Pharmacology and the Skin

Question 1

What are the main 3 routes of drug administration via the skin?

Answer 1

topical - mainly for local effects but also can treat underlying tissues
transdermal
Subcutenous/ depot - for systemic effects - goes across the whole body

Question 2

What are other epithelial drug routes

Answer 2

airways 
bladder 
conjunctival sac
nasal mucosa 
rectum 
vagina

Question 3

Typical topical drugs

Answer 3

topical non-steroidal anti-inflammatory drugs (NSAIDs)

Question 4

How do transdermal drugs work?

Answer 4

Insert a small needle
drug is delivered to the adipose layer
makes a reservoir of drug which can be slowly absorbed from the adipose tissue
to the capillaries circulation and then through the whole body

Question 5

What layer of the epidermis is important for drug delivery?

Answer 5

Stratum corneum

Question 6

What is a requirement to shed corneocytes from the skin?

Answer 6

Breakdown of corneodesmosomes

Question 7

What is the transcellular route

Answer 7

the movement into one cell and then the next until you reach the stratum corneum

Question 8

What is the intracellular route?

Answer 8

Do not move through the cell, squeeze in between them

Question 9

What is a limitation of the intracellular route?

Answer 9

Only small drugs and very hydrophillic drugs can move through this route

Question 10

How does the topical route of administration occur?

Answer 10

Direct application onto the skin

Question 11

What vehicles are used in topical drug administration?

Answer 11

(Oily -> Watery order)

Ointments; creams; gels; pastes; powders

Question 12

What is the choice of vehicle determined by?

Answer 12

1) Physicochemical properties of the drug

2) The chemical condition

Question 13

How to measure the rate of absorption of a drug

Answer 13

J = (DKm/L)Cv

J = Flux 
D = Diffusion Coefficient 
Km = The partition coefficient 
L = Length of the diffusion pathway 
Cv = The concentration of drug in the vehicle

Question 14

What is the role of the vehicle?

Answer 14

The vehicle can profoundly influence the rate and extent of absorption of a topically applied drug

Question 15

What important factors are there in relation to a vehicle?

Answer 15

• Solubility of the drug in the Vehicle

- Maximizing the partition of a drug from a vehicle in relation to the stratum corneum

Question 16

How do you measure the Maximizing the partition of a drug from a vehicle in relation to the stratum corneum (Km)

Answer 16

Km = Csc/Cv

Cv - solubility of a drug in a vehicle
Csc - the solubility of a drug in the stratum corneum

Question 17

What is the effect when a lipophillic drug is put in a lipophillic vehicle?

Answer 17

It does not want to move

Accumulates in the mortar

Question 18

What is the mortar in the ‘Brick and Mortar’ analogy?

Answer 18

multiple bilayers of lamellar structures of intracellular lipids

Question 19

What is the bricks in relation to the ‘Brick and Mortar’ analogy?

Answer 19

Corneocytes containing aggregated keratin filaments embedded in a matrix of filaggrin

Question 20

What is the effect when a lipophillic drug is put in a hydrophillic vehicle?

Answer 20

Does not want to be in contact with the water and therefore will more to the intracellular route between the corneocytes

Question 21

What is the effect when a hydrophillic drug is put in a lipophillic vehicle?

Answer 21

Want to move away from the oily environment and moves into the stratum corneum
Little movement within the skin

Question 22

What is the effect when a hydrophillic drug is put in a hydrophillic vehicle?

Answer 22

Does not want to move, stays on the surface of the skin

Question 23

What can be added to a vehicle to enhance solubility?

Answer 23

Excipients - means that a higher proportion will move into the skin

Question 24

State chemical and physical factors which can improve partitioning

Answer 24

hydration of the skin by occlusion
- may be achieved by choice of vehicle
- cling film
Inclusion of excipients which also increases the solubility of hydrophobic drugs

Question 25

How can the partition coefficient be improved?

Answer 25

Physical and chemical factors

Reduction in the barrier function of the stratum corneum