Pregnancy Pharm

Question 1

Increased _________ levels –> delayed gastric emptying, increased intestinal transit time, decreased gastric acid production (increased gastric pH).

Answer 1

Increased progesterone levels –> delayed gastric emptying, increased intestinal transit time, decreased gastric acid production (increased gastric pH).

Question 2

Placenta derived hCG causes what?

Answer 2

Nausea and vomiting.

Question 3

Why do pregnant women experience gastric reflux?

Answer 3

Due to increased gastric pressure, decreased LES tone.

Question 4

How does pregnancy affect the liver?

Answer 4

Altered liver enzyme synthesis and decreased serum proteins (albumin).

Question 5

In pregnancy oral drug absorption may increase. This accompanied by:

Answer 5

Increased Tmax

Decreased Cmax

Question 6

What could potentially cause oral drug absorption to decrease in pregnancy?

Answer 6

Vomiting and/or reflux

Question 7

How does pregnancy affect weak acids?

Answer 7

Increased ionization of weak acids –> decreased absorption

Question 8

What some the main cardiovascular changes in pregnancy?

Answer 8

Increased blood volume
Increased HR
Increased SV
Increased CO

Question 9

What causes vasodilation in pregnant women?

Answer 9

Progesterone, PGs, and NO –> Decreased PVR, Increased venous capacitance

Question 10

How does pregnancy affect blood flow?

Answer 10

Increased blood flow.

Increased extravascular water (breasts, uterus, peripheral edema)

Question 11

How do cardiovascular changes affect drug disposition?

Answer 11

Increased space for hydrophilic drug distribution –> increased Vd (may need higher doses for therapeutic levels)

Decreased protein bound drug conc. –> increased unbound drug fraction (ex: drugs w/ high albumin binding ex: phenytoin)

Enhanced IM, SC absorption

Question 12

Renal changes in pregnancy

Answer 12

Increased renal size, dilation of urinary collecting system

Increased renal blood flow, increased GFR

Question 13

How does renal changes affect drug disposition?

Answer 13

Increased CL of renally eliminated drugs (lithium, ampicillin, cephalosporins)

Decreased peak conc. of hydrophilic drugs

Question 14

Respiratory changes in pregnancy

Answer 14

Increased tidal volume and minute ventilation

Decreased FRC (due to increased intra-abdominal pressure, fluid)

Question 15

How does respiratory changes affect drug disposition?

Answer 15

Increased absorption of drugs administered via inhalation.

Question 16

What MW can readily cross the placenta?

Answer 16

<500 Da

MW > 1000 Da do not cross the placenta

ex: heparin is large and polar

Question 17

CYP1A2

Answer 17

Decreases metabolism of caffeine and theophylline

Question 18

CYP2A6

Answer 18

Increases the metabolism of nicotine

Question 19

CPY2D6

Answer 19

Increases the metabolisms of metoprolol and dextromethorphan

Question 20

CYP2C19

Answer 20

Decreases the metabolism of proguanil

Question 21

________ drugs of appropriate size diffuse readily across the placenta. Increases potential fetal effects.

Answer 21

Lipophilic drugs of appropriate size diffuse readily across the placenta. Increases potential fetal effects.

Question 22

__________ drugs cross the placenta slowly. Decreases potential fetal effects.

Answer 22

Hydrophilic drugs cross the placenta slowly. Decreases potential fetal effects.

Question 23

What is the exception to the lipid solubility?

Answer 23

High maternal-fetal conc. gradients –> polar compounds may cross the placenta in significant concentrations (ex: salicyclic acid)

Question 24

What is the pH of maternal blood? What is the pH of fetal blood?

Answer 24

Maternal: pH 7.4
Fetal: pH 7.3

Weakly basic drugs with pKa > 7.4 will be more ionized in fetal compartments –> more ion trapping, resulting in higher fetal drug levels.

Question 25

Complete Transfer Exceeding Transfer Incomplete Transfer

Answer 25

Complete Transfer: drug rapidly crosses placenta, equilibrium occurs, conc. in fetal blood = maternal blood Exceeding Transfer: conc. in fetal blood > maternal blood Incomplete Transfer: drug is unable to cross the placenta completely, conc. in fetal blood < maternal blood

Question 26

Route Blood Uses to Pass through the Placenta

Answer 26

Maternal blood --> intervillous spaces --> synctiotrophoblasts --> fetal connective tissue --> endothelium of fetal capillaries

Question 27

Free drugs/metabolites cross the placenta via _______ and/or ________

Answer 27

Free drugs/metabolites cross the placenta via passive diffusion and/or transporter-mediated transfer.

Question 28

Where in the placenta can drugs undergo phase I and phase II metabolism?

Answer 28

The syncytium.

Question 29

What is the milk reservoir in the lactating gland?

Answer 29

Lactiferous duct ampulla (sinus)

Question 30

Route of drugs into the breast milk

Answer 30

Alveolar capillary beds --> lactiferous ducts --> passive diffusion down conc. gradient

Question 31

Drug conc. achieved in breast milk is usually ____.

Answer 31

Drug conc. achieved in breast milk is usually low. Daily drug conc. received by infant < therapeutic dose

Question 32

Recommendations for breast-feeding mothers taking meds:

Answer 32

Nursing mother should take meds 30-60 min after nursing or 3-4 hrs before nursing.

Question 33

The _______ the MW, the greater the penetration into milk.

Answer 33

The lower the MW, the greater the penetration into milk. Drugs with MW <200 Da easily pass into the breast milk. Drugs with MW >600 Da cannot.

Question 34

Lipid soluble drugs pass __________ into breast milk.

Answer 34

Lipid soluble drugs pass more freely into breast milk. Milk contains fat --> sequestration. Increases conc. of lipid soluble drugs.

Question 35

Normal pH range of breast milk? What kind of drugs are most likely to pass into breast milk?

Answer 35

Normal milk pH ranges from 6.5 to 7.4. Nonionized drugs are more likely to pass into breast milk. Basic drugs transfer >>>> acidic drugs.

Question 36

Plasma protein binding and milk:

Answer 36

Both plasma and milk contain proteins that can bind drugs: plasma > milk. Highly plasma protein bound drugs usually remain in teh plasma and pass into the milk in small quantities.

Question 37

What are some other factors that help determine the drug transfer into breast milk?

Answer 37

Quantity of milk available | Drug bioavailability and t1/2

Question 38

ACE Inhibitors Ethanol Misoprostol

Answer 38

ACE Inhibitors (All esp 2 and 3) = Renal Damage Ethanol (All) = Risk of fetal alcohol syndrome and neurodevelopmental defects Misoprostol (1st Trimester) = Mobius Sequence (characterized by facial paralysis and the inability to move the eyes from side to side. underdevelopment of CN 6 and 7)

Question 39

NSAIDs Smoking

Answer 39

NSAIDs (3rd trimester) = Premature closure of ductus arteriosus Smoking (All) = Intrauterine growth retardation, prematurity, SIDS

Question 40

Tetracycline Warfarin

Answer 40

Tetracycline (All) = discoloration and defects of teeth and altered bone growth. Warfarin (All) = Hypoplastic nasal bridge (depressed nasal bridge) and chondropdysplasia, CNS malformations, bleeding risk