Drug Absorption

Question 1

4 types of junctions that facilitate paracellular absorption

Answer 1

1. Tight junction
   Neighbouring cell membranes fused by cell surface proteins. RATE LIMITING step. Allows passage of small hydrophilic mol
2. Adherens junctions: connection of ACTIN filaments in cyctoskeletons of neighbouring cells
3. Desmosomes: MOST COMMON junction. Fibrous proteins cross the gap bw cells and anchor keratin in cytosk together.
4. Gap junctions: aqueous pores. intercellular, hydrophilic pores. Allow passage of AA sugars also cell to cell electrical conductance.

Question 2

4 common and 1 not so common type of TRANScellular pathways

Answer 2

Passive diffusion -MAIN
Facilitated diffusion -selective
Aqueous pores -continuous. (Some allow small neutral solute: urea, glycerol to pass)
Active transport -selective, E. e.g. L-DOPA
Not common :Endocytosis

Question 3

Define endocytosus

Answer 3

Internalisation of the plasma membrane which engulfs extra cellular fluid.

Question 4

What is pinocytosis

Answer 4

Cell drinking
Small solutes or fluid engulfed.
Occurs constantly

Question 5

An example of substance which absorbed by cells via endocytosis

Answer 5

Nerve GF/ epidermal GF

Sabin polio vaccine

Question 6

What is Ph partition hypothesis

Answer 6

Drug accumulates on the side of the mem where pH ionisation

Question 7

Limitation of ph partition hypothesis

Answer 7

Doesn’t take into account of

Type of epithelium
SA of absorption site
IONISED drug will be absorbed to a small extent
ACTIVE TRANSPORT of drug
RESIDENT time of drug delivery sites
Mass transfer of fluid
CHARGED drug may form ION PAIRS with oppositely charged spp.- ideal for absorption!

Question 8

Which form (ion/unionised) of WA/WB drug is optimal for mem transport? Which reduce membrane transport?

Answer 8

Unionised form is lipophilic - better mem transport

Ionised form- hydrophilic - reduced

Question 9

Lipinskis rule of 5 for oral dosage

Answer 9

MW<500
Donor<5
Acceptor<10
Log P<5

Question 10

What factors can affect drug’s lipophilicity–>partition coefficient

Answer 10

Drug structure (benzene ring?)
Ph/ ionisation (unionised free acid?)
H bond (not many?)

Question 11

Advantages of buccal

Beampe

Answer 11

Avoid 1st pass E
Access and easy 
Relatively LARGE SA
Rich BLOOD supply
Low metabolism 
Prolonged contact

Question 12

Disad of buccal

Answer 12

High mw drugs must be potent
Adverse rxn
Saliva n mucus
Acceptance 
Cost

Question 13

Ad of rectal. Soaped

Answer 13

Safe painless 
Avoid DEGRADATION in git 
Avoid 1st psss
Range of dosages
EXTENDED adsorption 
When oral route is difficult
Protein delivery

Question 14

Disad of rectal

Answer 14

Acceptability 
Upwards move. Leads to 1st passE
Insertion tissue 
Slow ab. Compare to oral IV 
Leakage