Pharmacology Ch.

9 Outline

Drug therapy during pregnancy and breast feeding

Basic considerations:

About 2/3 of pregnant women take meds during pregnancy (OTC, pregnancy
related, prescribed or illicit)

The risks for most drugs used during pregnancy have not been determined

It is only recommended when the benefit is to both baby and mother

Physiologic changes during pregnancy

Pregnancy can alter drug disposition due to changes in kidney, liver, and GI tract.

By the 3rd trimester, renal blood flow is doubled, causing an increase in glomerular
filtration rate.

Elimination of lithium is increased by 100%

For some drugs, hepatic metabolism increases during pregnancy.

Tone and motility of bowel decrease in pregnancy, causing intestinal transit time to
increase, which increases time for drugs to be absorbed.

Placental drug transfer

All drugs can cross the placenta, although some more easily than others.
Factors that determine drug passage across the membranes include lipid soluble
drugs. Ionized drugs or protein bound drugs cross with more difficulty
- clinician should assume any drug will reach the fetus!

Adverse rxn during pregnancy

Drugs taken during pregnancy can adversely affect both mother and fetus (i.e.
heparin – causes osteoporosis in pregnant women.)

Prostaglandins can cause miscarriage

Drug therapy during pregnancy

Teratogenesis – birth defects from drugs.

The incidence of major structural abnormalities is about 6%.

congenital abnormalities are caused by genetic heritage, environmental chem.. and
drugs.
Teratogenesis and stage of development
see pg. 87

Varies by stage of development

Identification of teratogens

Few drugs are PROVEN teratogens because

- the incidence of congenital anomalies is low
- Animal tests may not be applicable
- Prolonged exposure may be required
- Behavioral effects are difficult to document
- Controlled experiments can’t be done in humans

To prove that a drug is a teratogen – 3 criteria

1. the drug must cause a characteristic set of malformations

2. It must act only during a specific window of vulnerability (wk 4 – 7)

3. The incidence of malformations should increase with increasing dosage and

duration of exposure

The best we can do is systematically collect and analyze data on drugs taken during
pregnancy

** Lack of teratogenicity in animals is not proof of safety in humans

Some teratogens act quickly, while others need prolonged exposure

Teratogens that produce delayed effects are the hardest to identify.

Teratogens that affect behavior may be nearly impossible to identify

FDA pregnancy risk categories

1983 – est. a system for classifying drugs according to their probably risks to the
fetus.

5 categories:

A – Remote risk of fetal harm

B – Slightly more risk than A

C – Greater risk than B

D – Proven risk of fetal harm

X – Proven risk of fetal harm

** see pg 88 and 89

Minimizing the risk of teratogenesis

Best way to minimize risk is to minimize use of drugs during pregnancy
- At least elim all unnecessary drugs!

If a woman is on drugs with strong contraindication for pregnancy, termination

should be considered.

Reducing risk applies to women who MAY become pregnant and are on
contraindicated drugs

Responding to Teratogen exposure

- when a pregnant woman is exposed to a know teratoge, the first step is to
determine exactly when the drug was taken.
- If drug exposure was not during wks 3 – 8 ( oraganogenesis) the pt should be
reassured that the risk is minimal (drug induced mal formation)
- If has occurred during those weeks, should consult a reference and conduct 2
ultrasounds to determine extent of malformation

Drug therapy during breast feeding

If drug concentrations are high enough, in milk, a pharmacologic effect is possible.

When drugs must be taken during breast feeding, the following guidelines should be
followed:

– Dosing immediately after breast feeding

– Avoiding drugs w/ long half life
– Choosing drugs that tend to be excluded from milk
– Choosing drugs that are least likely to affect the infant
– Avoiding drugs that are know to be hazardous