Pharmocology of the Skin Flashcards
what are the 3 major routes of administration through the skin?
topical
transdermal
subcutaneous/depot
what is topical administration used for?
applied to surface of skin for local effect but also to treat underlying disease
good for local effect as it achieves high conc of drug only at desired site without systemic disease
what routes are used for systemic effects?
transdermal
subcutaneous/depot
name 6 other routes of epithelial drug administration
airways bladder lining conjunctival sac nasal mucosa rectum vagina
what is the stratum corneum?
keratin layer made of dead keratinocytes and corneocytes
most important barrier to drug penetration into/across skin
what is the structure of the stratum corneum?
brick and mortar model
bricks = corneocytes containing aggregated keratin filaments
mortar = intercellular lipids (highly hydrophobic)
describe the structure of the “bricks” in the brick and mortar model
corneocytes containing keratin filaments embedded in a filaggrin matrix surrounded by a cornified envelope
envelope is cross linked to adjacent corneocytes by corneodesmosomes
how do drugs move across the stratum corneum?
most through the intercellular route through the hydrophobic lipids
some small molecules can travel through the corneocytes via the transcellular route but not many
what sort of issues are topical drugs used to treat?
superficial skin disorders (psoriasis, eczema etc)
skin infections (antifungals, antibacterials etc)
itching
dry skin
warts
what is a vehicle and what types can be used?
inactive substance in which the drug is dissolved to be applied
types = ointments, creams, gels, lotions, pastes, powders
what determines the type of vehicle used?
the type of drug (eg. hydrophobic drug will dissolve in hydrophobic vehicle like ointment, hydrophilic drug will dissolve in hydrophilic vehicle like lotion)
and the clinical condition of skin (dry vs weeping etc)
how are transdermal drugs conventionally delivered? how is this quantified?
passive diffusion as the conc of drug in the vehicle > conc of drug in the skin described by ficks law: J = KpCv - J = rate of absorption - Kp = permeability coefficient Cv = concentration of drug in vehicle
what does ficks law show in terms of the importance of the vehicle?
concentration of drug in the vehicle and the partition coefficient (therefore rate of absorption) are highly dependant on the vehicle
how can the choice of vehicle affect the rate of absorption of the drug? give 4 examples
- lipophilic drug in lipophilic base = limited absorption as drug is just as happy in vehicle as in lipophilic skin
- lipophilic drug in hydrophilic base = great absorption as drug is happier in hydrophobic skin than hydrophilic vehicle
- hydrophilic drug in lipophilic base = limited absorption as drug doesn’t like lipophilic vehicle or hydrophobic skin
- hydrophilic drug in hydrophilic base = no absorption
what drives absorption of a drug from the vehicle into the skin?
only the dissolved drug
concentration gradient
undissolved drug doesn’t affect absorption
what are excipients?
increase the solubility of the drug in its vehicle, increasing the concentration and therefore the absorption
how can excess, undissolved drug in a vehicle affect the length of effectiveness and rate of delivery?
as undissolved drug is removed and absorbed into skin, the conc in vehicle decreases so more undissolved drug can now dissolve, replacing the lost drug and maintaining the concentration and therefore the rate of absorption for longer
used in nicotine patches
why are topically applied drugs generally poorly absorbed? how can this be improved?
only a small fraction partitions into the stratum corneum and enters the deeper layers of the skin
can be improved by hydration of the skin by reducing water loss from skin - can be achieved by use of oily vehicle (ointment) or cling film
why does hydration of the skin improve partitioning?
reduction in he barrier function of the stratum corneum due to reversible development of a pore pathway
how can the nature of the skin influence absorption of topically applied drugs?
thickness of stratum corneum at site of application (drug less effective at thick stratum corneum like sole of foot compared to face)
hydration of the skin
integrity of epidermis (trauma, inflammation, moist/weeping, dry, hairy) can all influence choice of vehicle, even for cosmetic reasons in case of hair
how can the pharmaceutical preparation influence absorption of topically applied drugs?
drug concentration/properties
the drug salt (i.e different salt in same drug can change its effectiveness in certain environments - eg. hydrocortisone)
the vehicle
how are glucocorticoids used in skin disease?
used topically in atopic eczema, psoriasis and pruritic
can be mild, moderate, potent or extremely potent depending on severity and site of disease
what are the effects of glucocorticoids?
anti-inflammatory
immunosuppressant
vasoconstricting
anti-proliferating effects on keratinocytes and fibroblasts
what can cause the penetration and potency of glucocorticoids to differ?
body site state of skin occlusion vehicle conc of drug form of drug
