PCL201H1 Lecture Notes - Lecture 7: Pinocytosis, Active Transport, Aquaporin

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14 Sep 2016
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PCL201
Winter 2014
Lecture 7 and 8 Mechanisms of Drug Absorption
1. Review the physicochemical drug properties
2. Examine barriers to drug movement
Epithelial and capillary barriers
Blood-brain and blood-CSF barriers
Placenta, peritoneum, and lung barriers
Functional barriers (transporters)
3. Examine mechanisms of drug absorption
Passive diffusion
Facilitated diffusion
Active transport
Transcytosis (endocytosis and exocytosis)
Passive filtration
Movement through gap junctions
1. Review the physicochemical drug properties
Molecular size
Lipid and water solubility
Extent of ionization
2. Examine barriers to drug movement
Physical or anatomical barriers include cell membranes and tight junctions. Functional barriers
are transport systems that carry the drug out of the cell.
The plasma membrane has an unstirred water layer and glycocalyx.
Capillaries of excretory/secretory organs have fenestrations (pores)
Epithelial and capillary barriers
o Epithelial cells have tight junction, forcing drugs to pass through cells
o Most capillaries have maculae, pores that allow passage of large molecules
Transcytosis may occur
o Other capillaries have fenestrations, transient or long-lasting openings
Molecules >45kDa (i.e. protein-bound) cannot pass the basolateral membrane)
(need some more clarification on the difference between maculae and fenestrations)
Blood-brain and blood-CSF barriers
o Joined by tight junctions almost everywhere in the brain
o Exceptions include: pituitary gland, pineal gland, area postrema (vomit center), median
eminence, choroid plexus
o Many compounds are excluded from the CNS due to the BBB
o CSF has unrestricted flow to brain cells (the epithelial cells lining the ventricles have no occluding
zonulae)
Intrathecal injection into CSF is an effective way to deliver drugs to the brain
Placenta, peritoneum, and lung barriers
o Assume all drugs cross the placenta
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