PCL201H1 Lecture Notes - Lecture 4: Placenta, Uric Acid, Amphiphile

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11 Jan 2018

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Hydrophilic require energy
Ionization/law of mass action
Propranolol (pKa of 9): more charged in stomach
When unionized move out, more become unionized
Physical: cell membranes (amphipathic, proteins, unstirred water layer), intercellular links
Must pass to be absorbed, distribute, reach site, be eliminated
GI tract — Endothelium —Lungs, cell membranes — Kidney
Partition coefficient: Higher is more absorbed but cut off phenomenon
Adjoining epithelial and endothelial cells form a barrier
Epithelial: tight junctions/occluding zonulae, must pass THROUGH cells
Maculae: most, intercellular space, pinocytotic vesicles, fenestrations, up to 10 kDa
can pass
Fenestrations: excretory and secretory organs, long lasting, 45 kDa can pass
Occluded: at BBB, few fenestrae, exceptions at endocrine organs (area postrema,
median eminence, choroid plexus)
CSF Barrier: epithelial cells of choroid plexus (connected by zonulae)
Can pass by diffusion, ion channels, facilitated transport
CSF-Brain does not zonulae
Intrathecal injections into CSF deliver drugs to brain (if unfavourable)
Ie. histamine drugs Loratadine made not to cross BBB so no drowsy effects
Placenta: all drugs cross, limited flow, physiochemical properties determine ability to cross,
Peritoneum: Macular junctions to blood, permeate between cells
Lungs: 1 cell thick, zonulae, fenestrations do occur, all solubility readily cross
Functional barriers: transport systems
Passive (downhill)
Facilitated (carrier)
Active (uphill)
Transporters in enterocytes, hepatocytes (sinusoidal, canalicular), renal cells, BBB (abluminal-
brain, luminal-blood)
Solute Carrier Transporters
52 families
SLC21/22 broad range
SLC6/12 important
Organic anion (OAT)
Secondary active and facilitative
Penicillin, furosemide, cAMP, cGMP, ketoglutarate, urate (gout)
Organic cation (OCT)
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