Eab Summary of Pharmacokinetic Changes Process Changes Absorption √个 00 Distribution 个 Metabolism 个 Elimination o000oc0= Consult literature Therapeutic drug monitoring Cautions Inter-individual variation Small studies Changes in each trimester of pregnancy Drug-drug interactions Therapeutic ranges are usually not validated for pregnant individuals KENTUCKY College of Pharmacy
Summary of Pharmacokinetic Changes Process Changes Absorption ↓↑ Distribution ↑ Metabolism ↑↓ Elimination ↑ • Consult literature • Therapeutic drug monitoring • Cautions • Inter-individual variation • Small studies • Changes in each trimester of pregnancy • Drug-drug interactions • Therapeutic ranges are usually not validated for pregnant individuals
Eab Drug Use in Pregnancy Teratogenesis: dysgenesis of fetal organs as evidenced either structurally or functionally O.:Congenital malformations: structural abnormalities of prenatal origin that are present at birth and seriously interfere with viability or physical well being Congenital anomalies: malformations and those o000oc0= defects related to change in function Spina Binda (Open Defect] KENTUCKY College of Pharmacy
Drug Use in Pregnancy • Teratogenesis: dysgenesis of fetal organs as evidenced either structurally or functionally • Congenital malformations: structural abnormalities of prenatal origin that are present at birth and seriously interfere with viability or physical well being • Congenital anomalies: malformations and those defects related to change in function
Eab Pregnancy outcomes 3-6%of pregnancies have malformations or 00 anomalies 1% 25% Medications o000oc0= ■ Genetic ■ Materna conditions /infections 64% 10%口 Unknown KENTUCKY College of pha
Pregnancy Outcomes • 3-6% of pregnancies have malformations or anomalies 1% 25% 10% 64% Medications Genetic Maternal conditions/infections Unknown
Placental transfer 6· Passive diffusion oE: Molecular weight wastes and carbon dioxide 00 delivered from the baby MW= 250-500 k- easily cross Oxygen, nutrients, and ormones delivered to the baby ADAM MW= 500-1000 kDa-cross more slowly o000oc0= MW=>1000 kDa- generally don't cross 9家:· Protein binding Maternal albumin decreases Fetal albumin increases Protein-bound medicines may have higher concentrations in the fetus KENTUCKY Yaffe SJ. Drugs in pregnancy and lactation. 2005; 7: xii-xix College of Pharmacy
Placental Transfer • Passive diffusion • Molecular weight – MW= 250-500 kDa – easily cross – MW= 500-1000 kDa – cross more slowly – MW = >1000 kDa – generally don’t cross • Protein binding – Maternal albumin decreases – Fetal albumin increases – Protein-bound medicines may have higher concentrations in the fetus Yaffe SJ. Drugs in pregnancy and lactation. 2005;7: xiii-xix
Eab Placental transfer ° Lipophilicity 2· Ionization Fetal ph is lower than maternal ph Weak bases cross placenta easier o000oc0= lonization occurs and then molecule cant return to maternal circulation KENTUCKY Yaffe SJ. Drugs in pregnancy and lactation. 2005; 7: xii-xix College of Pharmacy
Placental Transfer • Lipophilicity • Ionization – Fetal pH is lower than maternal pH – Weak bases cross placenta easier – Ionization occurs and then molecule can’t return to maternal circulation Yaffe SJ. Drugs in pregnancy and lactation. 2005;7: xiii-xix