Dermatologic Pharmacology (Pharm)

Variables that determine response to topical dermatologic medications

-Physicochemical properties (charged/uncharged, hydrophobic/hydrophilic, pH, etc)

-Regional drug penetration (face, scalp, axillae)

-Concentration gradient

-Dosing schedule

-Vehicle/occlusion

-Skin condition/health and integrity (skin damage, trauma=increased drug penetration)

Purpose of a dermatologic vehicle

Carries the active ingredient and facilitates application to the skin

What factors should be considered when choosing a dermatologic vehicle?

Solubility, rate of release, hydration, stability, and interactions

types of dermatologic vehicles

tinctures, wet dressings, lotions, gels, aerosols, powders, pastes, creams, foams, ointments

Acute inflammation with oozing, vesiculation, and crusting

Use DRYING preparations: tinctures, wet dressings, or lotions

Chronic inflammation with xerosis, scaling, or lichenification

Use LUBRICATING preparations: creams or ointments

Best vehicles for the scalp/hairy areas

Tinctures, lotions, gels, foams, and aerosols

Vehicles and type of medication influence

strength more than percentage of medication dissolved in vehicle

Vehicle potency from greatest → least

Ointment (most potent) > cream > lotion

Cream

Water-based (oil in water), rapidly absorbed, allows air/fluid exchange, drying: open lesions, and has good spreadability

When are creams especially useful?

Open lesions and larger areas of skin

Ointment

Oil-based (water in oil), holds in moisture, and is useful for dry/cracked skin, difficult to remove from skin

When should ointments be avoided?

Open or weeping lesions because they may trap fluid and bacteria

Gels

May contain alcohol and can cause irritation/burning on open lesions

Sprays

Easy to apply to large areas, but propellants may cause inflammation

Best formulations for oily-to-normal skin

Gels, solutions, and lotions

Best formulations for normal-to-dry skin

Lotions and creams

Factors affecting topical corticosteroid absorption

Chemical structure, anatomical location, normal skin vs. inflamed skin, vehicle, and drug solubility in vehicle

how does the vehicle affect topical corticosteroid absorption?

solubility - "optimized vehicles"

Which vehicle increases corticosteroid absorption the most?

Ointments more potent > creams or lotions

Does increasing the concentration of a topical steroid always proportionally increase its effect?

No

Topical corticosteroid potency categories

Very low → low → moderate → high → very high

Hydrocortisone 0.25-2.5% potency

Very low

-lowest a patient can get OTC

Triamcinolone acetonide 0.1% potency

Moderate

Betamethasone diproprionate 0.05% potency

High

Local adverse effects of topical corticosteroids

Skin atrophy, striae, hypopigmentation, and steroid-induced acne

*longterm use

When are systemic adverse effects from topical corticosteroids more likely?

When used over extensive areas for prolonged periods

Systemic adverse effects of topical corticosteroids

HPA-axis suppression (oral vs. topical) , Cushing syndrome, and growth retardation

Why should topical corticosteroids be limited in children?

Greater concern for systemic effects and growth retardation

corticosteroid use in children -how should it be used?

shortest course, lowest potency

Where are HIGH-potency steroids appropriate?

Areas with poor penetration, such as elbows and knees

Where should LOW-potency steroids be used?

Areas with high penetration, such as face, axillae, and groin

*choose in infants and children

General steroid rule

Thicker skin = higher potency may be needed; thin/sensitive skin = lower potency

Contact dermatitis

Dermatitis resulting from contact with a triggering factor

Two types of contact dermatitis

Irritant contact dermatitis + allergic contact dermatitis

Common irritant contact dermatitis triggers

Soaps, detergents, cosmetics, solvents, acids, and alkalis

Allergic contact dermatitis mechanism

Delayed hypersensitivity

Common allergic contact dermatitis triggers

Poison ivy/oak/sumac, metals, latex/rubber, cigarette smoke, and local anesthetics

First step in treating contact dermatitis

Identify and remove the offending agent

Purpose of topical steroids in contact dermatitis

Reduce erythema, inflammation, pain, and itching

When are systemic steroids used for contact dermatitis?

Severe dermatitis, particularly severe poison ivy dermatitis

Why should very short systemic steroid courses be avoided in severe contact dermatitis?

Risk of rebound dermatitis

Rebound dermatitis treatment

short course

-six-day course of methylprednisolone (Medrol) dose pack

Systemic steroid regimen for severe contact dermatitis from the lecture

Prednisone 1 mg/kg/day, maximum initial dose 60 mg/day, tapered over 3 weeks

Role of oral antihistamines in contact dermatitis

Treat pruritus

Example of a sedating antihistamine used for pruritus

Diphenhydramine (Benadryl)

Sedative side effects of sedating oral antihistamines

dizziness, blurred vision, confusion, hypotension

Why aren't topical antihistamines preferred?

Risk of sensitization

Atopic dermatitis

Eczema characterized by chronic, relapsing, itchy, inflamed skin

Standard nonpharmacologic treatment for atopic dermatitis

Frequent moisturizers throughout the day

Bathing recommendation for atopic dermatitis

Lukewarm baths followed immediately by moisturizer

Cleansers recommended for atopic dermatitis

Nonsoap cleansers

Main goal of nonpharmacologic atopic dermatitis treatment

Promote skin hydration

Standard-of-care pharmacologic treatment for atopic dermatitis

Topical corticosteroids

Topical immunomodulators for atopic dermatitis

Tacrolimus and pimecrolimus

Options for refractory atopic dermatitis

UV radiation, oral corticosteroids, cyclosporine, azathioprine, methotrexate, or interferon-γ

Tacrolimus and pimecrolimus drug class

Topical calcineurin inhibitors/macrolide immunosuppressants

Tacrolimus and pimecrolimus MOA

Inhibit T-lymphocyte activation and prevent release of inflammatory cytokines after stimulation by antigen-IgE complexes

Tacrolimus and pimecrolimus indication

Short-term and intermediate long-term treatment of atopic dermatitis

Contraindication to tacrolimus/pimecrolimus

Hypersensitivity

Major adverse effect of topical calcineurin inhibitors

Burning at the application site, which usually improves with continued use

Black box warning for topical calcineurin inhibitors

Rare malignancies, including skin malignancy and lymphoma, have been reported, although a causal relationship has not been established

Should topical calcineurin inhibitors be used continuously long-term?

No; continuous long-term use should be avoided

Minimum age for topical calcineurin inhibitors in this lecture

Not indicated in children

Tacrolimus formulation

0.03% (children) or 0.1% ointment

Pimecrolimus formulation

1% cream

Crisaborole (Eucrisa)

2% ointment (Emollient-ruch Vehicle)

Topical phosphodiesterase-4 (PDE-4) inhibitor used for atopic dermatitis

Crisaborole indication

Mild-to-moderate atopic dermatitis in patients ≥3 months old

Crisaborole MOA

PDE-4 inhibition; thought to reduce excessive inflammatory cytokine release

-similar to calcineurin inhibitors, affects immune dysregulation

Crisaborole dosing

Apply a thin layer twice daily; may decrease to once daily after clinical response

Crisaborole adverse effects

Burning and stinging at application site

Crisaborole contraindication

Hypersensitivity

Key principle of acne treatment

Multimodal therapy combining multiple mechanisms of action is recommended

Noncomedogenic facial washes

Recommended for mild acne

*gentle/non-irritating: Cetaphil, Pears

OTC acne add-on options

Benzoyl peroxide (BPO) or salicylic acid

*can increase irritation

*caution with sensitive skin, skin drying

Salicylic acid

Keratolytic agent

*irritating

FDA Type 1 acne

Almost clear: rare noninflammatory lesions and ≤1 small inflammatory lesion

FDA Type 2 acne

Mild: some noninflammatory lesions, few inflammatory papules/pustules, NO nodules

FDA Type 3 acne

Moderate: many noninflammatory lesions, some inflammatory lesions, and ≤1 nodule

FDA Type 4 acne

Severe: many inflammatory/noninflammatory lesions, numerous large cysts, and severe scarring

Topical retinoids used for acne

Tretinoin, adapalene, tazarotene, and trifarotene

Main indication for topical retinoids

First-line therapy for mild-to-moderate inflammatory acne and comedonal acne

Can topical retinoids be used for acne maintenance?

Yes

What should be combined with topical retinoids for moderate inflammatory acne to maximize efficacy?

Topical antibiotics or BPO

Topical retinoid adverse effects (ADRs)

Irritation, dryness, erythema, peeling, burning, pruritus, initial acne flare, and photosensitivity

Topical retinoids ranked most → least irritating

Tazarotene > tretinoin > adapalene

Topical retinoids should be avoided in

Pregnancy and children

Tretinoin MOA

Topical vitamin A analog that increases follicular cell turnover → extrudes existing comedones and prevents new comedones

Adapalene

Third-generation retinoid with comedolytic, keratolytic, and anti-inflammatory activity

-retinoidmimetric compound (a naphthoic acid derivative)

-selective affinity for retinoic acid receptor (RAR) subtypes RAR-B and RAR-Y found in epidermis

Major advantage of adapalene

Less skin irritation/discoloration than first-generation tretinoin

Tazarotene

Prodrug converted to tazarotenic acid after topical application; affects genes involved in cell proliferation, differentiation, and inflammation

-Comedolytic, keratolytic, and anti-inflammatory activty

Trifarotene

Newest retinoid class; selectively targets RAR-γ

How should topical retinoids be applied?

Small pea-sized amount over the entire face once daily at bedtime

Where should topical retinoids NOT be applied?

Abraded skin, mucous membranes, eyes, mouth, or nose

When should patients expect visible improvement with topical retinoids?

4-8 weeks

When may full topical retinoid effect occur?

Up to 3 months

What may happen when first starting a topical retinoid?

Acne may initially worsen

Important counseling with topical retinoids

Avoid excessive sun exposure and wear sunscreen

Topical antibiotics used for acne

Erythromycin, clindamycin, and minocycline

Topical antibiotic actions in acne

Bactericidal against P. acnes with comedolytic and anti-inflammatory effects