DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Nursing mothers constitute a second special situation
with respect to potential adverse effects of drugs.
Some drugs may interfere with milk production and/or
secretion (e.g., estrogen-containing oral contraceptives)
and thus should be avoided if possible in mothers who
wish to breastfeed. Other drugs may be secreted into
breast milk and expose the baby to potentially toxic levels
during the vulnerable perinatal period (Ito and Lee,
2003). The amount of drug that is secreted in breast
milk, like the amount that crosses the placenta, depends
on drug characteristics such as size, ionization, protein
binding, and pharmacokinetics of clearance. The
American Academy of Pediatrics Committee on Drugs
periodically reviews agents transferred into human milk
and their effects on the infant or on lactation (Hale,
2005). Product information sheets that provide available
information regarding the potential for adverse
effects of specific drugs on breastfed infants should be
consulted before prescribing medications to nursing
mothers.
Pregnancy-Induced
Hypertension/Pre-eclampsia
Hypertension affects up to 10% of pregnant women in
the U.S.; with the increasing prevalence of hypertension
in the general population and the tendency to
delay childbearing, drug therapy for maternal hypertension
likely will be given greater consideration in the
future. A consensus panel has issued guidelines for the
management of hypertension in pregnancy (National
High Blood Pressure Education Program Working
Group, 2000).
Hypertension that precedes pregnancy or manifests
before 20 weeks of gestation is believed to
overlap considerably in pathogenesis with essential
hypertension. These patients appear to be at increased
risk for gestational diabetes and need careful monitoring.
In contrast, pregnancy-induced hypertension, or
pre-eclampsia, generally presents after 20 weeks of gestation
as a new-onset hypertension with proteinuria
(>300 mg of urinary protein/24 hours); pre-eclampsia is
thought to involve placenta-derived factors that affect
vascular integrity and endothelial function in the
mother, thus causing peripheral edema, renal and
hepatic dysfunction, and in severe cases, seizures
(Maynard et al., 2008). Chronic hypertension is an
established risk factor for pre-eclampsia, but there is
no conclusive evidence that antihypertensive therapy
during pregnancy affects the incidence or outcome of
pre-eclampsia in women with mild to moderate hypertension
(Abalos et al., 2007). Nonetheless, the consensus
panel recommended initiation of drug therapy in women
with a diastolic blood pressure >105 mm Hg or a systolic
blood pressure >160 mm Hg (National High Blood
Pressure Education Program Working Group, 2000). If
severe pre-eclampsia ensues, with marked hypertension
and evidence of end-organ damage, then termination of
the pregnancy by delivery of the baby is the treatment of
choice, provided that the fetus is sufficiently mature to
survive outside the uterus. If the baby is very preterm,
then hospitalization and pharmacotherapy (expectant
management) may be employed in an effort to permit
further fetal maturation in utero.
Many pregnant women already carry the diagnosis of hypertension
and are on drug therapy, which may be continued with careful
monitoring, provided that blood pressure control is effective. In
this setting, however, some drugs that commonly are used for hypertension
in non-pregnant patients (e.g., angiotensin-converting
enzyme inhibitors, angiotensin-receptor antagonists) should not be
used due to unequivocal evidence of adverse fetal effects in animal
models and humans (Podymow and August, 2008). Many experts
will convert the patient to the centrally acting α adrenergic agonist
α-methyldopa (ALDOMET) at an initial dose of 250 mg orally twice
daily (FDA category B), which rarely is used for hypertension in
non-pregnant patients. Other drugs with reasonable evidence of
safety (category C) also may be used, including the combination α 1
-
selective, β-nonselective adrenergic antagonist labetalol (TRANDATE;
100 mg twice daily) and the Ca 2+ channel blocker nifedipine (PRO-
CARDIA XL, ADALAT CC; 30 mg once daily).
Similar considerations apply in previously normotensive
women who develop pre-eclampsia; α-methyldopa again is a reasonable
choice for outpatient management if the blood pressure
exceeds the threshold for therapy. If severe pre-eclampsia or impending
labor requires hospitalization, blood pressure can be controlled
acutely with hydralazine (5 or 10 mg intravenously or intramuscularly,
with repeated dosing at 20-minute intervals depending on
blood pressure response) or labetalol (20 mg intravenously, with
dose escalation to 40 mg at 10 minutes if blood pressure control is
inadequate).
In addition to drugs for blood pressure control, women with
severe pre-eclampsia or those who have central nervous system manifestations,
such as headache, visual disturbance, or altered mental
status, are treated as inpatients with magnesium sulfate, based on its
documented efficacy in seizure prevention and lack of adverse
effects on the mother or baby (Altman et al., 2002). Such treatment
also should be considered for postpartum women with central nervous
system manifestations, because ~20% of episodes of eclampsia
occur in women who are more than 48 hours after delivery.
Prevention or Arrest of Preterm Labor
Scope of the Problem and Etiology. Preterm birth,
defined as delivery before 37 weeks of gestation, occurs
in >10% of pregnancies in the U.S. and is increasing in
frequency; it is associated with significant complications,
such as neonatal respiratory distress syndrome,
pulmonary hypertension, and intracranial hemorrhage.
1847
CHAPTER 66
CONTRACEPTION AND PHARMACOTHERAPY OF OBSTETRICAL