+

Pharmacokinetics and pharmacodynamics

during pregnancy

Group: 3

Presented by: Reem Alyahya

+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,

+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

+

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.

+

+Drug therapy during pregnancy

+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

+Conti…

Hypertension Asthma Epilepsy

Migraine Mental health disorders

long-term anticoagulant therapy use

+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.

+Pharmacotherapeutic decision-

making during pregnancy,

childbirth and lactation.

+

+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

+Physiological changes and drug

toxicity.

+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

eliminationExcretion

distribution

+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.

+

The altered gastrointestinal

functioning caused by these

changes could influence the rate

and extent of absorption of orally

administered drugs.

+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).

+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.

+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.

+Drug toxicity during pregnancy

+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.

+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.

+Cross-placental transfer of drug

molecules and their metabolites

+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.

+Transport Across the Placenta

+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.

+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 drugs2-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

+Placental Exchange

+Excretion of drugs in breast milk

+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.

+Drug safety + ABCDX

+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.

+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

+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.

+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

+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.

+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

+

Any questions?