24 Questions
What is the primary reason why monitoring is essential during pregnancy when using LMWH or UFH?
To ensure the therapeutic index is not exceeded
What is the effect of increased plasma volume during pregnancy on LMWH blood concentrations?
It decreases the anticoagulant effects of LMWH
Why is UFH preferred over LMWH during labor and delivery?
UFH is more easily reversed with protamine sulfate
What is the mechanism behind the increased renal clearance of amoxicillin during pregnancy?
Increased GFR and decreased reabsorption caused by progesterone
What is the primary source of progesterone production during the term of pregnancy?
Placenta
What is the primary reason why penicillins and cephalosporins are dosed above the necessary MIC during pregnancy?
To ensure adequate treatment of maternal infections
Which of the following is a common disorder during pregnancy?
Vomiting
What is the incidence of Deep Vein Thrombosis (DVT) during pregnancy?
0.5 to 7 per 1,000 pregnancies
What is the effect of increased renal blood flow and GFR during pregnancy on LMWH clearance?
It increases the clearance of LMWH
Why may higher doses of LMWH be needed during pregnancy?
To compensate for increased plasma volume
Which of the following is a physiological response during pregnancy that contributes to DVT?
Pregnancy-induced hypercoagulability
What is the concentration of progesterone during the luteal phase of pregnancy?
30-40 ng/ml
When can LMWH be restarted after delivery?
12-24 hours after delivery
Which hormone levels increase during pregnancy?
Estradiol and progesterone
What is the primary mechanism by which pregnancy affects the pharmacokinetics of different drugs?
Changes in drug absorption and distribution
Which of the following is NOT a common disorder during pregnancy?
Fetal tachyarrythmia
What is the primary initial therapy for fetal tachyarrythmias?
Digoxin
Why is it difficult to achieve therapeutic levels of digoxin in the fetus?
P-glycoprotein is expressed in the placenta
What is the recommended dose of cefazolin for caesarean delivery in pregnancy?
2 gm at 1 h prior to surgery
What happens to the clearance of lamotrigine during pregnancy?
It increases by 240%
What is the effect of pregnancy on albumin concentrations?
It decreases to 3.6 gm/dl
What should be monitored for drugs with a narrow therapeutic index that are highly protein bound during pregnancy?
Free drug concentration
Why is prescribing at the upper dosing range and shorter dosing frequency recommended in pregnancy?
To ensure free drug concentration above the MIC for 60-70% of the dosing interval
What is the effect of birth control pills on lamotrigine levels?
They similarly affect lamotrigine levels as pregnancy
Study Notes
Cephalosporins in Pregnancy
- Cefazolin clearance increases by 74% in pregnancy, making it difficult to maintain free cefazolin concentrations above 8 mg/L (MIC for susceptible Gram-positive bacteria) when 1 hour prior to surgery.
- Recommendation: Cefazolin 2 gm at 1 hour prior to surgery.
Digoxin in Pregnancy
- Fetal tachyarrythmias occur in approximately 0.5% of all pregnancies.
- If untreated, it can lead to fetal cardiac failure.
- Digoxin is the primary initial therapy, but it is difficult to achieve therapeutic levels in the fetus (fetal levels are very low/sub-therapeutic) due to P-glycoprotein (Pgp) expression in the placenta, which inhibits its penetration into the fetus.
- Direct injection of digoxin intramuscularly into the fetal thigh (increased fetal risk) or addition of a second anti-arrhythmic drug (flecainide, sotalol, amiodarone) can help overcome the problem.
Plasma Proteins in Pregnancy
- Mean albumin concentrations:
- 2nd trimester: 3.6 gm/dl
- Nonpregnant: 4.2 gm/dl
- Drugs with narrow therapeutic index that are highly protein bound: monitor free fraction, not total drug.
Pregnancy and Drug Metabolism
- Lamotrigine (LTG) levels decrease as pregnancy progresses, suggesting enhanced clearance of LTG during pregnancy.
- Clearance (CL) increases by 240% and returns to pre-pregnancy level by 3 weeks postpartum with a mean increase in dose of 250% to maintain plasma LTG levels.
- Lamotrigine levels are similarly affected by birth control pills (COC).
Changes in LMWH PK
- Normally, the Vd of LMWHs is approximately plasma volume.
- Normally, LMWHs are cleared by hepatic desulfation and depolymerization + renal clearance.
- In pregnancy:
- There is an increase in plasma volume during pregnancy (~ 1200 - 1300 mL above the non-pregnant state, 40%).
- Renal blood flow and GFR increase in pregnancy.
- Based on the increase in Vd and increase in renal clearance, LMWH blood concentrations and their anticoagulant effects are expected to decrease.
- Normal dose is 100 IU/Kg bid, but doses up to 140 IU/Kg may be needed during pregnancy.
Intrapartum Management
- In anticipation of labor (≥36 weeks), change to UFH.
- LMWHs have longer half-lives than UFH, increasing the risk of bleeding with epidural and caesarean section.
- Anticoagulant effects of UFH are more easily reversed with protamine sulfate.
- UFH can be stopped 3-6 hours prior to caesarean or epidural.
- Restart LMWHs 12-24 hours after delivery.
- Anticipate the need to decrease dose as renal clearance normalizes.
Renal Clearance of Amoxicillin
- The increase in amoxicillin renal clearance is due to:
- Increased GFR
- Decreased reabsorption caused by inhibition of PEPT1 transcription by progesterone
Quiz about the use of cephalosporins in pregnancy, including dosage and clearance rates. Focuses on cefazolin prophylaxis for Caesarean delivery.
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