Routes Of Admin Lec 1 PDB Flashcards
An epithelium with one layer is a _____ epithelium.
Give 3 examples of types of these epithelia and where they can be found in the body…
Simple e.g Squamous epithelium such as Alveoli Columnar epithelium in GI or Nasal cav Cuboidal epithelium not involved in abs
Transcellular pathway goes across or between cells?
Across cells
Between = paracellular
An epithelium with more than one layer is a _____ epithelium. This type of epithelium must be able to withstand large amounts of wear and tear. Where is it found?
Stratified
E.g Stratified squamous epithelium like cornea, skin, mouth
The Paracellular pathway is a minor pathway - which of the following is rate limiting in this path…
Tight junctions
Adherens junctions
Desmosomes
Gap junctions
Tight junctions are membranes of neighbouring cells fused by connections between cell surface proteins, forming a band around the entire cell.
Allows passage of small, hydrophilic molecules generally
Desmosomes are the most common cell junction - what are they?
Fibrous proteins that cross the gap between cells and anchor keratin filaments in the cytoskeletons together
-less of a barrier for molecules to cross
Gap junctions are sits of intracellular information exchange. Do they have hydrophobic or hydrophilic pores?
Hydrophilic pores
Membranes close but not fused
Small molecules (AA,sugars,nucs,vits) pass between neighbouring cells
Adherens junctions connect what filaments in cytoskeletons of neighbouring cells together?
Actin filaments
Is the lipid bilayer a minor or major barrier to drug absorption?
Major - it’s hydrophobic nature prevents passage of most polar and charged (water soluble) molecules
Transcellular abs = major pathway
Passive diffusion is the minor or main pathway of drug absorption?
What must they do to get into the cytoplasm?
MAIN - diluted diffuse into cells down a conc grad. Must partition into lipid bilayer and then out into cytoplasm
Aqueous pores are involved in transcellular absorption and allow transport of what?
Small neutral solutes such as urea and glycerol - drugs are normally too large to be absorbed in this way
Is facilitated diffusion selective?
Yes - carrier mediated trans of drug down conc grad
Endocytosis = minor pathway that can be split into Pinocytosis and phagocytosis
Pinocytosis is what?
Cell drinking that occurs constantly
- small solute or fluid engulfed.
Absorptive or receptor mediated
What is Endocytosis?
Internalisation of plasma mem which engulfs extracellular fluid
Phagocytosis not relevant for soluble drug abs.
What is it and what does it?
Engulfment of particles by monocytes and macrophages
Endosomes may fuse with ______ and contents are then degraded by ______ enzymes. Drugs may escape ______ degradation and released through basolateral membrane in process called transcytosis. E.G ABS OF NGF, EGF, VACCINES (This could be useful in absorption of higher molecular weight drugs - proteins)
Lysosomes, lysosomal, lysosomal
Tight junctions allow the passage of what?
Allows passage of small, hydrophilic molecules generally
What type of molecules do gap junctions allow to pass directly between neighbouring cells?
- Small molecules
- e.g amino acids, sugars, nucleotides and vitamins
- ALSO enables direct cell to cell electrical conductance
Out of the following, which are less of a barrier to molecules wishing to pass?
Desmosomes
Adherents junctions
Tight junctions
Gap junctions
- Adherens junctions
- Gap junctions
- Desmosomes
REMEMBER: Tight junctions are membranes of neighbouring cells fused by intimate connections between cell surface proteins, forming a band around the entire cell and are RATE LIMITING for PARACELLULAR PATHWAY
Drugs can be absorbed by transcellular absorption by active transport. What is active transport?
- Selective, carrier mediated transport of a drug down or against a concentration gradient.
- It requires energy import (ATP)
Passive diffusion is the main pathway of drug absorption.
The ___ a system from equilibrium, the ____ it moves towards equilibrium
This is the reason behind passive diffusion
- The FURTHER the system from equilibrium, the FASTER it moves towards equilibrium
What is the equation for Fick’s first law of diffusion?
J (flux) = A * D * K * change in C / h
A = Area D = Diffusivity K = Partition coefficient Change in C = Conc grad across membrane h = membrane thickness
What drug properties are proportional to flux?
- Change in concentration across membrane
- Partition coefficient
What drug AND membrane property is proportional to flux?
- Diffusivity
Drugs administered orally must cross the __ __ epithelium to be absorbed and enter the systemic circulation.
GI tract epithelium
