Pregnancy

Question 1

PK Changes - Absorption
- Gastric Emptying

Answer 1

Slows gastric emptying, delayed

Question 2

PK Changes - Absorption
- Intestinal Motility

Answer 2

Decreased intestinal mobility

Question 3

PK Changes - Absorption
- Blood Flow

Answer 3

Increased blood flow to GI tract

Question 4

PK Changes - Absorption
- Enzymes

Answer 4

Changes in intestinal and hepatic metabolic enzymes

Question 5

PK Changes - Distribution
- Total Body Water

Answer 5

Increase in total body water

Question 6

PK Changes - Distribution
- Plasma Volume

Answer 6

Increase in plasma volume
- Is greater than erythrocyte volume resulting in hemodilution (Pregnancy Anemia)

Question 7

PK Changes - Distribution
- Body Fat

Answer 7

Increase in body fat

Question 8

PK Changes - Distribution
- Albumin

Answer 8

Decrease in albumin concentration

Question 9

PK Changes - Distribution
- Alpha-1-acid glycoprotein

Answer 9

Decrease in alpha-1-acid-glycoprotein concentration

Question 10

PK Changes - Distribution
- Cardiac Output

Answer 10

Increase in cardiac output at 9 weeks post gestation (Peaking in latter pregnancy)
- Increases blood flow to organs

Question 11

PK Changes - Elimination
- CYP3A4

Answer 11

Increases in pregnancy

Major metabolite (more than 50% of drug is metabolized by this pathway)

Low E Drug: Increase in intrinsic clearance = Decrease concentration of drug
- Have to titrate dose up

HIV Drugs are metabolized by CYP3A4

Question 12

PK Changes - Elimination
- CYP2E1

Answer 12

Increases in Pregnancy

Question 13

PK Changes - Elimination
- CYP2D6

Answer 13

Increases in Pregnancy
- Except in poor-metabolizers as they do not express CYP2D6

Clearance is higher in pregnancy compared to post partum
Clearance is higher in intermediate metabolizer compared to normal

Question 14

PK Changes - Elimination
- CYP2C9

Answer 14

Increases in pregnancy

Drug will be more cleared in pregnancy
- May have to increase dose of drugs that are major metabolites

Question 15

PK Changes - Elimination
- CYP1A2

Answer 15

Decreases in Pregnancy

Ex. Caffeine
- Clearance in 3rd trimester is lower than 1st trimester

Question 16

PK Changes - Elimination
- UGT1A4

Answer 16

Increase in Pregnancy
- Avoids CYP pathway

Ex. Lamotrigine
Increased clearance during pregnancy
- Will have to Increase dose
- Return dose to normal post-partum

Question 17

PK Changes - Elimination
- Renal Transport

Answer 17

Increase in transporter activity during pregnancy
- OCT2, P-gp, OAT1

Question 18

PK Changes - Elimination
- OCT2

Answer 18

Uptake transporter
- Increase in metformin clearance

Question 19

PK Changes - Elimination
- P-gp

Answer 19

Efflux Transporter
- Increase in digoxin clearance

Question 20

PK Changes - Elimination
- OAT1

Answer 20

Uptake Transporter
- Increases in amoxicillin renal clearance

Question 21

PK Changes - Elimination
- Hepatic Blood Flow

Answer 21

No effect

Question 22

PK Changes - Elimination
- Renal Clearance

Answer 22

• Increase in Renal Blood Flow
• Increase in Glomerular Filtration
• Increase in Creatinine Clearance

Question 23

PK Changes - Elimination
- Creatinine Clearance

Answer 23

• Increases in 1st trimester
• Increases by 30-50% mid-pregnancy
• Decreases in last few weeks of pregnancy

Question 24

High E Drug given IV

Answer 24

Dependent on Hepatic Rate Flow

Question 25

High E Drug given Orally

Answer 25

Dependent on Intrinsic Clearance and Free Fraction

Question 26

Low E Drug

Answer 26

Dependent on Intrinsic Clearance and Free Fraction

Question 27

Should we measure Free or Total Concentration

Answer 27

Measure the free concentration
- It is the active form of the drug
- Does not change proportionally unlike true concentration. Thus, if you were to measure true concentration you may mistakenly believe there was a proportional change