DRUG THERAPY FOR

PREGNANCY AND
NURSERY WOMEN

Anggelia Puspasari, MD
Pharmacology and Therapeutic Dept.
Medical Faculty University of Jambi
DRUG THERAPY IN
PREGNANCY
FACTORS AFFECTING PLACENTAL DRUG
TRANSFER AND DRUG EFFECTS ON THE FETUS
(PHARMACOKINETIC)

a. Physicochemical drug
b. Rate drug crosses placenta amount
of drug reaching fetus
c. Duration drug exposure
d. Distribution in different fetal tissues
e. Placental and fetal development stage
f. Effects of drugs used in combination
PHARMACOKINETIC (DRUG)
LIPID SOLUBILITY
Lipophilic drug diffuse readily across the placenta
and enter the fetal circulation
exe: thiopental
Highly ionized cross the placenta slowly and achieve
very low concentrations in the fetus
Exe : succinylcholine and tubocurarine

MOLECULAR SIZE
Cross placenta easly ≤ 600 kDa,,,poorly cross placenta ≥
1000 kDa.
Placenta transporter can carry drug to fetus.
Exe: heparin safe than warfarin as anticoagulant for
pregnancy women.
PHARMACOKINETIC (PLASENTA AND
FETUS)
PLACENTAL TRANSPORTER
P-glycoprotein transporter low fetal
concentration…antiviral, protease inhibitor
PROTEIN BINDING
Drug very lipid soluable more depend on placenta blood
flow.
Poorly lipid-soluble and ionized, impeded by its binding
to maternal plasma proteins.
PLACENTAL DAN FETAL DRUG METABOLISM
Placenta is semipermeable barrier and as a site of
metabolism.
Drugs that have crossed the placenta enter the fetal
circulation via the umbilical vein ( fetal liver
metabolism)
PHARMAKOKINETIC
(PREGNANCY PHYSIOLOGY)
 GASTRO INTESTINAL TRACT
 Gastric emptying and small intestine motility are reduced
in pregnancy due to elevation of progesterone
increase Tmax and reduce Cmax
 Increase in gastric pH absorption weak acid reduced
than weak base
 Reduced efficacy of single dose drug

 RESPIRATORY & CARDIOVASCULAR

 Increased cardiac output and tidal volume increased
absorbing inhale drug
 Increased plasma volume and extravascular water
increasing Vd hydrofilic drug, decreasing Cmax
 Decreased plasma albumin concentration Increasing
free drug (albumin bound)
PHARMAKOKINETIC
(PREGNANCY PHYSIOLOGY)
 HEPATIC METABOLISM
Hepatic cytochrome P-450 system are induced by
oestrogen/progesterone, resulting in a higher rate
of metabolism…exe: phenytoin.
 RENAL CLEARANCE

RBF is increased by 60±80%, GFR rises by 50%,

leading to enhanced elimination of drugs that are
normally excreted unchanged…. penicillin and
digoxin
PHARMACODYNAMIC
 MATERNAL DRUG ACTION
 Reproductive tissues (breast, uterus, etc) are
sometimes altered
 Other maternal tissues (heart, lungs, kidneys,
central nervous system, etc) are not changed
significantly
 THERAPEUTIC DRUG ACTIONS IN THE
FETUS
 Drug administration to the pregnant woman with the
fetus as the target of the drug.
 Corticosteroid, phenobarbital, zidovudin
PHARMACODYNAMIC
 PREDICTABLE TOXIC DRUG ACTIONS IN
THE FETUS
 ACEI…..renal damage
 DES…..adenocarcinoma vagina
 OPIOID…withdrawl syndrom

TERATOGENIC DRUG ACTIONS

Teratogen:
 Result in a characteristic set of malformations,
indicating selectivity for certain target organs
 Exert its effects at a particular stage of fetal
development
 show a dose-dependent incidence
TERATOGENIC DRUG
FOOD AND DRUG ADMINISTRATION
SYSTEM FOR TERATOGENIC POTENTIAL
Controlled studies in women fail to demonstrate a risk to the fetus in the
A first trimester (and there is no evidence of a risk in late trimesters), and the
possibility of fetal harm appears remote.
Either animal-reproduction studies have not demonstrated a fetal risk, but
there are no controlled studies in pregnant women, or animal-reproduction
B studies have shown an adverse effect (other than a decrease in fertility) that
was not confirmed in controlled studies in women in the first trimester (and
there is no evidence of a risk in later trimesters).

Either studies in animals have revealed adverse effects on the fetus

C
(teratogenic or embryocidal or other) and there are no controlled studies in
women or studies in women and animals are not available. Drugs should be
given only if the potential benefit justifies the potential risk to the fetus.
There is positive evidence of human fetal risk, but the benefits from use in
D
pregnant women may be acceptable despite the risk (eg, if the drug is needed
in a life-threatening situation or for a serious disease for which safer drugs
cannot be used or are ineffective).
Studies in animals or human beings have demonstrated fetal abnormalities
or there is evidence of fetal risk based on human experience or both, and the
X risk of the use of the drug in pregnant women clearly outweighs any possible
benefit. The drug is contraindicated in women who are or may become
pregnant.
 Because any medication can present risks in
pregnancy, and because not all risks are known,
the safest pregnancy-related pharmacy is as little
pharmacy as possible.
NURSERY WOMEN
INTRODUCTION
As most drugs are excreted into the milk by passive
diffusion, the drug concentration in milk is directly
proportional to the corresponding concentration in
maternal plasma.
The milk to plasma (M:P) ratio, which compares
milk with maternal plasma drug concentrations,
serves as an index of the extent of drug excretion in
the milk.
For most drugs the amount ingested by the infant
rarely attains therapeutic levels.
PHARMACOKINETIC ( DRUG)
 Greater Vd (Volume distribution) lower plasma
drug coencentration lower breast milk
coencentration…..1-20L/kg, compatible for breast
feeding women.
 High PB (protein binding) reduced infant
exposure…..≥90%, compatible
 ≥800kDa less likely pass into breast milk
 Greater pH drug, increased breast milk
coencentration
 Water soluable drug, decreased breast milk
coencentration
 Shorter T1/2, decreased infant exposure
 M/P ratio < 1, safe for nursery women
 Passive transport
PHARMACOKINETIC (INFANT &
MATERNAL)
 Infant should be categorized low (6-18 mo) risk,
moderate (younger 6 mo), or high (preterm
infant, unstable infant, who have poor renal
output) risk for the medication interest.
 Infant can absorbed, metabolized and secreted
the drug, altough extensively different….
 Infant have higher body water percentage
 Immature stratum corneum
 Clearance of teophilin, phenytoin higher than adult
 GIT less acidic transit time longer than adult
PHARMACOKINETIC (INFANT &
MATERNAL)
 Maternal factor (breast milk) secretion higher in
the morning but breast milk late at the morning
rich of fat.
 Milk production in 1st or 2nd day post partum is
so low that the overall dose of medication
transferred is usually insignificant.
 Drug that are not absorbed by the mother
generally (topically, inhaled or applied to the eye)
don’t produced significant level in the plasma
compartement.
MINIMIZING THE RISK TO THE
INFANT
 Avoid feeding infant at Cmax (this only work with
short T1/2 and only useful in few case)
 Choose medication that produced minimal level in
milk
 Choose medication that are used commonly in
pediatric patient and are considered safe
 Choose medication that have high protein binding
(lower level at milk)
 Choose medication that have poor blood/brain
penetration (lower level at milk)
 Choose medication that have higher molecular weight
 With really hazardous medication temporarily
withhold breast feeding for brief exposure
(elimination T1/2). Milk produced during the
exposure should be pumpout/ discard.
DRUG THERAPY
 Drug coencentration in breast milk lower than in
plasma.
 Infant dosage can minimized by breast feeding
just prior to drug administration, when maternal
drug serum in lowest.
Maternal medication usually compatible for with
breast feeding read more at

Official American academic of pediatric

THAX FOR Ur ATTENTION