Pregnant women commonly use prescribed and over-the-counter medications with the average US and Canadian pregnant woman using more than two drugs during the course of their pregnancy. Almost one third of them used four or more drugs.1 One reason for this is that some women enter into pregnancy with preexisting medical conditions that require pharmacotherapy; and for many others, pregnancy itself can lead to medical conditions such as nausea, vomiting, and gestational diabetes that require treatment. Moreover, human pregnancy is characterized by profound anatomic and physiologic changes that affect virtually all systems and organs and induce profound alterations to the pharmacokinetic and pharmacodynamics properties of many medications. Many of these changes begin since early gestation. Whereas, some of these changes are secondary to hormonal changes in pregnancy, others are essential to support the growing fetus and the pregnant mother. Understanding pregnancy physiology is essential to the clinician because of the potential implications on pharmacotherapy during pregnancy. The goal of this chapter is to summarize some of the systems, physiologic changes during pregnancy that may affect medication pharmacokinetics.
A 30-year-old G1P0 at 28 weeks of gestation presents for prenatal care. Patient has a history of epilepsy, and takes phenytoin 600 milligrams daily. During the clinic visit, you noted slurred speech, ataxia, and nystagmus. You ordered phenytoin levels and found that her total phenytoin level was 17 mg/L (normal 10-20 mg/L), and her free phenytoin level was 2.6 mg/L (normal 1-2 mg/L). After decreasing the dose, the symptoms completely resolved. It appears that this patient had phenytoin toxicity. In pregnancy, because of the decrease in serum albumin, the amount of free or unbound phenytoin may increase leading to increased risks of toxicity. The latter reflects the importance of measuring free levels of medications with significant protein binding during pregnancy.
The cardiovascular system is one of the most affected systems as pregnancy leads to significant anatomic and physiologic changes. Myocardial contractility, compliance, and ventricular wall mass increase in normal pregnancy.2 Maternal cardiac output (CO) is increased by 30% to 50% because of increases in both heart rate and stroke volume.3 The majority of the increase occurs early in pregnancy such that by the end of the first trimester 75% of such increment has already occurred.4 At 28 to 32 weeks, CO plateaus and remains relatively stable until delivery.5 During the third trimester, the increase in heart rate becomes the main contributor to the increased CO. This increase in CO allows uterine blood flow to increase by 10-fold (17% of total CO compared with 2% prepregnancy) and renal blood flow to increase by 50%. Minimal changes occur on liver and brain blood flow.6 In addition, when compared with nulliparous women, multiparous women have higher CO (5.6 vs 5.2 L/min), stroke volume (73.5 vs 70.5 mL), and higher heart rates....