Pharmacology and the skin Flashcards
layers of epidermis
- Stratum corneum
- Stratum lucidum
- Stratum granulosum
- Stratum spinosum
- Stratum basale
characteristics of stratum corneum
brick and mortar structure
bricks being an insoluble keratin matrix
mortar being an intercellular lipid layer made of ceramides , cholesterol and fatty acuds
what do drugs have to go through when administered directly to skin
stratum corneum
factors affecting absorption
water solubility
molecular weight
oil/ water partition coefficent
differing water solubility of drugs
hydrophilic drugs are poorly absorbed when applied topically due to low partitioning through the lipid matrix of the stratum corneum
hydrophobic drugs such as glucocroticoids are readily absorbed as hey can easily penetrate the intercellular lipid matrix
what is useful in psoriasis
suppression of fibroblast and lymphocyte proliferation by glucocorticoids
MOA of glucocorticoids
enter cells by diffusion as they are lipophilic
combine with glucorticoid receptor in cytoplasm ; inactive
in cytoplasmic form
undergoes a conformational change
activated form translocates to nucleus by importins
complex binds to specific dna sequences in promoter regions of target genes
can lead to upregulation or downregulation of gene transcription
what are glucocorticoids classified in
seven classes of potency - I being most potent
what is the base of lipohpilic ointments made of
paraffins, vegetable oils, animal fats, synthetic glycerides, or waxes.
what is the base of water soluble ointments made of
polyethene glycol. These ointments may absorb water from the skin.
what does topical application sllow for
diffusion into the stratum corneum and then to epidermis, the dermis and finally to the subdermis where the drug can enter the systemic circulation
what is transdermal drug delivery
method of delivery that involves applying a drug formulation directly onto intact and healthy skin
advanatges of transdermal drug delivery
No first pass metabolism in the liver as you would have with oral administration
Simple, convenient, painless, excellent for a steady and prolonged administration of drug over time
disadvantages of transdermal drug delivery
Slow delivery to site of action and longer time required to reach steady state
local irritation possible
only useful for lipophilic drugs with higih skin permeability and low required dose
chemical strategies to enhance TDD
Penetration enhancers:
Water (in liquid preparations) can accumulate in the stratum corneum resulting in swelling of the corneocytes and the formation of pores that increase permeability
Alcohols (e.g. ethanol) disrupt the lipid bilayer in the stratum corneum and increase flux
prodrugs
what are prodrugs
biologically inactive compound that can be metabolised in the body to produce a drug
physical strategies to enhance TDD
Electroporation: involves creating new pores and temporary paths through the skin using electric pulses
Iontophoresis: involves applying a low voltage electric field to drive ionised drugs through the skin.
Sonophoresis: involves the use of ultrasounds (FDA approved for pain medications).
routes of administration
topical; drug in a pharmacologically inactive vehicle applied to the surface of the skin
transdermal for systemic effects
subcutaneous- delivered by needle
how is a drug deliivered into and across the stratum corneum
through diffusion
what do glucocorticoids supress
production of pro-inflammatory cytokines and increases the expression of anti-inflammatory proteins. This leads to a reduction in inflammation, immune response, and modulation of metabolism
absorption rate of subcutaneous administration
relatively slow due to poor vascualr supply
