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Placental ion exchange

Fetal capillaries lie in maternal vascular (intervillous) spaces; therefore, they readily exchange substances with maternal blood. Placental exchange happens only through diffusion, bulk flow, active transport (including certain ions) and pinocytosis. In general, drugs with a MW <500 Da easily cross the placenta unless they are highly ionized, and most drugs with MW >1000 Da DON’T cross the placenta. Non-ionized drugs cross more easily than ionized. Fetal pH is also usually less than maternal pH, which can lead to ion trapping and greater drug concentrations in the fetus (H+ ions bind to non-ionized form, trapping drug in fetal circulation). Local anesthetics are weakly basic drugs that are principally bound to alpha-1-acid glycoprotein. Increased protein binding in the mother reduces the amount of local anesthetic that is free and able to diffuse across the placenta. Chloroprocaine has the LEAST placental transfer as it is rapidly eliminated by plasma cholinesterase. Highly protein-bound local anesthetic agents diffuse poorly across the placenta. For example, bupivacaine and ropivacaine are more highly protein bound when compared with lidocaine, therefore lidocaine has higher fetal blood levels. Transfer of Na+ and Cl- ions occurs through simple diffusion. Na+ is also transferred through a Na+/K+ pump at the fetal surface of the placenta. Fetal concentrations of Na- and Cl- are similar to maternal levels. K+ levels are very tightly regulated in the fetus, despite changes in maternal concentrations. Calcium channels are present at the maternal surface of the placenta; these allow ionized calcium to flow in by diffusion. Atropine (MW 289 Da) and scopolamine (MW 303 Da) are both non-polar tertiary amines which penetrate lipid barriers easily and cross the placenta. Glycopyrrolate (MW 398) is similar in molecular weight, but is a highly polar ionized quaternary ammonium structure and does not cross the placenta. Succinylcholine is <500 Da but has a quaternary amine group and non-depolarizers have high molecular weights, which both result in minimal transfer to fetus.