Biological Barriers

Question 1

Hepatic Portal Vein Outline

Answer 1

All systemic blood vessels drain into hepatic portal vein for detoxification

Question 2

Organ Usually targeted for absorption

Answer 2

Small intestines

Question 3

Simple Def

Answer 3

Single layer of cells (absorption)

Question 4

Stratified Def

Answer 4

Multiple layers of cells (protection)

Question 5

Simple Squamous Def

Answer 5

Single, flattened, interlocking cells. Blood vessel lining and aveoli. Excellent permiability

Question 6

Simple Columnar Def

Answer 6

Single, rectangular cells. Stomach, small intestine and upper respitory. Very good permiability

Question 7

Stratified Squamous, non-keratinised

Answer 7

Multiple layers, flattened, nucleated cells. Buccal, sublingual, esophagus, vagina and cornea. Intermediate to very good permiability

Question 8

Stratified Squamous Keratinised

Answer 8

Multi-layer, flattened, non-nucleated cells. Gums and skin. Poor permiability

Question 9

Skin/Muscle/Adipose/Lung/ Intestinal Capillary Outline

Answer 9

continuous (don’t really have pores) cells with tight junctions ), 5nm in diameter

Question 10

Hepatic Capillary Outline

Answer 10

Sinusoidal (large canals in tissue), open fenestrate (large gaps). 180nm wide

Question 11

Connective Tissue Outline

Answer 11

Fenestrated (pores in vessels). 6-15 nm

Question 12

Retinal/ Spinal Chord/ Enteric NS

Answer 12

Continuos, tight junctions (tightest). <1nm

Question 13

Which are more permeable endothelia or epithelia

Answer 13

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

Question 14

Extrinsic Barrier of Intestinal Epithelium Outline

Answer 14

Mucus (gel hydrocarbon) produced by goblet cells. Traps gel of opposite charge and viscosity slows particle movement. Requires molecules to be lipophilic

Question 15

What reduces mucus layers

Answer 15

Surfactant. Can result in opportunistic infection. Evaluate

Question 16

Keratinised Def

Answer 16

Dense layer of protein. Reduces permiability

Question 17

What regions of body have leakiest vessels

Answer 17

further away from skin the leakier the vessels. this prevents contamination of blood

Question 18

Continuous Def

Answer 18

No gaps between cells. Low permiability

Question 19

Fenestrated Def

Answer 19

Moderate gaps between cells. Moderate permiability

Question 20

Sinusoidal Def

Answer 20

Large canal gaps between cells. Best permiability

Question 21

Ways for substances to permiate cell barriers

Answer 21

Paracellular and Transcellular. Passive, active, endocytosis and carrier mediated. Moves from apical to basolateral side

Question 22

Paracellular Movement Def

Answer 22

Diffusion of substances between gaps in cells

Question 23

Transcellular Movement Def

Answer 23

Passive or active transport. Substances move through cell independently or with the help of proteins (efflux carriers and unflux carriers)

Question 24

Where can drugs act in relation to cells

Answer 24

They might act outside cell (hydrophilic) or inside cells (lipophilic)

Question 25

Better Transcellular diffusion is associated with

Answer 25

Higher lipophilicity, lower molecular weight (particle size) and no charge

Question 26

Association between dproperties of barrier (k) and diffusion coefficent

Answer 26

The higher the diffusion constant = the higher the permiability of barrier

Question 27

Relationship between properties of membrane and surface area exposed

Answer 27

More surface area = higher permiability of barrier

Question 28

4 types of endocytosis

Answer 28

phagocytosis, receptor mediated cytosis, phingocytosis (vesicles engulf small particles from interstitial fluid)

Question 29

Rate of dissolution association with dissolution rate constant (k)

Answer 29

Faster dissolution = higher constant

Question 30

Rate of dissolution association with surface area

Answer 30

Higher surface area = faster dissolution rate

Question 31

Relationship between Staurated solubility of drug (Cs) and dissolution rate

Answer 31

Higher saturated solubility = faster dissolution

Question 32

Relationhip between conc of drug already dissolved in solvent at given time (C) and rate of solution

Answer 32

Higher amount of drug dissolved = slower dissolution

Question 33

Molecular composition of epethilial barrier

Answer 33

Polar head (choline/phosphate/glycerol) and 2 non-polar tail (fatty acids)

Question 34

Dissolution rate constant association with Diffusivity

Answer 34

Higher dissusivity = higher dissolution rate constant

Question 35

association between dissolution rate constant and thickness of surrounding liquid (h)

Answer 35

Thicker liquid = smaller constant

Question 36

Association between dissolution rate constant and volume of solvent

Answer 36

The higher the solvent volume = the lower the constant

Question 37

Barriers and Log P

Answer 37

Different barriers have different log Ps. Eg rectal 0-5 and cornea 1-2

Question 38

Drug Transporters Outline

Answer 38

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

Question 39

Uniports Def

Answer 39

Carriers move substrate in 1 direction

Question 40

Symport Def

Answer 40

Carries 2 substances in 1 direction

Question 41

Antiport Def

Answer 41

Carries 2 substances in opposite directions

Question 42

Pept 1 Transporter Outline

Answer 42

Natural substrate: peptide. Drugs: ace inhibitor, lactam antibiotics and bestastin

Question 43

DMT-1 Outline

Answer 43

Substrate: Fe^2+ (heme iron)

Question 44

CNT 1 Transporter Outline

Answer 44

Natural substrate: amino acids. Drugs: zidovuldine and gemcitabine

Question 45

How does Fe3+ cross membrane and stay inside cell

Answer 45

Reduced to Fe2+. Taken up by DMT1

Question 46

Pinocytosis Def

Answer 46

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)

Question 47

Receptor mediated endocytosis Outline

Answer 47

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

Question 48

Tight Junction Def

Answer 48

Multiprotein complexes adjoin adjacent cells forming seals. Maintains cell polarity and barrier functions. Modulated by chemical signalling and/or exogenous ligands

Question 49

4 Protein Classes

Answer 49

Tight Junction (eg claudin), Tight junction associated proteins (eg ZO-1), scaffolding proteins and signalling proteins

Question 50

Relationship between perfusion, flow rate and distribution

Answer 50

High perfusion = high flow = fast distribution times = greater extent of absorption

Question 51

Efflux Pumps Def

Answer 51

Membrane transport proteins. Actively pump drugs out of cell in direction they're absorbed, against conc gradient. Maintains low conc in cells

Question 52

Multidrug ressistance Transporters Outline

Answer 52

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