Derm drugs Flashcards
what is in a cream
–
mixture of ~half water/half oil (oil in water) with emulsifier (e.g. cetyl alcohol),
water evaporates
–
spread easily (i.e., good for large areas), are well absorbed , and wash off with
water
–
too thick to pump, so packaged in a tub or tube
–
better than ointments for oozing/”wet” skin conditions
–
lotions are similar albeit less viscous
what is in an ointment
mixture of ~20% water in ~80% oil
–
oil component is made from hydrocarbons such as mineral oil or petroleum jelly
–
feel greasy and are “occlusive “, meaning they stay on the surface of the skin and
are not well absorbed
–
best used on dry skin since they trap moisture
–
provide for more complete absorption of the active ingredient or medication
–
ointments are less likely to cause an allergic reaction than creams, which
contain preservatives
what are gels and pastes made from
(
Gels are made from polyionic colloids expanded with water)
(
Pastes are mixtures of oil, water and powder
what are emollients
Moisturizer component:
form an oily layer on top of the skin that traps water in the skin common emolients : petrolatum, lanolin, mineral oil and dimethicone
what are humectants
Moisturizer component
draw water into the outer layer of the skin
common humectants
: glycerin, lecithin, and
propylene glycol
what are horny substance
keratin softners
part of a moisturizer component
loosening the bonds between the top layer of
cells helps dead skin cells fall off, helps the skin
retain water, and gives it a smoother, softer
feeling
common agents
: urea, alpha hydroxy acids
(e.g., lactic, citric, glycolic), allantoin
based on the skin type what moisturizer should i choose?
Normal
choose a water based moisturizer that has a light, nongreasy feel
•
these moisturizers often contain lightweight oils, such as cetyl alcohol,
or silicone derived ingredients, such as cyclomethicone
based on the skin type what moisturizer should i choose?
dry
choose a heavier, oil based moisturizer that contains ingredients such
as antioxidants, grape seed oil or dimethicone , which helps keep your
skin hydrated
•
petrolatum based products are preferable for very dry, cracked skin
since they prevent water from evapopating
based on the skin type what moisturizer should i choose?
oily
•
choose a water based product that is labeled “ noncomedogenic ” to
provide moisture while limiting acne breakouts
based on the skin type what moisturizer should i choose?
sensitive
choose a moisturizer with soothing ingredients such as chamomile or
aloe that does not contain potential allergens (e.g., fragrances, dyes) or
acids to minimize skin irritation
based on the skin type what moisturizer should i choose?
mature
choose an oil based moisturizer that contains petrolatum as the base to
keep skin hydrate plus antioxidants or alpha hydroxy acids to combat
wrinkles
what are the chemical compounds in sunscreens
UVB radiation (280 320 nm) causes most erythema/sunburn
and skin aging and photocarcinogenesis
•
UVA radiation (320 400 nm) causes skin aging and cancer
•
Sunscreens: chemical compounds that absorb ultraviolet light
–
p aminobenzoic acid ( PABA ) and its esters: active in UVB range
–
benzophenones : wider 250 360 nm range but less effective than PABA
–
dibenzoylmethanes : active in UVA range , particularly useful for
conditions such as drug induced photosensitivity and cutaneous lupus
erythematosus
what are the chemical components in sunshades
opaque materials that reflect light… classic
example is titanium dioxide
what bacteria can alcohol based hand disinfection not kill that you need soap and water?
alcohol based hand disinfection – is easier/faster than soap and water – rapidly effective against gram positive, gram negative and viral pathogens – not effective against C. difficile so must use soap and water
MOA of antiseptics and disinfectants: Cell envelope
glutaraldehyde
cross
linking of proteins
EDTA,
other permeabilizers gram
negative bacteria: removal of Mg 2+2+, release of some LPS
MOA of antiseptics and disinfectants: Cytoplasmic inner membrane
quaternary amines
generalized
membrane damage involving phospholipid bilayers
chlorhexidine
low concentrations affect membrane integrity, high concentrations
cause congealing of cytoplasm
diamines
induction of leakage of amino acids
PHMB,
alexidine phase separation and domain formation of membrane lipids
phenols
leakage, some cause uncoupling
MOA of antiseptics and disinfectants: cross linking of macromolecules
formaldehyde
cross
linking of proteins, RNA and DNA
glutaraldehyde
cross
linking of proteins in cell envelope and elsewhere in cell
MOA of antiseptics and disinfectants: DNA intercalation
acridines
intercalation of
acridine molecule between two layers of base pairs in
DNA
MOA of antiseptics and disinfectants: Interaction with thiol groups
silver compounds
membrane
bound enzymes (interaction with thiol groups)
MOA of antiseptics and disinfectants: effects on DNA
halogens
inhibition of DNA synthesis
hydrogen
peroxide, silver ions DNA strand damage
MOA of antiseptics and disinfectants: oxidizing agents
peroxygens
hydrogen peroxide: activity due to formation of free hydroxyl radicals
(•HO), which oxidizes thiol groups in enzymes and proteins
peracetic
acid: disruption of thiol groups in proteins
importance of chlorhexidine
a broad spectrum antimicrobial agent widely used in homes and hospitals
due to general efficacy on skin (including oral mucosa) and low irritability
bacterial spores
not
sporicidal but prevents development of spores;
inhibits spore outgrowth but not germination
mycobacteria
mycobacteriostatic
(mechanism unknown) but not
mycobactericidal
other
nonsporulating bacteria membrane
active agent, causing protoplast and
spheroplast lysis ; high concentrations cause
precipitation of proteins and nucleic acids
yeasts
membrane
active agent, causing protoplast lysis and
intracellular leakage, high concentrations cause
intracellular coagulation
viruses
low activity against many viruses; lipid enveloped
viruses more sensitive than nonenveloped ; effect
possibly on viral envelope (e.g., lipid moieties)
protozoa
has activity against
trophozoites , less toward cysts
Antibiotic resistance mechanism of biofilms
they neutralize the antibiotic and limit penetration
how does glycemic control play a factor in wound healing
poor glycemic control is significantly associated with worse outcomes
purpose of Becaplermin
Platelet derived growth factor that promotes cell proliferation and angiogenesis
only approved for treatment of chronic diabetic foot ulcers
black box warning for malignancy
does epidermal growth factor improve wound healing
no! does not significantly improve epithelialization
proper wound dressing?
general principles: wounds should be kept moist ,
and should not be exposed to air as done historically
–
occluded wounds heal 40% faster and have less scarring
–
wounds are exposed to their own fluid, a mix of
metalloproteases and cytokines
•
consensus opinion on choices:
–
hydrogels for debridement stage
–
foam and low adherence dressings for the granulation stage
–
hydrocolloid and low adherence dressings for
epithelialization stage
Bacitracin
Topical antibacterial agent
peptide antibiotic, inhibits bacterial cell wall synthesis • active against gram positive organisms, also active against most anaerobic cocci, neisseriae , tetanus bacilli, diphtheria bacilli • often causes allergic contact dermatitis, and rarely immunologic allergic contact urticaria • poorly absorbed through the skin, so systemic toxicity is rare
Neomycin
Topical antibacterial agent
aminoglycoside antibiotic, binds to 30S ribosomal subunit to inhibit protein synthesis • active against gram negative organisms • o ften causes allergic contact dermatitis, and cross sensitization to other aminoglycosides can occur • poorly absorbed through the skin, so systemic detection is rare
Polymixin B
peptide antibiotic, binds to phosphor lipids to alter permeability and damage bacterial cytoplasmic membrane • effective against gram negative organisms, including P. aeruginosa, E. coli, Enterobacter , and Klebsiella • rarely causes allergic reaction
Topical antifungal agents?
topical imidazoles , block ergosterol synthesis, have a wide
range of activity against dermatophytes and yeasts
–
miconazole … topical application as a cream or lotion; vaginal cream
or suppositories for use in vulvovaginal candidiasis
–
clotrimazole … topical application to the skin as a cream or lotion;
vaginal cream and tablets for use in vulvovaginal candidiasis
–
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
ciclopirox
Topical antifungal agent
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
Topical antifungal agent
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 and rarely causes irritation or allergic contact
dermatitis
Nystatin
Topical antifungal agent
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
Topical antifungal agent
binds to fungal sterols, alters membrane permeability
–
limited to topical treatment of cutaneous candida infections
–
well tolerated, but may cause a temporary yellow staining of the
skin
Topical antiviral agent
synthetic guanine analog with inhibitory activity against herpes simplex types 1 and 2 – u sed for the treatment of recurrent orolabial herpes simplex virus infection (herpes labialis ) in immunocompetent adults – o intment, cream and buccal tablet formulations available
what are some non pharmacological interventions for pruritis
Skin moisturization dry skin can cause or exacerbate pruritus;
thus, all patients with generalized symptoms should use gentle
cleansers and apply emollients daily
•
Cool environment heat can worsen symptoms, so light weight
clothing, air conditioned environments, and the use of
lukewarm water during showers or baths may reduce symptoms;
cooling lotions (calamine, those with menthol) can provide
additional relief.
•
Avoidance of skin irritants wool clothing and cleansing
products are among common irritants
•
Stress reduction psychological support and behavioral
interventions that help patients to cope are important including
holistic approaches such as meditation, acupuncture, and yoga.
•
Physical interventions Break the itch scratch cycle by
occluding localized areas of pruritus with occlusive dressings
Topical therapies for Pruritus: Topical calcineurin inhibitors
Tacrolimus 0.03% and 0.1% ointment Particularly useful in anogenital pruritus , may experience transient burning and stinging Pimecrolimus 1% cream
Topical therapies for Pruritus: Doxepin
H1 antagonist
5% cream
Avoid in children, 20 to 25 percent risk of sedation
Topical therapies for Pruritus: Menthol
TRPM8 agonist
0.025 to 0.1% cream
Particularly useful in
neuropathic itch , may
experience initial transient burning
Topical therapies for Pruritus: Local anesthetics
Pramoxine 1 to 2.5% found in a variety of OTC remedies along with hydrocortisone; e.g., useful for pruritus on face and that associated with CKD Lidocaine patch 5% Useful in neuropathic pruritus Eutectic mixture of lidocaine 2.5% and prilocaine 2.5% Useful in neuropathic pruritus
how are topical steroids administered
Use low potency on face, genitals and skin folds (class 7)
elsewhere, generally start high potency to gain control and titrate downward for maintenance (class 1)
Capsaicin
Activates TRPV1 (heat) channels
topical sensation for pruitus
substance derived from chili peppers that has been used for the treatment of
chronic pain and pruritus
•
t he mechanism of action for capsaicin involves its ability to activate transient
release potential vanilloid 1 (TRPV1), an ion channel in cutaneous nerve fibers
•
activation of TRPV1 stimulates neurons to release and eventually deplete certain
neuropeptides, including substance P
•
c apsaicin also induces lasting desensitization of neurons to a variety of stimuli
function of salicylic acid
known since ancient times for its anti inflammatory activities
–
a COX inhibitor
–
unripe fruits are natural sources
•
also found in many skin care products (e.g., for treatment of acne,
dandruff)
–
causes epidermal cells to shed more readily ( keratolytic ), has
antibacterial properties, and opens clogged pores
–
keratolytic effects caused by its ability to dissolve the intercellular
cement; applied in more concentrated solutions (e.g., 6% in
petrolatum) to calluses for 1 hr before washing away
–
treated areas are photosensitized, need protection from sun
•
prolonged use can cause salicylate toxicity, especially in children
and those with reduced kidney or liver function
Systemic therapies for pruritus: NaSSA
antidepressant
m irtazapine 7.5 to 15 mg at night Useful in nocturnal pruritus , may cause increased weight and appetite
Systemic therapies for Pruritus: SSRIs
paroxetine 10 to 40 mg per
day
Consider in psychiatric patients with pruritus and paraneoplastic
pruritus
fluvoxamine 25 to 150 mg
per day
Consider in psychiatric patients with pruritus and paraneoplastic
pruritus
sertraline 75 to 100 mg per
day
Useful in
cholestatic pruritus
Systemic therapies for pruritus: µ
opioid receptor
antagonists
naltrexone 25 to 50 mg per
day
Useful in patients with
cholestatic and CKD associated pruritus ; may
cause nausea, vomiting and drowsiness; reverses analgesia and may
precipitate acute withdrawal in patients receiving opioid analgesics
systemic threapies for pruritus: κ
opioid receptor
agonist/µ opioid
receptor antagonist
butorphanol 1 to 4 mg
intranasally per day
Useful in
nocturnal and intractable pruritus ; may cause nausea and
vomiting as well as drowsiness; may precipitate acute withdrawal in
patients receiving opioid analgesics; some potential for abuse due to
concomitant weak µ opioid receptor agonist activity
systemic therapies for pruritus: anticonvulsants
gabapentin 100 to 3600
mg per day useful
in neuropathic pruritus , may cause drowsiness and weight gain;
usually given in two to three divided daily doses; dose alteration for
renal insufficiency may be needed
pregabalin
150 to 300 mg
per day
systemic therapies for pruritus: substance P antagonists
aprepitant 80 mg per day
more commonly used to control nausea/vomiting of
chemotherapy, but
has shown benefits in patients with intractable pruritus (e.g., Sézary
syndrome)
treatment for rosacea to get the red out
•
brimonidine … α 2 adrenergic agonist applied as a
topical gel , vasoconstricts by stimulating post
synaptic vascular α 2 receptors.
•
oxymetazoline … mixed α 1A α 2 adrenergic agonist
vasoconstrictor applied as a topical cream , approved
2017
treatment for eyes to get the red out
naphazoline , tetrahydrozoline , phenylephrine and
oxymetazoline … eye drops are all adrenergic
receptor agonists
what drugs kill ectoparasites
•
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
Tretinoin
Topical retinoids for acne
Once daily, at bedtime Creams: 0.025%, 0.0375%, 0.05%, 0.1% Polyolprepolymer 2 cream: 0.025% Gels: 0.01%, 0.025%, 0.05% Microsphere gels: 0.04%, 0.1% Polyolprepolymer 2 gel: 0.025% Gel (micronized): 0.05% Local skin irritation, dryness, and flaking; sun sensitivity NOTE: Atralin ® contains soluble fish proteins, use with caution in patients with known sensitivity or allergy to fish
Adapalene
topical retinoid for acne
Once daily, at bedtime Cream: 0.1% Gels: 0.1%, 0.3% Lotion: 0.1% Local skin irritation, dryness, and flaking; sun sensitivity
tazarotene
Topical retinoid for acne
Tazarotene Once daily, at bedtime Creams: 0.05%, 0.1% Gels: 0.05%, 0.1% Pregnancy category X; local skin irritation, dryness, and flaking; sun sensitivity
Benzoyl
peroxide
Topical antimicrobial for acne
Twice daily Multiple 2.5 to 10% gels, lotions, creams, pads, masks, cleansers Local skin irritation; may bleach hair or clothing
Clindamycin
Topical antimicrobial for acne
Twice daily Once daily ( 1% gel, lotion, pledget, solution, foam Rare risk of pseudomembranous colitis
Erythromycin
Topical antimicrobial for acne
Twice daily
2% gel, solution, pledget
oral antibiotic
500 mg twice daily (base)
Gastrointestinal distress
Azaleic acid
Topical antimicrobial for acne
Twice daily
20% cream, 15% gel
Local skin irritation
•
a dicarboxylic acid , a white powder found in wheat, rye
and barley where it is involved in the plant defense
response to an infection
•
it kills acne bacteria and decreases the production of
keratin
•
it is used to treat mild to moderate acne, and also treats
post inflammatory hyperpigmentation
Tetracycline
Oral antibiotic for acne 500 mg twice daily Photosensitivity, gastrointestinal distress; contraindicated in pregnancy and young children
Doxycycline
Oral antibiotic for acne 50 to 100 mg twice daily or 150 mg once daily Photosensitivity, gastrointestinal distress; contraindicated in pregnancy and young children
Minocycline
Oral antibiotic for acne
50 to 100 mg twice daily or 1 mg/kd/day of extended release formulation (round to nearest available strength: 45, 65, 90, or 135 mg tablets) Dizziness, drug induced lupus, skin discoloration; contraindicated in pregnancy and young children
Azithromycin
oral antibiotic for acne
Intermittent dosing due to
long drug half life; optimum
regimen unknown
Gastrointestinal distress
Trimethoprim
sulfamethoxazole
oral antibiotic for acne
160 mg/800 mg once to twice daily Stevens Johnson syndrome, toxic epidermal necrolysis
Hormonal agents for acne:
Oral contraceptives
Once daily
Nausea, breast tenderness, weight
gain, thromboembolic events
Hormonal agents for acne Spironolactone
25 to 200 mg/day in one or two equally divided doses; doses of 50 to 100 mg/day may be as effective as higher doses and reduce side effects especially useful for adult women with menstrual cycle related breakouts of acne on lower face, etc.; some dermatologists combine with oral contraceptives Contraindicated in pregnancy; menstrual irregularity, breast tenderness, minor gastrointestinal symptoms, orthostatic hypotension, hyperkalemia, dizziness, headaches, fatigue
Oral retinoid for acne
0.5 mg/kg/day, increasing to 1 mg/kg/day in one or two equally divided doses; total dose 120 to 150 mg/kg over 20 weeks Teratogenicity (absolutely contraindicated in pregnancy), mucocutaneous effects, hypertriglyceridemia, others
topical therapies for Psoriasis
Emollients and Corticosteroids for initial choice for mild to moderate psoriasis
Topical Vitamin D analogs
Calcipotriene and calcitriol to reduce the keratinocyte proliferation
tar
Tazarotene (retinoid gel)
Calcineurin inhibitors (tacrolimus, pimecrolimus)
Anthralin
Salt water bath
UV light therapies for Psoriasis
photochemotherapy (PUVA) … uses UVA radiation
(under strict medical supervision), which penetrates
deeper into the skin without causing sunburn
•
patients typically ingest the plant photosensitizer psoralen ~
2 hrs before treatment ~ 3X/week until remission;
mechanism unknown
•
must be protected from sun exposure
•
increases risk of melanoma
Apremilast
for psoriasis inhibits phosphodiest erase 4 (PDE4) specific for cyclic adenosine monophosph ate ( cAMP ) cAMP levels in cells regulates numerous inflammatory mediators… nitric oxide synthase, TNF α, IL 23 IL 10 • moderate to severe plaque psoriasis • active psoriatic arthritis • LIBERATE trial shows ~55% patients have ≥ 75% reduction in Psoriasis Area and Severity Index (PASI)… comparable to etanercept administered orally , well absorbed hepatic metabolism, primarily CYP3A4 half life of 6 9 hrs pills ~$70 ea severe diarrhea, nausea and vomiting possible; weight loss headache most common CNS complaint, but depression, suicidal ideation, mood changes have been observed
Crisaborole
PDE4 inhibitor for topical therapy of dermatitis
Ustekinumab
human monoclonal antibody, targets proinflammatory cytokines IL 12 and IL 23 blunts IL 12/IL 23 effects, so : natural killer cell activation CD4+ T cell differentiation and activation MCP 1, TNF α , CXCL 10, IL 8 expression plaque psoriasis psoriatic arthritis Crohn disease given subQ at 8 12 week intervals following induction at 0 and 4 wks •>$13k/dose generally well tolerated, but increases risk for infections may increase risk for squamous cell carcinomas hypersensitivity reactions
secukinumab
human monoclonal antibody, targets proinflammatory cytokine interleukin 17A blunts IL 17A effects, thereby decreasing its ability to induce the production of many other proinflammatory signaling molecules: cytokines IL 6, GC CSF, IL 1 β , TGF β , TNF α chemokines IL 8, GRO α abd NCP 1 prostaglandins ankylosing spondylitis plaque psoriasis psoriatic arthritis administered subcutaneously… typically 150 mg at weeks 0, 1, 2, 3,and 4 and then every 4 weeks thereafter may need 300 mg/dose for severe plaque psoriasis •>$3k/150 mg generally well tolerated, but increases risk for infections may causes exacerbations of inflammatory bowel disease hypersensitivity reactions
ixekuzumab
a humanized monoclonal
antibody against iL 17A with similar indications similar to secukinumab
Treatment options for hypertropic actinic keratosis
Liquid nitrogen cryotherapy
•
Surgical therapy
•
Pharmacotherapy
–
Topical 5 fluorouracil (see
–
Imiquimod … a topical immune response modifier that stimulates local
cytokine induction, is an effective therapy
–
Ingenol mebutate …a substance derived from the sap of the Euphorbia peplus
plant, is an effective treatment; has two stages: 1) initial disruption of cell
plasma membranes and mitochondria leading to cell necrosis ( chemoablation )
ans 2) neutrophil mediated antibody dependent cellular cytotoxicity that
eliminates remaining tumor cells
–
Topical diclofenac … an NSAID, benefits suggest PG’s may be important for skin
carcinogeneis
–
Retinoids … (discussed
•
Photodynamic (Red Light) therapy : LED emits strong 635 nm light
•
Dermabrasion : surgical skin planing
•
Chemical peels : e.g., with trichloroacetic acid
Topical 5-fluorouracil
inhibits thymidylate synthetase , a critical enzyme
in the synthesis of DNA
•
the lack of DNA synthesis in fast growing
dysplastic cells prevents cell proliferation and
causes cell death
•
has been used with good success in patients with
multiple AKs; effective in >90% who can tolerate
it and also treats undectable AKs
•
causes inflammation and destruction of the
lesions (see next slide) rash looking inflammatory response
•
after 4 6 weeks skin will have progressed from
erythema through blistering, necrosis with
erosion, and then re epithelialization
Treatment of basal cell or squamous cell carcinoma
• surgical removal/ablation: – curettage and electrodessication – Mohs micrographic surgery – X ray radiation – cryosurgery – photodynamic therapy – laser surgery • topical medications: – imiquimod – 5 fluorouracil • advanced BCC – vismodegib or sonidegib : both oral “hedgehog” signaling pathway inhibitors
management of alopecia areata
chronic, relapsing immune mediated inflammatory
disorder affecting hair follicles resulting in non
scarring hair loss
–
disorder ranges from small patches of alopecia on any hair
bearing area to the complete loss of scalp, eyebrow,
eyelash, and body hair
–
u ntreated, ~50% will grow hair back in < 1 year, but
recurrence is likely
–
intralesional or topical corticosteroids
–
topical immunotherapy … contact allergen such as
diphenylcyclopropenone ( is used to cause contact dermatitis,
which causes hair growth for unknown reason
male pattern baldness treatment
–
minoxidil :
•
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
•
oral inhibitor of dihydrotestosterone (DHT) production, can cause
sexual dysfunction
•
use increases hair count
–
s urgery … transplantation of hair follicle units (natural
groupings of ~ 4 hairs) from regions resistant to hair loss
into regions of hair loss
Female pattern hair loss treatment
–
minoxidil (first line)line):
•
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
–
anti androgens (second line when minoxidil fails)
•
spironolactone (androgen partial
•
finasteride (blocks dihydrotestosterone synthesis)
•
f lutamide (androgen
