Pharm E2 Derm

Which areas of the body are more permeable?

scrotum, face, axilla, scalp (thinner skin)

What effect does occlusion have on efficacy?

increase

What is the most drying dermatologic vehicle?

tinctures

Which dermatologic vehicles are the least drying?

ointments

What kind of vehicle would you use for oozing, vesiculation, crusting?

tincture (drying)

What vehicle would you use in scaling, lichenificaiton, xerosis?

ointments (least drying)

What four major factors affect acne?

inc sebum production

alteration in keratinization process and hyper proliferation of ductal epidermis

bacterial colonization (propionibacterium acnes)

release of inflammatory mediators in acne sites

How does stress affect acne?

increases glucocorticoid secretion → suppresses immune system → can’t fight bacteria as well

pathogenesis of acne

pooling of sebum creates anaerobic conditions → proliferate propionibacterium acnes

T cell response → inflammation

lipase from bacteria hydrolyze TG into FFA → inc keratinization and microcomdeone formation → block pore

cytokine production and chemokine generate pus

What is noninflammatory acne?

open and close comedones

what is inflammatory acne?

papulopustular / nodular lesions (more severe)

how long after initiation of systemic corticosteroids might acne appear?

2-6 weeks

(removal leads to initial worsening due to inc inflammation)

What drugs may induce acne?

systemic corticosteroids, antiepileptics, tuberculostatics, lithium

What is the critical target for tx of acne?

microcomedone → eliminating follicular occlusion arrests cascade

what kind of therapy would you use for mild-moderate acne?

topical therapy

what kind of therapy would you use for moderate-severe acne?

systemic therapy

Why are soaps not always the best products to tx acne?

once rinsed off no further active product remains

high pH may degrade some ctivitiy of other agents and may be less tolerable on skin

What are disadvantages to topical therapy?

only works where its applied (not ideal for large areas) and most cause skin irritation

What is the mechanism of benzoyl peroxide?

penetrates stratum corneum unchanged and then is converted to benzoic acid which has activity against P. acnes

has peeling and comedolytic effects

What are adverse reactions of benzoyl peroxide?

can bleach hair, clothes, skin/mucous membrane irritation

How should benzoyl peroxide be prescribed?

start at a low concentration (2.5%) once daily then inc strength and frequency as tolerated

What is azelaic acid (azelex)?

straight chain dicarboxylic acid; topical tx for acne

start once daily then inc to twice daily

What is the mechanism of azelaic acid (azelex)?

not fully understood but likely due to antimicrobial activity and inhibiting conversion of testosterone to dihydrotestosterone

What are adverse rxns of azelaic acid (azelex)?

mild skin irritation / dryness and hypopigmentation

improves over 6-8 weeks w/ continuous therapy

What is retinoic acid (Retin-A)?

aka tretinoin; acid form of vitamin A

topical tx for acne, wrinkles, and dyspigmentation (first line for noninflammatory; can be combined w/ other agents for inflammatory)

What is the mechanism of tretinoin?

not completely understood but corrects abnormal follicular keratinization, reduces P. acnes counts, and reduces inflammation

What is the first line therapy for noninflammatory (comedonal) acne?

retinoic acid / tretinoin

What are adverse effects of topical retinoids?

erythema, desquamation, burning/stinging → decreases w/ time and use of emollients

photosensitivity and severe sunburn

avoid during pregnancy (fat soluble vitamin)

What 2 things are important to educate pt on when prescribing Tretinoin?

photolabile - apply at night

benzyl peroxide inactivates tretinoin

What is Adapalene (Differin)?

topical retinoid that’s stable in sunlight and w/ benzoyl peroxide

tends to be less irritating

What is Tazarotene (Tazorac)?

3rd gen retinoid used for acne and psoriasis

sometimes combined w/ topical steroids to reduce skin irritation

What topical retinoid is used in Kaposi sarcoma?

Alitretinoin (Panretin)

What topical retinoid is used in T-cell lymphoma?

Bexarotene (Targretin)

What are examples of topical abx for acne?

Clindamycin (Cleocin-t) and Erythromycin (Eryderm)

(lacks systemic SE but losing efficacy over time due to P. acnes resistance)

What is Isotretinoin?

systemic retinoid tx for acne that effective in 1-3 mos

very strong, severe teratogenicity- has iPledge program committed to pregnancy prevention

What is Isotretinoin contraindicated in?

pregnancy / breast feeding; men should avoid as well

What are adverse reactions to Isotretinoin?

retinoid dermatitis → erythema, pruritus, scaling

photophobia

arthralgia, HA, alopecia, brittle nails

inc serum lipids

monitor for signs of developing depression

What are examples of systemic abx used to treat more extensive acne?

Tetracylines, trimethoprim / sulfacetamide (bactrim), azithromycin (Zithromax), ciprofloxacin (cipro)

Which systemic abx are most commonly used when tx acne?

tetracylines- doxycycline, minocycline

What is salicyclic acid?

tx for acne but not great evidence to support use

keratinolytic

mild anti-inflammatory / anti-microbial activity

What is spironolactone (aldactone)?

antiandrogen used to tx acne by dec testosterone activity

available in a gel

What oral contraceptives are used to tx acne?

ethinyl estradiol and norethindrone / ethinyl estradiol

Intralesional steroid tx for acne

effective for individual inflammatory nodules

systemic absorption can occur causing adrenal suppression; can also cause local tissue atrophy

Oral corticosteroid therapy for acne

low dose can reduce sx in adrenal hyperactivity

short course may be beneficial in highly inflammatory dz

what is tx for type I acne?

topical retinoid is drug of choice; can also consider benzoyl peroxide or salicylic acid

what do you prescribe next if type I acne tx fails?

topical retinoid plus benzoyl peroxide, topical, or abx

what do you prescribe next if type II acne tx fails?

systemic abx plus topical retinoid or benzoyl peroxide

What do you prescribe next if type III acne tx fails?

add oral contraceptive or anti androgen (women only) then oral isotretinoin if that fails

What is the tx for type IV acne?

systemic abx plus topical retinoid, and benzoyl peroxide ± oral contraceptive or anti androgen

consider oral isotretinoin if not responding

what are major indicators of atopic dermatitis?

pruritus, rash in typical areas, chronic or repeated sx, family history

What are minor indicators of atopic dermatitis?

dry & patchy scales, inc serum IgE, positive allergy skin tests, susceptibility to skin infx

what are the goals of tx for atopic dermatitis?

provide sx relief

identify and eliminate triggers

minimize/prevent adverse rxns to tx

tx secondary skin infx

What is the gold standard therapy for atopic dermatitis?

topical corticosteroids

Why strength of steroids is better for long term therapy?

low potency- suitable for face, intertriginous areas, infants

What strength steroid is used for the body?

medium potency

What strength steroids are used for exacerbations of atopic dermatitis?

medium- high potency; use for 1-2 wks then switch to lower potency

What are local adverse effects of topical steroids?

skin atrophy, acne, rosacea, allergic dermatitis (related to vehicle)

what are systemic adverse effects of topical steroids?

adrenal suppression, infx, hyperglycemia, glaucoma, cataracts, growth retardation

what is the least potent steroid?

hydrocortisone

What 4 things can affect steroid potency?

the drug itself

strength/concentration

salt form of drug

dosage form (occlusiveness)

What are examples of topical immunomodulators?

Tacrolimus ointment (Protopic)

Pimecrolimus cream (Elidel)

What is the mechanism of topical immunomodulators?

inhibit activation of T cells, mast cells, and keratinocytes

What is second line after topical steroid tx for atopic dermatitis?

topical immunomodulators

What are adverse rxns of topical immunomodulators?

burning sensation, possible cancer risk, avoid w/ weakened immune system, use high SPF sunscreen

What are examples of oral corticosteroids?

prednisone (deltasone), dexamethasone (decadron), methylprednisolone (medrol dose pack)

What is sometimes used for short courses during atopic dermatitis exacerbations?

oral corticosteroids - provides rapid relief but needs tapering dose to prevent flare up

what is topical Bacitracin?

peptide abx that prevents cell wall synthesis, has broad antimicrobial coverage, and can be used alone or in combo w/ neomycin and polymyxin B

What are adverse effects of bacitracin ointment?

allergic dermatitis (rare)

no systemic toxicitiy

What is mechanism of Mupirocin (Bactroban)?

binds to bacterial t-RNA preventing protein synthesis

covers most gram positive aerobes (esp. MRSA) and used to eliminate nasal carriage of S. aureus

What are SE of Mupirocin (Bactroban)?

not absorbed but may cause mucous membrane irritation

What is polymyxin B?

peptide abx that interrupts cytoplasmic membrane

effective against gram negative organisms (pseudomonas, E. coli, klebsiella)

What are adverse effects of polymyxin B?

risk for neuro/nephrotoxicity- avoid using on open wounds / denuded skin in high doses

What are examples of aminoglycosides?

neomycin and gentamicin

What is mechanism of aminoglycosides?

inhibit bacterial protein synthesis

good activity against gram neg organisms

can have systemic accumulation

Which aminoglycoside frequently causes sensitization?

neomycin

What is the mechanism of azole antifungals?

inhibits fungal P450 preventing cell wall formation

Azole antifungals

used for topical and vaginal uses

sometimes combined w/ corticosteroids for more rapid sx relief

tx generally prolonged (2-3 wks)

What is mechanism for ciclopirox (penlac)?

inhibit uptake molecular precursors at fungal cell wall

What is ciclopirox (penlac) typically used for?

dermatomycosis, candidiasis, tinea versicolor, nail lacquer for onychomycosis

What are allylamines?

Naftifine and Terbinafine (Lamisil)

antifungals that inhibits production of ergosterol and prevents cell wall synthesis

What is Tolnaftate (Tinactin)?

anti fungal that is well tolerated but must be used for long term to prevent recurrence

no candida activity

What is nystatin?

used for candidal infx (cutaneous and mucosal)

no oral absorption

What is acyclovir (Zovirax) and Penciclovir (Denavir)?

synthetic guanine analogs that are active against HSV

used for recurrent orolabial HSV infection

What is Imiquimod (Aldara)?

anti viral used for external and perianal warts, AKs, and BCC

applied 2-5 times per week

What is the mechanism of Imiquimod (Aldara)?

immunomodulator that stimulates peripheral mononuclear cells to release interferon-a and stimulates macrophages to produce TNF a and interleukins

What are adverse rxns in Imiquimod (Aldara)?

skin irritation in virtually all pts → edema, vesicles, erosions, ulcers ; degree of inflammation parallels efficacy