Biological Barriers Flashcards
Hepatic Portal Vein Outline
All systemic blood vessels drain into hepatic portal vein for detoxification
Organ Usually targeted for absorption
Small intestines
Simple Def
Single layer of cells (absorption)
Stratified Def
Multiple layers of cells (protection)
Simple Squamous Def
Single, flattened, interlocking cells. Blood vessel lining and aveoli. Excellent permiability
Simple Columnar Def
Single, rectangular cells. Stomach, small intestine and upper respitory. Very good permiability
Stratified Squamous, non-keratinised
Multiple layers, flattened, nucleated cells. Buccal, sublingual, esophagus, vagina and cornea. Intermediate to very good permiability
Stratified Squamous Keratinised
Multi-layer, flattened, non-nucleated cells. Gums and skin. Poor permiability
Skin/Muscle/Adipose/Lung/ Intestinal Capillary Outline
continuous (don’t really have pores) cells with tight junctions ), 5nm in diameter
Hepatic Capillary Outline
Sinusoidal (large canals in tissue), open fenestrate (large gaps). 180nm wide
Connective Tissue Outline
Fenestrated (pores in vessels). 6-15 nm
Retinal/ Spinal Chord/ Enteric NS
Continuos, tight junctions (tightest). <1nm
Which are more permeable endothelia or epithelia
endothelia. Blood vessel walls begin with epithelial (extrinsic, less gaps) and move to endothelial (intrinsic, more gaps) cells. Permiability increases as you move away from lumen
Extrinsic Barrier of Intestinal Epithelium Outline
Mucus (gel hydrocarbon) produced by goblet cells. Traps gel of opposite charge and viscosity slows particle movement. Requires molecules to be lipophilic
What reduces mucus layers
Surfactant. Can result in opportunistic infection. Evaluate
Keratinised Def
Dense layer of protein. Reduces permiability
What regions of body have leakiest vessels
further away from skin the leakier the vessels. this prevents contamination of blood
Continuous Def
No gaps between cells. Low permiability
Fenestrated Def
Moderate gaps between cells. Moderate permiability
Sinusoidal Def
Large canal gaps between cells. Best permiability
Ways for substances to permiate cell barriers
Paracellular and Transcellular. Passive, active, endocytosis and carrier mediated. Moves from apical to basolateral side
Paracellular Movement Def
Diffusion of substances between gaps in cells
Transcellular Movement Def
Passive or active transport. Substances move through cell independently or with the help of proteins (efflux carriers and unflux carriers)
Where can drugs act in relation to cells
They might act outside cell (hydrophilic) or inside cells (lipophilic)
Better Transcellular diffusion is associated with
Higher lipophilicity, lower molecular weight (particle size) and no charge
Association between dproperties of barrier (k) and diffusion coefficent
The higher the diffusion constant = the higher the permiability of barrier
Relationship between properties of membrane and surface area exposed
More surface area = higher permiability of barrier
4 types of endocytosis
phagocytosis, receptor mediated cytosis, phingocytosis (vesicles engulf small particles from interstitial fluid)
Rate of dissolution association with dissolution rate constant (k)
Faster dissolution = higher constant
Rate of dissolution association with surface area
Higher surface area = faster dissolution rate
Relationship between Staurated solubility of drug (Cs) and dissolution rate
Higher saturated solubility = faster dissolution
Relationhip between conc of drug already dissolved in solvent at given time (C) and rate of solution
Higher amount of drug dissolved = slower dissolution
Molecular composition of epethilial barrier
Polar head (choline/phosphate/glycerol) and 2 non-polar tail (fatty acids)
Dissolution rate constant association with Diffusivity
Higher dissusivity = higher dissolution rate constant
association between dissolution rate constant and thickness of surrounding liquid (h)
Thicker liquid = smaller constant
Association between dissolution rate constant and volume of solvent
The higher the solvent volume = the lower the constant
Barriers and Log P
Different barriers have different log Ps. Eg rectal 0-5 and cornea 1-2
Drug Transporters Outline
Can help facilitate active and passive transport. Apical and basolateral membranes have different transporters (ensure substances move in 1 direction). Transporters can be proteins on membrane and vesicles. Selective for what substrate they’re using
Uniports Def
Carriers move substrate in 1 direction
Symport Def
Carries 2 substances in 1 direction
Antiport Def
Carries 2 substances in opposite directions
Pept 1 Transporter Outline
Natural substrate: peptide. Drugs: ace inhibitor, lactam antibiotics and bestastin
DMT-1 Outline
Substrate: Fe^2+ (heme iron)
CNT 1 Transporter Outline
Natural substrate: amino acids. Drugs: zidovuldine and gemcitabine
How does Fe3+ cross membrane and stay inside cell
Reduced to Fe2+. Taken up by DMT1
Pinocytosis Def
Engulfment of molecules in extracellular fluid by membrane vesicles. Cells involves internalization despite metabolism needs of cell. Fat soulble vitamine (A, D, E and K)
Receptor mediated endocytosis Outline
Receptors are on cell surface, receptors break off from membranes to form coated vesicles. Confirmational changes in membrane initiates process. Coating is lost and delivered to cell compartments. Receptors return to membrane. Eg insulin
Tight Junction Def
Multiprotein complexes adjoin adjacent cells forming seals. Maintains cell polarity and barrier functions. Modulated by chemical signalling and/or exogenous ligands
4 Protein Classes
Tight Junction (eg claudin), Tight junction associated proteins (eg ZO-1), scaffolding proteins and signalling proteins
Relationship between perfusion, flow rate and distribution
High perfusion = high flow = fast distribution times = greater extent of absorption
Efflux Pumps Def
Membrane transport proteins. Actively pump drugs out of cell in direction they’re absorbed, against conc gradient. Maintains low conc in cells
Multidrug ressistance Transporters Outline
Pump structurally diverse drugs out of cell in ATP dependent fashion. Mainly cationic and lipophilic drugs (but substartes of all types). Expression increases at villi tips
