Obat pd perempuan hamil

& janinnya

 Hormon plasenta mempengaruhi

fungsi traktus digestivus & motilitas
usus , peningkatan filtrasi
glomerulus, peningkatan reabsorpsi
inhalasi alveoli paru
Pada trimester 2 &3 terjadi
hidraemia, volume darah meningkat
sehingga kadar obat relatif turun

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Molecules not bound to protein are
available for transfer.
Molecules highly soluble in fat & in
unionized state ll quickly pass to the
fetus.
Molecules low solubility in fat & in an
ionized state ll slowly pass to the
fetus.

The Effect of a drug on

offspring :
A-The dose absorbed by the mother.
B-The period of gestation .

The period of gestation:

In the early days of conception; before
implantation-NO TERATOGENICITY- Gregg
1940.The harmful drug ll kill the embryo or
leave it unharmful.
After the implantation; drugs like
THALIDOMIDE may act as Teratogens.
Congenital Malformation of
embryo,occurs 20 -50 days of gestation
,but from the 4th month no teratogenic
effect , but injury to fetal organs& placenta
may occur.

Drugs which may affect the

embryo:
1)Cytotoxic drugs can lead to teratogenic
effects & death.
a-Anti-metabolites
e.g.Allopurinol,6mercaptopurine,methotrex
ate.
B-Alkylating agents
e.g.Chlorambucil,Cyclophosphamide,
Explanation: These drugs owe their
therapeutic action due to their ability to
kill rapidly dividing cells.These drugs
shouldnt be use unless the pregnant
woman is suffering from malignant
leukaemia or some form
reticulosis( termination of pregnancy is

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Methotrexate : has been used in
therapeutic abortion & in ectopic
pregnancy.The incidence of fetal
abnormality is around 10%.

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2) Thalidomide: was used to prevent
vomiting in 1968 but it caused fetal
anomalies ( phocomelia + amelia ).
3) Cortisone:large dose in pregnant
rabbits,mice,monkeys caused cleft
palate,hare lip.In human pregnant
woman trials showed no
abnormalities.

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4)Tolbutamide,Chlorpropamide:were
regarded with considerable suspicion
in the management of the pregnant
diabetic woman.No confirmation
that these drugs are teratogenic .
5)Nicotine:no teratognicity,but it
causes small for dates,increase in
abortion rate &incease in perinatal
mortality(P.N.M.).

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6)Salicylate:large dose in mice is
teratogenic or can lead to resorption
of the embryo.Na salicylate (acute
rheumatic fever),the dose used, wt
for wt approaches that which is
teratogenic in pregnant mice.A study
from CANADA reported premature
closure of the ductus arteriosis,
pulmonary hypertension leading to
blue babies.

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7)Phenothiazide,Ancoloxin,Metronida
zole,Cannabis,L.S.D. :
All these drugs have been suspected
at one time & this was based on few
individual case reports but further
experience of these drugs didnt
suggest that they are harmful in
normal dose.

Summary of teratogenic
effects:
Lithium (cardiac
e.g.ebsteinscomplex)-<5%.
Warfarin(chondrodysplasia
punctate)10-25%.
Phenytoin(cranio facial/limb)2-26%.
Valproate(CNS) 1-2%.
Carbamazepine(CNS/LIMB/CARDIAC)
0.6-36%.

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Primidone&Phenobarbitone(facial
cleft/cardiac) unknown.
Sex hormones(cardiac/limbs)unknown.
Danazol(Masculination)-unknnown
incidence
Isotretinoin ie Roaccutane(CNS)high
incidence &the same for other
retinoids.

Drugs which may affect the

fetus:
A number of drugs may cause ill-effects in
developing fetus although they arent
teratogenic.
1) Anti-thyroid drugs;
(carbimazole,neomercazole,thiouracil);these drugs cross placenta,interfere
with synthesis of thyroid hormone in
fetal thyroid gland causing compensatory
overaction of pitiutary leading to fetal
goitre which may cause neonatal
respiratory obstruction.

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Lack of thyroid hormone ll cause fetal
cretinism& mental retardation.
If anti-thyroid drugs are used, they
should be combined with L-Thyroxine.
In the past Iodides were used in
expectorant mixtures & asthma
powders , large doses ll impair the
inorganic binding of iodine in the
thyroid gland causing fetal goitre.

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Radio Active Iodine ;shouldnt be
used in pregnancy, because the fetal
thyroid gland ll be destroyed if Iodine
131 is ingested by the mother.

2) Hypotensive Drugs :
Beta-Blockers;(eg propanol=inderal,
atenalol=hypoten,tenormin).
These drugs may cause
hypotonia,hypoglycaemia&
intrauterine growth retardation of the
fetus ,in addition increase in
P.N.M.due to placental insufficiency.

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Reserpine=Adelphan, the fetus ll
sufer of marked lethergy,nasal
blockage & discharge leading to
respiratory difficulty & inspiratory
costal retraction of the fetus.
Methyldopa=Aldomet,is relatively
harmless,may cause +ve Coombs
test in the fetus.

Emergency Hypotensive:
Hydralazine=Apresoline:causes
decrease of syst.BP without decrease
renal flow,but S.L.E. like picture in
the treating mother.
Dioxide=Hyperstat:causes mother
hyperglycaemia due to decrease
insuline + fetal alopcia.
Nowadays we are treating PET by :
Methyldopa,NIFEDIPINE(adalat),LABE
TATOL(trendate),& HYDRALLAZINE.

3)Drugs causing kernicterus&

jaundice.
The causitive drugs ll cause dissociation of
the bilirubin from its protective binding to
serum albumin in the fetus.The free
bilirubin diffuse readily into the CNS
producing Kernicterus:eg the following;
Sulphonamide(sulphafurazole),Long acting
Sulpha(sulphamethoxazole+trimethoprim
=septrin)
Salicylates,Phenylbutazone(butazolidin)
Phenothiazides + water soluble vit K(not
used now
Vit K1 is ok- NO KERNICTERUS.

4)Antibiotic drugs:
Tetracycline;after 4th month of
pregnancy it enters fetal
circulation ,chelates with Ca &
deposites in teeth,bones,nails.When
teeth erupt in infant ,they are at 1st
light yellow & fluoresce in ultraviolat
light & later the colour fades
gradually to a non florescent brown,
in addition to hypoplasia of enemal
leading to dental caries
Large doses may cause Acute Fatty

Ampicillin& penicillin :safe

Cephalosporins :safe
Chloramphenicol :B.M. depression in
mother & very dangerous to
premature neonate Grey Syndrome.
Metronidazole:not teratogenic in man
,but is teratogenic in rats its not used
in pregnancy in USA,but it is used in
routine dose in 2nd & 3rd trimester in
UK.

Anti-TB drugs:
Isoniazid,PAS,Streptomycin,Rifampicin,
& Ethambutol.
The risk of fetal ototoxicity with
strept,is 3-11%.
Rifamp, causes 3% malformation rate
(toxic labyrinthine damage).

Aminoglycoside:
Streptomycin, risk of ototoxicity in the
fetus as it affects the auditory
components of 8th cranial nerve ,
this is rare in normal dose, but
consider this risk before prescribing .

Nitrofuratin:
This drug may be used to treat UTI.
It may produce neonatal haemolysis
because it acts on neonatal RBCs
which is deficient in Glutathione &
Glucose 6 phosphatase
dehydrogenase.

5) Drugs causing fetal or

neonatal haemorrhage:
Warfarin, Phenindione( small M.W.) may
cause retroplacental He or cerebral He in
fetus if level of prothrombin in blood is
brought too low.In 5% of cases facial &
CNS anomalies may occur.
Heparin (large M.W.) doesnt pass to the
fetus.
Thiazides diuretics used in PET to produce
fluid loss may cause thrombocytopenic
purpura in the neonate ( the risk is small).

6) Oral Hypoglycaemic
agents:
Long acting agents Chlorpropamid
pass to the fetus from mother
causing severe & prolonged neonatal
hypoglycaemia & neonatal death.

7) Anti-Convulsant drugs:
Phenobarbitone,Phenytoin,Primidone ;
Retrospective study suggested that
cleft lip & palate may occur in the
fetus, but prospective study of 16
neonates of mother on anticonvulsant drugs showed that
7neonates had severe coagulation
defects similar to vitamin K
deficiency.
Prophylactic RX of mother with vit,K
may prevent this risk.

8) Sex Hormones :
Androgens & progestogens; have been
used in management of threatened
abortion ,causing masculinization of
female fetus with clitorial enlargement &
labial fusion.
Oestrogens carry the risk of adenosis or
adenocarcinoma of vagina of the female
offspring 15-20 years later, in addition
hypospadias in sons of pregnant women
treated on Diethyl still-boestrol.
O.C.pills , risk of fetal limb reduction &
cardiac abnormality.

Vitamin A (retinoids):
CNS malformation (5-6000iu /
day );in addition anomalies in the
eye,palate & uro-genital tract
occurred in experimental animals.

Folic acid tablets:

Prospective studies showed a
decrease in the incidence of CNS
anomalies in women taking folic
tablets.

Adverse effects of drugs on

fetal growth & development :
Drugs used to treat hyperthyroidism can
cause fetal & neonatal hypothyroidism.
Tetracycline antibiotics may inhibit growth
of fetal bones &teeth.
Aminoglycoside antibiotics can cause 8th
nerve damage.
Drugs such as
opiates,benzodiazepines,dextropropoxyph
ene ,can lead to fetal drug dependence &
withdrawal symptoms if taken regularly
during pregnancy.

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An important structural defect that
may occur in later pregnancy is
premature closure of ductus
arteriosus; this results from taking
potent prostaglandin synthetase
inhibitors, such as indomethacin.
ACE inhibitors (captopril) may reduce
fetal & neonatal blood pressure &
cause renal impairment.

Drugs acting on the

neonate:
A number of drugs when taken by
mother are by her milk & therefore
pass to infant.
Most of these drugs are secreted in
such small amounts that is seldom
necessary to discontinue breast
feeding.
a) iodide,
sulphonamides,antihistamines.
b) Bromides;lead to skin eruption in
neonate

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c)Diazepam, chlordiazepoxide, the level of
these drugs in milk is 1/8 that in
maternal blood,if given in large doses
,neonatal lethergy & hypotonia.
d) Phenobarbitone ;secreted in sufficient
amounts in milk & makes infant
drawzy ,
The rate of elimination of drug by neonate
is slow,also it induces glycuronil
transferase enzyme & so it is used to
decrease free bilirubin.It is similar to
withdrawal symptoms of Heroin addicted
mother.

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e)Two groups of drugs; lead to discontinue
Breast feeding.
-Anti-thyroid drugs:carbamazole, thiouracil.
-Anti-coagulants : warfarin, phenindone.
N.B.Heparin ,is safe,doesnt cross to milk.
f)Chloramphenicol ,( B.M. suppression).
g)Tetracyclines:(discoloured teeth).
h)Sulphonamides:(kernicterus ,haemolysis
inG6PD deficiency ).

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i)Isoniazid;causes neurological
complications(convulsions,
neuropathy).
j) Aspirin; possible risk of Reyes
syndrome.

Maternal drug addiction &

neonate
Heroin ,2/3 of infants will have
withdrawal symptoms within 24
hours.Light B.W., low Apgar score
,irritability ,tremors,
twitching,piercing cry,RDS,frequent
yawning & sneezing.