Drug therapy in

pregnancy and
lactation
Mydhily Dinesh

2022 batch
Why?
● In pregnancy and labour the body
becomes a complex physiological
unit which consist of
mother,placenta and fetus.
● Various physiological changes
take place.
● These changes may lead to
important variations in the
pharmacokinetic processes of
absorption, distribution and
elimination of drugs.
Pharmacokinetics in pregnancy
Drug absorption: High circulating levels of progesterone slow the gastric
emptying as well as gut motility, thus increasing the intestinal transit time. As a
result, one might expect slower drug absorption during pregnancy.

Drug distribution: It is affected due to increased plasma volume that

accompanies pregnancy and which may result in increased volume of
distribution of certain drugs.

Pregnancy brings about a decease in blood albumin level,which could result in

an increased fraction of free drug metabolites.
Drug metabolism: Hepatic drug metabolising enzymes are induced during
pregnancy, probablyby the high concentrations of circulating progesterone. This
can lead to more rapid metabolic degradation, especially of the highly lipid soluble
drugs such as phenytoin and theophylline.

Drug excretion : The increased plasma volume inturn increases cardiac output and
GFR. This could increase the renal excretion of drugs that are significantly excreted
through this route.
Placental transfer
The placenta provides a link between
the circulations of two distinct
individuals but also act as a barrier to
protect the fetus from xenobiotics in
the maternal blood.

As pregnancy progresses and the

placenta develops, the surface
available for transfer between the
maternal and fetal circulations
increases; at the same time, the
placento-fetal barrier becomes
progressively thinner.
Transfer across this barrier is governed by the same properties of drugs which
regulate the transfer across other biological membranes:
Unbound, non-ionised, lipid-soluble molecules of low molecular weight cross the
barrier more easily than those which do not possess these attributes.
Most of the drugs in use fulfil these criteria and are able to cross the placental
barrier.Further, the placenta is always available to the fetus as a route of drug
elimination.
After birth, the placental route of drug elimination is no longer available and the
neonate is on its own.
Drug toxicity during pregnancy.
Drugs maybe toxic to the developing embryo and fetus.

The first trimester of pregnancy is particularly important since the teratogenic

effects of certain drugs will influence the normal development of the unborn
child on a structural and functional level.

A teratogen is a drug or chemical substance

that may affect normal embryonic development and

cause recognisable conginetal defects.

Drugs used in pregnancy, FDA categories

FDA rating Conditions Examples

A Controlled human studies shows no risk Folic acid

B No confirmatory evidence of risk in human Metronidazole

beings.

C Risk cannot be ruled out Most drugs

D Positive evidence of risk exists. Antiepileptics

X Absolutely contraindicated Cytotoxicz

Drug therapy in pregnancy
What should be considered?
● Physiological changes during pregnancy that may affect action of drugs
and it's kinetics.
● Drug toxicity during pregnancy.
● Placental transfer
● Drug safety during pregnancy and lactation.
Excretion of drugs in breast milk.

Most of the lipid soluble drugs get into breast milk, though not necessarily in
concentrations that can adversely affect the infant.

The amount of a drug transferred into the milk depends on various factors. The
maternal volume of distribution for lipid soluble drugs is larger than for water
soluble drugs; this results in low plasma levels relative to the dose.

It must be remembered that the elimination rate for most drugs is slower in
neonates than in the adults and this may lead to accumulation of the drug in
neonates, particularly when it is taken for long courses by the mother.
Drugs to be avoided/not recommended in breast feeding
women
● Radionuclides and radiopharmaceutical
● Antibacterials Suéforumides, Tetracyclines Chloramphenicol, Nalidixic acid,
Isoniazid Erythromycin estolate.
● Analgesics Indomethacin, phenylbutazone, Aspirin,Opioids
● Psychoactive drugs Diazepam, Lithium
● Antihypertensives: Reserpine, Clonidine.
● Antineoplastic drugs
● Miscellaneouse Amantadine, Phenindone, Cimetidine, Anthraquinones,
Ephedrine, Antinophylline, Ergotamine, Vitamin D(prolonged use of lage doses)