Pharmacology & the Skin Flashcards
What are the 2 major routes for drug administration using the skin, and when would you use them?
Topical (for local effects) and transdermal/subcutaneous (for systemic effects)
What is the most important barrier to drug penetration?
The stratum corneum
What is the stratum corneum made up of?
Consists of corneocytes (hardened, dead, keratinocytes) surrounded by intercellular lipids forming 10 - 30 sheets of tissue (typically 20) that are constantly shed (desquamated) and renewed. Like ‘bricks and mortar’
Topical drugs
Drug (in a pharmacologically inactive substance, or vehicle) applied directly to the surface of the skin
What drives transdermal absorption of topical drugs, and what determines the rate?
Diffusion, determined by Fick’s law
Fick’s Law
J = KpCv - where Kp is the permeability coefficient and Cv is the concentration of drug in the vehicle
Inclusion of what, can improve the solubility and absorption of drugs?
Excipients eg. propylene glycol and hydration of the skin by occlusion (using ointments or cling film)
What do glucocorticosteroids signal via?
Nuclear receptors (class 1), specifically GRα
Subcutaneous route of administration
Drug delivered by a needle inserted into the fatty (adipose) tissue just beneath the surface of the skin. Drug reaches systemic circulation by diffusion into either (i) capillaries, or (ii) lymphatic vessels
Why is the skin an attractive route of drug administration for a systemic effect?
- Application is simple and non-sterile (when drug is applied topically)
- Potentially allows for a steady-state plasma concentration (Cpss) of drug to be achieved over a prolonged period of time
- Avoids first pass metabolism
- Drug absorption can be terminated rapidly
Transdermal drug delivery
Drug is incorporated into an adhesive patch applied to the epidermis. Drug absorption is (partially) controlled by a drug release membrane - occurs by diffusion across cutaneous barrier.
For which kind of drugs should transdermal route be used?
Most suitable for drugs that are (i) low molecular weight (ii) moderately lipophilic; (iii) potent; (iv) of relatively brief half-life (t½)
What are the 2 main groups of strategies to enhance transdermal delivery?
Chemical enhancement (Enhancers interact with the lipid matrix of the stratum corneum to increase permeability) and Physical enhancement (eg. iontophoresis, electroporation, sonophoresis, micro needles)
Iontophoresis
Application of low voltage electrical pulses to the skin via a surface electrode over a prolonged period of time can drive low molecular mass molecules (of the same charge) through the skin.
Electroporation
Very brief high voltage pulses lead to ‘pore’ formation
