Topical Therapeutics Flashcards
Medications gain access to sites of action through three primary mechanisms? (3)
- passive diffusion - through the stratum corneum
- transportation through channels or pores within a lacunar system in the stratum corneum
- transportation via appendageal structures - such as sweat glands / follicles
Drug factors affecting percutaneous absorption? (4)
active drug concentration
composition of vehicle
molecular size of drug/prodrug
lipophilicity of drug
Patient factors affect percutaneous absorption (4)
presence of barrier disruption
anatomic location
skin hydration
occlusion
How drug concentration influences absorption
absorption is directly proportional to the concentration of the active ingredient in the medication
How molecular size influences drug absorption
diffusion of a compound is inversely proportional to the molecular size of the drug
lipophilicity of the drug and absorption
lipophilic topical agents are more likely to permeate the skin than hydrophilic
How can vehicle influence drug absorption?
given same active concentration - different vehicles can yield different absorptions
How does occlusion influence absorption?
Occlusion of the skin often leads to markedly increased skin hydration - therefore, active ingredients that are delivered in the form of ointment / tape / or to the skin folds reach a much higher concentration because occlusion prevents loss of medication by evaporation / friction / or exfoliation
how does anatomic location influence percutaneous absorption?
thicker stratum corneum –> lower absorption
Composition
ointment
water in oil emulsion
composition
cream
oil in water emulsion
composition
gel
semisolid emulsion in alcohol base
composition
lotion / solution
powder in water (some oil in water)
composition
foam?
pressurized collection of gaseous bubbles in matrix of liquid film
potency of active ingredient in ointment?
strong
ointment
- hydration?
- sensitization?
- irritation?
high hydration
low sensitization
low irritation
ointment
body sites?
non intertreginous
avoid use on face / hands / groin
creams potency? hydration? sensitization? irritation?
moderate potency
some hydration but not as much as oinment
significant sensitization
low irritation
creams
body sites?
all body sites
creams
avoid use with?
maceration = the softening and breaking down of skin resulting from prolonged exposure to moisture
gels potency? hydration? sensitization? irriatation?
potency - strong
hydration - drying
sensitization risk - high
irritation risk - high
gels
sites for use?
oral mucosa
scalp
gels
avoid?
fissures
erosions
macerated regions
lotions // solutions potency? hydration? sensitization? irritation?
potency - low
hydration - variably drying
sensitization - significant
irritation - moderate
lotions / solution
sites amenable?
scalp / intertriginous
lotions / solutions
avoid ?
fissures / erosions
foams
potency
strong potency
foams
MOA
Foam matrix is stable at room temp, but readily melts at body temp — after the foam is applied to the skin, the volatile components (such as alcohol and water) quickly evaporate, leaving behind lipid and polar components containing supersaturated active ingredients to interact with the stratum corneum - these supersaturated solutions enable maximal delivery of active ingredients into the skin
foam
what might alcohol do to influence absorption?
may play a role in altering the stratum corneum - lead to improve penetration of active ingredient
foam -
sites amenable
hair bearing areas
foam
aovid
fissures
erosions
when selecting vehicle
3 factors
anatomic location
contact allergy / sensitization
irritancy
for hair bearing regions, the clinician should consider choosing which vehicle
solution or foam
over
ointment
_____________ vehicles contain preservatives that may increase the risk of contact allergy and sensitization - these preservatives include known allergens such as parabens and formalin releasers
water-based
creams
lotions
solutions
irritancy is most notably associated with high concentration of _____________, other types of _____________ and certain __________ vehicle ingredients.
propylene alcohol
alcohol
acidic
avoid using formulations containing ________ or __________ on extensively fissured, eroded, or macerated areas
alcohol
salicylates
FTU
the amount of ointment dispensed from a 5 mm diameter nozzle that is
applied to the distal third of the index finger, from the crease under the distal
interphalangeal joint to the fingertip
0.5grams
ointment for face and neck
2.5 FTU
ointment fo trunk / front of back
7 FTU
Ointment arm
3 FTU
Ointment leg
6 FTU
Ointment hand - both sides
1 FTU
Ointment foot
2 FTU
1 gram cream covers?
10cmx10cm
1 gram ointment vs cream
ointment spreads 10% further
ointment grams necessary to cover body
20g adult male
Mechanism of action of glucocorticoids
bind intracellular receptor release HSP translocate to nucleus dimerize regulate transcription
glucorticoids downstream effects?
alter transcription rate - inflammatory pathways
glucocorticoids and CREB?
glucocorticoid receptor interacts with cAMP response element binding protein to effect inflammation
glucocorticoids and NF-kB?
inhibit NF-kB - reducing chronic inflammatory elements
glucocorticoids and AP-1
glucocorticoid receptor interats with ativating protein 1 - which controls transcription of cytokine genes
glucocorticoids and TNF-alpha
inhibit
Glucocorticoids and
granulocyte macrophage colony stimulating factor?
inihibt
glucocorticosteroids and IL-1,2,6,8
inhibit
Glucocorticoids and COX
adhesion
selectins
inhibit
glucocoricosteroids and potency
scale from 1-7
1 most potent - 7 least
“The Gentle Touch”
glucocorticosteroid
treat?
Hydrocortisone 2.5% (cream or ointment) belongs to class 7, the lowest potency class.
efficacious for mild eczema in children and adults and for treating inflammatory
dermatoses involving anatomic regions such as the face, intertriginous areas, or groin, where mid to high-potency topical steroids may be contraindicated.
“The Almost All-Purpose Weapon”
glucocorticoid
treat?
Triamcinolone Acetonide 0.1% (cream or ointment):
class 4, or
a mid-potency class of topical steroids. Triamcinolone 0.1% is effective against most
moderate spongiotic dermatoses (including eczematous dermatitis, atopic dermatitis,
allergic contact dermatitis, arthropod bites, id reactions, drug reactions) involving the
trunk and extremities. Long-term use of triamcinolone is not recommended for facial,
intertriginous, and groin lesions.
“Hercules”
glucocorticosteroid
treat?
Clobetasol propionate 0.05% cream or ointment belongs to Class 1 of topical steroids,
and it is considered one of the most potent topical steroids. Clobetasol is best used in
acute eruptions that necessitate relatively rapid amelioration, such as contact dermatitis or
acute drug eruptions. Clobetasol should be avoided on the face, intertriginous areas, or
the groin, where the skin is relatively thin. Longer-term use of clobetasol requires
monitoring of development of adverse effects
Why might the same active glucocorticosteroid ingredient in an ointment be more potent than in a cream / solution?
Due to the occlusive nature of an ointment vehicle, the same active glucocorticosteroid
ingredient in an ointment vehicle will often be more potent than the same ingredient in a
cream, lotion, or solution vehicle. This is because the ointment vehicle enhances
hydration of the stratum corneum, which leads to improved penetration of the medication
In general, where should you avoid potent / superpotent topical steroids and why?
hould be avoided for use on the face, skin folds (axillary and intertriginous folds), and groin areas due to the risk of epidermal atrophy and potential for steroid-induced rosacea/perioral dermatitis on the face
most common adverse affect of topical glucocorticosteroids
most
common adverse effect is skin atrophy, and this is most commonly associated with longterm
use of potent to super-potent topical steroids.
how does skin atrophy from glucocorticosteroid use manifest?
Skin atrophy may manifest as shiny,
thin skin, telangiectasia, and striae formation. Areas with baseline relatively thin
epidermis such as face and intertriginous areas are more susceptible to developing skin
atrophy compared to other areas of the body
How can you have systemic effects from glucocorticosteroids?
Extensive and long-term use of potent or super-potent topical steroids have been
associated with systemic side effects due to increased systemic absorption of
percutaneously delivered active ingredient.
Potential systemic effects of glucocorticosteroids
Potential systemic side effects include
adrenal suppression, Cushing’s syndrome, and growth retardation in children. For
example, psoriasis and atopic dermatitis patients may require longer-term use of potent
topical steroids to cover larger body surface areas than other dermatologic patient
populations. Systemic adverse effects of topical steroids are particularly relevant to these
populations
AAD guideline for max class I
Currently, the AAD guideline for maximum use of class I topical steroids is to not exceed 50 grams per week
why are brand names better if they have the same active ingredient?
because they have better vehicles
powder + grease =
protective paste
e.g. baby bottom
grease + liquid =
ointment, creams, lotions
oil in water
aqueous cream
water in oil
ointments
gel is good for treating which areas
hair
factors influencing absorption
active concentration
composition of vehicle
molecular size
lipophilicity
what type of vehicle would you choose for patient exposed to poison ivy?
ointment - best penetrating
how much ointment needed to cover palmar x2
0.5 grams
basic effetiveness of glucocorticosteroids
inhibit transcription of inflammatory cytokines e.g. NF-kB
NF-kB and glucocorticoids
GC inhibit NF-kB mediated transcription of inflammatory cytokines
vitamin D analog and retinoids block?
AP-1
Inhibit synthesis of cytokines
Inhibitors of calcineurin block?
NF-AT - inihibit synthesis of cytokines
Hydrocortisone
class?
7
Triamicinolone Acetonide
4
Clobetasol
1
what would you use to treat on baby face?
hydrocortisone 2.5%
step-down approach
start with very strong- 1
then step down
extensive dermatitis on trunk what would you use
tiamicinolone 0.1% ointment
best to use in
mild eczema children / adults
inflammatory dermatoses involving face / intertriginous / groin
hydrocortisone
best to use in
acute eruptions that necessitate rapid relief such as contact dermatitis of acute drug eruptions
clobetasol propionate
when should you avoid clobetasol propionate?
face
intertriginous
groin
long term
best to use in
moderate spongiotic dermatitis (including eczematous dermatitis, atopic, allergic contact, athropod bite)
use on trunk and extremities
triamcinolone acetonide
avoid triamcinolone acetonide
long term
facial
intertriginous
groin
