2. DRUG THERAPY IN PREGNANCY
During pregnancy most drugs can cross the placenta and
expose the baby to their effects
Factors affecting placental drug transfer and drug effects on
the fetus include
Drug physiochemical properties
Rate at which drug crosses placenta and amount reaching the fetus
Duration of drug exposure
Distribution in different fetal tissues
Stage of placental and fetal development
Effects of drugs used in combination
3. PREGNANCY INDUCED MATERNAL
PHYSIOLOGIC CHANGES
Gastrointestinal absorption
Decreased GI motility
Secondary to progesterone levels
Reduction in gastric acid secretion
Increase in gastric mucus secretion
Increase in gastric pH, therefore negatively affects drugs that require
acidic pH for absorption
Nausea and vomiting
Lung absorption
Cardiac and tidal volumes increase by approximately by 50% in
pregnancy.
Hyperventilation and increased pulmonary blood flow
Transdermal absorption
Increase in peripheral vasodilation and increase in blood flow to the
skin.
Enhanced transdermal absorption
4. PHYSIOLOGIC CHANGES IN PREGNANCY
Organ System Dynamic Change during pregnancy
Cardiovascular
Blood volume Increased by 30-50%
Cardiac output Increased by 30-50%
Systemic vascular resistance Decreased
Organ System Dynamic Change during pregnancy
Gastrointestinal
pH of intestinal secretions Increased
Gastric emptying time Increased
Gastric acid secretions Decreased
Intestinal motility Decreased
5. PHYSIOLOGIC CHANGES IN PREGNANCY
Organ System Dynamic Change During Pregnancy
Kidney
Renal Blood Flow rate Increased
Glomerular Filtration rate Increased
Organ System Dynamic Change during Pregnancy
Gynecologic
Uterine Blood Flow Increased
6. LIPID SOLUBILITY
Drug passage through the placenta is depended on lipid
solubility and degree of ionization
Example: Salicylate
Lipophilic drugs tend to diffuse readily across the placenta and
enter the fetal circulation
Example: Thiopental use during cesarean sections may cause apnea
in the newborn
Impermeability to polar compounds is relative rather an
absolute
Achieved during high enough maternal-fetal concentration gradient
7. MOLECULAR WEIGHT (MW)
Influences the rate and amount of drug transferred across the
placenta
Depending on lipid solubility and degree of ionization the
following rule for MW apply
250-500: Cross the placenta easily
500-1000: Cross with more difficulty
> 1000: cross very poorly
Clinical application
Heparin is large and polar, thus unable to cross the placenta
Provides alternative to coumadin, which is teratogenic
8. PLACENTAL TRANSPORTERS
Several drug transporters have been identified in the placenta
There is increasing recognition of their effects on drug transfer
to the fetus
P-glycoprotein transporter
Pumps back into maternal circulation a variety of drugs and other
agents
Example: cancer drugs and viral protease inhibitors
Clinical benefit
Prevention of toxic effects to the fetus
9. PHARMACODYNAMIC FACTORS
INFLUENCING DRUG THERAPY
Maternal drug actions
Physiology of some organs (heart, lungs, kidneys, CNS) may be
altered by pregnancy
May require the use of drugs not needed by the same woman when
she is not pregnant
Example: Diuretics in pregnancy induced HF
Fetal therapeutics
Involves drug administration to the pregnant woman with the fetus as
the drug target
Example: Corticosteroids to stimulate lung maturation when pre -term
birth is expected
10. PHARMACODYNAMIC FACTORS
INFLUENCING DRUG THERAPY
Predictable toxic drug actions in the fetus
Neonatal withdrawal syndrome
Caused by chronic use of opioids by the mother
Use of teratogenic drugs during pregnancy
ACEI causing renal damage to the fetus
Teratogenic mechanisms (multifactorial)
Direct drug effects on maternal tissues with indirect effects on fetal
tissue
Direct effects on processes for tissue differentiation
Deficiency in a critical substance
folic acid prevents spina bifida
11. PHARMACODYNAMIC FACTORS
INFLUENCING DRUG THERAPY
To be considered teratogenic a substance should
Result in a characteristic set of malformations
Exert its effects at a particular stage of fetal development
Show a dose dependent incidence
FDA teratogenic risk categories
Attempt to quantify teratogenic risk
Range from A (safe) to X (definite human teratogenic risk)
12. SELECTED DRUGS WITH SIGNIFICANT
ADVERSE EFFECTS ON THE FETUS
Drug Trimester Effect
ACEI All, Renal damage
TCAs Third Neonatal withdrawal syndrome
Barbiturates All Chronic use: Neonatal dependence
Carbamazepine First Neural tube defects
Cocaine, tamoxifen All Risk of spontaneous abortion
Ethanol All Fetal alcohol syndrome
Iodine All Congenital goiter, hypothyroidism
Lithium First Icreased ICP
Tobacco All Intrauterine growth retardation
Tetracycline All Discoloration of teeth and altered bone growth
Thalidomide & DES First Limb malformation (DES Cancer Risk Icreased)
Warfarin First Alters respiratory tract formation
Second CNS malformation
Third Risk of bleeding – IC hemorrhage
13. DRUG ABSORPTION
Absorption after IM or SC injections in neonates depends on
Blood flow to the area and gastrointestinal function
Blood flow is reduced by
Cardiovascular shock, vasoconstriction, HF, very little muscle mass
and diminished perfusion of area
GI function in the neonate changes significantly after birth
Full-term: GI secretions begin soon after birth
Pre-term: GI secretions begin more slowly
Gastric emptying time is by 6-8hrs
Peristalsis is irregular and may be slow
Gastrointestinal enzymes tend to be lower
14. DRUG USE DURING PREGNANCY
AND LACTATION
Most drugs given to lactating women are detectable
in breast milk
Concentrations are usually low, preventing infants
form receiving therapeutic amounts
Some drugs carry serious toxicities and must be
avoided
Example: Radioactive iodine, cancer chemotherapy
Recommendations for feeding mothers
Safe drug: Take it 30-60 minutes after nursing and 3-4
hours before the next feeding
No safety data: Avoid drug use or discontinue breast
feeding
15. POSSIBLE EFFECTS ON INFANT OF SELECTED
DRUGS USED DURING LACTATION
Drug Comments
Tetracycline Risk of permanent tooth staining in infant
Isoniazid Risk of pyridoxine deficiency in the infant
Barbiturates Lethargy, sedation and poor suck reflexes
Chloral hydrate Drowsiness if infant fed at peak
Diazepam Drug accumulation and sedation
Methadone Risk of withdrawal if breast feeding stops
Iodine Thyroid suppression and risk of cancer
Propylthiouracil Can suppress thyroid function in infant