derm drugs Flashcards
what is the treatment for localized BCC? advanced/metastatic?
topical fluorouracil, imiquimod
vismodegib
in general, how does imiquimod work? what four ways does it accomplish that? how is it administered?
topical stimulates immune response to tumor
- activates TLR-7/8 to initiate TH1 response
- inhibits adenosine receptor
- activates NFkB: TNF-alpha and IL’s upregulated
- may directly inhibit hedgehog signaling
what are two adverse effects of imiquimod?
photosensitivity
compromises condoms and diaphragms
describe the mechanism of action of fluorouracil
pyrimidine analog, antimetabolite
inhibits thymidylate synthase
describe the action of vismodegib. how is it administered?
oral SMO inhibitor (inhibits hedgehog pathway)
whats the most significant side effect of vismodegib? what are two other adverse effects?
- intra-uterine fetal death, male-mediated teratogenecity
- alopecia most common, GI toxicities
what are conventional therapies usually based on for BCC and SCC?
cisplatin
what conventional cytotoxic drugs are used for melanoma?
dacarbazine
temozolomide
lomustine
carmustine
what is the mechanism of action of aldesleukin? what are the results?
binds IL-2 receptor
- proliferation of immune cells
- also stimulates TRegs which can offset this
- stimulates cytokine cascade: IFNs, ILs, TNFs
what are the contraindications for aldesleukin use?
cardiac, pulmonary or CNS disease/dysfunction
what are the side effects of aldesleukin?
hypotension, capillary leak, pulmonary congestion, renal failure
what is the effect of IFN-alpha2b administration?
stimulates immune response by increasing ability to activate CTL’s and NK cells to lyse tumor cells
what are contraindications for IFN-alpha2b use?
autoimmune disease, cardiac dysfunciton, depression
what are the three major adverse effects of IFN-alpha2b use?
- worsening of autoimmune disease
- elevated LFTs
- pulmonary toxicity
what is the target of ipilumumab?
inhibits CTLA-4
-prevents dampening effect of CTLA-4 on CD80/86, thus increasing T cell stimulation
what is the target of pembolizumab?
inhibits PD1
-prevents PD-ligand from downregulating activity of T cells
what is the target of nivolumab?
inhibits PD1
-prevents PD-ligand from downregulating activity of T cells
what bad adverse effects are common to checkpoint inhibitors due to too much T cell activity?
dermatitis, inc. TEN
which checkpoint inhibitors have worse adverse effects? what are two of their BBW’s?
ipilumumab
-endocrinopathies and peripheral neuropathy
what is the target of dabrafenib?
BRAF V600E/K/D, wild-type BRAF
what is the target of sorafenib?
multiple kinases, inc. BRAF
what is the target of vemurafenib?
BRAF V600E
what is the target of trametinib?
MEK1 and MEK2
what is the mechanism of new skin tumors in treatment of melanoma with kinase inhibitors?
loss of inhibition by the inhibited pathway on an alternative oncogenic pathway allows proliferation of new clonal line of cells
what drugs used in melanoma should be avoided in pregnancy?
checkpoint inhibitors and kinase inhibitors
what drugs used in melanoma should be monitored with regular chest x-rays?
aldesleukin and IFN-alpha2b
what is the primary therapy for actinic keratoses? what else is administered and their action? how are each administered?
topical fluorouracil and imiquimod
topical diclofenac: NSAID, anti-inflammatory
topical trichloroacetic acid: chemical peel, cauterizes skin, keratin, tissue
what biologic drug in psoriasis treatment is contraindicated in heart failure? what other drugs have CV side effects?
infliximab
-adalimumab and rituximab
what psoriasis biologic drug may increase LFTs?
infliximab
what three psoriasis biologics may cause lupus-like syndrome?
infliximab
adalimumab
etanercept
what molecule do retinoids mimic? what is the difference between RXR and RAR receptors?
Vitamin A
RAR: affects cell differentiation and proliferation
RXR: induces apoptosis
what are five main beneficial effects of retinoid therapy in acne/psoriasis?
- increased keratinocyte turnover
- inhibit keratinization
- decreases sebum production/decreased gland size
- anti-inflammatory
- antimicrobial against P. acnes
describe the adverse effects of retinoids that mimic Vit A intoxication
dry skin/mucous membranes, conjunctivits, reduced night vision, hair loss
what are four adverse effects of systemic retinoids?
- teratogens
- elevated serum lipids
- elevated LFTs
- blood dyscrasias
what are three adverse effects of topical retinoid use?
- increased susceptibility to sunburn
- burning, stinging
- desquamation
how are steroids used in psoriasis? acne?
psoriasis: topical, not oral (risk of flare on discontinuation)
acne: topical, oral for moderate/severe (move to retinoids)
what topical therapy should NOT be applied to face?
fluorinated steroids
what are some adverse effects of topical steroid use?
dermal atrophy: cigarette-paper skin corticoid rosacea/perioral dermatitis steroid acne hypopigmentation ACD hypertrichosis
what drug similar to retinoids is used in psoriasis? what is its mechanism of action? how is it administered? what is its adverse effect? what is an alternative for sensitive/intertriginous areas of skin?
calcipotriene
binds RXR and DNA Vit D response elements
administered with steroids, b/c topical irritant
hypercalcemia/hypercalciuria with high doses
calcitriol (hormonally active Vit D)
adalimumab: target, disease
TNF-alpha
psoriasis
etanercept: target, disease
TNF-alpha
psoriasis