Trandate

Chronic hypertension during pregnancy--hypertension that is present before conception or develops during the first 20 weeks of gestation--is a common problem, affecting an estimated 1%-5% of women giving birth in the United States. Although they all cross the placenta, most antihypertensive drugs have not been associated with significant fetal risks, with some important exceptions. The most notable are the [beta]-blockers, which can cause intrauterine growth retardation (IUGR), and angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), which are teratogens. The strongest evidence of risk exists for the ACE inhibitors, followed by IUGR in atenolol-exposed fetuses. Everything that is known about the other antihypertensives is based on limited data.

Methyldopa (Aldomet) is considered the front-line drug for chronic hypertension in pregnancy, based on evidence showing that it is safe for the fetus; this includes data on about 500 women in clinical trials. There is little or no experience with the other centrally acting adrenergic agents.

Hydralazine, a vasodilator, is also considered safe during pregnancy and has now been used enough so that it can be dosed to avoid the wide swings in blood pressure seen with other antihypertensives. There is no evidence that it is teratogenic, although experience with first-trimester exposure is limited.

Minoxidil, the other vasodilator used for hypertension, is not recommended during pregnancy because hypertrichosis has been observed in newborns exposed in utero. It's also difficult to titrate, increasing the risk of maternal hypotension.

The use of cardioselective [beta]-blockers during pregnancy has been associated with IUGR, which is thought to be related to increased peripheral vascular resistance in the mother and the fetus. These agents include atenolol (Tenormin) and metoprolol (Lopressor).

Some noncardioselective [beta]-blockers may also increase the risk of IUGR when used in the second and third trimesters.

The use of any [beta]-blocker during pregnancy should be examined on a case-by-case basis, weighing the potentially serious fetal adverse effects with potential maternal benefits. These concerns also apply to the [alpha]- and [beta]- adrenergic blockers, like labetalol (Normodyne, Trandate) and carvedilol (Coreg). When started in the second trimester, they can cause a significant reduction in fetal weight. But if used only in the third trimester, placental weight is reduced, but no increase in the risk of small-for-gestations-age infants.

ACE inhibitors are teratogenic in the second and third trimesters. These drugs, which block the conversion of angiotensin I to angiotensin II, are toxic to the kidneys and cause fetal hydramnios, hypotension, and skull defects. ARBs also block the conversion of angiotensin I to II and are assumed to have the same effects.

Concerns about the effect of diuretics on plasma volume have nor been a clinical problem in pregnancy but they can cause electrolyte disturbances and maternal hyperglycemia, which can make the newborn hypoglycemic. The risk of blood dyscrasias in newborns is low, but they should be checked for such abnormalities.

Peripherally acting antiadrenergic agents, like reserpine, are rarely used in pregnancy so experience is limited and there are better-tolerated agents. The same applies to ganglionic and [[alpha].sub.1]-adrenergic blockers.

Of the calcium channel blockers, nicardipine (Cardene) and nifedipine (Adalat, Procardia) have been tried the most and are safe in pregnancy but there is little information on first-trimester use.

Most antihypertensives can be used during lactation. However, [beta]-blockers should be avoided, because they become concentrated in breast milk, creating the potential for a [beta]-blockade in breast-feeding infants, which is also a risk when [beta]-blockers are used near term. Diuretics may initially decrease milk production.

GERALD B. BRIGGS is clinical professor of pharmacy at the University of California San Francisco, and coauthor of the textbook "Drugs in Pregnancy and Lactation."

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