THE SAFETY PHARMACOTHERAPY DURING PREGNANCY
ABSORPTION DURING PREGNANCY
GASTRO-INTESTINAL ABSORPTION
 delayed gastric emptying ( with about 30-50% )
 decreased intestinal motility
An increase in plasma progesterone level during pregnancy is responsible for the reduction in
intestinal motility.
 reduction in gastric acid secretions
( with about 40% during the first two semester of pregnancy )
 increase in mucus secretion
The consequence of the changes is increase in gastric pH.
pH increase influences the drugs ionization and their gastro-intestinal absorption.
CUTANEOUS AND VAGINAL ABSORPTION
 the increase of regional blood flows facilitates drugs’ penetrations at cutaneous level
 at vaginal mucosa level drugs absorption is higher
DISTRIBUTION DURING PREGNANCY
 maternal plasma volume expands from 30 to 50% during the first trimester
 as a result of haemodilution plasma albumin declines
 the concentration of 1-glycoproteins (which bind basic drugs) also decreases during
pregnancy
HEMODYNAMICS CHANGES
 total blood flow increase with about 30%, reaching the maximum between weeks 30
and 34 of pregnancy
 cardiac flow increases with 50%
 renal and pulmonary flow are increased in parallel with the cardiac flow
 hepatic flow remains unmodified
 uterine blood flow also increase
BODY HYDRIC COMPARTMENT
 plasma volume increases with about 50%, reaching its maximum between weeks 30
and 34 of pregnancy
 total body water increase very much;
60% of this amount is for the fetus, placenta and amnion, and the remaining 40%
refers to the body of the mother
BODY COMPOSITION
 adipose tissue content might grow from 3-4 kg to about 19 kg at the end of pregnancy
 this fat tissue accumulation during pregnancy explains the raise of distribution
volume for liposoluble substances
(e.g. diazepam, petidine, thiopental ) and the persistence of a high drug concentration
after anesthesia ( thiopental, bupivacaine )
 drug distribution in pregnant body is also influenced by the presence of fetus and
placenta ( new distribution compartments ) which might play a very important role
concerning drugs’ quantity and transport speed, from mother to fetus
 placenta can not be considered a barrier that protects the fetus against any drugs used
by mother
METABOLISM DURING PREGNANCY
MOTHER’S METABOLISM
 hepatic metabolism depends on: drug binding of plasma proteins, blood hepatic flow
 furthermore, progesterone stimulates the activity of hepatic microsomal enzymes
(P450 cytochrome) and therefore accelerates the metabolism of some drugs
( e.g., fenytoine, valproic acid, carbamazepine )
 induction of: CYP3A4, CYP2D6, CYP2C9
 inhibition of: CYP1A2, CYP2C19
RENAL EXCRETION DURING PREGNANCY
MOTHER’S EXCRETION
As a result, the renal excretion of drugs during pregnancy is much accelerated, due especially
to the weak bindings between drugs and plasma proteins, as a result of hypoalbuminemia
caused by hemodilution
PREGNANCY - RISK CATEGORIES
The Food and Drug Administration (FDA) currently divides medications into 5 different
pregnancy-risk categories
A - Controlled studies show no risk to the fetus in the first trimester ( and there is no evidence
of a risk in later trimesters ), and the possibility of fetal harm appears remote.
Example: vitaminum E
B- Either animal-reproduction studies have not demonstrated a fetal risk but there are no
controlled studies in pregnant women or animal-reproduction studies have shown
an adverse effect (other than a decrease in fertility) that was not confirmed in controlled
studies in women in the first trimester (and there is no evidence of a risk in later
trimesters).
Example: penicillins
C- Either studies in animals have revealed adverse effects on the fetus ( teratogenic or
embryocidal, or other ) and there are no controlled studies in women or studies in
women and animals are not available.
Drugs should be given only if the potential benefit justifies the potential risk to the fetus.
Example: gentamicin
D - There is positive evidence of human fetal risk, but the benefits from use in pregnant
women may be acceptable despite the risk (e.g., if the drug is needed in a lifethreatening situation or for a serious disease for which safer drugs cannot be used or are
ineffective).
Example: chloramphenicol
X - Studies in animals or human beings have demonstrated fetal abnormalities, or there is
evidence of fetal risk based on human experience, or both, and the risk of the use of the
drug in pregnant women clearly outweighs any possible benefit.
The drug is contraindicated in women who are or may become pregnant.
Example: etretinate