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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
concentrationantiviral, 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
metabolismexe: phenytoin.
RENAL CLEARANCE
RBF is increased by 6080%, 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
OPIOIDwithdrawl 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
A
Controlled studies in women fail to demonstrate a risk to the fetus in the first
trimester (and there is no evidence of a risk in late trimesters), and the possibility
of fetal harm appears remote.
B
Either animal-reproduction studies have not demonstrated a fetal risk, but there
are no controlled studies in pregnant women, or animal-reproduction 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).
C
Either studies in animals have revealed adverse effects on the fetus (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.
D
There is positive evidence of human fetal risk, but the benefits from use in
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).
X
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 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 1
st
or 2
nd
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) dont
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