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AS - N926 Pharmacology > Tocolytics & Uterotonics > Flashcards

Tocolytics & Uterotonics Flashcards

1
Q

Tocolytics

A

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

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2
Q

Magnesium Sulfate

A

1st choice tocolytic
Vascular, bronchial, & uterine smooth muscle relaxation ↓BP
Depresses motor endplate sensitivity; potentiates NMBDs
Antagonizes α agonists

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3
Q

Magnesium Sulfate

Preeclampsia Treatment

A

Relaxes VSMC, ↓SVR/BP, anticonvulsant, ↓fibrin deposition improving circulation to visceral organs

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4
Q

Magnesium Sulfate

Neonatal SE

A

Hypotonia & respiratory depression

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5
Q

Magnesium Sulfate MOA

A

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

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6
Q

Magnesium Sulfate Dose

A

Loading dose 4-6g IV over 20-30min
Infusion 1-2g/hr
Therapeutic level 4-9mEq/L
Continue through delivery & 24hrs post-delivery

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7
Q

Normal Serum Magnesium

A 
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
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8
Q

MAGNESIUM

Tocolytic Range

A

Serum Mg2+ 4-8mg/dL

EKG changes: ↑PQ & QRS

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9
Q

MAGNESIUM

Anticonvulsant

A

7-9mg-dL

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10
Q

MAGNESIUM

Tendon Reflexes Abolished

A

10-12mg/dL

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11
Q

MAGNESIUM

Respiratory Depression

A

> 12mg/dL

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12
Q

MAGNESIUM
SA & AV Block
Respiratory Arrest

A

15-20mg/dL

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13
Q

MAGNESIUM

Apnea

A

18mg/dL

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14
Q

MAGNESIUM

Cardiac Arrest

A

25mg/dL

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15
Q

Magnesium Sulfate SE

A 
Transient HoTN*
Sedation*
Skeletal muscle weakness*
CNS depression*
Flushing 
Palpitations
Chest pain
Nausea
Blurred vision
Pulmonary edema
Vascular dilatation
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16
Q

Magnesium Sulfate Overdose

TREATMENT

A
  1. Discontinue infusion
  2. Secure airway
  3. IV calcium chloride admin
  4. Diuresis (Mg2+ excretion)
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17
Q

Magnesium Sulfate Anesthetic Implications

A

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

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18
Q

Calcium Channel Blockers

A

2nd choice tocolytic
Nifedipine commonly used PO or sublingually
Delays birth b/w 2-7 days when used as tocolytic

19
Q

Ca2+ Channel Blockers MOA

A

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

20
Q

Ca2+ Channel Blockers SE

A 
Hypotension exaggerated w/ neuraxial or general anesthesia
Dyspnea
Pulmonary edema
Tachycardia
Headache
21
Q

Ca2+ Channel Blockers Anesthetic Implications

A

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

22
Q

β2 Agonists

A

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

23
Q

β2 Stimulation Causes

A

↑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

24
Q

β2 Agonists SE

A 
Maternal & fetal tachycardia
Dysrhythmias
Ischemia
Hypotension d/t vasodilation
Pulmonary edema
Headache
Hyperglycemia
Hypokalemia
↑ plasma renin & vasopressin
25
Q

β2 Agonists Anesthetic Implications

A

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

26
Q

Nitric Oxide Donors MOA

A

Nitric oxide - endogenous substance necessary for smooth muscle tone
↑cyclic guanosine monophosphate (cGMP)
Inactivates MLCK causing smooth muscle relaxation
Example: Nitroglycerin

27
Q

Nitric Oxide Donors SE

A

Maternal HoTN

Headache

28
Q

Cyclooxygenase Inhibitors

A

NSAIDs
COX inhibitors prevent arachidonic acid conversion to prostaglandin H2
↓prostaglandin levels ↓uterine contraction
Non-selective: Indomethacin
COX-2 selective: Celecoxib

29
Q

Cyclooxygenase MOA

A

COX converts arachidonic acid → prostaglandin H2
Prostaglandins enhance myometrial gap junction formation
↑available intracellular Ca2+

30
Q

COX Inhibitors Anesthetic Implications

A

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

31
Q

Tocolytics Anesthetic Implications

A

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

32
Q

Uterotonics

A

Uterine atony leading postpartum hemorrhage cause

  1. Fundal massage
  2. Administer oxytocin
33
Q

Oxytocin

A

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

34
Q

Oxytocin Anesthetic Implications

A

Vasodilation and/or ↓SVR
Significant hypotension & tachycardia
Avoid IV boluses → HoTN

35
Q

Ergot Alkaloids

A

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)

36
Q

Methergine (Synthetic)

A 
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
37
Q

Methergine Anesthetic Implications

A

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

38
Q

Prostaglandins

A

80-90% effective in post-partum hemorrhage refractory to oxytocin and ergot alkaloids
Second option when Methergine contraindicated

15-Methylprostaglandin F2a (Hemabate/Carboprost)

39
Q

Prostaglandins MOA

A

↑myometrial Ca2+ levels subsequently ↑myosin light-chain kinase activity & uterine contraction
Reduced need for post-op hysterectomy r/t uterine atony

40
Q

Hemabate

A

15-Methylprostaglandin F2a (Carboprost)
250mcg IM or directly into the myometrium
Repeat 15-30min
Max dose 2mg

41
Q

Misoprostol

A

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

42
Q

Misoprostol Contraindications

A

HTN

Active cardiac, pulmonary, renal, or hepatic diseases

43
Q

Prostaglandins Anesthetic Implications

A

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
Ø 1st line DOC

AS - N926 Pharmacology (18 decks)

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