UNIT 4:

PHARMACOLOGY AND PREGNANCY

 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
 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
 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
 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
 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
 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
 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
 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
 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
 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)
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
 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
 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
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