PHARM I: EXAM #2 (DERM)

In general, what Dermatologic Vehicle(s) are better for Oozing, vesiculation, crusting?

- Tinctures (most drying)

- Wet dressings

- Lotions

- Gels

- Aerosols

(**I split the list in half = not a hard list!)

In general, what Dermatologic Vehicle(s) are better for Scaling, lichenification, xerosis?

- Powders

- Pastes

- Creams

- Foams

- Ointments (least drying)

(**I split the list in half = not a hard list!)

___________: Oil in water emulsion

> 31% water

- Pharmacologic Advantage: ***Leaves conc. Drug on skin surface

- Advantages: Spreads and removes easily, no greasy feel

- Most locations

- Disadvantages: Needs preservatives

- Occlusion: Low

- Composition Issues: Requires humectants

Cream

__________: Water in Oil

< 25% water

- Pharmacologic Advantage: Protective oil film on skin

- Spreads easily

- **Avoid intertriginous areas**

- Greasy feel, stains clothes

- Occlusion: Moderate to high

- Composition Issues: Needs surfactants to prevent phase separation

Ointment

_____________: Water-soluble emulsion

- Water-soluble polyethylene glycols

- Non-staining, greaseless

- Foams well for scalp & hairy locations

- Needs preservatives, alcohol bases can dry skin

Gel/Foam

_________________: Solution-dissolved drug base

- Lotion-suspended drug

- Aerosol propellant with drug

- May be aqueous or alcoholic

- Low residue on scalp

Lotion/Solution/Foam

Four major factors of ________:

1. INC sebum production

2. Alteration in keratinization process and hyperproliferation of ductal epidermis

3. Bacterial colonization (Propionibacterium acnes)

4. Release of inflammatory mediators in acne sites

Acne

Drug-Induced Acne

___________________:

- Pustular inflammation on the trunk

2-6 weeks after initiation of therapy

- Not with hydrocortisone

- Removal leads to initial worsening (due to increased inflammation)

- Antiepileptics

- Tuberculostatics

- Lithium

Systemic corticosteroids

ACNE Treatment:

_____________: systemic therapy

Moderate-severe

ACNE Treatment:

______________: topical therapy

Mild-moderate

Non-Pharmacologic Therapy

___________: Surfactant systems to disperse and remove fat/oils from skin surface

- Must balance between cleanliness & drying/irritation

Soaps are not always the best products

- Once rinsed off, no further active product remains

- High pH may degrade some activity of other agents

-- Also less tolerable on the skin

Don’t wash too frequently (twice a day)

Cleansing

Mechanism: penetrates Stratum Corneum unchanged and is then converted to Benzoic Acid

- Benzoic acid has activity against P. acnes

- Peeling and comedolytic effects

Start @ low concentration (2.5%) once daily

- INC strength and frequency as tolerated

Available OTC***

Often found in combination with antibiotics

- Erythromycin, clindamycin, etc.

Adverse reactions: can bleach hair, clothes, skin/mucous membrane irritation

Benzoyl Peroxide

______________: Straight chain Dicarboxylic Acid

Mechanism: not fully understood, likely d/t antimicrobial activity & inhibiting the conversion of testosterone to dihydrotestosterone (LOCALLY)

Start 1x/daily then INC to 2x/daily

Adverse reactions: mild skin irritation/dryness

- Improves over 6-8 weeks with continuous therapy

- Hypopigmentation**

Azelaic Acid (Azelex)

Topical Retinoids

________________– acid form of Vitamin A

Mechanism: not completely understood

- Corrects abnormal follicular keratinization

- Reduces P. acnes counts

- Reduces inflammation

***1ST-LINE therapy for Noninflammatory (Comedonal) Acne

Often combined with other agents for inflammatory acne

Useful for wrinkles and dyspigmentation

Retinoic acid (AKA tretinoin, Retin-A)

Adverse effects:

- Erythema, desquamation, burning/stinging

- DEC with time and use of emollients

- **Photosensitivity & severe Sunburn**

- ***AVOID during pregnancy*** (Vit A = fat-soluble... don't mess with those during pregnancy!)

Tretinoin

- Photolabile (apply nightly)

- Benzoyl peroxide inactivates tretinoin

Topical Retinoids

"-l/tene + Alitretinoin"

_______________:

Adapalene (Differin®)

- Stable in sunlight, stable with benzoyl peroxide

- Tends to be less irritating

Tazarotene (Tazorac®)

- 3rd Gen retinoid used for acne and psoriasis

- Sometimes combined w/topical steroids to reduce skin irritation

Alitretinoin (Panretin®)

- Used in Kaposi sarcoma

Bexarotene (Targretin®)

- Used in T-cell lymphoma

Topical Retinoids

"-l/tene + Alitretinoin"

__________________ for Acne

- Clindamycin (Cleocin-t®) – preferred**

- Erythromycin (Eryderm®)

- Losing efficacy over time due to P. acnes resistance

- Lack systemic side effects

Topical Antibiotics

"-mycin"

____________________:

***Isotretinoin (Accutane®): effective in 1-3 months

***CONTRAINDICATED in PREGNANCY/breastfeeding

- MEN should avoid as well (SEMINAL FLUID)

- iPledge

Adverse reactions:

- Retinoid dermatitis – erythema, pruritus, scaling

- Photophobia

- Arthralgia, headaches, alopecia, brittle nails

- INC serum lipids

- ***Monitor for signs of developing depression/SI

Systemic Retinoids

________________: Used for more extensive/difficult to treat disease

Tetracyclines: Tetracycline, doxycycline (Vibramycin), minocycline (Minocin)

- M/C used, safe/effective, inexpensive

- Chelate calcium ions that prevent neutrophil and monocyte chemotaxis

- C/I in children < 8 years and pregnant women

Trimethoprim/sulfacetamide (Bactrim)

Azithromycin (Zithromax)

Ciprofloxacin (Cipro)

Systemic Antibiotics

______________:

- Used for many years, few studies to support use

- Keratinolytic

- Mild anti-inflammatory/anti-microbial activity

Salicylic acid

___________:

- Spironolactone (Aldactone)

- Gel available

Antiandrogens

____________________:

- Useful in some women

- Ethinyl estradiol & norethindrone/ethinyl estradiol

Oral contraceptives (OCs)

_______________:

- Effective for individual inflammatory nodules

- Systemic absorption can occur adrenal suppression

- Local tissue atrophy

Intralesional steroids

______________:

- Low dose therapy can reduce symptoms in adrenal hyperactivity

- Short course therapy may be beneficial in highly inflammatory disease

E.g., Prednisone (Deltasone), Dexamethasone (Decadron)

Oral corticosteroids

___________: Mainly comedones with an occasional small inflamed papule or pustule; no scarring present

Topical retinoid is the DOC; can also consider benzoyl peroxide or salicylic acid

Continue until lesions are completely cleared and then stop or taper therapy.

If it doesn't work: Treat as Type Il acne

Type l

__________: Comedones and more numerous papules and pustules (mainly facial); mild scarring.

Topical retinoid plus benzoyl peroxide, topical or antibiotic

Continue until lesions are completely cleared and then stop or taper therapy

If it doesn't work: Treat as Type Ill acne

Type Il

____________: Numerous comedones, papules, and pustules spreading to the back, chest, and shoulders, with an occasional cyst or nodule; moderate scarring.

Systemic Abx plus topical retinoid, or benzoyl peroxide

Oral Abx Rx for daily use over 4-6 mo. Tapering & D/C as acne improves. Other agents can also be stopped/tapered @ this time.

No response after 3 months: Add OC or antiandrogen (women only)

Oral isotretinoin (except in women who are or who may become pregnant). Consider safety endpoints (potential adverse effects) before initiating therapy.

Type Ill

___________: Numerous large cyst on the face, neck & upper trunk; severe scarring

Systemic Abx plus topical retinoid, and benzoyl peroxide +/- OC or

antiandrogen (females only)

Oral Abx Rx for daily use over 4-6 mo, with tapering & D/C as acne improves. Other agents can also be stopped or tapered @

this time.

If no response after 3-6 mo, Oral Isotretinoin (except in women who are or who may become pregnant). Consider safety end points (potential

adverse effects) before initiating therapy.

Type IV

Atopic Dermatitis

______________________ are gold standard

- Choice of agent depends on severity and site of disease

Low potency steroids

- Suitable for face, intertriginous areas, infants

- Better for long term therapy

Medium potency

- Used for the body

Exacerbations

- Medium-high potency corticosteroids warranted

- Use for 1-2 weeks then switch to lower potency

Topical corticosteroids

Adverse reactions:

Related to potency, duration, area of the body covered, occlusiveness of the preparation (ointment > cream > lotion)

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

Systemic: adrenal suppression, infections, hyperglycemia, glaucoma, cataracts, growth retardation (in children)

(Same as systemic corticosteroids! Just not as much...)

Topical Steroids

Are Hydrocortisone Butyrate 0.2 % ointment and Hydrocortisone Valerate 0.2% ointment MORE or LESS powerful than Hydrocortisone 0.5%? Why?

MORE powerful (Salt form makes it more lipophilic)

_____________________:

Available agents:

Tacrolimus ointment (Protopic®)

Pimecrolimus cream (Elidel®)

- Reduce extent, severity, and symptoms

Mechanism: inhibit activation of T cells, mast cells, and keratinocytes

***2ND-LINE agents after topical steroids

- Possible cancer risk

- Avoid in patients with weakened immune systems

Adverse reactions: burning sensation

***Use high SPF sunscreen

Topical Immunomodulators

__________________ – sometimes used for short courses during exacerbations

Provide rapid relief

Need tapering dose to prevent flare-up

E.g., Prednisone (Deltasone), Dexamethasone (Decadron), methylprednisolone (Medrol dose pack)

Oral corticosteroids

__________________: Peptide antibiotic – prevents cell wall synthesis

Broad antimicrobial coverage

- Streptococci, staphylococci

- Anaerobic cocci

- Tetanus bacilli

Use alone or in combination:

- Neomycin, polymyxin B

Adverse effects – allergic dermatitis rarely

- No systemic toxicity

Bacitracin

___________________: Binds to bacterial t-RNA preventing protein synthesis

Coverage – most gram-positive aerobes (esp. MRSA)

- Used to eliminate nasal carriage of S. aureus

- Not absorbed, but may cause mucous membrane irritation

-- Polyethylene glycol vehicle

Mupirocin (Bactroban®)

___________________: Peptide antibiotic – interrupts cytoplasmic membrane

Effective against gram-negative organisms

- Pseudomonas, E. coli, Klebsiella, etc.

Allergic reactions uncommon

Avoid using on open wounds/denuded skin in high doses – risk for neuro/nephrotoxicity

(**Big wide road rash, this is NOT GOOD FOR IT. Use Bacitracin!)

Polymyxin B

______________: Inhibit bacterial protein synthesis

- Good activity against gram negative organisms

- Neomycin & gentamicin

Can have a systemic accumulation

Neomycin frequently causes sensitization

Aminoglycosides

Agents include: Clotrimazole, Ketoconazole, Miconazole, Sertaconazole

Mechanism: inhibits fungal ***P450*** preventing cell wall formation

- Used for topical and vaginal uses (vulvovaginal candidiasis)

- Sometimes combined with corticosteroids (more rapid symptom relief)

- Treatment is generally prolonged (2-3 weeks)

Adverse reactions: local irritation

Azole Antifungals

Mechanism: inhibits uptake molecular precursors at the fungal cell wall

- Used topically for dermatomycosis, candidiasis, and tinea versicolor

- Also marketed as a nail lacquer for onychomycosis of fingernails and toenails (< 12% effective)

Efficacy is super f*cking low!

Ciclopirox (Penlac®)

________________:

- Naftifine

- Terbinafine (Lamisil®)

Mechanism: inhibits the production of ergosterol and prevents cell wall synthesis

Adverse reactions: local irritation

Allylamines

Acyclovir (Zovirax), penciclovir (Denavir)
Synthetic guanine analogs
Active against herpesvirus (simplex 1 and 2)
- Used for recurrent orolabial herpes simplex infection
Adverse reactions: local irritation

Topical Antivirals

_______________: immunomodulator – stimulates peripheral mononuclear cells to release interferon-α and stimulates macrophages to produce TNF-α and interleukins

Indications: external and perianal WARTS, actinic keratoses, basal cell carcinoma

Applied 2-5x/week

Adverse reactions: SKIN IRRITATION in virtually ALL patients

- Edema, vesicles, erosions, ulcers – degree of inflammation parallel efficacy

Imiquimod (Aldara®)