Pharmacology and Neuraxial Anesthesia in Pregnancy Flashcards
What law/ principle explains how drugs traverse a biologic membrane?
Fick prinicple
What is the Fick principle? (formula)
Rate of diffusion = [diffusion coefficient x surface area x concentration gradient (between mom and fetus)] / membrane thickness
What are the most important variables in determining rate of diffusion of a drug?
Diffusion coefficient
Concentration gradient between mother and fetus
How does fetal acidosis affect drug transfer from mom to fetus?
It can increase the concentration gradient, leading to ion trapping
What drug characteristics favor placental transfer of the drug?
Low molecular weight (< 500 Daltons)
High lipid solubility
Non- ionized
Non- polar
What drugs have significant placental transfer?
Local anesthetics (except choloroprocaine)
IV anesthetics (usually not a problem)
Volatile anesthetics
Opioids
Benzodiazepines
Atropine
Beta- blockers
Magnesium (not lipophilic, but small)
What are special considerations for bupivicaine administration in pregnancy?
Low placental transfer d/t high protein binding and ionization
Greater sensory block relative to other locals
Risk of cardiac toxicity > cardiac sx before seizures in toxic doses
How does neuraxial ropivacaine compare to bupivacaine?
Less cardiac toxicity
Less potent
Less motor block
Why is lidocaine unpopular for labor analgesia?
Strong motor block
Risk of neurotoxicity if given in the subarachnoid space
How is 2-Chloroprocaine helpful for neuraxial labor analgesia?
Useful for emergency C-section when epidural is already in place d/t fast onset
How does 2-Chloroprocaine affect neuraxial opioids?
Antagonizes opioid (mu and kappa) receptors and reduces the efficacy of epidural morphine
When administered in a neuraxial block, what is the relationship between opioids and local anesthetics?
Synergistic
How are neuraxial opioids beneficial when administered alone?
No loss of sensation or proprioception
No sympathectomy
Do not impair ability to push
What opioid has local anesthetic properties?
Meperidine
What are side effects of neuraxial opioids?
Pruruitus (most common)
Nausea/ vomiting
Sedation
Respiratory depression
What are downsides of administering neuraxial opioids alone?
Lack of perineal relaxation
Less analgesia vs locals
Why is lidocaine not used as a continuous epidural infusion?
Tachyphlylaxis is more likely to develop
Crosses the placenta to a greater degree than other locals
What are three ways a patient can develop a total spinal?
An epidural dose injected into the subarachnoid space
An epidural dose injected into the subdural space
A single shot spinal after a failed epidural block
What is the patient management when an epidural dose is injected into the subarachnoid space?
Intubate the patient and stabilize her
How is subdural placement of an epidural catheter ruled out?
It is rare, but cannot be ruled out. Neither a test dose or catheter aspiration will rule out subdural placement.
What are the symptoms of an epidural catheter placement in the subdural space?
Symptoms will occur 10- 25 minutes after epidural placement
The space is very low volume > higher block height than expected for the given dose in the epidural space
Sensory and autonomic block is usually more intense than a motor block
What is the presentation of a total spinal?
Usually rapid progression of sensory and motor block (prolonged onset in subdural injection)
Dyspnea, difficulty phonating, hypotension
Loss of consciousness occurs as a result of cerebral hypoperfusion sectondary to severe hypotension
What is the anesthetic management for a total spinal?
Vasopressors, IVF, LUD, leg elevation to manage hemodynamics
Intubate trachea if pt loses consciousness or is unable to protect airway
What are differential diagnoses for total spinal?
anaphylactic shock, eclampsia, amniotic fluid embolism
What is the objective of tocolytics?
Delay labor by suppressing uterine contractions (up to 24-48 hours). Provide a bridge for corticosteroids to take effect.
Why are corticosteroids given in the setting of preterm labor?
To hasten fetal maturity
How long does it take for corticosteroids to begin to take effect for lung maturity in the preterm fetus?
18 hours
How long does it take for corticosteroids to reach peak effect for lung maturity in the preterm fetus?
48 hours
How do beta-2 agonists work in the setting of premature labor?
Increase intracellular cAMP > turns on protein kinase, turns off myosin light-chain kinase, increases progesterone > relaxes the uterus
Also increases progesterone release > myometrial relaxation
What are the side effects of beta-2 agonists to the fetus/ neonate?
Hyperglycemia (mother) > hypoglycemia (neonate)
Hypokalemia
Increase FHR
What is the mechanism of action of magnesium sulfate as a tocolytic and anticonvulsant in the parturient?
Ca++ antagonist > relaxes smooth muscle by turning off myosin light- chain kinase in the vasculature, airway, and uterus
Hyperpolarizes membranes in excitable tissues = seizure prophylaxis
How is Mg++ eliminated?
Renal elimination = careful with mothers with renal insufficiency
How might Mg++ toxicity be tested at the bedside?
Reflex testing - if present > low risk of serious side effects, if absent > early sign of toxicity
What is the range for normal magnesium level?
1.8-2.5 mg/dL
What are symptoms of hypomagnesemia <1.2 mg/dL?
Tetany
Seizures
Dysrhythmias
What are symptoms of hypomagnesemia 1.2-1.8 mg/dL?
Neuromuscular irritability
Hypokalemia
Hypocalcemia
At what level does hypermagnesemia typically begin to become symptomatic?
~5 mg/dL
What are symptoms consistent with a patient whose Mg++ level is 5-7 mg/dL?
Diminished deep tendon reflexes
Lethargy/ drowsiness
Flushing
N/V
What are symptoms consistent with a patient whose Mg++ level is 7-12 mg/dL?
Loss of deep tendon reflexes
Hypotension
EKG changes
Somnolence
What symptoms are consistent with a patient whose Mg++ level is >12 mg/dL
Respiratory depression -> Apnea
Complete heart block
Cardiac arrest
Coma
Paralysis
How does hypermagnesemia affect a patient’s response to medications?
Skeletal muscle weakness -> potentiates neuromuscular blockers
Reduces responsiveness to ephedrine and phylephrine
What are potential respiratory side effects of hypermagnesemia?
Pulmonary edema
Respiratory depression/ apnea
How is hypermagnesemia treated?
Supportive measures based on symptoms
Diuretics > to facilitate excretion
IV calcium gluconate 1g over 10 minutes
What is the mechanism of action of calcium channel blockers in the treatment of premature labor?
Block the influx of Ca++ into the uterine muscle > reduces Ca++ release from the sarcoplasmic reticulum > turns off myosin light- chain kinases and relaxes uterine muscle
What is the first-line calcium channel blocker in the treatment of premature labor?
PO nifedipine
How might co-administration of a calcium channel blocker with Mg++ affect the patient?
Increased skeletal muscle weakness
What is the mechanism of action of nitric oxide donors in the treatment of premature labor?
Increases cGMP > turns off myosin light - chain kinases > relaxes uterine muscle
Why are nitric oxide donors rarely used in the treatment of premature labor?
Risk of hypotension
Where is endogenous oxytocin synthesized?
Paraventricular nuclei of the hypothalamus
Where is endogenous oxytocin stored?
Posterior pituitary gland
From where is endogenous oxytocin released?
Posterior pituitary gland
What stimulates the release of endogenous oxytocin?
Cervical, vaginal, and breast stimulation
What is the synthetic equivalent of oxytocin?
Pitocin
What are indication for pitocin?
Augmentation of labor
Stimulate uterine contraction
Prevent hypotonia and hemorrhage post-delivery (administer after placental delivery in a c-section)
What are side effects of pitocin?
Water retention (structurally similar to vasopressin)
Hyponatremia
Hypotension
Reflex tachycardia
Coronary vasoconstriction
What are acceptable routes of administration for Pitocin?
IV
Injected directly into uterus
How might rapid IV administration of Pitocin affect the patient?
May result in cardiovascular collapse
How is Pitocin metabolized?
Hepatic metabolism
What is the half-life of oxytocin?
4-17 minutes
What is the first line uterontonic drug?
Pitocin
What is the second-line uterotonic drug?
Methergine (Ergot alkaloid)
What is the acceptable dose/ route of methergine?
0.2mg IM
How might IV administration of methergine affect the patient?
significant vasoconstriction > hypertension > cerebral hemorrhage
How is methergine metabolized?
Hepatic metabolism
What is the half-life of methergine?
2 hours
What is the third-line uterontonic?
Prostaglandin F2 (Hemabate or Carboprost)
What is the acceptable dose/ route of prostaglandin F2?
250 mcg IM or injected into the uterus
