Podcast
Questions and Answers
What is the primary reason why monitoring is essential during pregnancy when using LMWH or UFH?
What is the primary reason why monitoring is essential during pregnancy when using LMWH or UFH?
What is the effect of increased plasma volume during pregnancy on LMWH blood concentrations?
What is the effect of increased plasma volume during pregnancy on LMWH blood concentrations?
Why is UFH preferred over LMWH during labor and delivery?
Why is UFH preferred over LMWH during labor and delivery?
What is the mechanism behind the increased renal clearance of amoxicillin during pregnancy?
What is the mechanism behind the increased renal clearance of amoxicillin during pregnancy?
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What is the primary source of progesterone production during the term of pregnancy?
What is the primary source of progesterone production during the term of pregnancy?
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What is the primary reason why penicillins and cephalosporins are dosed above the necessary MIC during pregnancy?
What is the primary reason why penicillins and cephalosporins are dosed above the necessary MIC during pregnancy?
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Which of the following is a common disorder during pregnancy?
Which of the following is a common disorder during pregnancy?
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What is the incidence of Deep Vein Thrombosis (DVT) during pregnancy?
What is the incidence of Deep Vein Thrombosis (DVT) during pregnancy?
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What is the effect of increased renal blood flow and GFR during pregnancy on LMWH clearance?
What is the effect of increased renal blood flow and GFR during pregnancy on LMWH clearance?
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Why may higher doses of LMWH be needed during pregnancy?
Why may higher doses of LMWH be needed during pregnancy?
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Which of the following is a physiological response during pregnancy that contributes to DVT?
Which of the following is a physiological response during pregnancy that contributes to DVT?
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What is the concentration of progesterone during the luteal phase of pregnancy?
What is the concentration of progesterone during the luteal phase of pregnancy?
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When can LMWH be restarted after delivery?
When can LMWH be restarted after delivery?
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Which hormone levels increase during pregnancy?
Which hormone levels increase during pregnancy?
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What is the primary mechanism by which pregnancy affects the pharmacokinetics of different drugs?
What is the primary mechanism by which pregnancy affects the pharmacokinetics of different drugs?
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Which of the following is NOT a common disorder during pregnancy?
Which of the following is NOT a common disorder during pregnancy?
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What is the primary initial therapy for fetal tachyarrythmias?
What is the primary initial therapy for fetal tachyarrythmias?
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Why is it difficult to achieve therapeutic levels of digoxin in the fetus?
Why is it difficult to achieve therapeutic levels of digoxin in the fetus?
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What is the recommended dose of cefazolin for caesarean delivery in pregnancy?
What is the recommended dose of cefazolin for caesarean delivery in pregnancy?
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What happens to the clearance of lamotrigine during pregnancy?
What happens to the clearance of lamotrigine during pregnancy?
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What is the effect of pregnancy on albumin concentrations?
What is the effect of pregnancy on albumin concentrations?
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What should be monitored for drugs with a narrow therapeutic index that are highly protein bound during pregnancy?
What should be monitored for drugs with a narrow therapeutic index that are highly protein bound during pregnancy?
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Why is prescribing at the upper dosing range and shorter dosing frequency recommended in pregnancy?
Why is prescribing at the upper dosing range and shorter dosing frequency recommended in pregnancy?
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What is the effect of birth control pills on lamotrigine levels?
What is the effect of birth control pills on lamotrigine levels?
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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
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Description
Quiz about the use of cephalosporins in pregnancy, including dosage and clearance rates. Focuses on cefazolin prophylaxis for Caesarean delivery.
