U3 medicine - pharmacology of dermatitis, acne, psoriasis, sunburn

dermatitis

pathophysiology

toxin reaches keratinocyte leading to cytokine release and itching

contact dermatitis

an inflammation of the skin caused by having contact with certain chemicals or substances

atopic dermatitis

excess inflammation; dry skin, redness, and itching from allergies and irritants

goals of therapy

restore epidermal barrier

treat inflammation

control itching

contact dermatitis treatment

first line

-non pharm supportive care

-topical corticosteroids

-oral antihistamines

second line

-increase steroid potency

third line

-oral corticosteroids

allergic dermatitis treatment

first line

-non pharm

-topical corticosteroids

second line

-topical calcineurin inhibitors (TCIs)

-PDE-4 inhibitors

-phototherapy

third line

-oral corticosteroids

non pharm treatment of dermatitis

moisturizers

1. emollients: lubricate and soften skin

>ceramides, dimethicone, squalene oil

2. occlusive agents: prevent water evaporation

>petrolatum, lanolin

3. humectants: attract and retain water

>hyaluronic acid, glycerin, alpha-hydroxy acids (AHAs)

-bathing

-wet-wrap therapy

>apply topical therapies followed by wet bandages

antihistamines

topical

-diphenhydramine

oral

-diphenhydramine

-cetirizine

-fexofenadine

-hydroxyzine

* cause drowsiness

topical corticosteroids

mechanism

-anti inflammatory (decreases release of cytokines)

-antipruritic

-vasoconstriction

adverse effects

topical - burning, itching, hypopigmentation, folliculitis

systemic -hyperglycemia, HPA axis suppression, fluid retention, hypertension, psychiatric disorders, GI ulcers, osteoporosis, infection

dosing

-apply fingertip amount

-increased drug penetration w hydrated skin

topical corticosteroid potencies

very high potency

-Clobetasol propionate 0.05% lotion, cream, ointment

-Fluocinonide 0.1% cream

-Halobetasol propionate 0.05% ointment

high

-Betamethasone dipropionate 0.05% cream

-Fluocinonide 0.05% ointment

-Mometasone furoate 0.1% ointment

high-medium

-fluocinonide 0.05% cream -fluticasone propionate 0.005% ointment

medium

-mometasone furoate 0.1% lotion, triamcinolone acetonide 0.1% cream

lower

Fluticasone propionate 0.05% cream, lotion

mild

Fluocinolone acetonide 0.01% cream

lowest

hydrocortisone 0.5%, 1%, 2.5% cream, lotion

topical calcineurin inhibitors

calcineurin = protein phosphatase

-Tacrolimus 0.03% and 0.1% ointment

-Pimecrolimus 1% cream

black boxed warning

-malignancy

-use under age 2

-avoid long term use

adverse effects

-burning

-swelling

-headache

-itching

-immunosuppresion

dosing

-apply twice daily to lesion until resolved

-apply 2-3 times per week for recurrence prevention

-do not apply with occlusive dressing

PDE-4 inhibitors

inhibition PDE-4 enzyme leads to elevated cAMP levels which is helpful in reducing inflammation

adverse effects

-burning, stinging

-URIs

-nasopharyngitis

dosing

-apply twice daily to affected area

refractory atopic dermatitis

oral corticosteroids

-prednisone

antimetabolites

-methotrexate

oral calcineurin inhibitor

-cyclosporine

immunosupressants

-azathioprine

-mycophenolate

special populations

pediatrics

-use least potent topical corticosteroid since absorption is greater

geriatrics

-topical corticosteroids may cause skin atrophy

pregnancy

-systemic therapies pose harm to fetus

-avoid methotrexate

psoriasis

pathophysiology

genetics/stress/infection/med rxn causes an abnormal inflammatory response that results in hyperproliferation and abnormal differentiation of epidermal kertinocytes

psoriasis

goals of therapy

-decrease size/thickness of plaques

-decrease pruritis

-remission

-improve quality of life

mild/moderate psoriasis

plaques cover less than 10% of body surface

tx: topical agents

psoriasis treatment

first line

-topical corticosteroids (high-very high potency)

-moisturizers

second line

-1 week rest, then repeat 2x cycles

-topical corticosteroids and vitamin D analog

third line

-refer to derm

cold tar products

mechanism

-decreases dna synthesis

-anti inflammatory

-antipruritic

application

-dissolves in water and affected area submerged

-apply 3-7 times per week for 30-45 days

disadvantages

-stains clothing, skin, tubs, sinks

-odorous

-photosensitivity

vitamin D analogs

Calcipotriene and Calcipotriol

to the body, they look like vitamin D

bind to vitamin D receptors which inhibits the epidermal keratinocyte proliferation which reducs lesions

vitamin d analogs

contraindications

-hypercalcemia

-vitamin D toxicity

adverse effects

-skin peeling

-skin dryness

-hypercalcemia

-rash

application

-twice daily for 6-8 weeks

time to response

2-4 weeks

retinoids (vitamin A derivatives)

Tazarotene

modulates epithelial differentiation which decreases hyperproliferation which decreases inflammation

contraindications

-pregnancy

adverse effects

-itching

-burning

-erythema

interactions

-phososensitizing agents

-topical irritants

-oral vitamin A

applications

-once daily at bedtime, allow to air dry

time to response

-1 week-8 weks

combination products for psoriasis

Betamethasone 0.064% and calcipotriene 0.005%

Halobetasol propionate 0.01% and tazarotene 0.045%

systemic agents for psoriasis

Systemic Retinoids

>> Acitretin

Antimetabolites

>> Methotrexate

Calcineurin Inhibitors

>> Cyclosporine Phosphodiesterase-4 Inhibitors

>> Apremilast (Otezla)

biologics

TNF-alpha Inhibitors

-Etanercept (Enbrel)

-Infliximab (Remicade)

-Adalimumab (Humira)

-Certolizumab pegol (Cimzia)

IL-12 and IL-23 Inhibitors •

-Ustekinumab (Stelara)

IL-17 Inhibitors

-Secukinumab (Cosentyx)

-Ixekizumab (Talz)

-Brodalumab (Siliq)

IL-23 Inhibitors

-Guzelkumab (Tremfya)

-Tildrakizumab (Ilumya)

-Risankizumab (Skyrizi)

biologics

Considerations for all agents

-Tuberculosis testing

-Hepatitis B and C testing

-Injections

Contraindications

-live vaccines

-malignancy

-active infection

drugs that exacerbate psoriasis

lithium, antimalarials, beta blockers, systemic interferon drugs, alcohol, systemic corticosteroids (if stopped)

acne

pathophysiology

-increased androgen production/sebum production leads to comedones and inflammation (hormone)

-C. acnes produce enzymes that activate extracellular products, which attract leukocytes and monocytes and lead to inflammation

medications that can cause acne like presentation

corticosteroids

isoniazid

lithium

pheyntoin

trimethadione

*differentiate because reactive comedones here would have same shape/size/progression

comedonal acne

blackheads/whiteheads

mild inflammatory acne

papules

moderate inflammatory acne

pustules, cysts

severe cystic acne

cysts, nodules, scarring

acne

goals of therapy

-minimize number and severity of lesions

-prevent scarring

-improve patients appearance

acne

first line treatment

-topical comedolytic agents +/- a topical antibiotic

second line

-add oral antibiotic

-consider oral contraceptives

third line

-isotretinoin

-dermatology consult

mild = topicals

moderate/severe = orals

acne

non pharm treatment

-facial cleanser

-avoid picking/popping

-limit sugar and dairy intake

-water based, non comedogenic, fragrance free moisturizers and cosmetic

tretinoin

decreases epidermal cell cohesion which increases epidermal cell turnover, causing open comedones to be expelled and closed comedones to convert to open

tretinoin

contraindications

-pregnancy

-fish allergies

adverse effects

-erythema

-drying and peeling of skin

-photosensitivity

considerations

- if sensitive skin, start every other day or wash off after apply

adapalene

naphthoic acid derivate which binds to retinoid receptors whicih modulate cell differentiation, keratinization, and inflammation

adapalene

contraindications

-pregnancy

adverse effects

-erythema

-skin dryness/peeling

-photosensitivity

considerations

-apply in evening

-irritation subsides with continued use

-available OTC

tazarotene

contraindications

-pregnancy

adverse effects

-skin dryness/peeling

-burning

-redness

considerations

-apply alternating days at first to reduce irritation

-moisturize prior to application

benzoyl peroxide

bactericidal drug that decreases levels of C. acnes, which decreases leukocyte and monocyte attraction, reducing inflammation

benzoyl peroxide

contraindications

-none

adverse effects

-irritation

-erythema

-dryness

considerations

-available otc

-may bleach hair, towels, clothing

azelaic acid

inhibits DNA synthesis of bacteria leading to decreased bacterial growth and decreased inflammation

azelaic acid

contraindications

-none

adverse effects

-irritation

-erythema

-dryness

considerations

-alternate application days when starting

-more mild

-hypopigmentation in darker skin

dapsone

mechanism not well understood

antibacterial and antiinflammatory response

dapsone

contraindications

-none

adverse effects

-methemoglobinemia

-erythema

-sinusitis

-hemolysis in select patients

considerations

-orange discoloration when used with benzyl peroxide

topical antibiotics

clindamycin and minocycline

inhibit C acnes growth which decreases inflammation, which limits number of comedones, papules, pustules

topical antibiotics

contraindications

-none

adverse effects

-colitis/enteritis

considerations

-wash with benzyl peroxide first to prevent resistance

combination topical products

Erythromycin 3% and benzyl peroxide 5%

Clindamycin 1% and benzyl peroxide 5%

Clindamycin 1.2% and tretinoin 0.25%

Adapalene 0.1% and benzyl peroxide 2.5%

Adapalene 0.3% and benzyl peroxide 2.5%

oral antibiotics

tetracyclines and derivatives

-tetracycline

-doxycycline

-minocycline

-sarecycline

others

-TMP sulfas

-erythromycin

oral antibiotics

mechanism

-suppress C acnes growth

-inhibit neutrophil activity

-stop follicilar plugging

adverse effects

-photosensitivity

-GI upset

-blood dyscrasias

considerations

-tetracyclines for age > 12 and not in pregnancy

-long term use can lead to resistance

-agent specific drug interactions

isotretinoin

mechanism not fully understood

-Rrduces sebaceous gland size and sebum production which decreases follicular obstruction which then decreases bacteria

isotretinoin

dosing

-treat for 20-24 weeks

-must have 6 month break before 2nd round of treatment

adverse effects

-excessive skin and mucous membrane dryness

-bone density effects

-muscle aches

-visual disturbances

-hepatic effects

considerations

-baseline CBC, chemistry, lipid panel and repeat every month

-black box warning for aggression and violence

iPLEDGE REMS program

uses isotretinoin

teratogenic

2 negative pregnacy tests prior to initiation and 2 forms of bc for 30 days

1 negative test each month

1 month after discontinuation

hormonal therapies

oral contraceptive

-Ethinylestradiol

-Levonorgestrel

-Norgestimate

-Drospirenone

and

spironolactone

spironolactone

mechanism

-androgen blocker

adverse effects

-hyperkalemia

-gynecomastia

common adverse effects

-GI upset and dizziness

sunburn

UV rays cause DNA damage, causing mast cells to release cytokines, leading to inflammation and skin cell apoptosis, vasodilation, and erythema

sunburn

goals of therapy

-prevent skin cancer

-pain relief

-prevent dehydration

-prevent aging skin

sunburn

treatment

-cool bath/shower

-aloe vera, soy products, colloidal oatmeal bath

-ibuprofen or aspirin

-extra water intaje

-keep blisters clean and protected w petroleum jelly

sunburn prevention

avoid direct sun from 10 AM - 4 PM

wear protective clothing

sit in shaded areas

wear broad spectrum sunscreen (covers UVA and UVB)

time to burn

TTB (with sunscreen) = SPF x TTB (no sunscreen)

medication induced photosensitivity

Hydrochlorothiazide, furosemide

Naproxen, ibuprofen, ketorolac

Levofloxacin, ciprofloxacin, moxifloxacin

Amiodarone

Doxycycline, tetracycline

Voriconazole

SSRIs, SNRIs, TCAs