USMLE Step 1/2CK Question
TOPIC: Pharm / OB
The following is a high-yield USMLE question applicable to both the Step 1 & Step 2CK exams.
To get the most out of this practice question deep-dive, I recommend doing the following:
Go through the question using our test-taking strategy (read about it HERE)
Formulate your answer and find it in the answer choices
If you believe you’ve identified the correct answer, you can scroll to the bottom of the post to see if you’re right; if you are - congrats! Be sure to read through the deep-dive section to extract more knowledge from the question
If you aren’t 100% sure about the answer, start with the deep-dive section to get clear on the concept(s), then try to formulate an answer from there; once you believe you’ve found the answer, scroll to the bottom of the page (if you were wrong, re-read the deep-dive to figure out why)
QUESTION
A 26-year-old woman gives birth to a boy with multiple congenital anomalies. The boy has craniofacial abnormalities, including microcephaly, cleft palate, and a small, abnormally shaped nose. The baby also has limb defects, such as bilateral limb reduction and missing fingers. The mother reports that she had been taking a medication for her seizure disorder during the first trimester of pregnancy. She cannot remember the name of the drug but recalls that her doctor prescribed it to replace her previous antiepileptic medication due to concerns about potential birth defects. Which medication is most likely to have caused the congenital anomalies in this newborn?
A. Valproic acid
B. Levetiracetam
C. Lamotrigine
D. Topiramate
E. Carbamazepine
F. Gabapentin
G. Phenytoin
DEEP-DIVE:
This question presents us with a clinical scenario involving congenital anomalies in a newborn, likely due to maternal medication exposure during pregnancy. Let's break down each medication and discuss its mechanism of action and teratogenic effects:
A. Valproic Acid
Mechanism of Action: Valproic acid works by increasing the availability of GABA in the brain, which inhibits neuronal firing. It also affects ion channels and may influence gene expression through histone deacetylase inhibition.
Teratogenic Effects: It is known for its high teratogenic potential, which is associated with neural tube defects, craniofacial abnormalities, cardiovascular malformations, limb defects, and cognitive impairments.
B. Levetiracetam
Mechanism of Action: Levetiracetam's exact mechanism is not fully understood, but it is believed to modulate neurotransmitter release through binding to the synaptic vesicle protein SV2A, which may influence neural conduction.
Teratogenic Effects: It is considered to have a lower risk of major congenital malformations, with limited evidence suggesting significant teratogenicity.
C. Lamotrigine
Mechanism of Action: Lamotrigine inhibits voltage-sensitive sodium channels, stabilizing neuronal membranes and inhibiting the release of excitatory neurotransmitters like glutamate and aspartate.
Teratogenic Effects: It is generally considered to have a lower teratogenic risk, though there may be a slightly increased risk of cleft lip and palate.
D. Topiramate
Mechanism of Action: Topiramate's antiepileptic effects are achieved through multiple mechanisms, including blocking voltage-dependent sodium channels, augmenting GABA activity, antagonizing AMPA/kainate subtype of the glutamate receptor, and inhibiting carbonic anhydrase.
Teratogenic Effects: It is associated with an increased risk of oral clefts (cleft lip and palate) and potentially other congenital malformations, with the risk appearing to be dose-dependent.
E. Carbamazepine
Mechanism of Action: Carbamazepine stabilizes the inactivated state of voltage-gated sodium channels, making fewer of these channels available to open, which inhibits repetitive and sustained firing of action potentials.
Teratogenic Effects: Increased risk of neural tube defects, craniofacial defects, and developmental delays, though generally considered to have a lower risk profile than valproic acid.
F. Gabapentin
Mechanism of Action: Gabapentin binds to the α2δ subunit of voltage-dependent calcium channels in the central nervous system, which reduces the release of excitatory neurotransmitters.
Teratogenic Effects: The teratogenic risk profile is less well-defined, with current data not strongly linking gabapentin to a high risk of congenital anomalies.
G. Phenytoin
Mechanism of Action: Phenytoin limits the repetitive firing of action potentials by prolonging the inactivation state of voltage-sensitive sodium channels in neurons.
Teratogenic Effects: Associated with fetal hydantoin syndrome, which includes craniofacial anomalies, limb defects, and growth retardation.
THE VERDICT: Considering the detailed description of the newborn's anomalies in the question, including craniofacial abnormalities, limb defects, and cleft palate, the cause is likely one of the drugs with more significant risks of teratogenicity.
FINAL ANSWER: A. Valproic Acid. Valproic acid is well-documented for its wide range of teratogenic effects, including those described in the newborn. While phenytoin is also a possible candidate, the broad spectrum and severity of the anomalies are more characteristic of the teratogenic effects of valproic acid.
