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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 pregnancy Nausea and vomiting of early 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 haemodilution Plasma and blood volume causes haemodilution
affecting drug concentration affecting drug concentration
PLASMA PROTEINS:PLASMA PROTEINS:
↓ ↓ In plasma proteins affect drugs that are bound In plasma proteins affect drugs that are bound
to proteins e.g. diazepam, phenytoin leading to to proteins e.g. diazepam, phenytoin leading to
↑ free drug in circulation ↑ 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