Fundal massage
- Administer oxytocin
Oxytocin
Endogenous hormone produced by posterior pituitary gland - lowers threshold for uterine smooth muscle depolarization (depolarization enhanced by Ca2+ channel activation & ↑prostaglandin production)
Synthetic oxytocin (Pitocin, Syntocinon) are octapeptides
- Fewer side effects than endogenous oxytocin r/t antidiuretic hormone (water intoxication)
Routinely administered after delivery
20-40u/L isotonic IV solution over 15-20min
Used prophylactically to reduce blood loss after delivery
Infusions at low controlled rate are used to induce labor
Oxytocin Anesthetic Implications
Vasodilation and/or ↓SVR
Significant hypotension & tachycardia
Avoid IV boluses → HoTN
Ergot Alkaloids
2nd line uterine atony treatment
Effective to decrease postpartum blood loss & PPH
Produce tetanic uterine contractions restricting their use during post-delivery period
MOA not clear - α adrenergic agonist effect?
Examples: Methergine (synthetic) & Ergotrate (semi-synthetic)
Methergine (Synthetic)
0.2mg IM (deltoid) Contractions occur w/in minutes Repeat dose in 15-20min Total 0.8mg Ø IV bolus administration → Profound hypertension → Severe N/V → Cerebral hemorrhage
Methergine Anesthetic Implications
Do NOT use:
- Pre-existing HTN pregnancy-induced or chronic
- Peripheral vascular disease or ischemic heart disease (MI risk)
Monitor BP carefully and have vasodilating drugs available
N/V occurs in 10-20% women
Effect on vomiting center - cerebral vasodilation admin phenylephrine
Prostaglandins
80-90% effective in post-partum hemorrhage refractory to oxytocin and ergot alkaloids
Second option when Methergine contraindicated
15-Methylprostaglandin F2a (Hemabate/Carboprost)
Prostaglandins MOA
↑myometrial Ca2+ levels subsequently ↑myosin light-chain kinase activity & uterine contraction
Reduced need for post-op hysterectomy r/t uterine atony
Hemabate
15-Methylprostaglandin F2a (Carboprost)
250mcg IM or directly into the myometrium
Repeat 15-30min
Max dose 2mg
Misoprostol
Prostaglandin E1 Analog
Reduced blood loss (as effective as oxytocin)
800-1000mcg sublingual or buccal
Not preferable to other uterotonics for active 3rd stage labor management
Misoprostol Contraindications
HTN
Active cardiac, pulmonary, renal, or hepatic diseases
Prostaglandins Anesthetic Implications
Hemabate (Carboprost) in women w/ reactive airway disease → bronchospasm & ventilation-perfusion mismatch & hypoxemia (asthma patients at risk)
- Monitor SpO2 & lung sounds
Misoprostol used in patients w/ reactive airway disease or pulmonary hypertension
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