Sweatman Psoriasis and Acne Flashcards
most common autoimune dz in the US
psoriasis
drugs that treat psoriasis target….
the cytokines involved that cause over growth of normal skin cells
Pro inflammatory cytokines involved in psoriasis released by t cells
TNF
IFN
Nomenclature for adalimumab
lim=immune system
u- humanized
Human Mab
Adalimumab
receptor-antibody fusion protein
etanercept
chimeric monoclonal antibody
infliximab
administration routs for the TNF blockers
sc= adamlimumab and etanercept
infliximab=IV
binding site and overall goal for these drugs–>
bind to TNF-alpha–> and prevent them from receiving TNF signal (prevent damage from happening to the TNF cell target)
components of Adalimumab
IgG1
components of etanercept
p75 TNF receptor and Fc IgG1
components of INfliximab
variabel region of mouse Mab on human IgG1
only tnf blocker with hypersensitivity as a possibility
inflixiamab (murine derived)
BBW’s for tnf blockers
infection *FUNGAL,/MYCOBACTERIAL/VIRAL
NEOPLASIA
TUBERCULOSIS
DO NOT USE TNF BLOCKERS WITH
VACCINES
IMMUNOSUPRESSIVES
ABSOLUTE CONTR’S WITH ADALIMUMAB
NONE
ABSOLUTE CONTRA’S WITH ETANERCEPT
SEPSIS
ABSOLUTE CONTRA’S WITH INFLIXIMAB
HEART FAILURE
MURINE HYPERSENSISTIVITY
MAB THAT TARGETS IL 12 and IL23
overexpressed in psoiriasis plaques
ustekinumab (stelara)
- -> bind p40 subunit integral to IL 12/23 activation
- therebydisrupting signal transuction
supresses Th1 and Th17 cell populations
ustekinumab
adverse effects of ustekinumab
inc. risk of infection and neoplasia
-live virus vaccines contra
test for tb
anaphylaxis
retinoids to treat psoriasis
acitretin
tazarotene
main effect retinoid has on acne tx
decreased sebum secretion and sebaceous gland size (isotretinoin)
discuss retinoid in tx of acne
psoriasis mechs unknown
retinoids bind to RXR/RAR receptors in SUBBASAL KERATINIOCYTES–> travel to nucleus to increase transcription of HB-EGF and Amphiregulin–> these act on egf-r –cause proliferation of basal keratinocytes–> thickend epidermis–> peeling/flaking of stratum corneum
what to retinoid NOT DO
they do not affet the bacteria involved with acne
they do not affect sebum production
what do retinoids in acne do
increase epidermal cell turnover and mitotic activity–> thickened corneum and this leads to sloughing and expulsion of exisiting comedones
human tissue composition of rar/rxr receptors
RAR (alpha,gamma) and RXR (alpha, beta)
taargetting RAR’s leads to
cellular diff. and prolif
targetting RXR’s leads to
apoptosis
rar targetters
acne, psoriasis, photaging
tretinoin, adapalene, tazarotene
targetters of rxr’s
mycosis fungiodoides, and kaposi’s sarcoma
beXarotene, alitretinoin
all oral retinoids are
teratogenic (vitamin a is crucial to embryogenesis)
accutane pt.’s also need
monitor for suicide
before oral oral retinoid check
blood (CBC)
liver
lipids(most common abnormality)
babies (preg test)
RAR selective retinoids…monitor
mucocutaneous and musculoskeletal changes
RXR selective retinoids…monitor
physiochemical changes
retinoids and UV
increase photosensitivity and risk for severe sunburn
topical retinoids are used for
acne and photaging
topical retinoids and photoaging
inhibit MMP’s in response to UV radiation and also induce epidermal hyperplasia in atrophic skin–> reducting keratinocyte atypia
two more nuclear target drugs for tx of psoriasis
Calcipotriene
Calcitriol
main side effect with calcipotriene
hyeprcalcemia and hypercalcuria with excesss dose
MOA for calcipotriene
binds Vit-D receptor, complex associates with RXR-alpha subunit and binds DNA vit response element–> modulates epidermal diff, and inflamm, leading to improved psoriasis plaques
with calcipotriene migiht have to co-admin
topical steroids
it is an irritant
calcipotriene can icnrease chances for
skin cancer-UV induced
active for of vitamin D
calcitriole–> topically only
better tolerated in intertrignois and sensitive regions
calcitriole
calcipotriene is selective for which receptors
RXR–> apoptisis
Benzoyl peroxide MOA
prodrug converted to benzoic acid on the skin–> ROS liberation is lethal for P. acnes
benzoyl peroxide is usually formulated with
adapalene or
antibiotics like erythromycin and clindamycin (macrolides)
macrolide MOA
inhibit 50 s ribosomal subunit
static or cidal dep. on concentration
bad news for clinda
P. acnes is resistant to topical form*change if no improvement in 4-8 weeks
drier skins
creams
oilier skins
gels or solutions
overall accomplishments of corticosteroids
> increased antiimflammatory lipocortins
>decreased endogenous inflammatory mediators
antinflammatory, anti-itch, vasoconstricitve
corticoctseroids
effectiveness of topical steroids is judged by
ability to cause blanching of the skin
list the corticosteroids in order of poentcy
MILD-MOD-POtent-Very POtent
Hydrocortisone
Betamethasone
Flucinonide
Clobetasol
steroid tx respose is varied by
condition and anatomic location
HIGHLY resonsive to scorticosteroids
Psoriasis (Intertrginous)
Atopic dermatitis (children)
Seborrheic dermatitis
Intertigo
