Pharmacology and the Skin Flashcards
What are the main 3 routes of drug administration via the skin?
topical - mainly for local effects but also can treat underlying tissues
transdermal
Subcutenous/ depot - for systemic effects - goes across the whole body
What are other epithelial drug routes
airways bladder conjunctival sac nasal mucosa rectum vagina
Typical topical drugs
topical non-steroidal anti-inflammatory drugs (NSAIDs)
How do transdermal drugs work?
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
What layer of the epidermis is important for drug delivery?
Stratum corneum
What is a requirement to shed corneocytes from the skin?
Breakdown of corneodesmosomes
What is the transcellular route
the movement into one cell and then the next until you reach the stratum corneum
What is the intracellular route?
Do not move through the cell, squeeze in between them
What is a limitation of the intracellular route?
Only small drugs and very hydrophillic drugs can move through this route
How does the topical route of administration occur?
Direct application onto the skin
What vehicles are used in topical drug administration?
(Oily -> Watery order)
Ointments; creams; gels; pastes; powders
What is the choice of vehicle determined by?
1) Physicochemical properties of the drug
2) The chemical condition
How to measure the rate of absorption of a drug
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
What is the role of the vehicle?
The vehicle can profoundly influence the rate and extent of absorption of a topically applied drug
What important factors are there in relation to a vehicle?
- Solubility of the drug in the Vehicle
- Maximizing the partition of a drug from a vehicle in relation to the stratum corneum
How do you measure the Maximizing the partition of a drug from a vehicle in relation to the stratum corneum (Km)
Km = Csc/Cv
Cv - solubility of a drug in a vehicle
Csc - the solubility of a drug in the stratum corneum
What is the effect when a lipophillic drug is put in a lipophillic vehicle?
It does not want to move
Accumulates in the mortar
What is the mortar in the ‘Brick and Mortar’ analogy?
multiple bilayers of lamellar structures of intracellular lipids
What is the bricks in relation to the ‘Brick and Mortar’ analogy?
Corneocytes containing aggregated keratin filaments embedded in a matrix of filaggrin
What is the effect when a lipophillic drug is put in a hydrophillic vehicle?
Does not want to be in contact with the water and therefore will more to the intracellular route between the corneocytes
What is the effect when a hydrophillic drug is put in a lipophillic vehicle?
Want to move away from the oily environment and moves into the stratum corneum
Little movement within the skin
What is the effect when a hydrophillic drug is put in a hydrophillic vehicle?
Does not want to move, stays on the surface of the skin
What can be added to a vehicle to enhance solubility?
Excipients - means that a higher proportion will move into the skin
State chemical and physical factors which can improve partitioning
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
How can the partition coefficient be improved?
Physical and chemical factors
Reduction in the barrier function of the stratum corneum
