Patient Encounter Part 1

LC, a 28-year-old woman thinks that she is pregnant. She has not had a period in 9 weeks. A few days ago, she used a home pregnancy test which was positive. In your office, a repeat urine pregnancy test confirms that the patient is pregnant.

What counseling would be appropriate at this time?

What are the estimated postconceptional age (PCA) and gestational age (GA) of the embryo?

What prenatal screening would you perform at this time?

Distribution

The volume of distribution increases for most drugs during pregnancy due to plasma volume expansion and the presence of amniotic fluid, the placenta, and the fetus. This results in a decrease in maximal concentrations of drugs and in their half-life. In addition, hypoalbuminemia and decreased protein binding of drugs increases free fraction of some medications.13,14

Metabolism

During pregnancy the activity of some isoenzymes is increased (e.g., CYP3A4, CYP2A6, CYP2D6, CYP2C9), and the activity of others is decreased (e.g., CYP1A2,

CYP2C19). It is difficult to predict the net impact on drug effect since there is a wide interindividual variability and since some drugs are metabolized by several isoen-

13_15

zymes. The activity of uridine diphosphate glucuronosyltransferase (UGT) is

also increased during pregnancy. Renal Elimination

Renal blood flow and glomerular filtration are increased significantly during pregnancy. The impact of this increase is more important for drugs that are eliminated unchanged in the urine.14

Table 47-6 shows clinical recommendations based on pharmacokinetic changes during pregnancy for several drugs.

Medication and Lactation

According to a 2005 policy statement from the American Academy of Pediatrics (AAP), new mothers should breastfeed exclusively for 6 months.

Approximately 46% of new mothers report that they breast-feed exclusively at birth. However, this figure drops to 17% at 6 months, as many new mothers supplement breastfeeding with other foods or quit entirely by this point.46

For the breast-feeding mother it is important to balance the need for treatment against the potential toxicity to the infant.

Drug Transfer Into Breast Milk

To study drug effects in a breast-fed infant, serum drug levels could be measured to help evaluate safety in the infant; however, that is often not possible. Therefore, in most instances, the approximate quantity of drug ingested by the breast-fed infant is estimated using published measured drug concentrations in breast milk. With these data, one can calculate the percentage of pediatric dose or the relative infant dose (percentage of maternal dose adjusted by weight) (assuming an average of 150 mL/kg/day of milk ingested by a breast-fed infant). Usually, a percentage of less than 10% of the pediatric dose, or when a pediatric dose is not available, a percentage of less than 10%

of maternal dose adjusted by weight is acceptable in full term infants.

Table 47-6 Altered Pharmacokinetics During Pregnancy: Clinical Implications and Management

Druqt

PharroatpUnetk Ch>nget RgcoTuncndatloni and MonllorJng

ArtlidÉíntiviriiH Cif'ílnt

Carbamazep'ine Digoiin

FhjoxHint

HefurinLMWH

Lamotrlglne

Levothyrüxlne HI

I iihiuno NlCCJdrtfr

Nifedipine Phmyisin

trUJ J. Od til f (Batiefnal (. I i ruk-rndl Í T O (T¿

tgnCyj r ri cr,. t \i iff ta ur v) if ifj reía i; tan" J

Monfltir t III IK ,il IK-sptiVj (JiuQ KvcKun tk1 UiíÍLil toinljiri! (fcuijiJf>j<|<*[5Í

saKvxiitm^ijii piiti cí iptf e fiitiueiv jod pnAinyed vck' effete deoeJií ÍJ"¡&Í"*l corsumpilon

Mej'uie 'rn!(>!rjtti(jri (pf^lphitíy), ¡ntreawdow .sc-otiding lo clinkal rajóme and levels

Follow ploimj Icnoli, Incicii» doom if ncccsu'v, I'J Ln-Jl 1otjl dibt'iiM.-, fnyiKf ítoseini^tn be requinto

Increase flííí ,ví™iiní| rrjtliriH. jl response

Coralde* ¡rKreaamj (he frequent y oí admininiai ion

Mpaaji? (iifl levels at least eveiy trimester; increase (tose arwfdlnq lorllntil response and level i, deiiej* 1o prepieyiunt i (Josage jfto deüvety Increase dase f rhe beíiinneii flf pfeqrurr/; tillas T$H IWiek « lemr evpry

(rlmeslei, (Jet lease done af(ei deliveiy Mwímie iIiijíi levels at le¿4rew?iv irtnéwet maease (V>se arccudiníi io levels ¡í

neteisdty; docn-use (tose topri^egrkMíty (Jouqs ¿tier ctHivcry I Ikjhei do*1* (rikHn be in ^uiuil [smolciiii] n^isi kn i|, ir r and T j however, inc lojuvi transdermal jüíoi ption mlghl hud ta high« nicotine p'jmi.i levels

Moniloi clinical efleci; Inc lease dcsips/lrequency of administration rl necessary HH5niiefiwíí3f(iofi: do« jca*ÍOQ to<b*al (esponje and s^íis

K* r¡f m «sure fu» frjí ítf> í j pfloc^fkiot)' "Cfeieiv» leve< (tose iwi reniaift the vme in most cases. Urease dose KCOfdmq dq clinical response and le^ls

í, i■ ■ = leav . i. itiH' iM^e. t-h. iinr-, :rw|iv1; ■ LMrtH, low molecular wet^it heparins:^

Adapledand liartslalecd fiocn Kef. 6.

, ii-jiHin i'.irvi ?efiíiiií<)n(en(íj(ig<x ((.(leiii^ixíjíí, hf*e lijfllot I. irimesjer;

, total concentration.

. iStfiilriailgn luir- ir-

Drug Pharmacokinetics

If clinical data are not available on drug transfer into breast milk, choose drugs that are highly protein bound, have a high molecular weight, have a short half-life, have

no active metabolites, and are well tolerated by children. Milk/Plasma Ratio

The milk/plasma ratio is reported in several references but does not take into account the absolute amount of drugs ingested by the infant. For example, propranolol has a milk to plasma ratio of 1.65, indicating that it concentrates into milk; however, it is

estimated that the breast-fed infant will ingest less than 1% of the neonatal dose. AAP Tables

Since 1983, the AAP has been publishing their position on the compatibility of drug during breast-feeding. Although useful, these tables do not take into consideration the dose, infant characteristics, and maternal conditions.19

Drugs of Concern During Breast-Feeding

^^ Most drugs are safe during breast-feeding. However, use of some drugs creates some concern and requires a more thorough assessment by the clinicians (Table 47-7).

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