Dermatologic Pharmacology (Wolff) Flashcards
emollients:
- component of moisturizers
- form an oily layer on top of the skin that traps water in the skin
- petrolatum
- lanolin
- dimethicone
- mineral oil
humectants:
- component of moisturizers
- draw water into the outer layer of the skin
- glycerin
- lecithin
- propylene glycol
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
- alpha hydroxyacids
- salicyclic acid
- urea
- allantoin
sunscreen/sunshade:
- 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
nonflammable safe multipurpose antiseptic w/ residual activity:
- chlorhexidine
platelet-derived growth factor:
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
topical antiviral agent:
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
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
- 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
topical vasoconstrictors:
- 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
common topical antibacterial agents:
- bacitracin
- neomycin
- polymixin B
ectoparasite drugs:
- 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
topical anti-itch agents:
- calamine
- menthol: cold (TRPM8)
- camphor: cold (TRPM8)
- capsaicin: heat (TRPV1)
- hydrocortisone
- doxepin
- pramoxine
acne treatments:
- 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
psoriasis treatments:
- 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)
actinic keratosis treatments:
- 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
wart removers:
- salicylic acid
- imiquimod
alopecia tx:
- 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
advanced basal cell carcinoma tx:
- vismodegib or sonidegib: both oral “hedgehog” signaling pathway inhibitors
melanoma tx:
- 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)
- 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
chlorhexidine
- 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
C. difficile infection
Biofilms mechanisms of resistance to abx:
- 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
Factors to consider w/ wound healing:
- glycemic control: elevated glucose has been a/w worse surgical outcomes
- oxygenation
- nutrition
How should wounds be dressed?
- 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
- 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
salicylic acid
biologic agents that target this are among the agents useful for psoriasis and RA
TNF-alpha
component of plant defenses against bacteria, active against P. acne
azaleic acid
local anesthetic, similar to lidocaine, blocks Na+ channels preferentially in small unmyelinated nerve fibers to prevent depolarization needed for pain transmission
pramoxine
effective treatment for acne primarily because of its simple/easy to follow strategy
proactiv
blocking this radiation was ~only goal of early sunscreens; also used to treat psoriasis
UVB
among the imidazole drugs commonly used to treat vulvovaginal candidiasis
miconazole
mixture of zinc oxide and iron oxide in lotion that cools the skin, relieves itch
calamine
characterizes the topical glucocorticoids that should be applied to face, genitals and skin folds
low potency
retinoid administered orally for treatment of severe acne, powerful teratogen that mandates participation by prescribers and users in the iPledge program
isotretinoin
titanium dioxide is an example that could be applied, for example, to your nose when on the beach
sunshade
example of a body region where topically applied agents would be rapidly absorbed
axilla
treatment for actinic keratoses derived from Euphorbia peplus sap, causes chemoablation with neutrophil-mediated antibody dependent cellular cytotoxicity eliminating remaining tumor cells
ingenol mebutate
most common handwashing error in clinical settings
inadequate time
effective topical therapy for actinic keratoses, causes fast- proliferating dysplastic cells to die a thymidine-less death; necrosis/erosion gives way to re-epithelialization over several weeks
5-fluorouracil
inhibitors of this signaling pathway can be used to treat advanced basal cell carcinoma (but usually treated surgically and/or topically)
hedgehog
among OTC drugs used to treat jock itch and athlete’s foot; like terbinafine, inactive against yeasts
tolnaftate
chronic kidney disease, biliary obstruction, diabetes, hypo- and hyperthyroidism, Hodgkin’s disease, polycythemia vera and pregnancy are among the common systemic causes of this
pruritis
topical antihistamine
doxepin
topical antimicrobial agent commonly used to treat acne; local skin irritant and may bleach hair or clothing
benzoyl peroxide
drug class useful for systemic treatment of acne, photosensitivity, GI distress and contraindication in pregnancy and young children due to gray discoloration of permanent teeth are noteworthy adverse effects
tetracycline
broad-spectrum antimicrobial agent widely used in homes and hospitals due to efficacy on skin and oral mucosa with low irritability, nonflammable
chlorhexidine
late choice for treating ectoparasites, works by disrupting GABAergic transmission
lindane
refers to substances in moisturizers that form an oily layer to trap water in the skin/treat dry skin; petrolatum, lanolin and mineral oil are among common examples
emollients
topical immune response modifier used to treat actinic keratoses and basal or squamous cell carcinomas; also used to treat genital warts
imiquimod
peptide antibiotic with activity against gram-positive organisms and some anaerobes; only applied topically to limit systemic toxicity, often causes contact dermatitis
bacitracin
antibiotic that works similar to macrolides, kills anaerobes, useful for range of infections including topical treatment of acne and for osteomyelitis; associated with increased risk of C. difficile
clindamycin
platelet-derived growth factor that stimulates diabetic ulcer repair, but must use cautiously as too much increases risk of malignancy
becaplermin
aminoglycoside antibiotic of Neosporin with activity against gram- negative bacteria
neomycin
anti-inflammatory agent known since ancient times, keratolytic effects due to its ability to dissolve intercellular cement makes it useful for treatment of acne, dandruff, calluses and warts
salicylic acud
monoclonal antibody against IL-12 and IL-23, a biologic agent used to treat psoriasis
ustekinumab
oral hedgehog pathway inhibitor that can be used for advanced basal cell carcinoma
vismodegib
benzophenones and dibenzoylmethanes are now widely used in these to protect skin
sunscreen
imidazole antifungal drug applied topically for range of fungal infections, also noteworthy as a classic inhibitor of cytochrome P450
ketoconazole
MAP kinase pathway inhibitor useful for melanoma BRAF V600E mutation
vemurafenib
biologic DMARD directed against IL-17a, used to treat psoriasis and psoriatic arthritis and, for some, works much better than anti-TNF therapies
secukinumab
class of drugs administered topically to treat rosacea or red eyes; oxymetazoline and tetrahydrozyline are among the examples
alpha adrenergic agonists
alpha2 adrenergic agonist used as topical vasoconstrictor to treat rosacea
brimonidine
counterirritant that provides sensation of cool by stimulating TRPM8 receptors, used topically to relieve pain and itching
menthol
topical retinoid administered for the treatment of acne, alters gene expression to normalize keratinization, decrease keratinocyte cohesiveness and reduce microcomedone formation
tretinoin
topical imidazole used to treat nail fungus
efinaconazole
refers to agents such as glycerin, lecithin and propylene glycol found in moisturizers to draw water into the outer layer of skin
humectants
useful topically for fungal infections such as jock itch and athlete’s foot and systemically for fungal nail infections
terbinafine
class of antifungal drugs with a wide range of activity, blocks ergosterol synthesis
imidazoles
antifungal agent reluctantly used systemically but also has topical effects limited to candida infections, may temporarily stain the skin yellow
amphotericinb
chemotherapeutic agent useful for melanoma
dacarbazine
urea, alpha-hydroxyl acids and allantoin are among the agents found in moisturizers to soften this and give skin a smoother feeling
horny substance
prototypical non-steroid androgen antagonist, uses include treatment of prostate cancer and male pattern baldness in women
flutamide
synthetic insecticide similar to that of chrysanthemums, ectoparasite therapy (Nix) that disrupts Na+ channel current to prevent membrane repolarizing
permethrin
good wound coverings during the debridement phase of healing
hydrogels
peptide antibiotic with efficacy against gram-negative bacteria including pseudomonas, has a detergent-like effect that damages the bacterial cell membrane
polymixinb
widely used OTC antifungal agent for topical and vaginal infections
clotrimazole
potent vasodilator due to hyperpolarization via activation of K+ channels, applied topically to grow hair
minoxidile
applied to skin to kill microbes, repeated administration can be detrimental
antiseptic
counterirritant that stimulates TRPV1 channels to cause sensation of heat, can be useful for pain or itch
capsaicin
macrolide antibiotic, among uses is for topical or systemic treatment of acne; among the well known cytochrome P450 inhibitors
erythromycin
tetracycline used to treat acne, noteworthy for its ability to cause dark pigmentation in skin and sclera
minocycline
organophosphate anticholinesterase insecticide, kills ectoparasites
malathion
prescription synthetic topical antimycotic agent with broad spectrum of activity
ciclopirox
orally administered phosphodiesterase type 4 inhibitor used to treat moderate-to-severe plaque psoriasis
apremilast
orally administered insecticide to treat ectoparasites, binds glutamate-activated Cl- channels to hyperpolarize the nerve and muscle cells
ivermectin
