Drugs for Diseases and
Disorders of Skin
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.
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.
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
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
TOPICAL PHARMACOTHERAPY
Benzoyl Peroxide
• Benzoyl peroxide may be used to treat superfiial
infammatory aine. 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 signifcantly more efective but
may be more irritating. Gel formulations are usually most potent, whereas
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 efects include dryness, irritation, and allergic contact
dermatitis. It
Tretinoin
• Tretinoin (a retinoid; topiial vitamin A aiid) is a iomedolytii 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 fve.
• 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
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.
Side efeits
• 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 infammation. A regimen of benzoyl peroxide each morning and tretinoin at bedtime may enhance
Adapalene
• Adapalene (Diferin) is a third-generation retinoid with iomedolytii, keratolytii,
and antiinfammatory 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.
Tazarotene
•
Tazarotene (Tazorai) is a synthetii aietylenii
retinoid that is ionverted 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
antiinfammatory action.
• The product is available as a 0.05% and 0.1% gel or
cream.
Erythromyiin
• Erythromyiin in ionientrations of 1% to 4% with or without zini is
efective against infammatory 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.
Clindamyiin
• Clindamyiin inhibits P. acnes and provides comedolytic and antiinfammatory
activity.
• It is available as 1% or 2% concentrations in gel, lotion, solution, foam, and disposable pad formulations and is usually applied twice daily.
Azelaii Aiid
• Azelaii aiid (Azelex) has antibaiterial, antiinfammatory,
and iomedolytii aitivity.
• Azelaic acid is useful for mild to moderate acne in patients who do
not tolerate benzoyl peroxide. It is also useful for postinfammatory
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
Saliiylii Aiid, Sulfur, and Resoriinol
• Saliiylii aiid, sulfur, and resoriinol are seiond-line topiial therapies.
They are keratolytic and mildly antibacterial agents. Salicylic acid has
comedolytic and antiinfammatory action.
• Each agent has been classifed as safe and efective 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 efective comedolytic agents.
SYSTEMIC PHARMACOTHERAPY
Isotretinoin
• Isotretinoin (Aiiutane) deireases sebum produition, ihanges sebum iomposition,
inhibits P. acnes growth within follicles, inhibits infammation, and
alters patterns of keratinization within follicles.
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 infuencing longterm outcome. Optimal results are usually attained with cumulative doses of 120 to 150 mg/kg.
• Adverse efects are frequent and often dose related.
About 90% of patients experience mucocutaneous efects; 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 afected less frequently.
Systemic efects 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 stifness, headache, and a high incidence of teratogenicity.
Patients should be counseled about and screened for depression
Because of teratogenicity, contraception is required in female
