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Reproductive > Induction And Analgesia During Labor > Flashcards

Induction And Analgesia During Labor Flashcards

1
Q

Pharmacology of Parturition (Labor) - 4

A
  1. Pharmacologically relevant targets in parturition regulate smooth muscle contraction
  2. Tocolytics PREVENT/DELAY labor onset by REDUCING smooth muscle contraction
  3. Oxytocics (a.k.a. uterotonics) INDUCE labor by PROMOTING smooth muscle contraction
  4. Pathways converge on myosin light-chain kinase (MLCK)
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2
Q

Myosin light-chain kinase (MLCK) and Uterine Muscle (3)

A
  1. ACTIVE MLCK is essential in smooth muscle CONTRACTION
  2. MLCK is ACTIVATED by Ca2+/calmodulin complex
    - Myometrial cell CONTRACTION is mediated by increased Ca2+ levels
  3. MLCK is DEACTIVATED by phosphorylation
    - Myometrial cell RELAXATION is promoted by phosphorylation of MLCK
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3
Q

Pharmacological targets of MLCK activity (2)

A
  1. Agonism of CRH, PGE2, and ß2-adrenergic receptors promotes RELAXATION
    - Agonism of Gs coupled-receptors INCREASES cAMP-mediated PHOSPHORYLATION
  2. Agonism of thrombin, oxytocin, and prostaglandin F receptors promotes CONTRACTION
    - Agonism of Gq coupled-receptors INCREASES intracellular Ca2+ levels
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4
Q

General Principles of Tocolytic Pharmacology (3)

A
  1. Preterm delivery = delivery occurring before 37 weeks of gestation
    - > 10% of pregnancies in the U.S. are preterm
    - Associated with neonatal respiratory distress syndrome, pulmonary hypertension, and intracranial hemorrhage
  2. Tocolytic agents are effective in delaying preterm delivery in ~80% of women
    - Indicated when delaying delivery up to 48 hours is beneficial to fetus and cervical dilation is not advanced
    - Generally not used past 34 weeks gestation
  3. These agents do not decrease overall occurrence of preterm labor or alleviate complications!
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5
Q

Tocolytics postpone delivery long enough to: (3)

A
  1. Administration of corticosteroids to the fetus to promote fetal lung development
  2. Transportation to a facility equipped to deal with high-risk deliveries
  3. Prolongation of pregnancy in the presence of underlying, self-limited conditions that can cause labor
    - E.g., pyelonephritis, abdominal surgery, or other conditions unlikely to cause recurrent preterm labor

Pregnancy can be prolonged by 48 hours to 1 week

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6
Q

Contraindications of tocolytic therapy (8)

A
  1. Previability
  2. Intrauterine fetal demise
  3. Lethal fetal anomaly
  4. Intrauterine infection
  5. Fetal distress
  6. Severe preeclampsia
  7. Vaginal bleeding
  8. Maternal hemodynamic instability
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7
Q

General MOA of Tocolytic Agents and their Classes (2 MOA, 6 Classes)

A
  1. Decreased Ca2+/calmodulin availability (decreases uterine contractility)
  2. Increased phosphorylation (increases uterine relaxation)

Most effective classes:

  1. COX inhibitors
  2. Ca2+ channel blockers
  3. B2-adrenergic receptor agonists

Less effective classes:

  1. Oxytocin receptor antagonists
  2. MgSO4 (magnesium sulfate)
  3. Nitric oxide (NO) donors
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8
Q

COX inhibitors: indomethacin (General, MOA, PK, ADRs, contraindications)

A

General: First-line agent for tocolysis between 24-32 weeks of gestation

MOA: Non-specific COX inhibitor (reduced PGF synthesis). Reduce stimulation of uterine contractions by decreasing available intracellular Ca2+.

PK: Administered orally or rectally

Maternal ADRs:

  • COX-2 inhibitors carry BLACK BOX WARNING: CV toxicity (myocardial infarction, stroke)
  • Risk of inhibited platelet function
  • N/V, GERD, gastritis, and emesis

Fetal ADRs:

  • May induce closure in utero of ductus arteriosus causing impaired circulation
  • May reduce amniotic fluid and cause oligohydramnios

Contraindicated beyond 32 weeks of gestation

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9
Q

Ca2+ channel blockers: Nifedipine (General, MOA, PK, ADRs)

A

General: First-line agent for tocolysis between 32-34 weeks of gestation or for contraindication to indomethacin (24-32 weeks)

MOA: Blocks voltage-gated Ca2+ channels. Reduces stimulation of uterine contractions.

PK: Administered parenterally or orally

Maternal ADRs:

  • Peripheral vasodilator: headache, flushing, and dizziness, palpitations, severe hypotension possible
  • No direct effect on pacemaking or AV node conduction
  • Safer than ß2-adrenergic agonists

No discernible impact on fetus.

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10
Q

Selective B2-adrenergic receptor agonists: terbutaline and ritodrine (General, MOA, PK, ADRs)

A

General: Terbutaline is FDA-approved for asthma with off-label tocolytic use. Used as second-line agents for 32-34 weeks of gestation.

MOA: B2-adrenergic receptor agonists RELAX myometrium by stimulating cAMP and MLCK phosphorylation.

PK: Administered PO, IV, or subcutaneously

Maternal ADRs:

  • Tachycardia, hypotension, pulmonary edema, metabolic effects
  • BLACK BOX WARNING: maternal cardiotoxicity and death with prolonged use

Fetal ADRs:

  • Drug crosses the placenta
  • Similar ADR profile as maternal side

*Ritodrine was FDA-approved for tocolysis, but has been withdrawn from market due to unfavorable ADRs

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11
Q

Oxytocin receptor antagonists: Atosiban (MOA, PK, ADRs)

A

MOA: Decreases intracellular Ca2+ concentration and decreases uterine contractions. Mimics effectiveness of B2-adrenergic receptor agonists.

PK: Administered IV for 2-48 hours

ADRs:
- Hypersensitivity

*Not FDA approved

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12
Q

MgSO4 and NO (MOA, PK, ADRs, and Contraindications)

A

MgSO4
MOA: Competes with Ca2+ at voltage-gated and ligand-gated Ca2+ channels. Decreases intracellular Ca2+ and decreases uterine contractions. Also used to treat preeclampsia.

PK: Administered parenterally. Renally excreted.

Maternal ADRs:
- Diaphoresis, flushing, Mg2+ toxicity

Fetal ADRs:
- Bone abnormalities with long-term exposure

Contraindicated in myasthenia gravis, cardiac compromise.

NO
MOA: Activates phosphokinase G via cGMP signaling to phosphorylate MLCK and promote uterine relaxation.

Contraindicated in hypotensive patients.

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13
Q

Indications for Agents Used to Induce Labor - Oxytocics (Uterotonics) - Maternal Factors (9) and Fetal Factors (9)

A

Maternal factors:

  1. Preeclampsia
  2. Eclampsia
  3. HELLP (hemolysis, elevated liver enzymes, low platelet count)
  4. Diabetes (pregestational or gestational)
  5. Chronic hypertension
  6. Heart disease
  7. Intrauterine infection
  8. Augmentation of protracted labor
  9. Postpartum hemorrhage (uterine atony)

Fetal factors:

  1. Late-term or postterm pregnancy
  2. Fetal abnormality
  3. Chorioamnionitis
  4. Premature rupture of membranes
  5. Placental insufficiency
  6. Oligohydramnios
  7. Suspected intrauterine growth restriction
  8. Fetal demise
  9. Multiple gestation
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14
Q

Prostaglandins, Oxytocin, and Parturition (4)

A
  1. PGE2 and oxytocin are required for the onset of parturition
  2. PGE2 or PGF2a produces DOSE-DEPENDENT increases in:
    - Uterine tone
    - Frequency of contractions
    - Intensity of contractions
  3. Effects of prostaglandins increase as pregnancy progresses
  4. Prostaglandins and oxytocin used in sequence to promote cervical ripening and induction, respectively
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15
Q

Prostaglandin Agents (Dinoprostone and Misoprostol) MOA and PK

A

Indications: Cervical ripening prior to labor induction

  1. Dinoprostone (PGE2) (FDA-approved)
    - Available as a gel
    - Administered intracervically or as a vaginal insert (next to cervix) - 12 hours for cervical ripening, remove 30 minutes prior to induction, induce with oxytocin
  2. Misoprostol (PGE1) (off-label use)
    - Available in tablets that can be administered orally, vaginally, or rectally
    - Allow at least 4 hours before induction with oxytocin
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16
Q

Prostaglandin Agents (Dinoprostone and Misoprostol) ADRs - 8 and Contraindications - 7

A

ADRs:

  1. Fetal heart rate deceleration
  2. Fetal distress
  3. Emergency cesarean section
  4. Uterine hypertonicity
  5. Nausea
  6. Vomiting
  7. Fever
  8. Peripartum infection

Prostaglandin contraindications:

  1. History of asthma (smooth muscle contraction effect can worsen asthma)
  2. Glaucoma
  3. Myocardial infarction
  4. Unexplained vaginal bleeding
  5. Chorioamnionitis
  6. Ruptured membranes
  7. Previous cesarean section
17
Q

Induction of Labor with Oxytocin (2)

A
  1. Regimen and quantity of oxytocin must be individualized
    - Use lowest effective dose for each patient
    - Precise IV administration via continuous-infusion pump
    - Begin with low dose infusion (ex: 0.5-2 mU/mL)
    - Increase every 30-60 minutes as needed to maintain labor (maxiumum 20 mU/min)
    - Constant observation is required
  2. Discontinue if tachysystole (> 5 contractions per 10 min) or fetal distress occurs
18
Q

Oxytocin ADRs and Contraindications

A

ADRs:

  • Excessive uterine contractions
  • Placental blood flow to fetus is transiently reduced
  • Deceleration of fetal heart rate/fetal hypoxia may require immediate C-section
  • Off-target activation of vasopressin receptors (fluid retention/water intoxication) causing hyponatremia, heart failure, seizures, death; hypotension

Contraindications:

  • Fetal distress or malpresentation
  • Placental abruption or other risk of uterine rupture (previous surgery)
19
Q

Contraindications to Labor Induction (8)

A

Any problem that could be made worse by intensifying contractions is always a contraindication or cause for concern!

  1. Contracted pelvis
  2. Placenta previa
  3. Vasa previa
  4. Previous classical cesarean section
  5. Myomectomy entering the endometrial cavity
  6. Breech presentation (relative)
  7. Previous C-section with low transverse uterine scar (relative)
  8. Complications: oligohydramnios; multiple gestation; grand multiparity; prematurity; suspected fetal macrosomia (all relative)
20
Q

Labor Induction (Complications)

A

Maternal considerations:

  • Induction of labor may be more distressing than judicious delay or c-section
  • Failure of induction
  • Prolonged labor (uterine inertia)
  • Tetanic contractions of the uterus (tumultuous labor)
  • Premature placental separation, uterine rupture, cervix laceration
  • Intrauterine infection
  • Postpartum hemorrhage

Fetal considerations:

  • Induction of labor increases risk of prematurity
  • Calculation of date of conception may be inaccurate
  • Cord prolapse (amniotomy)
  • Fetal heart rate abnormalities (oxytocin) or poor Apgar score
21
Q

Non-pharmacologic methods of obstetric pain management (2)

A
  1. Continuous support during labor provides best outcomes
    - Nurses, midwives, coaches, doulas, childbirth educators
    - Fewer operative vaginal or cesarean deliveries
    - Fewer requests for pain medication
  2. Warm baths and acupuncture temporarily reduce pain
22
Q

General principles of obstetric analgesia and anesthesia (7)

A
  1. Psychologically prepared patients require less medication
  2. Do not promise painless labor
    - Anticipate and address anxieties before and during early labor
  3. Treatment must be individualized to each patient
    - Variations in response, preference, and adverse reactions
  4. Know the limitations, dangers, contraindications and advantages of each drug administered
  5. Analgesia is the loss or modulation of pain perception
  6. Anesthesia is the total loss of sensory perception
  7. Transplacental drug transfer occurs with systemic analgesics and CNS depressant effects may affect fetus or newborn
23
Q

Analgesics & Anesthetics used during labor (6)

A
  1. Tranquilizers: Benzodiazepines - Used for anxiety; midazolam’s SHORT HALF LIFE reduces risk of fetal kernicterus, hypotonia, hyperthermia, heart rate abnormalities compared to longer acting (diazepam).
  2. Narcotic Agents: Codeine (IM), Merperidine (IM/IV), Fentanyl (epidural) - Most common choice; Parenteral opioids (compared with epidural analgesia). Lower rate of oxytocin augmentation; shorter stages of labor; fewer instrumental deliveries and cesarean sections for fetal distress.
  3. Inhalation anesthetics: NO, sevoflurane, desflurance, isoflurane - Significant fetal concentrations achieved. Pregnant patients are more sensitive than nonpregnant patients, increased risk of obutndation and aspiration. SHOULD BE INTUBATED.
  4. Propofol: Ideal for induction of general anesthesia in pregnant patients.
  5. Etomidate: Minimal cardiorespiratory effects makes it useful for hemodynamically unstable patients.
  6. Ketamine: Widely used as adjunctive agent; maternal cardiovascular status and uterine blood flow are well-maintained, blood pressure and cardiac output are stimulated; useful in major blood loss setting when rapid induction of anesthesia is required; narrow margin of safety and hallucinogenic.
24
Q

Non-systemic analgesia and major sites of placement (5)

A
  1. Indication: maternal request (~60% of patients choose epidural analgesia)
  2. Epidural analgesia
    - Catheter introduced into epidural space
    - Opioid and/or anesthetic administered
  3. Spinal-epidural (intrathecal) analgesia
    - Injection of single opioid bolus into subarachnoid space followed by epidural catheter (immediate and sustainable pain relief)
  4. Major benefit: the patient-controls analgesia
    - Lower total dose over the course of labor compared with continuous IV infusion
  5. Risks of epidural analgesia:
    - Prolongation of the first and second stages of labor
    - Higher numbers of instrumental deliveries and cesarean sections (for fetal distress)
    - Maternal fever
25
Q

Regional anesthesia with local anesthetics (5)

A
  1. Prevents transmission of sensory information from a portion of the body
  2. Regional nerve blocks used in obstetrics:
    - Lumbar epidural and caudal epidural block
    - Subarachnoid (spinal) block
    - Combined spinal epidural block
    - Pudendal block
  3. Narcotics can be added to improve analgesia and reduce side effects of local anesthetics
  4. Indications:
    - Labor analgesia
    - Cesarean delivery
    - Obstetric operative procedures such as postpartum tubal ligation, cervical cerclage
  5. Patient may prefer to maintain consciousness rather than undergo general anesthesia
26
Q

Local anesthetic overdose and toxicity (4)

A
  1. Risks increase dramatically if local anesthetic is inadvertently injected into vasculature
  2. Toxic central nervous system reaction (seizure)
    - Monitor for prodrome signs: ringing in the ears, diplopia, perioral numbness, deep, slurred speech
    - Maintain adequate airway, 100% oxygen with respiratory assistance if necessary
    - Immediate injection of THIOPENTAL 50 mg or MIDAZOLAM 1–2 mg to stop convulsion
  3. Cardiotoxicity (ventricular arrhythmia, cardiac arrest)
    - Bupivacaine overdose, treat with IV infusion of lipid emulsion
  4. Sympathetic block (hypotension), countered by coadministration of epinephrine
27
Q

Epidural anesthesia (General and Risks)

A
  1. First stage of labor is unaffected by epidural anesthesia
  2. Local anesthetic injected into the epidural space
    - Sacral hiatus (caudal anesthesia, not common) or in the lumbar, thoracic, or cervical regions of the spine
    - Epidural block targets spinal nerve roots: Spinal cord and paravertebral nerves may also be affected
  3. Risks:
    - Placement of needle with caudal block
    - Rapid absorption syndrome (hypotension, bradycardia, hallucinations, and convulsions)
    - Sympathetic block
    - Postpartum backache
    - Paresthesias
    - Inadvertent massive spinal anesthesia
28
Q

Spinal (intrathecal) anesthesia (General, benefits, and risks)

A
  1. Delivery to subarachnoid space (CSF)
    - Intrathecal injection
  2. Benefits:
    - Rapid onset
    - Much lower doses of anesthesia is required, serum levels are decreased
    - Reduced risk of direct cardiotoxicity
  3. Risks:
    - Blockade of sympathetic nerves at T1-T4 can be detrimental to patients with hypovolemia or CHF
    - The higher the block is placed, the greater the risk of cardiovascular complications
    - Post–lumbar puncture headaches
29
Q

Pudendal nerve block (General, benefits, and risks)

A
  1. Injection of lidocaine into pudendal nerve on each side may achieve anesthesia for ~30–45 minutes
  2. Transvaginal and transcutaneous (perineal) methods for administration
  3. Benefits:
    - Rapidity of onset
    - Infant is not depressed (CNS)
    - Blood loss is minimal
  4. Risks and disadvantages:
    - Difficult to detect puncture of sacrospinous ligament or pudendal artery
    - “Skip areas” of pain relief may occur, not all perineal nerves are affected
    - Variable efficacy/failure
    - Discomfort during administration
30
Q

Anesthesia for C-section (3)

A
  1. Most cesarean deliveries are performed with spinal, epidural, or general anesthesia
  2. Indications of general anesthesia for cesarean delivery:
    - Coagulopathy, infection, hypovolemia, urgency, or patient preference
  3. IV agents, inhalational anesthetics, and NMJ blockers are indicated
    - Time from anesthesia induction to delivery should be kept under 10 minutes
31
Q

Considerations for general anesthesia for C-section (5)

A
  1. Anesthesia is responsible for 10% of maternal mortality
  2. Most common cause: failure to intubate the trachea at induction of general anesthesia
    - Rapid desaturation if intubation is unsuccessful
  3. Greater risk of aspiration
    - Full stomach
    - Difficulty with laryngoscopy and intubation
  4. Inadvertent intravascular injection of local anesthetic (toxic reaction)
  5. Inadvertent intrathecal injection of anesthetic (total spinal)

Reproductive (6 decks)

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