Lecture 7 Absorption Barriers

13 views3 pages
11 Apr 2012

For unlimited access to Class Notes, a Class+ subscription is required.

Lecture 7 PCL201 Factors Affection Drug Absorption
Physical properties of drugs
1. Lipid Solubility
a. Partition coefficient (polarity)
2. Extent of ionization (ionization decreases change of passing though membrane).
Charged or uncharged at specific pH and pKa
3. Molecular size/shape
a. Avogadro’s number 1.6 x 1024 Da
b. Most drugs (nonpeptides) are fairly small
c. Peptides 1000-2000Da
d. Small proteins 6000 Da and others 1000s of kDa
Physical or Anatomical factors: Drugs must cross through multiple membranes
Transport or functional factors: drugs must overcome these barriers in order to be effective.
Active transport via efflux pumps.
Review: The Cell
Single cel: Plasma membrane and nuclear membrane, phospholipids, proteins,
unstirred water layer, glycosylation charges associated
Layers of Cells
Drugs must diffuse across membrane including basolateral membrane
1. Epithelial membranes: tight junctions/occluding zonulae
a. Blocks movement of chemicals between cells (paracellular transport)
b. Drug must be extremely lipophillic to cross tight junctions
c. Prevents intercellular communications
d. Mechanism to keep molecules out
e. Intercellular spaces completely blocked
f. Drugs do not pass between therefore drugs must permeate cells
g. Transcellular transport: endocytosis of chemical in vesiclediffusion
sometimes receptor mediated or nonspecific (pinocytosis)
2. Capillaries with maculae (noncontinuous junction; allows for transport)
a. Macular junctions are not continuous
b. Intercellular spaces allow transport
c. Drugs ~500Da ~100kDa may move through maculae
3. Capillaries with fenestrations (windows always open)
a. Slits allow movement of chemical interstitial fluid
b. Excretory or secretory organs
c. Long lasting pores
d. Permits non-protein bound drugs to cross (45-69kDa)
e. Keeps out large molecules (will be too large to cross basolateral membrane,
glucose normally kept out)
4. Occluded Capillaries: BBB
a. Keeps chemicals out of CNS
b. No intercellular spaces: Occluding zonulae exceptions are relatively
permeable to drugs:
Unlock document

This preview shows page 1 of the document.
Unlock all 3 pages and 3 million more documents.

Already have an account? Log in

Get access

$10 USD/m
Billed $120 USD annually
Homework Help
Class Notes
Textbook Notes
40 Verified Answers
Study Guides
1 Booster Class
$8 USD/m
Billed $96 USD annually
Homework Help
Class Notes
Textbook Notes
30 Verified Answers
Study Guides
1 Booster Class