Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.

A 25-year-old woman comes for a preconception evaluation. She has a history of hypertension that is well controlled with lisinopril. Medical history is otherwise unremarkable.

On physical examination, blood pressure is 134/86 mm Hg in both upper extremities; other vital signs are normal. Results of the cardiovascular examination are unremarkable. There is no edema, cyanosis, digital clubbing, or radial artery-femoral artery pulse delay.

Laboratory studies reveal normal electrolytes, complete blood count, thyroid-stimulating hormone level, kidney function, and urinalysis.

An electrocardiogram is normal.

In addition to starting a prenatal vitamin, which of the following medication adjustments should be made before this patient proceeds with pregnancy?

A: Discontinue lisinopril
B: Substitute labetalol for lisinopril
C: Substitute losartan for lisinopril
D: Substitute spironolactone for lisinopril

MKSAP Answer and Critique

The correct answer is B: Substitute labetalol for lisinopril.

This patient has essential hypertension and should be switched from lisinopril to labetalol before pregnancy. Exposure to ACE inhibitors such as lisinopril during the first trimester has been associated with fetal cardiac abnormalities, and exposure during the second and third trimesters has been associated with neonatal kidney failure and death. Angiotensin receptor antagonists such as losartan have been associated with similar fetal toxicity as ACE inhibitors, most likely because of the dependence of the fetal kidney on the renin-angiotensin system. Therefore, both of these agents are pregnancy category X drugs and are contraindicated throughout pregnancy and in women planning to conceive.

Labetalol is a pregnancy risk category C drug and is commonly used during pregnancy owing to its combined α- and β-blocking properties and because it does not compromise uteroplacental blood flow. Methyldopa also is used extensively in pregnancy and is one of the only agents in which long-term follow-up of infants exposed in utero has proved to be safe. Furthermore, methyldopa is the only agent classified as a pregnancy category B drug. However, controlling blood pressure with single-agent methyldopa is often difficult, and many women are bothered by its sedating properties.

Cessation of antihypertensive therapy in a patient with hypertension is not recommended before pregnancy.

Aldosterone antagonists such as spironolactone have an antiandrogenic effect on the fetus when exposure occurs during the first trimester and should be avoided in women planning to conceive.

Key Point

• ACE inhibitors, angiotensin receptor blockers, and aldosterone antagonists should be avoided during pregnancy and in women planning to conceive.

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