Adverse Drug Effects V

Drug Toxicity in Pregnancy and
Lactation
Drugs taken by the mother can be
passed on transplacentally or via breast
milk and adversely affect the unborn or
the neonate.
Pregnancy
Limb malformations induced by the
hypnotic, thalidomide, first focused attention
on the potential of drugs to
cause malformations (teratogenicity).
Drug effects on the unborn fall into two
basic categories:
1. Predictable effects that derive from
the known pharmacological drug
properties. Examples are: masculinization
of the female fetus by androgenic
hormones; brain hemorrhage
due to oral anticoagulants; bradycardia
due to !-blockers.
2. Effects that specifically affect the developing
organism and that cannot
be predicted on the basis of the
known pharmacological activity profile.
In assessing the risks attending
drug use during pregnancy, the following
points have to be considered:
a) Time of drug use. The possible sequelae
of exposure to a drug depend on
the stage of fetal development, as
shown in A. Thus, the hazard posed
by a drug with a specific action is limited
in time, as illustrated by the tetracyclines,
which produce effects on
teeth and bones only after the third
month of gestation, when mineralization
begins.
b) Transplacental passage. Most drugs
can pass in the placenta from the maternal
into the fetal circulation. The
fused cells of the syncytiotrophoblast
form the major diffusion barrier.
They possess a higher permeability to
drugs than is suggested by the term
“placental barrier”.
c) Teratogenicity. Statistical risk estimates
are available for familiar, frequently
used drugs. For many drugs,
teratogenic potency cannot be demonstrated;
however, in the case of
novel drugs it is usually not yet possible
to define their teratogenic hazard.
Drugs with established human teratogenicity
include derivatives of vitamin
A (etretinate, isotretinoin [used
internally in skin diseases]), and oral
anticoagulants. A peculiar type of damage
results from the synthetic estrogenic
agent, diethylstilbestrol, following its
use during pregnancy; daughters of
treated mothers have an increased incidence
of cervical and vaginal carcinoma
at the age of approx. 20.
In assessing the risk: benefit ratio, it is
also necessary to consider the benefit
for the child resulting from adequate
therapeutic treatment of its mother. For
instance, therapy with antiepileptic
drugs is indispensable, because untreated
epilepsy endangers the infant at least
as much as does administration of anticonvulsants.
Lactation
Drugs present in the maternal organism
can be secreted in breast milk and thus
be ingested by the infant. Evaluation of
risk should be based on factors listed in
B. In case of doubt, potential danger to
the infant can be averted only by weaning.