Medication And Pregnancy Flashcards
Which classification system is used?
FDA
FDA category A?
Adequate and well-controlled human studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters)
FDA category B
Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women Or Animal studies have shown an adverse effect, but adequate and wellcontrolled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester
Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks
There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks
Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits
Dosing requirements are unchanged or mildly reduced for ultrashortacting barbiturates and propofol (10–15%) Propofol TIVA: reduce dose by <10% Equilibration with fetal tissues is rapid Fetal elimination strongly depends on reverse diffusion to mother
Equilibration with fetal tissues is rapid Fetal elimination strongly depends on reverse diffusion to mother Intravenous induction agents reduce fetal heart rate variability
Endogenous endorphin production reduces exogenous opioid requirement Peripartum oxytocin release has been implicated in reduced narcotic requirements Remifentanil has the shortest half-life in the newborn and has become a popular agent for labor analgesia when a neuraxial technique is contraindicated (usual starting dose is 0.03 μg/kg/min increased as needed to 0.1 μg/kg/min)
Narcotics reduce fetal heart rate variability Short-acting rapid-onset opioids have been reported to cause fetal bradycardia Intrathecal narcotic requirements are reduced by 30–50% when compared with nonpregnant patients There are no clear data for IV narcotic dose reduction
Benzodiazepines are traditionally avoided in pregnant patients Dexmedetomidine has been reported for labor analgesia (insufficient data for assessment of safety of drug)
Sensitivity to muscle relaxants is unchanged Pseudocholinesterase activity is reduced by 30% in the pregnant patient; this has no effect on the onset and duration of succinylcholine
NMBs do not cross the placenta in significant amounts Magnesium sulfate therapy may increase sensitivity to nondepolarizing NMB (no effect on succinylcholine)
Dosing requirements are unchanged
Neostigmine and glycopyrrolate do not cross the placenta Atropine crosses the placenta
Anticholinesterase Agents Neostigmine, pyridostigmine, and edrophonium are quaternary ammonium compounds that are ionized at physiologic pH and consequently undergo limited transplacental transfer.124 Maternal administration of neostigmine does not reverse atropine-induced fetal tachycardia. However, small amounts of these agents do cross the placenta, and fetal bradycardia after maternal administration of neostigmine and glycopyrrolate has been reported.125 Neostigmine may cross the placenta to a greater extent than glycopyrrolate; therefore, the combination of neostigmine and atropine should be considered for the reversal of nondepolarizing muscle relaxants in pregnant patients.125 Physostigmine crossed the placenta in 9 minutes and reversed the fetal heart rate effect of scopolamine.
MAC reduced by 30%
Volatile anesthetics reduce fetal heart rate variability
Nerves are more sensitive to local anesthetic effect (faster block onset)
Possible progesterone effect
Factors affecting drug transfer via placenta
Lipid solubility protein binding tissue binding pKa pH Blood flow
Lipid solubility
High lipid solubility may readily enable cell membrane (lipid bilayer) penetration but may also cause the drug (e.g., sufentanil) to be trapped within the placental tissue.
Protein binding
Highly protein-bound drugs are affected by the concentration of maternal and fetal plasma proteins, which varies with gestational age and disease. Some drugs (e.g., diazepam) bind to albumin, whereas others (e.g., sufentanil, cocaine) bind predominantly to α1-acid glycoprotein (AAG). Although the free, unbound fraction of drug equilibrates across the placenta, the total drug concentration is greatly affected by both the extent of protein binding and the quantity of maternal and fetal proteins; fetal blood typically contains less than one-half the concentration of AAG than maternal blood.
Albumin binds primarily acidic and lipophilic compounds, whereas AAG binds more basic compounds; fetal levels of both albumin and AAG increase from the first trimester to term.
