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DERMATOLOGICALPHARMACOLOGY
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Directly treat D/O of skin
Deliver drugs to other tissues Stratum corneum
Major barrier to percutaneous absorption of
drugs and loss of water from the body
Possesses multiple proteins and lipids
Reversibly/irreversibly bind drugs
Thickestpalm and sole
Thinnest-facial and post-auricular regions
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Dermis and its BV
Superficial capillary plexus between epidermis
and dermis
Site of majority of systemic absorption of cutaneous
drugs
Cells in dermis-targets for drugs
Mast cells
Infiltrating immune cells
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Pharmacologic Implications
Dosage
Covering skin w/ a topical preparation
Requires 30g of spreadable material
Regional Anatomical Variation
Permeability-inversely proportional to thickness of
stratum corneum
Higher on face, intertriginous areas and perineum
Altered Barrier Fxn in Disease
Stratum corneum is abnormal
Increased percutaneous absorptionsystemic toxicity
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Vehicle
Cream
Oil in water emulsion
>31% water
Leaves concentrated drug at skin surface
Spreads and removes easily, no greasy feel
Ointment Water in oil
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Gel/Foam
Water-soluble emulsion
Concentrates drug at surface after evaporation
Non-staning
Greaseless
Clear appearance Foams well for scalp and other hairy locations
Lotion/Solution/Foam
Solution-dissolved drug base
Lotion-suspended drug
Aerosol propellant with drug
Foam drug w/ surfactant
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May be aqueous or alcoholic
Low residue on scalp
Age
Children
>ratio of surface area to mass than adults
>systemic exposure
Application Frequency
Often applied twice daily
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GLUCOCORTICOIDS
Immunosuppressive and anti-inflammatory
Topical glucocorticoids
Selected on basis of potency, site of involvement,
severity of skin dse
Tx uses: Inflammatory skin diseases
Usually use more potent steroid 1st
Toxicity:
Chronic use of class 1 Skin atrophy
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7 classes in order of decreasing potency
Class 1
Betamethasone dipropionate cream, ointment0.05%
Clobetasol propionate
Diflorasone diacetate
Halobetasol propionate
Class 2
Amcinonide
Betamethasone dipropionate Desoximetasone
Fluocinonide
Halcinonide
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Class 3
Betamethasone valerate
Triamcinolone acetonide
Class 4
Amcinonide
Flurandrenolide
Hydrocortisone valerate
Mometasone furoate
Class 7
Dexamethasone sodium phosphate Class 1-most potent
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Striae
Telangiectasias
Purpura
Acneiform eruptions
Systemic glucocorticoids
For severe dermatological illnesses
Allergic contact dermatitis to plants, life-
threatening vesiculobullous dermatosis
Daily morning dosing Side effects: dose dependent
Long-term use: psychiatric problems, cataracts,
myopathy, osteoporosis, avascular bone
necrosis,glucose intolerance, HPN
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Retinoids
Natural and synthetic compounds that exhibitvitamin A-like biological activity or bind to
nuclear receptors for retinoids
1stgeneration
Retinol (vitamin A) Tretinoin
Isotretinoin
Alitretinoin
2nd generation
Acitretin
Methoxsalen
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3rd generation
Tazarotene Bexarotene
adapalene
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Topical Retinoids
Acne: caused by Sebaceous gland hyperplasia
Follicular hyperkeratosis
Propionibacterium acnes colonization
Inflammation
1stline therapy for non-inflammatory (comedonal)
acne
Improves fine wrinkles and dyspigmentation
(photoaging)
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Toxicity and monitoring
Erythema Desquamation
Burning
Stinging
Photosensitivity reactions Decrease w/ time, w/ use of emollients
Exposure avoided during pregnancy
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Tretinoin
Applied once nightly for acne and photoaging Not applied together w/ Benzoyl
peroxide(inactivates Tretinoin)
Tazarotene
3rd generation
Psoriasis, photoaging, acne vulgaris
OD
Side effects: burning, itching, skin irritation
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Alitretinoin
Kaposis sarcoma-2-4x daily
Bexarotene
Early stage (IA,IB) cutaneous T-cell lymphoma
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Systemic Retinoids
For Tx of acne, psoriasis and T-cell lymphoma contraIx in pregnant women, contemplating
pregnancy or breastfeeding
Highly teratogenic
Common malformations Craniofacial, CVS, thymic CNS
Men-avoid retinoid Tx when trying to father children
Toxicities
Cheilitis, xerosis, blepharoconjunctivitis, cutaneous
photosensitivity, photophobia, myalgia, arthralgia,
headaches, alopecia, nail fragility, > susceptibility to
Staph infections
Retinoid dermatitis: erythema, pruritus, scaling
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IsotretinoinTx of recalcitrant and nodular acne vulgaris
Clinical effects seen w/in 1-3 monthsSevere acne
Induce prolonged remissions after single
course of Tx
Normalizes keratinization in sebaceous
follicle
Reduces sebocyte no. w/ dec. sebum
synthesis
Reduces P. acnes
Preteens, males, patients w/ acne conglobataor androgen excess-risk of relapse
Usually w/in 3 yrs
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Acitretin
For cutaneous manifestations of psoriasis
Pustular psoriasis
Clinical effect: w/in 4-6 weeks
Female pts of childbearing age
Avoid pregnancy for 3 yrs after Txavoid retinoid
induced embryopathy
Bexarotene
Cutaneous T-cell lymphoma
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Vitamin analogs
carotene Present in green and yellow vegetables
Reduce skin photosensitivity in patients with
erythropoietic protoporphyrin
Not approved by FDA
Calcipotriene
Topical vitamin D analog
Tx of psoriasis
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Antimicrobial Agents
Antibiotics Tx of superficial cutaneous
infections(pyoderma)
Non-infectious diseases
Acne rosacea Perioral dermatitis
Hidradenitis suppurativa, etc
Tx of superficial bacterial infections and acne
vulgarismost common D/O treated w/ topicalor systemic antibiotics
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Commonly used topical antimicrobials
Clindamycin Erythromycin
Benzoyl peroxide
Antibiotic-benzoyl peroxide combinations
Also Sulfacetamide
Sulfacetamide/Sulfur
Metronidazole
Azelaic acid
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Tetracyclines
Most commonly used Inexpensive, safe and effective
1 g in divided doses
Common complication: vaginal candidiasis
Cutaneous infections Pyoderma
S. aureus, s. pyogenes
Impetigo
Topical therapy-Mupirocin
Active against staph and strep except D
Inactive against normal skin flora
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Inhibits protein synthesis
Activity enhanced by acid pH of skin surface
2% ointment or cream, applied TID
Deeper bacterial infections of skin
Folliculitis
Erysipelas Cellulitis
Necrotizing fasciitiis
Penicillins, Cephalosporins-used
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Antifungal agents
Most effective agents Griseofulvin
Topical and oral imidazoles
Triazoles
Allylamines
Tinea corporis/Tinea pedis
Miconazole
Naftifine/Terbinafine
Localized cutaneous candidiasis/T. versicolor
Azoles
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T. capitis/follicular-based fungal infections
Systemic therapy Oral Griseofulvin
Oral Terbinafine-children
Onychomycosis
Dermatophytes and Candida Griseofulvin for 12-18 months50% cure rate
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Antiviral agents
Verrucae (HPV) Herpes simplex virus
Condyloma acuminatum
Mollusacum contangiosum
Chicken pox Acyclovir, Famciclovir, Valacyclovir
HSV and VZV infections-systemic
Mucocutaneous HSV
Acyclovir, Docosanol, Penciclovir
Condylomata
Podophyllin, Podofilox
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Agents used to treat infestations
Lice and scabies Permethrin
Interferes with insect sodium transport
proteins neurotoxicity and paralysis
5% cream-scabies 1% cream, cream rinse, topical solutionlice
Infants >= 2 mos old
Lindane
Organochloride
Induces neuronal hyperstimulation and
eventual paralysis of parasites
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2nd line drug in Tx of Pediculosis and scabies
Potential for neurotoxicity in children and adults=6 y.o.
Benzyl alcohol
Inhibits lice from closing their resp.spiraclesasphyxia
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Ivermectin
Other less effective Tx 10% crotamiton cream and lotion
For patients in whom Lindane pr Permethrin is
contraIx
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Antimalarial agents
Chloroquine Hydroxychloroquine
Quinacrine
For cutaneous LE
Cutaneous dermatomyositis Polymorphous light eruption
Porphyria cutanea tarda
sarcoidosis
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Cytotoxic and Immunosuppressive drugs
For psoriasis Auto-immune blistering diseases
Leukocytoclastic vasculitis
Antimetabolites
Methotrexate Moderate to severe psoriasis
Suppresses immunocompetent cells in the
skin
expression of CLA + T cells and endothelialcell E-selectin
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Equally effective to oral cyclosporine in achieving
partial or complete clearing of psoriasis
Used in combination w/ phototherapy and
photochemotherapy
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Azathioprine
Ateroid-sparing agent for auto-immune andinflammatory dermatoses
Pemphigus vulgaris
Bullous pemphigoid
Dermatomyositis
Atopic dermatitis
Chronic actinic dermatitis
LE
Psoriasis
Pyoderma gangrenosum Behcets disease
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Alkylating agents
Cyclophosphamide Cytotoxic and immunosuppressive agent
Advanced cutaneous T-cell lymphoma
Pemphigus vulgaris
Bullous pemphigoid TEN
Wegeners granulomatosis
2-3 mg/kg/day
4-6 week delay in onset of action
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Calcineurin inhibitors
Cyclosporine Inhibits calcineurininhibits T cell activation
Present in Langerhans cells, mast cells and
keratinocytes
Tx of psoriasis Atopic dermatitis, alopecia areata,
epidermolysis bullosa acquisita, etc
Side effects: hypertension, renal dysfunction
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Tacrolimus
Available in topical form for Tx of skin disease Atopic dermatitis in adults and children >=2
y.o.
Intertriginous psoriasis, vitiligo, mucosal
lichen planus, allergic contact dermatitis,rosacea
Major benefit compared w/ steroids:
Does not cause skin atrophy used safely in
the face and intertriginous areas Side effect: transient erythema, burning and
pruritusimprove w/ constant Tx
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Due to potential for malignancy
productiontopical calcineurin inhibitors NOT
CONSIDERED 1ST LINE Tx in childhood atopic
dermatitis
Used only as 2nd line agents for short-term and
intermittent Tx of atopic dermatitis (eczema) in
pts unresponsive/intolerant to other Tx
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Other Immunosuppressive and Anti-inflammatory
agents
Mycophenolate mofetil
Inflammatory and auto-immune diseases in
dermatology
Imiquimod Immunomodulatory effects
For Tx of genital warts
Applied to lesions 2x a week for 16 weeks
Vinblastine Kaposi sarcoma
Advanced cutaneous T cell lymphoma
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Dapsone
Anti-inflammatory in sterile, pustular diseases ofskin
Dermatitis herpetiformis and leprosy
Side effects: methemoglobinemia, hemolysis
Thalidomide Anti-inflammatory, immunomodulating, anti-
angiogenic agent
Tx of erythema nodosum leprosum
Causes phocomelia
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Biologic agents
Target specific mediators of immunologicalreactions
For psoriasis
1. T-cell Activation inhibitors
Alefacept 1stagent approved for moderate to severe
psoriasis
Efalizumab
Interferes w/ T-cell activation andmigration and cytotoxic T-cell function
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2. TNF Inhibitors
TNF-prod by macrophages, T cells, dendritic
cells, keratinocytes in active psoriasis
Reduces inflammation, keratinocyte
proliferation, vascular
adhesionimprovement in psoriatic lesions
risk for serious infection
All patients-screened for TB, personal/family
Hx of demyelinating D/O, cardiac failure,
active infection, malignancy prior to Tx
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Etanercept
Recombinant, fully human TNF receptor fusion
protein
For pediatric psoriasis
Infliximab
Complementfixing antibody that inducescomplement-dependent and cell-mediated
lysis
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Sunscreens
Chemical agents that absorb incident solar
radiation in the UVB and or UVA ranges
Provide a broad spectrum of protection
Photostable
Remain intact for sustained periods on the skin Non-irritating, invisible and non-staining to
clothing
UVA Sunscreen agents
Avobenzone Oxybenzone
Titanium dioxide
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Zinc oxide
Ecamsule
UVB Sunscreen Agents
PABA esters
Cinnamates
Octocrylene Salicylates
SPF (sun protection factor)
Major measurement of sunscreen
photoprotection
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Ratio of the minimal dose of incident sunlight
that will produce erythema or redness (sunburn)
on skin w/ the sunscreen in place and the dose
that evokes the same reaction on skin w/o the
sunscreen
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Treatment of Pruritus
Symptom unique to skin
Occurs in a multitude of dermatological D/O
Dry skin/xerosis
Atopic eczema
Urticaria Infestations
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Agents used for the Tx of Pruritus (table 65-11)
Pruritoceptive pruritus-due to inflammation or
other cutaneous disease
Emollients
Coolants
Capsaicin Antihistamines
Topical steroids
Topical immunomodulators
Phototherapy
Thalidomide
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Neuropathic pruritus-due to disease of afferent N
Carbamazepine
Gabapentin
Topical anesthetics
Neurogenic pruritus-from NS
Thalidomide Opioid-receptor antagonists
Tricyclic antidepressants
SSRIs
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Psychogenic pruritus-due to psychological illness
Anxiolytics
Antipsychotics
Tricyclic antidepressants
SSRIs
Drugs for Hyperkeratotic D/O Keratolytic agents
For paoriasis, seborrheic dermatitis, xerosis,
ichthyoses, verrucae
-Hydroxy acids
Glycolic, lactic, malic, citric, hydroxycaprylic,
hydroxycapric, and mandelic
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Reduce the thickness of stratum corneum by
solubilizing components of the desmosome
Activating endogenous hydrolytic enzymes
Drawing water into stratum corneum
Salicylic acid
Solubilization of intercellular cement
reducedcorneocyte adhesionstratum corneum
softening
Prolonged and widespread use: Salicylism
Urea skin absorption and retention of water
flexibility and softness of skin
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Drugs for Androgenetic Alopecia
Male and female pattern baldness
Most common cause of hair loss in adults >40 y.o.
Tx: reducing hair loss, maintaining existing hair
Minoxidil
Anti HPN w/ hypertrichosis as side effect Enhances follicular sizethicker hair shafts
Stimulates and prolongs anagen phase of hair
cyclelonger and inc # of hair
Finasteride
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Tx of hyperpigmentation
Most effective on hormonally or light-induced
pigmentation w/in epidermis
Hydroquinone
1stline agent
melanocyte pigment production by inhibitingconversion of dopa to melanin thru inhibition
of tyrosinase