Dermatologic Pharmacology (Wolff) Flashcards
1
Q
emollients:
- component of moisturizers
- form an oily layer on top of the skin that traps water in the skin
A
- petrolatum
- lanolin
- dimethicone
- mineral oil
2
Q
humectants:
- component of moisturizers
- draw water into the outer layer of the skin
A
- glycerin
- lecithin
- propylene glycol
3
Q
horny substance softeners:
- component of moisturizers
- loosen bonds between top stratum corneum layer of skin, helps dead skin cells fall off, helps the skin retain water, and gives it a smoother/softer feeling in thicker areas (e.g., callus) where surface gets hard like a horn
A
- alpha hydroxyacids
- salicyclic acid
- urea
- allantoin
4
Q
sunscreen/sunshade:
A
- p-aminobenzoic acid (PABA): active in UVB range; classic, less used now due to hypersensitivity concerns
- benzophenones: wider 250-360 nm range (e.g. oxybenzone, octocrylene) with salicylate stabilizers (homosalate, octisalate)
- dibenzoylmethanes: active in UVA range (avobenzone), particularly useful for conditions such as drug-induced photosensitivity and cutaneous lupus erythematosus
- titanium dioxide: sunshade, reflects light
5
Q
nonflammable safe multipurpose antiseptic w/ residual activity:
A
- chlorhexidine
6
Q
platelet-derived growth factor:
A
bacaplermin
- platelet-derived growth factor that promotes cell proliferation and angiogenesis
- only agent approved for treatment of chronic diabetic foot ulcers
- black box warning for malignancy: use of >3 tubes increases malignant complications risk ~4x
7
Q
topical antiviral agent:
A
acyclovir
- synthetic guanine analog with inhibitory activity against herpes simplex types 1 and 2
- used for the treatment of recurrent orolabial herpes simplex virus infection (herpes labialis) in immunocompetent adults
- ointment, cream and buccal tablet formulations available
8
Q
commom topical antifungal agents:
- 1-2X/day application to the affected area typically clears superficial dermatophyte infections in 2–3 weeks
- adverse local reactions: stinging, pruritus, erythema, and local irritation; allergic contact dermatitis is uncommon
A
- miconazole: topical application as a cream or lotion; vaginal cream or suppositories for use in vulvovaginal candidiasis (Monistat)
- clotrimazole: topical application to the skin as a cream or lotion (Lotrimin for athlete’s foot); vaginal cream and tablets for use in vulvovaginal candidiasis (Mycoten)
- efinaconazole: onychomycosis treatment, given for 48 weeks, complete cure in ~15% -18%
- ketoconazole: cream for topical treatment of dermatophytosis and candidiasis, shampoo or foam for seborrheic dermatitis (Nizoral)
- ciclopirox: prescription synthetic broad-spectrum topical antimycotic agent, disrupts macromolecular synthesis; activity against dermatophytes, Candida and Malassezia; low incidence of adverse reactions and contact dermatitis
- terbinafine: allylamine, selectively inhibits squalene epoxidase, a key enzyme for the synthesis of ergosterol; highly active against dermatophytes but less active against yeasts; cream can cause local irritation, avoid contact with mucous membranes
- tolnaftate: synthetic antifungal compound, mechanism uncertain but distorts hyphae/stunts mycelial growth; effective topically against various dermatophyte and Malessezia infections but not Candida; generally well tolerated but rarely causes irritation or allergic contact dermatitis
- nystatin: binds to fungal sterols, alters membrane permeability; limited to topical treatment of cutaneous and mucosal candida infections (hold in mouth before swallowing) because of its narrow spectrum and negligible absorption from the gastrointestinal tract following oral administration; non-irritating topically; mild nausea and diarrhea if swallowed
- amphotericin B: binds to fungal sterols, alters membrane permeability; limited to topical treatment of cutaneous candida infections; well tolerated topically, but may cause a temporary yellow staining of the skin
9
Q
topical vasoconstrictors:
A
- brimonidine: α2-adrenergic agonist applied as a topical gel, vasoconstricts by stimulating post-synaptic vascular α2 receptors
- tetrahydrozoline: eye drops are all adrenergic receptor agonists
- oxymetazoline: mixed α1A/α2-adrenergic agonist vasoconstrictor applied as a topical cream, approved 2017
- phenylephrine: eye drops are all adrenergic receptor agonists
10
Q
common topical antibacterial agents:
A
- bacitracin
- neomycin
- polymixin B
11
Q
ectoparasite drugs:
A
- malathion: topical agent, organophosphate cholinesterase inhibitor
- permethrin: topical agent, binds to insect Na+ channels, blocks membrane repolarization
- ivermectin: administered orally, binds to glutamate-gated Cl- channels in invertebrates, hyperpolarizes the nerve and muscle cells
- lindane: topical agent, toxicity causes to be used only after other agents fail, disrupts GABAergic transmission in insects
12
Q
topical anti-itch agents:
A
- calamine
- menthol: cold (TRPM8)
- camphor: cold (TRPM8)
- capsaicin: heat (TRPV1)
- hydrocortisone
- doxepin
- pramoxine
13
Q
acne treatments:
A
- tretinoin: topical retinoid; causes local skin irritation, dryness, and flaking; sun sensitivity; Atralin® contains soluble fish proteins, use with caution in patients with known sensitivity or allergy to fish
- benzoyl peroxide: topical antimicrobial; causes local skin irritation, may bleach hair/clothing
- clindamycin: topical antimicrobial; rare risk of pseudomembranous colitis
- azaleic acid: topical dicarboxylic acid; kills acne bacteria and decreases prod of keratin (tx mild-mod acne and post-inflammatory hyperpig)
- erythromycin: topical antimicrobial and oral abx, causes GI distress
- tetracycline: oral abx; causes photosensitivity, gastrointestinal distress; contraindicated in pregnancy and young children
- oral contraceptives: hormonal agent; causes nausea, breast tenderness, weight gain, thromboembolic events
- spironolactone: hormonal agent, esp useful in adult women w/ menstrual cycle acne; causes menstrual irregularity, breast tenderness, minor gastrointestinal symptoms, orthostatic hypotension, hyperkalemia, dizziness, headaches, fatigue; contraindicated in pregnancy
- isotretinoin: oral retinoid; causes teratogenicity (absolutely contraindicated in pregnancy), mucocutaneous effects, hypertriglyceridemia, others
14
Q
psoriasis treatments:
A
- psoralen
- apremilast (Otezla): inhibits PDE4 > ^ cAMP levels > dec NO synthase, TNF-α, IL-23, inc IL-10 (regulates inflammatory mediators); application (mod-severe plaque psoriasis and active psoriatic arthritis, liberate trial shows ~55% patients > 75% reduction in psoriasis compared to etanercept)
- TNF-alpha blockers
- ustekinumab (Stelara): targets proinflammatory cytokines IL-12 and IL-23 > dec NK cell activation, CD4+ diff/act, and MCP-1, TNF-α, CXCL-10, IL-8 expression; application (plaque/arthritic psoriasis, Crohn dz); increases risk for infections and SCC
- secukinumab (Cosentyx): targets proinflammatory cytokine IL-17A > dec cytokines IL-6, GC-CSF, IL-1β, TGF-β, TNF-α, chemokines IL-8, GRO-α, NCP-1, and prostaglandins; application (ankylosing spondylitis, and plaque/artritic psoriasis); increases risk of infections
- topicals: emollients and corticosteroids (first line), topical vit D, Tar (ancient), tazarotene (retinoid gel), calcineurin inhibitors, anthralin, salt water bath
- UV light therapy: UVB (radiation to erythema, narrow band UVB also avail but more expensive), photochemotherapy (PUVA) must injest photosensitizer psoralen 2 hr before tx
- systemic therapies: methotrexate, apremilast, retinoids, systemic calcineurin inhibitors, biologic agents (mabs)
15
Q
actinic keratosis treatments:
A
- 5-fluorouracil: inhibits thymidylate synthase (needed for DNA syn) > prevents cell prolif = cell death; good success in patients w/ multiple AK’s; causes inflammation/destruction of lesions; after 4-6 weeks skin progresses from erythema > blistering > necrosis w/ erosion > re-epithelialization
- imiquimod: topical immune response modifier, stimulates local cytokine induction > inflammatory cell infiltration, is an effective therapy; also used for genital warts
- ingenol mebutate: substance derived from sap of Euphorbia peplus plant, is an effective treatment; has two stages 1) initial disruption of cell plasma membranes and mitochondria leading to cell necrosis (chemoablation), 2) neutrophil-mediated antibody dependent cellular cytotoxicity that eliminates remaining tumor cells
all options:
- liquid nitrogen cryotherapy
- surgical therapy
- pharmacotherapy (see above)
- photodynamic (red light) therapy: LED emits strong 635 nm light
- dermabrasion: surgical skin planing
- chemical peels: e.g., with trichloroacetic acid
16
Q
wart removers:
A
- salicylic acid
- imiquimod
17
Q
alopecia tx:
A
- minoxidil: first line in males/females; vasodilates due to K+-channel opening; promotes hair growth by increasing the duration of anagen (growth phase), shortening telogen (rest phase), and enlarging miniaturized follicles
- finasteride: second line in males/females; oral inhibitor of dihydrotestosterone (DHT) production (anti-androgen), can cause sexual dysfunction; use increases hair count
- spironolactone: second line in women; partial agonist of androgen (anti-androgen)
- diphenylcyclopropenone (DPCP): topical immunotherapy contact allergen used to cause contact dermatitis which causes hair growth (in alopecia areata) for unknown reasons
18
Q
advanced basal cell carcinoma tx:
A
- vismodegib or sonidegib: both oral “hedgehog” signaling pathway inhibitors
19
Q
melanoma tx:
A
- dacarbazine: conventional chemo; ± (carmustine and tamoxifen) or (cisplatin and vinblastine)
- vemurafenib: MAP kinase pathway inhibitor, use if BRAF V600E gene mutation present (seen in ~60%), inhibits cell prolif and results in apoptosis
general course of melanoma tx:
- surgical excision often w/ sentinel node biopsy
- conventional chemo (dacarbazine)
- MAP kinase pathway inhibitors (vemurafenib)
20
Q
- a broad-spectrum antimicrobial agent widely used in homes and hospitals due to safety, general efficacy on skin (including oral mucosa) and low irritability
- microbial targets: bacterial spores, mycobacteria, other nonsporulating bacteria, yeasts, viruses, protozoa
A
chlorhexidine
21
Q
- spore forming bacteria that causes and increasing amount of US hospital deaths d/t antiseptic/disinfectant resistance
- bleach or other EPA-approved agent w/ sporocidal must be used to disinfectant this bacteria
A
C. difficile infection
22
Q
Biofilms mechanisms of resistance to abx:
A
- contain persistant cells that are non-replicative
- limited penetration of abx within the film
- neutralize abx
- prod enzymes that breakdown abx
- certain biofilm phenotypes are resistant
- slow growth
23
Q
Factors to consider w/ wound healing:
A
- glycemic control: elevated glucose has been a/w worse surgical outcomes
- oxygenation
- nutrition
24
Q
How should wounds be dressed?
A
- general: kept moist, shouldn’t be exposed to air (occluded wounds heal 40% faster, have less scarring, and are exposed to their own fluid w/ metalloproteases/cytokines)
- debridement stage: use hydrogels
- granulation stage: use foam and low-adherence dressings
- epithelialization stage: use hydrocolloid and low-adherence dressings
25
Q
- known since ancient times for its anti-inflammatory activities
i. a COX inhibitor
ii. unripe fruits are natural sources
- found in many skin-care products (e.g., for treatment of acne, dandruff)
i. causes epidermal cells to shed more readily (“keratolytic”), has antibacterial properties, and opens clogged pores
ii. skin softening effects caused by its ability to dissolve the intercellular cement… applied in more concentrated solutions to calluses and warts
iii. useful for treating thickened scaly skin associated with repeated itching/scratching (lichen simplex chronicus) due to dermatitis, etc.
iv. treated areas are photosensitized, need protection from sun
- prolonged use can cause toxicity, especially in children and those with reduced kidney or liver function
A
salicylic acid
26
Q
biologic agents that target this are among the agents useful for psoriasis and RA
A
TNF-alpha
27
Q
component of plant defenses against bacteria, active against P. acne
A
azaleic acid
28
Q
local anesthetic, similar to lidocaine, blocks Na+ channels preferentially in small unmyelinated nerve fibers to prevent depolarization needed for pain transmission
A
pramoxine
29
Q
effective treatment for acne primarily because of its simple/easy to follow strategy
A
proactiv
30
Q
blocking this radiation was ~only goal of early sunscreens; also used to treat psoriasis
A
UVB
31
Q
among the imidazole drugs commonly used to treat vulvovaginal candidiasis
A
miconazole
32
Q
mixture of zinc oxide and iron oxide in lotion that cools the skin, relieves itch
A
calamine
33
Q
characterizes the topical glucocorticoids that should be applied to face, genitals and skin folds
A
low potency
34
Q
retinoid administered orally for treatment of severe acne, powerful teratogen that mandates participation by prescribers and users in the iPledge program
A
isotretinoin
