Chapter 9 - Drug Therapy During Pregnancy

CHAPTER 9 DRUG THERAPY DURING PREGNANCY & BREAST FEEDING Clinical challenge is to provide effective treatment for the mother while avoiding harm to the fetus or nursing infant

I.

DRUG THERAPY DURING PREGNANCY: BASIC CONSIDERATIONS

- between ½ and 2/3 of pregnant women take at least one medication while pregnant - some drugs are used to treat pregnancy-related conditions, such as nausea, constipation, and preeclampsia - some drugs are used to treat chronic disorders such as hypertension, diabetes, epilepsy, infectious diseases or cancer - frequently, pregnant women take drugs of abuse such as alcohol, cocaine and heroin - benefits of treatment must balance the risks (risks apply to the fetus as well as the mother) - despite the imposing challenge of balancing risks versus benefits, drug therapy during pregnancy cannot and should not be avoided - health of the fetus depends on the health of the mother A.

PHYSIOLOGIC CHANGES DURING PREGNANCY & THEIR IMPACT ON DRUG DISPOSITION & DOSING - changes in the kidney, liver and GI tract are of particular concern

1. Renal Blood Flow – by third trimester, renal blood flow is doubled, causing a large increase in glomerular filtration rate - as a result, there is accelerated clearance of drugs that are eliminated - to compensate for accelerated excretion, dosage must be increased 2.

Liver Function – hepatic metabolism increases during pregnancy

3. GI Tract Function – tone and motility of the bowel decrease in pregnancy causing intestinal transit time to increase - because of prolonged transit, there is more time for drugs to be absorbed - a reduction in dosage might be needed B.

PLACENTAL DRUG TRANSFER - factors that determine drug passage across membranes of the placenta are the same factors that determine drug passage across all membranes

- the clinician should assume that any drug taken during pregnancy will reach the fetus C.

ADVERSE REACTIONS DURING PREGNANCY - teratogenesis (production of birth defects) is the effect of greatest concern - ex. When heparin (anticoagulant) is taken by pregnant women, it can cause osteoporosis, which in turn can cause compression fractures of the spine. Use of prostaglandins (e.g., misoprostol), which stimulate uterine contraction, can cause abortion. Use of aspirin near term can suppress contractions in labor and also increases the risk of serious bleeding. - regular use of dependence-producing drugs (e.g., heroin, barbiturates, alcohol) during pregnancy can result in the birth of a drug-dependant infant with symptoms that include shrill crying, vomiting, and extreme irritability - certain pain relievers used during delivery can depress respiration in the neonate

II.

Drug Therapy During Pregnancy: Teratogenesis - derived from the Greek word teras meaning monster and genesis = to

produce - thought of as birth defects of gross malformations, such as cleft palate, clubfoot, and hydrocephalus - some birth defects also include behavioral and biochemical anomalies A.

TERATOGENESIS & STAGE

OF

DEVELOPMENT

1.

Three Major Stages: preimplantation / presomite period – conception through week 2 - teratogens act in an “all or nothing” fashion (if the dose is sufficiently high, the result is death of the conceptus; however,if the dose is sublethal, the conceptus is likely to recover fully embryonic period – weeks 3 through 8 - gross malformations are produced by exposure to teratogens - interference at this stage results in conspicuous anatomic distortions fetal period – week 9 through term - usually disrupts function rather than gross anatomy

- disruption of brain development can result in learning deficits and behavioral abnormalities B.

IDENTIFICATION OF TERATOGENS - human teratogens are extremely difficult to identify: • incidence of congenital anomalies is generally low • animal tests may not be applicable • prolonged exposure may be required • teratogenic effects may be delayed • behavioral effects are difficult to document • controlled experiments can’t be done in humans - lack of proof of teratogenicity does not mean that a drug is safe - proof of teratogenicity does not mean that every exposure will result in a birth defect

Criteria: - drug must cause a characteristic set of malformations - it must act only during a specific window of vulnerability - incidence of malformations should increase with increasing dosage and duration of exposure C.

FDA PREGNANCY RISK CATEGORIES A - Remote Risk of Fetal Harm (REMEMBER: A-Okay to use) B – Slightly more Risk than A C – Greater Risk than B D – Proven Risk of Fetal Harm X – Proven Risk of Fetal Harm (REMEMBER: X is universal sign for poison)

III.

DRUG THERAPY DURING BREAST FEEDING

- drugs taken by lactating women can be excreted in breast milk - drugs that are lipid soluble enter breast milk readily, whereas drugs that are ionized, highly polar or protein bound tend to be excluded - if the nursing mother can avoid drugs, she certainly should; moreover, when drugs MUST be used, steps should be taken to minimize risk • dosing immediately AFTER breast feeding to minimize drug concentrations in milk at the next feeding • avoiding drugs that have a long half-life • choosing drugs that tend to be excluded from milk • choosing drugs that are least likely to affect the infant • avoiding drugs that are known to be hazardous