Pregnancy Pharm

Question 1

How does pregnancy affect drug administration?

Answer 1

• Progesterone slows gastric emptying and inc gut transit time
• Nausea and vomiting in preg (may vomit oral meds)
• May take antacids for nausea –> dec gastric acidity

Question 2

How does pregnancy affect drug distribution?

Answer 2

• Inc TBW and plasma - dilution
• Feto-placental compartment available for distribution
• Dec albumin so higher free levels of normally protein bound drugs (less holding of drug in plasma bound to proteins)
• Changes in regional blood flow - including kidneys so inc excretion of water-soluble drugs by kidneys); minimal dec flow to liver

Question 3

How does pregnancy affect drug metabolism?

Answer 3

• Metabolic enzyme affected by pregnancy (inc or dec in activity of CYPs can lead to need for inc or dec doses)
• Placental and fetal hepatic enzymes can affect drug metabolism
• Estrogen and progesterone also affect enzymes

Question 4

How does pregnancy affect drug excretion?

Answer 4

Inc renal blood flow so any renally excreted drug (water-soluble, polar) has inc elimination (ex - lithium)

Question 5

3 ways to protect fetus from placental transport of drugs?

Answer 5

• Placental transporters on apical membrane of syncytiotrophoblasts
• Efflux transport pumps (inc by estrogen and progesterone)
• Placenta has own drug metabolizing enzymes

Question 6

Old Classification System

Answer 6

• A - adequate, well-controlled studies done in pregnant women and have shown no risk of fetal abnormalities in any trimester (only 2% of drugs)
• B - animal studies w/ no evidence of harm to fetus but no studies in pregnant women OR animal studies have had adverse effects but not seen in pregnant women studies
• C - animal studies w/ adverse effect; no studies in pregnant women OR no studies in animals or pregnant women
• D - demonstrated risk to fetus in pregnant women studies
• E - pos evidence of fetal abnormalities in animals or pregnant women

Question 7

13 Known Teratogens

Answer 7

• Androgens
• ACE inhibitors - renal damage
• Alkylating agents - anomalies and absent digits
• Aminoglycosides - CN VIII
• Tetracyclines - discolored teeth
• Lithium -Ebstein heart anomaly
• Warfarin (use heparin) - eye and bone deformities; hemorrhage; abortion
• Thalidomide - limbs
• Folate Antagonists - neural tube defects
• Iodine - hypothyroid
• Anti-convulsants - carbamazepine, valproic acid (blocks
  folate absorption), phenytoin
• Isotretinoin (acutane) - abortion, CNS, cardiac
• Diethylstilbestrol (DES) - Mullerian abnormalities and clear cell adenocarcinoma

Question 8

Known Fetal Toxins

Answer 8

• NSAIDs - reversible oligohydraminos
• Sulfonamides
• Paxil (SSRI)
• Beta blockers - growth delay and bradycardia
• Sulfonurea
• Ketamine (anesthesia)
• Narcotics
• Sedatives/ hypnotics