Reproductive Pharmacology:

1. How are the PK/PD parameters (ADME) altered in a pregnant woman and the fetus?
(In general, volume of distribution is increased and clearance is
increased).
a. Pharmokinetics describes how the body handles medications, how it is
absorbed, distributed, and eliminated.
b. For many drugs during pregnancy, absorption is decreased and elimination
is increased making it hard to hit a therapeutic window. The action of drugs
is determined by the concentration in the plasma.
c. Oral absorption occurs by passive diffusion through the small intestine and
bioavailability is measured by the amount that reaches the blood stream.
Delivery to the systemic circulation can be decreased by first pass
metabolism in which the drug is metabolized in the liver before reaching
systemic circulation. NOTE: bioavailability gives only the extent of
absorption, NOT the rate of absorption.
i. Opioids = high first pass metabolism given intramuscularly
d. Pregnancy absorption:
i. Gastric emptying and intestinal motility are reduced leading to a
reduced PPC (peak plasma concentrations) and an increased TPPC
(time of peak plasma concentration).
ii. Gastric pH is more basic due to decreased H+ production leading to
increased ionization of weak acids and reduction of their absorption
more so than weak bases.
iii. Nausea and vomiting may lead to decreased absorption.
iv. Inhaled drugs may be enhanced due to increased CO and Tidal
Volume.
v. Intramuscular absorption is enhanced due to increased muscle and
peripheral perfusion secondary to vasodilation.
e. Pregnancy distribution:
i. Increased plasma volume creates a larger volume of distribution thus
decreasing PPC (peak plasma concentration).
ii. Plasma albumin concentrations are decreased due to hemodilution and
decreased albumin available, which offsets the larger volume of
distribution.
iii. Steroids and hormones displace drugs from binding sites leading to a
rise if free active drug concentrations.
iv. Body fat composition increases and creates a larger volume of
distribution for lipophilic drugs.
f. Pregnancy Metabolism:
i. Estrogen and progesterone may increase OR competitively inhibit
some enzymes in the cytochrome P450 complex and thus increase OR
decrease rate of metabolism.
g. Pregnancy Elimination:
i. Renal blood flow is increased up to 60-80% during pregnancy and
therefore glomerular filtration rate is increased by up to 50% leading
to enhanced secretion of drugs
2. How is protein binding and bioavailability altered in a pregnant woman and the
fetus?

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a. The degree to which drugs bind to plasma proteins alters their

bioavailability. Distribution of a drug into compartments depends on its
solubility in water, and solubility within membranes.
b. Volume of distribution = [VD = amount in body/amount in plasma] Volume
that the drug will be distributed in, IF it were uniformly and instantaneously
distributed at volumes equal to that in the plasma. Drugs confined to
intravascular compartments (such as blood) have a low volume of
distribution, while lipophilic drugs (in fat) have a high volume distributed.
The higher the VD, the more of the drug is needed because it is stored more
in the tissues.
What is the function of the placenta with regard to drugs?
a. Drug transfer occurs mainly through transfer through the placenta.
i. This favors transfer of lipophilic molecules and rate-limiting step is
blood flow.
b. Protein bound drugs and large molecular weight drugs do NOT cross the
placenta
c. The placenta can metabolize drugs as well as the fetal liver, however the
fetal liver is not efficient at metabolizing drugs because of the ductus
venousus shunt, and lack of an adequate amount of enzymes.
What factors t influence drug transfer across the placenta?
a. Lipophilic verses hydrophilic drugs (lipophilic drugs cross more readily)
b. Size, the larger the molecule the harder it is to cross the placenta and easier
for smaller molecules.
c. Weak acid/base, fetal pH is slightly more acidic, allowing weak bases to
cross the placenta with more ease; they are less likely to diffuse back to
maternal circulation.
d. Albumin levels, maternal albumin decreases while fetal albumin increases
resulting in higher protein bound drugs in the fetus.
What factors influence drug transfer into breast milk?
a. Most drugs reach the breast milk through passive diffusion but other drugrelated factors influence drug transfer from maternal circulation:
i. Degree of protein binding highly bound drugs transfer in low
amounts
ii. Size low molecular weight drugs passively diffuse into breast milk
iii. Lipid solubility lipophilic drugs passively diffuse into breast milk
iv. Excretion excretion of large amounts of the drug may pull drug back
out of milk
v. pH Breast milk is more acidic thus favoring transfer of weak base
drugs
What factors influence drug concentrations in a newborn that is breastfeeding?
a. Frequency and amount ingested during feedings
b. Exclusive breast feeding verses formula supplementation
c. Stability of the drug in the stomach and GI tract along with ability of drug to
be metabolized
What vaccines are recommended during pregnancy?
a. Influenza vaccine
b. Tetanus vaccine
What vaccines should be avoided during pregnancy?
a. Live attenuated vaccines should be avoided in pregnant women because of
theoretical risk of transmission to the fetus. These include measles, mumps,
polio, rubella, small pox, varicella, and yellow fever.

9. What are safe treatments for constipation, GERD, N/V and pregnancy-induced
hypertension?

Heparin
o Anti-coagulant
o Increases antithrombin III activity inactivates thrombin and associated
proteases
o Parenteral administration
Psyllium
o Used to treat constipation and high cholesterol
o Oral administration
Docusate sodium
o Stool softener for constipation and anal fissures.
o Does not stay in GI tract; enters blood stream and excreted via gall bladder.
Milk of Magnesia
o Treats constipation by drawing water into the small intestines.
o Oral administration
Calcium carbonate
o Used to treat heartburn
o Neutralizes acids that escape from relaxed esophageal sphincter
Ranitidine
o Histamine-2 receptor antagonist
o Used to treat GERD (gastro-esophageal reflux disease)
o By mouth or injection
Famotidine
o Histamine-2 receptor antagonist
o Used to treat GERD
o By mouth or injection
Dimenhydrinate (Dramamine)
o Inverse agonist (binds to same receptor as agonist, but induces opposite
affect) of Histamine-1 receptor; Histamine-1 receptor is a vasodilator.
o Anti-muscarinic as well (blocks Ach channels).
o Used to relieve allergies, motion sickness, nausea and vomiting.
Hydralazine
o Vasodilator
o Binds to potassium channel, causes efflux and hyperpolarization thus
blocking calcium mediated activation and vasoconstriction.
o First line of therapy for hypertension in pregnancy
Hydroxyzine
o Antihistamine with anticholinergic and sedative properties
o Used to relieve allergies, anxiety, tension, nausea, vomiting, and withdrawal.

Anti-hypertensives = Beta-blockers and calcium channel antagonist are frequently

used in pregnancy.
Antibiotics = most beta-lactams are hydrophilic and diffuse down concentration
gradient through placental circulation. They circulate through in the fetus through the
amniotic fluid.