Prophylaxis and Treatment of Pregnant Women for Emerging Infections and Bioterrorism Emergencies

Joanne Cono; Janet D. Cragan; Denise J. Jamieson; Sonja A. Rasmussen

Disclosures

Emerging Infectious Diseases. 2006;12(11) 

In This Article

Special Physiologic Features of Pregnancy

Physiologic changes in maternal organ systems during pregnancy, beginning in the first trimester and peaking in the second, can have effects on the pharmacokinetics of some drugs. A drug's pharmacokinetics (i.e., attainment and maintenance of the appropriate drug serum concentration) are affected by 4 major factors: absorption, distribution, metabolism, and elimination.[3] Because physiologic changes are evolving continuously during pregnancy, pharmacokinetic information must be interpreted with regard to gestational age.[4]

Changes in the maternal gastrointestinal and cardiovascular systems affect drug absorption. Delayed gastric emptying and decreased gastrointestinal motility, largely due to elevated levels of progesterone that relax smooth muscle, influence absorption of drugs taken orally. In addition, a decrease in gastric acid secretion results in higher gastric pH, which affects absorption of weak acids and bases.[4,5] Increased blood flow to the stomach and small intestine, resulting from changes in the cardiovascular system (most notably, a 30%-50% increase in cardiac output),[4] increases absorption of drugs taken orally.[3] Elevated blood flow also increases the absorption of drugs administered intramuscularly. However, late in pregnancy decreased blood flow to the lower extremities may result in decreased absorption in these areas.[6]

Plasma volume increases by 30%-50% during pregnancy to meet the increased requirements of uterine-placental circulation. This increase results in a higher volume of distribution for most drugs. As the plasma volume expands, the volumes of extracellular fluid and total body water also increase. Total body weight and body fat increase throughout pregnancy, resulting in a larger volume of distribution, particularly for fat-soluble drugs.[3] As plasma albumin concentrations decrease, so do concentrations of proteins available for binding, resulting in higher circulating amounts of free, unbound drug.[5] However, unbound drugs may be more easily cleared by the kidney and liver, which may offset the effect of the increased volume of distribution.[7]

During pregnancy, enzyme activity in the liver, a major site for drug metabolism, changes considerably. Activity of certain liver cytochromes (e.g., CYP3A4, CYP2D6) is increased during pregnancy. However, activity of CYP1A2, the enzyme responsible for metabolism of approximately half of all pharmacologic agents, is decreased. Increases in estrogen and progesterone during pregnancy also alter hepatic enzyme activity.[3,4]

Several factors affect drug elimination during pregnancy. Changes in kidney function parallel the changes in cardiac function, with a 60%-80% increase in renal blood flow and a 50% increase in the glomerular filtration rate. Renal secretion and reabsorption increase by ≈20%.[5] Drug elimination also occurs through respiration, which becomes a more important route during pregnancy because of changes in pulmonary function, including increased tidal volume, minute volume, and respiratory rate.[3]

Although these physiologic changes during pregnancy can have varied and substantial effects on drug pharmacokinetics, data about their effects are limited. No evidence-based guidelines exist for how drug dosing should be altered during pregnancy.[1] Thus, pregnant women are usually given medication doses and schedules identical to those of nonpregnant adults, despite evidence that effective therapeutic levels and toxicity may be altered by pregnancy.[4]

Vaccine efficacy during pregnancy is another area that merits further investigation. During pregnancy, the maternal immune system undergoes extensive changes. Although these changes are not well understood, a shift away from cell-mediated immunity and toward humoral immunity appears to occur. How these immune alterations affect maternal response to vaccination during pregnancy is unknown.[8] However, limited data on several vaccines (e.g., hepatitis B, influenza, group B Streptococcus) suggest that the immune response of pregnant women to these vaccines is similar to that of nonpregnant women.[9]

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