1. Drugs for Diseases and Disorders of Skin

2. Acne vulgaris
Acne vulgaris is a common, usually self-limiting, multifactorial disease involving inflammation of the sebaceous follicles of the face and upper trunk.
The four primary factors involved in the formation of acne lesions are
increased sebum production
sloughing of keratinocytes
bacterial growth
and inflammation.
Increased androgen activity at puberty triggers growth of sebaceous glands and enhanced sebum production.

3. The goals of treatment are to prevent the formation of new acne lesions, heal existing lesions, and prevent or minimize scarring.
TREATMENT
Patient education about goals, realistic expectations, and dangers of
overtreatment is important to optimize therapeutic outcomes. Treatment
regimens are targeted to types of lesions and acne severity
✓ Mild acne usually is managed with topical retinoids alone or with topical antimicrobials, salicylic acid, or azelaic acid.
✓ Moderate acne can be managed with topical retinoids in combination with oral antibiotics and, if indicated, benzoyl peroxide.
✓ Severe acne is often managed with oral isotretinoin.
Initial treatment is aimed at reducing lesion count and may last from a few months to several years; chronic indefinite therapy may be required to maintain control in some cases.

4. Topical treatment forms include creams, lotions, solutions, gels, and
disposable wipes. Responses to different formulations may depend on skin type and individual preference.
Antibiotics such as tetracyclines and macrolides are the agents of choice for papulopustular acne.
Oral isotretinoin is the treatment of choice in severe papulopustular acne and nodulocystic/conglobate acne. Hormonal therapy may be an effective alternative in female patients.

5. NONPHARMACOLOGIC THERAPY
Surface skin cleansing with soap and water has a relatively small effect on acne because it has minimal impact within follicles.
Skin scrubbing or excessive face washing does not necessarily open or cleanse pores and may lead to skin irritation.
Use of gentle, nondrying cleansing agents is important to avoid skin
irritation and dryness during some acne therapies.

6. TOPICAL PHARMACOTHERAPY
Benzoyl Peroxide
• Benzoyl peroxide may be used to treat superficial inflammatory acne. It is a nonantibiotic antibacterial that is bacteriostatic against P. acnes. It is decomposed on the skin by cysteine, liberating free oxygen radicals that oxidize bacterial proteins. It increases the sloughing rate of epithelial cells and loosens the follicular plug structure, resulting in some degree of comedolytic activity.
• Soaps, lotions, creams, washes, and gels are available in concentrations of 1% to 10%. The 10% concentration is not significantly more effective but
may be more irritating. Gel formulations are usually most potent, whereas
lotions, creams, and soaps have weaker potency. Alcohol-based gel preparations generally cause more dryness and irritation.

7. TOPICAL PHARMACOTHERAPY
Benzoyl Peroxide
• To limit irritation and increase tolerability, begin with a low-potency
formulation (2.5%) and increase either the strength (5% to 10%) or
application frequency (every other day, each day, then twice daily).
• Patients should be advised to apply the formulation chosen to cool, clean, dry skin no more often than twice daily to minimize irritation. Fair or
moist skin is more sensitive; patients should apply the medication to dry
skin at least 30 minutes after washing.
• Side effects include dryness, irritation, and allergic contact dermatitis. It
may bleach or discolor some fabrics (e.g., clothing, bed linen, towels).

9. Tretinoin
• Tretinoin (a retinoid; topical vitamin A acid) is a comedolytic agent that increases cell turnover in the follicular wall and decreases cohesiveness of cells, leading to extrusion of comedones and inhibition of new comedo formation. It also decreases the number of cell layers in the stratum corneum from about 14 to about five.
• Tretinoin is available as 0.05% solution (most irritating), 0.01% and
0.025% gels, and 0.025%, 0.05%, and 0.1% creams (least irritating).
• Treatment initiation with 0.025% cream is recommended for mild acne in people with sensitive and nonoily skin, 0.01% gel for moderate acne on easily irritated skin in people with oily complexions, and 0.025% gel for
moderate acne in those with nonsensitive and oily skin.

10. Tretinoin
• Patients should be advised to apply the medication to dry skin approximately 30 minutes after washing to minimize erythema and irritation. Slowly increasing the application frequency from every other day to daily and then twice daily may also increase tolerability.
• A flare of acne may appear suddenly after initiation of treatment, followed by clinical clearing in 8 to 12 weeks. Once control is established, therapy should be continued at the lowest effective concentration and the longest effective interval that minimizes acne exacerbations.

11. Side effects
include skin irritation, erythema, peeling, allergic contact dermatitis (rare), and increased sensitivity to sun exposure, wind, cold, and other irritants.
• Concomitant use of an antibacterial agent with tretinoin can decrease keratinization, inhibit P. acnes, and decrease inflammation. A regimen of benzoyl peroxide each morning and tretinoin at bedtime may enhance
efficacy and be less irritating than either agent used alone.

12. Adapalene
• Adapalene (Differin) is a third-generation retinoid with comedolytic, keratolytic,
and antiinflammatory activity. It is available as 0.1% gel, cream, alcoholic solution, and pledgets. A 0.3% gel formulation is also available.
• Adapalene is indicated for mild to moderate acne vulgaris. The 0.1% gel can be used as an alternative to tretinoin 0.025% gel to achieve better tolerability in some patients.
• Coadministration with a topical or oral antibiotic is reasonable for moderate forms of acne.

13. Tazarotene
• Tazarotene (Tazorac) is a synthetic acetylenic retinoid that is converted to its active form, tazarotenic acid, after topical application.
• It is used in the treatment of mild to moderate acne vulgaris and has comedolytic, keratolytic, and antiinflammatory action.
• The product is available as a 0.05% and 0.1% gel or cream.
• Dose-related adverse effects include erythema, pruritus, stinging, and burning.

14. Erythromycin
• Erythromycin in concentrations of 1% to 4% with or without zinc is
effective against inflammatory acne. Zinc combination products may enhance penetration of erythromycin into the pilosebaceous unit.
• Topical erythromycin formulations include a gel, lotion, solution, and disposable pads that are usually applied twice daily.
• Development of P. acnes resistance to erythromycin may be reduced by combination therapy with benzoyl peroxide.

15. Clindamycin
• Clindamycin inhibits P. acnes and provides comedolytic and antiinflammatory
activity.
• It is available as 1% or 2% concentrations in gel, lotion, solution, foam, and disposable pad formulations and is usually applied twice daily.
Combination with benzoyl peroxide increases efficacy.

16. Azelaic Acid
• Azelaic acid (Azelex) has antibacterial, antiinflammatory, and comedolytic activity.
• Azelaic acid is useful for mild to moderate acne in patients who do not tolerate benzoyl peroxide. It is also useful for postinflammatory hyperpigmentation because it has skin-lightening properties.
• It is available in 20% cream and 15% gel formulations, which are usually applied twice daily on clean, dry skin.
• Although uncommon, mild transient burning, pruritus, stinging, and
tingling may occur.

17. Salicylic Acid, Sulfur, and Resorcinol
• Salicylic acid, sulfur, and resorcinol are second-line topical therapies.
They are keratolytic and mildly antibacterial agents. Salicylic acid has
comedolytic and antiinflammatory action.
• Each agent has been classified as safe and effective by an FDA advisory panel. Some combinations may be synergistic (e.g., sulfur and resorcinol).
• Keratolytics may be less irritating than benzoyl peroxide and tretinoin, but they are not as effective comedolytic agents.
• Disadvantages include the odor created by hydrogen sulfide on reaction of sulfur with skin, the brown scale from resorcinol, and (rarely) salicylism from long-term use of high concentrations of salicylic acid on highly permeable (inflamed or abraded) skin.

18. SYSTEMIC PHARMACOTHERAPY
Isotretinoin
• Isotretinoin (Accutane) decreases sebum production, changes sebum composition,
inhibits P. acnes growth within follicles, inhibits inflammation, and
alters patterns of keratinization within follicles.
• It is the treatment of choice for severe nodulocystic acne. It can be used in patients who have failed conventional treatment as well as those who have scarring acne, chronic relapsing acne, or acne associated with severe psychological distress.

19. Isotretinoin
• Dosing guidelines range from 0.5 to 1 mg/kg/day, but the cumulative dose taken during a treatment course may be the major factor influencing longterm outcome. Optimal results are usually attained with cumulative doses of 120 to 150 mg/kg.
• A 5-month course is sufficient for most patients. Alternatively, an initial dose of 1 mg/kg/day for 3 months, then reduced to 0.5 mg/kg/day and, if possible, to 0.2 mg/kg/day for 3 to 9 more months may optimize the therapeutic outcome.

20. • Adverse effects are frequent and often dose related.
About 90% of patients experience mucocutaneous effects; drying of the mouth, nose, and eyes is most common. Cheilitis and skin desquamation occur in more than 80% of patients. The conjunctiva and nasal mucosa are affected less frequently.
Systemic effects include transient increases in serum cholesterol and triglycerides, increased creatine kinase, hyperglycemia, photosensitivity, pseudotumor cerebri, excess granulation tissue, hepatomegaly with abnormal liver injury tests, bone abnormalities, arthralgias, muscle stiffness, headache, and a high incidence of teratogenicity.
Patients should be counseled about and screened for depression during therapy, although a causal relationship to isotretinoin therapy is controversial.

21. Because of teratogenicity, contraception is required in female patients beginning 1 month before therapy, continuing throughout treatment, and for up to 3 months after discontinuation of therapy. All patients receiving isotretinoin must participate in the iPLEDGE program, which requires pregnancy tests and assurances by prescribers and pharmacists that they will follow required procedures.