Drugs

&
Pregnancy
Dr 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:
Uterus

950%

Kidney

60-80%

Liver

75%

Skin

600-700%

Body system functions

Physiological changes

Hematological system

Plasma volume
Red cell mass

Extent of change
50%
18-30%

Plasma albumin conc.

Respiratory system

GIT

Kidney function
Body composition

30%

Serum lipids

66%

Tidal volume

40%

Respiratory rate

Gastric tone/mobility

Intestinal motility

GFR

50%

Water

Fat

P/K changes during

Pregnancy

Absorption
Delayed in absorption lower peak plasma
conc.
intestinal transit time total absorption
Iron/antacid - absorption of some drugs

Distribution
total body water (8 lit) & plasma volume (50%)
plasma albumin level (30%)
total body fat (25%)
Increase in Vd of polar and non-polar drugs

Metabolism
Induction & Inhibition
Most of the hepatic enzymes are induced
(progesterone effect)
E.g. Phenytoin
Inhibition of enzymes that metabolize
caffeine

Excretion
renal plasma flow (80%) and GFR (50%)
excretion of drugs
E.g. Ampicillin, amino glycosides,
cephalexin, digoxin

Role of Placenta

Placental Metabolism
Phase I & II enzymes
CYP450 enzymes
sulfating and N-acetylating enzymes
glutathione transferase activity
E.g. - Prednisolone & Hydrocortisone
- Phenobarbitone

Effect Of Drug On The

Pregnancy

Harmful effect depends upon

Nature of drug & dose
& route of administration

Genetic constitution &

susceptibility of fetus

Stage of pregnancy

Pre-differentiation stage
(0-7 days of gestation)
Death or Abortion

Differentiation stage
(7-57 days of gestation)
Malformation

Post differentiation stage

(after 57 days of gestation)
Functional defects, Growth retardation

Teratogenicity
Teratos = monster
~ 5% of all malformed babies
Teratogens
an exogenous agent
congenital malformation or functional
defect during embryonic or fetal life, which
may manifest even later in life

Tetracyclines

Malformed teeth
Brown discoloration
Susceptibility to caries

Fetal alcohol syndrome

Fetal Warfarin Syndrome

Other Teratogenic Drugs

Drugs

Teratogenic Effects

Tetracycline

Anomalies of teeth & bone

Valproic acid

Neural tube defect

Methotrexate

CNS & limb malformations

ACE inhibitors

Renal tubular dysgenesis, decrease skull

ossification

Antithyroid drugs

Fetal & neonatal goiter and hypothyroidism

Diethylstilbestrol

Vaginal carcinoma & other genitourinary defect

in female and male

FDA Category for Drug use in

Pregnancy
Category-A (safe)
Human studies - no risk to the fetus
E.g. - Replacement dose of thyroid hormones,
- Prenatal vitamins & folic acid

Category-B (no evidence of risk in human)

Animal studies - no harm to fetus &
human studies - no adequate and well-controlled studies
OR
Animal studies - adverse effect &
human studies - failed to demonstrate any risk to the
fetus
E.g. - Penicillin,
- Acetaminophen,
- Insulin

 Category-C (risk can not rule be out)

Animal studies - adverse effect on the fetus
human studies - no adequate and well-controlled studies
potential benefits - allow use of the drug in pregnant
women
E.g. most of the drugs - Furosemide, - Rifampicin,-
blockers, - Chloroquine

Category-D (positive evidence of risk)

Human studies - positive evidence of fetal risk,
but benefits > risk for use in pregnant women
(life-threatening situation or for a serious disease)

E.g. - ACE inhibitors, - Phenytoin, - valporic acid,

- tetracycline, - Quinine

Category X
(definite human teratogenic risk)
Animals or Human studies - fetal abnormalities OR
Human experience - evidence of fetal risk OR
both
and the risk > possible benefit
E.g. - thalidomide, - retinoid etc.

 Golden rules of drug use in pregnancy:

Avoid all drug if possible and use non-drug
treatment first
Avoid all drugs in 1st trimester where possible
If required use safest drug, at lowest
effective dose, for shortest possible time
Discourage the patient from self administration
of OTC drugs
Give proper advice to mother about drug
safety (for better compliance)
Asses risk/benefit ratio for mother-infant pair
& do not sacrifice the mother interest

Drugs & Lactation

Drugs causing neonatal effect

Tetracycline

permanent tooth staining in infant

Isoniazid

signs of pyridoxine deficiency

Barbiturates

lethargy, sedation, and poor suck

reflexes

Chloral hydrate
& Diazepam

sedation

Lithium

concentrations equal to those in

maternal serum

Radioiodine

thyroid suppression

Most antibiotics detected in breast milk

Methods of decreasing toxicity

in nursing infant
Select safe drug
Breast feeding
immediately before taking drug
3-4 hours gap before next feeding
Avoid feeding when drug reaches peak
concentration in milk and plasma

Use drug with short half life

Instruct mother to monitor ADRs

Thank You