Skin Disorders Flashcards
What are skin functions? (not tested)
- barrier
- thermoregulation
- vitamin D synthesis
- sensory organ
Common Skin Disorders (not tested)
Acne: changes in circulating androgens stimulate sebaceous glands
Rosacea: chronic hyperaemia of facial skin
Eczema: a generic term referring to dry, itchy inflamed skin
Pruritus: itch
Urticaria: skin inflamm with raised wheals/bumps
Psoriasis: autoimmune, inflamm, hyperproliferation of keratinocytes
Warts: infection with HPV, small raised lesions
Glucocorticoids
what is it used to treat? (3)
MOA? (3 main)
- psoriasis, eczema, pruritus
MOA:
- turn on or off transc factors
- inhibit release of inflamm mediators from mast cells
- inhibit neutrophil activation, emigration
- inhibit immune cell activation
- *upregulate lipocortin expression (inhibits phospholipase A2), reducing formation of arachidonic acid-based inflamm mediators like prostaglandins and leukotrienes
- *inhibition of DNA synthesis, mitosis, reduce prolif of epidermal cells
- *vasoconstriction of skin (blanching rxn)
Glucocorticoids
AE (2)
- steroid rebound: Worsening of inflammation at site of skin
Downregulation of glucocorticoid receptor; circulating endogenous GC are no longer sufficient to maintain normal skin
Taper the patient off of it - skin atrophy (thinning) due to inhibition of DNA synthesis and mitosis, thinning of stratum corneum (top)
- spread of infection, systemic effects, steroid rosacea (reddening of facial skin), stretch marks
Glucocorticoids
How are they prepared?
Often formulated as fatty acid esters of the active drugs to promote absorption through the deep skin
Glucocorticoids
mild potency (1)
hydrocortisone
Glucocorticoids
moderate potency (4) (don’t need to know)
aclomethasone diproprionate, clobetasone butyrate, fludroxycortide, fluocortolone
Glucocorticoids
potent (7) (don’t need to know)
beclomethasone diproprionate, betamethasone, fluocinolone acetonide, flucocinonide, fluticasone, proprionate, mometasone fuorate, triamcinolone acetonide
Glucocorticoids
very potent (2)
clobetasol proprionate, diflucortolone valerate
Retinoids
derivatives of ___________ and metabolites of ______
Name 5
retinoic acid, vitamin A (retinol)
Tretinoin Isotretinoin (accutane) alitretinoin tazarotene bexarotene
Retinoids
What is vit A important? (2)
used to treat? (3)
dosage form?
healthy vision, cell differentiation
acne, eczema, psoriasis
topical, can be given orally for severe cases
Retinoids
MOA
- agonists of retinoic acid receptor (RAR) and retinoid X receptor (RXR) which are trans factors that induce/repress gene transcription
- reduce sebaceous gland activity and sebum production
- have some anti-inflamm actions
Retinoids
AE (2)
- *skin peeling
- *teratogenic (women should be using suitable contraception)
- dry flaky skin, stinging sensations, joint pain with oral admin
Retinoids
Bexarotene
Use?
MOA?
- cutaneous T-cell lymphoma
- 100x more potent for RXR than RAR
MOA:
- blocks cell cycle progression
- induces apoptosis and differentiation
- inhibits angiogenesis and metastasis
Vit D Analogues
Name 3 primary analogues
used to treat? (1)
dosage form?
-mixture of several substances and plays role in calcium phosphate metabolism in bone formation
3 analogues:
- calcitriol
- calcipotriol
- tacalcitol
- used to treat psoriasis
- topical, can be oral (sometimes combined w/ glucocorticoid therapy)
used when glucocorticoids are not that successful
Vit D Analogues
MOA?
- agonists of Vit D receptor (nuclear recport)
- reduce proliferation and increase apoptosis of keratinocytes
- inhibit T cell activation
Vit D Analogues
AE (1)
- skin irriation
- calcium, bone metabolism problems - need to avoid
oral/systemic admin - *hypercalcemia
- GI pain
- renal stones
Keratolytics
Name 2 a-hydroxy acids
used to treat? (1)
dosage form?
a-hydroxy acids:
- salicylic acid
- glycolic acid
- used to treat warts
- topical, can be oral (sometimes combined w/ glucocorticoid therapy)
Keratolytics
MOA?
- keratolytics break down keratin in skin
- by breaking down keratin, agents reduce thickness of stratum corneum:
- solubilize protein components of desmosomes
- activate endog. hydrolytic enzymes by lowering pH
- diffuse into stratum corneum and increase water content making tissue easier to debride
Keratolytics
AE
- open wounds should not be treated with salicylic acid
- local skin irritation (redness, itching)
- salicylic acid toxicity (children at risk)
Cryotherapy
MOA?
involves what substances?
- removal of wart by freezing
involve liquid nitrogen, CO2, dimethyl ether
Imiquimod
what is it?
what is it used for?
MOA?
- an immune modifier used to treat anogenital warts
MOA
- enhance both innate and acquired immune respones
- binds toll-like receptors on B cells
- increases release of inflamm mediators (TNFa and interleukins)
Immunosuppressants
use (general)?
name 2
- serious cases of eczema/psoriasis, glucocorticoid ineffective
- ciclosporin
- tacrolimus/pimecrolimus
Immunosuppressants
Ciclosporin
how does it work?
what does it inhibit?
what is the normal immune response?
- cylcic peptide that binds to cyclophilin and inhibits calcineurin which decrease IL-2 synthesis and prolif of T cells
- will not affect current inflamm, but will prevent future ones
normal immune repsonse
- increased intracellular Ca2+ activates calcineurin which dephosphorylates the nuclear factor of activated T cells (NFAT)
- dephosphorylated NFAT turns on transc and propgates inflamm response (turn on transc of IL-2, leading to activation of T cells)
Immunosuppressants
Ciclosporin
AE (3)
- *nephrotoxicity (unrelated to calcineurin, unknown mech)
- *hepatotoxicity
- *hypertension
Immunosuppressants
Tacrolimus/Pimecrolimus
how does it work?
AE? (2)
- macrolide compounds (antibiotics) that also inhibit calcineurin to decrease IL-2 synthesis and prolif of T cells
AE
- similar to ciclosporin
- also hyperglycemia and alopecia (tacro only)
Biologics for Psoriasis
name 5
- infliximab
- adalimumab
- secukinmab
- ixekizumab
- ustekinumab
Biologics for Psoriasis
Infliximab
Adalimumab
how do they work?
what does TNFa do?
Infliximab
- chimeric neutralizing antibody against tumor necrosis factor a (TNFa) same as for IBD/IBS
Adalimumab
-humanized monoclonal antibody against TNFa
both target membrane bound TNFa are given once every 2 weeks via sq injection
TNFa pro-inflamm cytokine
- promotes release of other inflamm cytokines and interleukin (1/6/8)
- promotes adhesion of leukocytes into target organs
Biologics for Psoriasis
Newer antibodies for treatment, more expensive
Secukinumab - against which IL?
ixekizumab?
ustekinumab?
Secukinumab: monoclonal antibody agianst IL-17
ixekizumab: IL-17A
ustekinumab: IL-12, IL-23
IL are key mediators of inflamm, reduce inflamm
