LECTURE # 05LECTURE # 05

77

DR. NAHEED BANODR. NAHEED BANOAssistant Professor, Obs/GynaeAssistant Professor, Obs/Gynae

Rawalpindi Medical College, Rawalpindi.Rawalpindi Medical College, Rawalpindi.

DRUGS IN PREGNANCYDRUGS IN PREGNANCY

IMPORTANT ASPECTS IMPORTANT ASPECTS

1.1. Physiological changes of pregnancy Physiological changes of pregnancy

affect affect DRUG METABOLISMDRUG METABOLISM

2.2. Drug may cross the placenta and affect Drug may cross the placenta and affect

the fetus the fetus (TERATOCENICITY)(TERATOCENICITY)

PHYSIOLOGICAL CHANGES OF PHYSIOLOGICAL CHANGES OF PREGNANCY THAT AFFECT DRUG PREGNANCY THAT AFFECT DRUG

METABOLISM METABOLISM

GIT:GIT:

Nausea and vomiting of early Nausea and vomiting of early

pregnancy pregnancy

Acid content of the stomach is Acid content of the stomach is ↓↓

Delayed gastric emptyingDelayed gastric emptying

↓ ↓ Intestinal motility Intestinal motility Continued:

SKIN AND MUCOUS MEMBRANE:SKIN AND MUCOUS MEMBRANE:

↑↑ Blood flow to the skin leads to more rapid Blood flow to the skin leads to more rapid

absorption e.g. glyceryl trinitrate patches absorption e.g. glyceryl trinitrate patches

used to suppress preterm labour used to suppress preterm labour

→ → Blood flow to nasal and oral mucous Blood flow to nasal and oral mucous

membrane membrane → → leads to more rapid leads to more rapid

absorption.absorption.

CNS:CNS:↑ ↑ Vascularity of epidural space e.g. opiates used Vascularity of epidural space e.g. opiates used

for analgesia are rapidly absorbed for analgesia are rapidly absorbed PLASMA AND BLOOD VOLUME:PLASMA AND BLOOD VOLUME:↑ ↑ Plasma and blood volume causes Plasma and blood volume causes

haemodilution affecting drug concentration haemodilution affecting drug concentration PLASMA PROTEINS:PLASMA PROTEINS:↓ ↓ In plasma proteins affect drugs that are In plasma proteins affect drugs that are

bound to proteins e.g. diazepam, phenytoin bound to proteins e.g. diazepam, phenytoin leading to ↑ free drug in circulation leading to ↑ free drug in circulation

URINARY SYSTEM:URINARY SYSTEM:↑ ↑ Renal blood flow and GFR affecting Renal blood flow and GFR affecting

concentration and elimination of many drugs.concentration and elimination of many drugs.

Drugs that affect Drugs that affect organogenesisorganogenesis are described are described as TERATOGENIC DRUGSas TERATOGENIC DRUGS

Drug exposure accounts for Drug exposure accounts for 2-3 %2-3 % of all birth of all birth defectsdefects

Most critical period is embrogenic period Most critical period is embrogenic period which is from which is from 22ndnd to 8 to 8thth week post conception or week post conception or day day 31 to day 71 from LMP in a 28 day cycle31 to day 71 from LMP in a 28 day cycle

Exposure Exposure prior to day 31 produces all or noneprior to day 31 produces all or none effect i.e. either the fetus dies in utero or has effect i.e. either the fetus dies in utero or has no effect.no effect.

Exposure from Exposure from day 31 to day 71day 31 to day 71 may lead to may lead to fetal abnormality or fetal death.fetal abnormality or fetal death.

TERATOGENICITYTERATOGENICITY

FACTORS THAT INFLUENCE FACTORS THAT INFLUENCE TERATOGENICITYTERATOGENICITY

Nature of the agent

Dose

Route

Frequency of exposure

Duration of exposure

FACTORS THAT INFLUENCE FACTORS THAT INFLUENCE TERATOGENICITYTERATOGENICITY

Gestational timingGestational timing

Concurrent exposuresConcurrent exposures

Concurrent illnessConcurrent illness

Genetic susceptibilityGenetic susceptibility

* Mother* Mother

* Fetus* Fetus

DIAGRAMATIC REPRESENTATIONDIAGRAMATIC REPRESENTATION

DRUG TOXICITY

14

31

71

209

Conception Heart & CNS

Ear & Palate Organogenesis

PRINCIPAL MECHANISMS OF TERATOGENESIS

� Cell growth or proliferation

� Cell death

� Cell migration

� Cell and tissue interactions

� Disruptions

Baird et al. AJHG 42:677, 1988

BIRTH DEFECTS IN CHILDHOOD

FDA CLASSIFICATION OF DRUG FDA CLASSIFICATION OF DRUG SAFETY IN PREGNANCYSAFETY IN PREGNANCY

United States food and drug United States food and drug

administration categories for drug use administration categories for drug use

in pregnancyin pregnancy

A.A. Controlled studies show no riskControlled studies show no risk

B.B. No evidence of risk in humansNo evidence of risk in humans

C.C. Risk cannot be ruled out Risk cannot be ruled out

D.D. Positive evidence of riskPositive evidence of risk

E.E. Contra – indicated in pregnancy Contra – indicated in pregnancy

Awareness of potential advise effects of Awareness of potential advise effects of drugs increased after THALIDOMIDE drugs increased after THALIDOMIDE

TRAGEDYTRAGEDY

FETAL HYDANTION SYDROMECranio- facial abnormalities , cardiac defects, IUGR

WARFARIN EMBRYOPATHYNasal hypoplasia, hydrocephaly, microcephaly, IUGR

NON –TERATOGENIC FETAL CONSEQUENCES IUGR, mental retardation, intracranial hemorrhage.

DRUGS & BREAST FEESING

Drug may affect the infant in various ways

Drug may inhibit lactation

TAKE HOME MESSAGE

DRUGS SHOULD BE PRESCRIBED TO

PREGNANT AND LACTATING

WOMEN WITH EXTREME

CAUTION