This presentation discuss the following objectives: -Drug therapy during pregnancy, childbirth, and lactation. -Physiological changes of drugs in pregnant women. -Drug toxicity -Cross-placental transfer of drugs -Exertion of drugs in breast milk -Drug safety + ABCDX

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Pharmacokinetics and pharmacodynamics
during pregnancy
Group: 3
Presented by: Reem Alyahya

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Introduction
 Pregnancy, childbirth and lactation pose unique challenges in
terms of drug therapy. The pregnant mother and her unborn
child are exceptionally vulnerable from a physiological, clinical
and ethical point of view. This warrants careful consideration of
a number of important aspects, which could influence the
decision for drug therapy,

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Objectives
 Drug therapy during pregnancy, childbirth, and
lactation.
 Physiological changes of drugs in pregnant women.
 Drug toxicity
 Cross-placental transfer of drugs
 Exertion of drugs in breast milk
 Drug safety + ABCDX

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Why?
 Drug therapy may pose a significant risk during each
of the following vulnerable periods in the human
reproductive cycle:
 Fertilization of the ovum, followed by complete
implantation.
 The fetus.
 The mother and infant.

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Drug therapy during pregnancy

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Drug therapy during pregnancy
Pharmacotherapy during pregnancy, childbirth and
lactation may be necessary for a number of reasons:

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 Chronic illness or disability, particularly:
HIV infection and
AIDS
Diabetes mellitus

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Conti…
Hypertension Asthma Epilepsy
Migraine Mental health
disorders
long-term
anticoagulant
therapy use

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Conti…
 Acute illness or trauma during
pregnancy.
 Pregnancy, labor related disorders and
emergencies.
 In a few instances, the fetus may
actually be the target of the drug
therapy administered to the mother, as
part of a fetal therapy regimen.

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Pharmacotherapeutic decision-
making during pregnancy,
childbirth and lactation.

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The following aspects must be
considered:
 Physiological changes during pregnancy that may
affect drug action and kinetics.
 Drug toxicity during pregnancy.
 Cross-placental transfer of drug molecules and their
metabolites.
 Excretion in breast milk.
 Drug safety during pregnancy and lactation

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Physiological changes and drug
toxicity.

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Physiological changes and drug
toxicity.
 Certain physiological changes during pregnancy
have implications for drug therapy and may affect
any of the four basic kinetic processes namely:
Absorption
Metabolism and
elimination
Excretion
distribution

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Conti…
 the following could alter the way in which drug
molecules are handled by the body:
1- Increased progesterone levels:
 Cause a decrease in gastrointestinal motility
(with resultant constipation)
 Decrease in oesophageal sphincter pressure
(which causes heartburn).
 In addition, placenta-derived human chorionic
gonadotropin (hCG) causes nausea and vomiting.

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 The altered gastrointestinal
functioning caused by these
changes could influence the rate
and extent of absorption of orally
administered drugs.

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Conti…
2- Pregnancy also results in:
 Increased lung perfusion and pulmonary alveolar
drug transfer due to improved cardiac output.
 Meaning that the absorption will be improved for
drugs that are administered via the pulmonary route
(i.e. nebulizers and inhalers).

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Conti…
3- Drug distribution may be affected due
to:
 The increased plasma volume that
accompanies pregnancy and which may
result in an increased volume of distribution
(Vd) of certain drugs.
 Pregnancy brings about a decreased blood
albumin level, which could result in an
increased fraction of free drug molecules.

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Conti…
4- Altered liver functioning may affect :
 the plasma concentrations of drugs that follow
hepatic metabolism.
5-The increased plasma volume, in turn:
 Increases cardiac output (CO), renal blood flow and
glomerular filtration rate (GFR).
 This could increase the renal excretion of drugs that
are significantly eliminated via this route.

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Drug toxicity during pregnancy

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Drug toxicity during pregnancy
 Drugs may be toxic to the developing embryo
and fetus.
 The first trimester of pregnancy is of particular
importance, since the teratogenic effects of certain
drugs will influence normal development of the
unborn child on a structural or functional level.

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Conti…
 A teratogen is a drug or other chemical substance that
may affect normal embryonic development and cause
recognizable congenital defects.
 Sufficient precautions in the form of patient education
and the use of highly effective contraceptive methods
must be taken when treating women of childbearing
age or potential.

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Cross-placental transfer of drug
molecules and their metabolites

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What is the placenta ?
 The placenta is a flattened circular organ in
the uterus of pregnant females that nourishes and
maintains the fetus through the umbilical cord.

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Transport Across the Placenta

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Placenta & Drugs
 The placenta provides a link between the
circulations of two distinct individuals but also acts
as a barrier to protect the fetus from xenobiotics in
the maternal blood.
 However, the impression that the placenta forms an
impenetrable obstacle against most drugs is widely
regarded as false.

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Placental exchange
Most drugs with MW < 500 Da cross the
placenta,
And with MW > 1000 Da do not
1-size
Non-ionized drugs tend to cross the
placenta more easily than ionized drugs
2-Electrical Charge
Traditionally it was taught that protein-
bound drugs did not cross the placenta,
however as these medications exist in
equilibrium with non-bound versions, it
appears that this is not true
3-Protein Binding
While lipophilicity is generally
advantageous with regards to placental
transfer, extreme lipophilicity (ex.
sufentanil) may impede transfer as highly
lipophilic substances can accumulate in the
placenta
4-Lipophilicity

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Placental Exchange

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Excretion of drugs in breast milk

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Excretion of drugs in breast milk
 During lactation, drugs may pass from the
bloodstream to the breast milk, especially if they are
lipid-soluble or basic drugs
 or if they are water-soluble molecules with a relative
molecular mass of less than 100 Da.

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Drug safety + ABCDX

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FDA Categories of Drug Safety
During Pregnancy
 The pregnancy risk classification used by the US Food
and Drug Administration (FDA) is often quoted and
consists of five different categories, namely A, B, C, D
and X.
 Category A drugs are considered to be relatively safe
during pregnancy
 Category X drugs are absolutely contraindicated.

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DescriptionCategory
Controlled human studies show no fetal
risks; these drugs are the safest.
A
Animal studies show no risk to the fetus
but no controlled human studies have been
conducted, or animal studies show a risk to
the fetus but well-controlled human studies
do not.
B
No adequate animal or human studies
have been conducted, or adverse fetal
effects have been shown in animals but no
human data are available
C
Evidence of human fetal risk exists, but
benefits may outweigh risks in certain
situations (eg, life-threatening disorders,
serious disorders for which
safer drugs cannot be used or are
ineffective).
D
Proven fetal risks outweigh any possible
benefit.
X

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Conti…
 It is of great importance to consult suitable drug
references when dispensing medicines to pregnant or
lactating mothers.
 Known teratogens should obviously be avoided during
pregnancy.

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examples of known teratogenic
drugs to avoid during pregnancy
EffectTeratogen
Valproate is associated with neural tube defects,
as is carbamazepine. Phenytoin may cause
malformations
in the central nervous system and adversely
affect foetal growth.
Anticonvulsants
Warfarin is associated with haemorrhage in the
foetus, as well as malformations in the central
nervous
system and skeletal system.
Anticoagulants
ACE inhibitors cause renal damage and may
restrict normal growth patterns in the unborn
child.
Antihypertensive agents
Premature closure of the ductus arteriosus.Non-steroidal anti-inflammatory
Drugs

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Summary
 The decision to choose pharmacotherapy during
pregnancy will not always be an optional one. Drug
treatment may be unavoidable, but will inevitably
expose the unborn child to the effects.
 Certain aspects and principles must be considered
first, to ensure that the intervention is safe, rational
and scientifically sound.

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References
 http://education-portal.com/academy/lesson/the-placenta-and-
the-fetus-structure-and-function.html
 http://www.ncbi.nlm.nih.gov/pubmed/15170365
 Pharmacotherapy during pregnancy, childbirth and
lactation: principles to consider
 http://www.merckmanuals.com/professional/gynecology_and_o
bstetrics/drugs_in_pregnancy/drugs_in_pregnancy.html?qt=dru
gs%20during%20pregnancy&alt=sh

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Any questions?