5. Drugs & Pregnancy 1

7/23/2019 5. Drugs & Pregnancy 1

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Drugs&

PregnancyDr Jatin Dhanani



Thalidomide disaster



Drug → affect the pregnancy

Non-pregnant woman

+

fetus

Pregnancy → affect drug



Physiological Changes

During Pregnancy Body system functions Physiological changes Extent of change

Cardiovascular system Cardiac output ↑30-35%

Heart rate ↑ 20%

Stroke volume ↑ 10%

Blood flow

!terus " #$%&

'idney " (%-)%&

*iver " $&

Skin ↑ 600-00%



Body system functions Physiological changes Extent of change

,ematological system Plasma volume " $%&

!ed cell ma"" ↑ 1#-30%

Plasma alumin conc. / 0%&

Serum lipid" ↑ 66%

1espiratory system $idal volume ↑ 0%

!e"pirator& rate '

234 2astric tone5moility /

3ntestinal motility /

'idney function 261 " $%&

Body composition 7ater "

6at "



P/K changes duringPregnancy



()"orption

Dela&ed in a)"orption * lo+er peak pla"ma

conc,

↑ inte"tinal tran"it time * ↑ total a)"orption

ron.antacid - / a)"orption o "ome dru"



Di"tri)ution

↑ total )od& +ater # lit 4 pla"ma volume 50%

/ pla"ma al)umin level 30%

↑ total )od& at 25%

ncrea"e in d o polar and non-polar dru"



eta)oli"m

3nduction 8 3nhiition

o"t o the hepatic en7&me" are inducedproe"terone eect

E.g. Phenytoin

nhi)ition o en7&me" that meta)oli7e

caeine



89cretion

↑ renal pla"ma lo+ #0% and :;! 50%

↑e9cretion o dru"

E.g. 9mpicillin: amino glycosides:

cephalexin: digoxin



!ole o <lacenta



<lacental eta)oli"m

<ha"e 4 en7&me"

CYP450 enzymes

sulfating and N-acetylating enzymes

glutathione transferase activit&

8,, - <redni"olone 4 H&drocorti"one

- <heno)ar)itone



Efect O Drug On ThePregnancy



Harmful eect depends upon

Nature of drug 8 dose

8 route of administration

2enetic constitution 8

susceptiility of fetus

;tage of pregnancy



Pre-differentiation stage

0- da&" o e"tation

Death or ()ortion

Differentiation stage

-5 da&" o e"tationalormation

Post differentiation stage ater 5 da&" o e"tation

;unctional deect"= :ro+th retardation





Teratogenicity

$erato" > mon"ter

? 5% o all malormed )a)ie"

$eratoen" @

an e9oenou" aent @

conenital malormation or unctional

deect durin em)r&onic or etal lie= +hich

ma& manie"t even later in lie



Tetracyclines

<alformed teeth

Brown discoloration

;usceptiility to caries



Fetal alcohol syndrome



Fetal Warfarin Syndrome



Other Teratogenic Drugs

Drugs 4eratogenic Effects

$etrac&cline (nomalie" o teeth 4 )one

alproic acid Aeural tu)e deect

ethotre9ate CAS 4 lim) malormation"

(C8 inhi)itor"!enal tu)ular d&"ene"i"= decrea"e "kullo""iication

(ntith&roid dru" ;etal 4 neonatal oiter and h&poth&roidi"m

Dieth&l"til)e"trolainal carcinoma 4 other enitourinar& deectin emale and male



FDA Category for Drug use inPregnancy

Category-9 =safe> ,uman studies - no ris? to the fetus

E.g. - 1eplacement dose of thyroid hormones:

- Prenatal vitamins 8 folic acid

Category-B =no evidence of ris? in human>

9nimal studies - no harm to fetus 8

human studies - no ade@uate and well-controlled studies A1

9nimal studies - adverse effect 8

human studies - failed to demonstrate any ris? to thefetus

E.g. - Penicillin:

- 9cetaminophen:

- 3nsulin



Category-C =ris? can not rule e out>

9nimal studies - adverse effect on the fetus

human studies - no ade@uate and well-controlled studies potential enefits - allow use of the drug in pregnant

women

E.g. most of the drugs - 6urosemide: - 1ifampicin:- loc?ers: - Chloro@uine

Category-D =positive evidence of ris?>

,uman studies - positive evidence of fetal ris?:

ut enefits ris? for use in pregnant women

=life-threatening situation or for a serious disease>

E.g. - 9CE inhiitors: - Phenytoin: - valporic acid:- tetracycline: - uinine



Category X

(denite human teratogenic risk

9nimals or ,uman studies - fetal anormalities A1

,uman experience - evidence of fetal ris? A1

othand the ris? possile enefit

E.g. - thalidomide: - retinoid etc.



2olden rules of drug use in pregnancy

9void all drug i po""i)le and u"e non-drug

treatment ir"t (void all dru" in 1"t trime"ter +here po""i)le

reBuired u"e safest drug= at lowest

effective dose= or shortest possile time

Di"courae the patient rom "el admini"tration

o A4C drugs

:ive proper advice to mother a)out drug

safety or )etter compliance (""e" ris?5enefit ratio or mother-inant pair

4 do not sacrifice the mother interest



Drugs ! "actation



Drugs causing neonatal efect

$etrac&cline permanent tooth "tainin in inant"onia7id "in" o p&rido9ine deicienc&

ar)iturate"lethar&= "edation= and poor "uckrele9e"

Chloral h&drate4 Dia7epam

"edation

ithiumconcentration" eBual to tho"e in

maternal "erum

!adioiodine th&roid "uppre""ion

o"t anti)iotic" detected in )rea"t milk



#ethods o decreasing to$icityin nursing inant

Select "ae dru

rea"t eedin

immediatel& )eore takin dru

3- hour" ap )eore ne9t eedin

(void eedin +hen dru reache" peak

concentration in milk and pla"ma

E"e dru +ith "hort hal lie

n"truct mother to monitor (D!"


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