Physiological changes during pregnancy and their implications for pharmacological treatment.

The decision when and how to treat a pregnant patient with drugs is difficult. The physician who prescribes a drug for the pregnant woman must make a rational decision in the absence of complete information on potential embryonic or fetal toxicity and on the contribution of drug or maternal disease to a fetal adverse effect as studies on propranolol have shown. Pharmacokinetic parameters change during pregnancy, with increases in plasma volume and estrogen stimulation of hepatic microsomal oxidation being two such changes which may have unpredictable effects. The placenta is not a general transfer barrier since most drugs cross the placenta readily and reach significant blood levels in the fetus. The timing of drug administration during the various stages of pregnancy is of major importance, since the conceptus has different vulnerabilities at different stages of development. Most anatomical malformations occur after drug exposure in the first trimester. However, the brain continues to develop throughout pregnancy and early infancy, so that subtle adverse effects, which require time to become evident, may occur with drugs acting on the central nervous system. Awareness of these special pharmacological features of the pregnant state and appreciation of the pitfalls of research in this area will aid the physician in evaluating published studies and in arriving at rational therapeutic decisions.