Drug Used in Skin & Mucous Membrane
Topical application for:
- Skin.
- Eye.
- Ear.
- Nose.
- Buccal cavity.
1. SKIN
Antibacterial Agents
Topical corticosteroids do not inhibit the effect of co-administered antibiotics.
In the treatment of secondarily infected dermatoses, combination therapy is superior to corticosteroid therapy alone.
Antibiotic-corticosteroid combinations are useful in diaper dermatitis, otitis externa, and impetiginized eczema.
The pathogens in surgical wounds are those resident in the environment so information about regional drug resistance is important.
Antibacterial agents include:
Bacitracin & gramicidin
Polymyxin B, neomycin and gentamicin
Topical antibiotics in acne
Bacitracin & Gramicidin
Bacitracin and gramicidin are peptide antibiotics, active against gram-positive organisms such as streptococci, pneumococci, and staphylococci.
Most anaerobic cocci, neisseriae, tetanus bacilli, and diphtheria bacilli are also sensitive.
Bacitracin is compounded in an ointment base alone or in combination with neomycin, polymyxin B, or both.
Bacitracin is poorly absorbed through the skin, so systemic toxicity is rare but allergic contact dermatitis is frequent.
Polymyxin B, Neomycin and Gentamicin
Polymyxin B is a peptide antibiotic effective against gram-negative organisms.
All gram-positive organisms are resistant.
Neomycin and gentamicin are active against gram-negative organisms.
Gentamicin generally shows greater activity against P aeruginosa than Neomycin.
Neomycin causes sensitization, particularly in eczematous dermatoses or if compounded in an ointment vehicle.
Topical Antibiotics in Acne
Currently, four antibiotics are so utilized: clindamycin, erythromycin, metronidazole, and sulfacetamide.
The effectiveness of topical therapy is less than that achieved by systemic administration of the same antibiotic.
Topical therapy is suitable in mild to moderate cases of inflammatory acne.
Clindamycin has activity against Propionibacterium Acne.
Erythromycin: the mechanism of action of topical erythromycin in inflammatory acne vulgaris is unknown.
Adverse local reactions to erythromycin solution include a burning sensation at the time of application and drying and irritation of the skin.
The topical water-based gel is less drying and may be better-tolerated.
Metronidazole : Topical metronidazole is effective in the treatment of acne rosacea. The mechanism of action is unknown.
Topical use during pregnancy and by nursing mothers and children is n recommended.
Adverse local effects of the water-based gel formulation (MetroGel) include dryness, burning, and stinging.
Caution should be exercised when applying metronidazole near the eyes to avoid excessive tearing.
Sodium Sulfacetamide: The mechanism of action is thought to be inhibition of P acnes by competitive inhibition of p-aminobenzoic acid utilization.
4% of topically applied sulfacetamide is absorbed so its use is contraindicated in patients having hypersensitivity to sulfonamides.
Antifungal Agents
Antifungal agents include:
1. Topical antifungalagents:
Topical imidazoles
Nystatin
2. Oral antifungal agents:
Oral azoles
Griseofulvin
Topical Imidazoles
They have a wide range of activity against dermatophytes, Candida albicans and Pityrosporum orbiculare.
Clotrimazole
Econazole
Ketoconazole
Miconazole
Oxiconazole
Sulconazole
Once- or twice-daily application will result in clearing of dermatophyte infections in 2-3 weeks.
The medication should be continued until eradication of the organism is confirmed.
Paronychial and intertriginous candidiasis can be treated by any of these agents when applied three or four times daily.
Seborrheic dermatitis should be treated with twice-daily applications of ketoconazole until clinical clearing is obtained.
Nystatin
Topical nystatin is used in cutaneous and mucosal candida infection.
It is not effective against dermatophytes.
Oral candidiasis (thrush) is treated by holding 5 mL (infants, 2 mL) nystatin oral suspension in the mouth for several minutes four time daily before swallowing.
An alternative therapy for thrush is to retain a vaginal tablet in the mouth until dissolved four times daily.
Vulvovaginal candidiasis may be treated by insertion of 1 vaginal tablet twice daily for 14 days, then nightly for an additional 14-21 days.
Oral Azoles
Classified as :
Ketoconazole
Fluconazole
Itraconazole
Tinea versicolor is very responsive to short courses of once-daily dose of 200 mg Ketoconazole.
Significant side effects of Ketoconazole include gynecomastia and hepatitis.
Caution is advised when using ketoconazole in patients with a history hepatitis.
Routine evaluation of hepatic function is advisable for patients on prolong therapy.
The newer azole derivatives for oral therapy include fluconazole and itraconazole.
Fluconazole has a half-life of 30 hours. daily doses of 100 mg are sufficient for candidiasis; alternate-day doses are sufficient for dermatophytes.
The half life of Itraconazole is similar to fluconazole, with therapeutic concentrations remaining in the skin for 28 days.
Itraconazole should not be given to patients with ventricular dysfunction cause heart failure.
Routine evaluation of hepatic function is recommended for patients receiving itraconazole for onychomycosis.
Administration of oral azoles with midazolam or triazolam potentiate hypnotic effects of these agents.
Administration with HMG-CoA reductase inhibitors causes a significant risk of rhabdomyolysis.
Administration of the oral azoles with midazolam, triazolam, or HMG-CoA inhibitors is contraindicated.
Griseofulvin
Griseofulvin is effective orally against dermatophyte infections.
It is ineffective against candida and Porbiculare.
The adult dosage of the micronized (“microsize”) form of the drug is 500mg daily in single or divided doses with meals.
Griseofulvin is most effective in treating tinea infections of the scalp and glabrous skin.
Infections of the scalp respond in 4-6 weeks, and infections of glabrous skin respond in 3-4 weeks.
Griseofulvin is derived from a penicillium mold, and cross-sensitive with penicillin may occur.
In prolonged therapy, routine evaluation of the hematopoietic, hepatic and enal systems is advisable.
Immunomodulators
Tacrolimus and pimecrolimus are macrolide immunosuppressant’s that have significant benefit in atopic dermatitis.
Both agents inhibit T-lymphocyte activation and prevent degranulation of most cells by antigen-IgE complexes.
Both agents are indicated for mild to moderate atopic dermatitis.
Neither medication should be used with occlusive dressings.
Ectoparasiticides
Ectoparasiticides include:
Permethrin
Lindane (Hexachlorocyclohexane)
Crotamiton
Sulfur & Malathion.
Permethrin
Permethrin is toxic to Pediculus humanus, Pthirus pubis, and Sarcoptes scabiei.
Residual drug persists up to 10 days following application.
permethrin 1% cream rinse is applied undiluted to affected areas of pediculosis for 10 minutes and then rinsed off with warm water.
For the treatment of scabies, a single application of 5% cream is applied to the body from the neck down, left on for 8-12 hours, and then washed off.
Lindane (Hexachlorocyclohexane)
Lindane is available as a shampoo or lotion.
10% of a dose applied to the forearm is absorbed and concentrated in fatty tissue including the brain.
For pediculosis capitis or pubis, 30 mL of shampoo is applied to dry hair on thr scalp or genital area for 4 minutes and then rinsed off.
No additional application is indicated unless living lice are present 1 week after treatment.
In scabies a single application is applied to the entire body from the neck down, left on for 8-12 hours, and then washed off.
Patients should be retreated only if active mites can be demonstrated, and never within 1 week of initial treatment.
Crotamiton
Crotamiton is available as a cream or lotion.
Crotamiton, is a scabicide with some antipruritic properties.
For scabies two applications are applied from the chin down at 24- hour intervals, with a cleansing bath 48 hrs. after the last application.
Crotamiton is can be used as an alternative to lindane.
Sulphur & Malathion
Sulfur remains a possible alternative drug for use of infant and pregnant women.
The usual formulation is 5% precipitated sulphur in patrolium.
Malathion is available as a 0.5% lotion that should be applied to the hair when dry; 4-6 hours later, the hair is combed to remove nits and lice.
Agents Affecting Pigmentation
Hydroquinone, mequinol and monobenzone reduce hyper-pigmentation of the skin.
these compounds inhibit tyrosinase, interfering with the biosynthesis of melanin.
Topical hydroquinone & mequinol result in temporary lightening, but monobenzone causes irreversible depigmentation.
Monobenzone may cause hypopigmentation at sites distant from the area of application.
Trioxsalen and methoxsalen are psoralens used for the repigmentation of depigmented macules of vitiligo.
Psoralens must be photoactivated by long-wave-length ultraviolet light in the range of 320-400 nm (UVA) to produce a beneficial effect.
The risks of psoralen photochemotherapy are cataracts and skin cancer.
Sunscreens
Topical medications against sunlight include:
Sunscreens: Contain chemical compounds that absorb ultraviolet light.
Sunshades: Contain opaque materials such as titanium dioxide that reflect light.
The three classes of compounds used in sunscreens are:
p-aminobenzoic acid (PABA) and its esters
The benzophenones
The dibenzoylmethanes
Sunscreens are designed to absorb ultraviolet B (UVB) wavelength (from 280 to 320 nm).
UVB is the range responsible for most of the erythema and tanning associated with sun exposure.
Chronic exposure to light in this range induces aging of the skin and photocarcinogenesis.
Para-aminobenzoic acid and its esters are the most effective available absorbers in the B region.
The benzophenones include oxybenzone, dioxybenzone, and sulisobenzone.
The benzophenones absorb from 250 to 360 nm, but their effectiveness the UVB erythema is less than that of PABA.
The dibenzoylmethanes include Parasol and Eusolex.
The dibenzoylmethanes absorb wavelengths throughout the ultraviolet A range (320 to 400 nm), with maximum absorption at 360 nm.
Patients sensitive to UVA include: those with cutaneous lupus erythematosus and drug-induced photosensitivity.
In these patients, dibenzoylmethane-containing sunscreen may provide improved photoprotection.
The sun protection factor (SPF) of a given sunscreen is a measure of its effectiveness in absorbing erythrogenic ultraviolet light.
Fair-skinned individuals who sunburn easily are advised to use a product with an SPF of 15 or greater.
Acne Preparations
Retinoic acid (tretinoin), is the acid form of vitamin A. It is an effective topical treatment for acne vulgaris.
Its action in acne is due to decreased cohesion between epidermal cells and increased epidermal cell turnover.
Isotretinoin (Accutane) is used in the treatment of severe cystic acne that is recalcitrant to standard therapies.
Isotretinoin may act by inhibiting sebaceous gland size and function.
Benzoyl peroxide is an effective topical agent in the treatment of acne vulgaris.
It is active against P acnes and has peeling and comedolytic effects.
Corticosteroids
The antimitotic effects of corticosteroids on epidermis accounts for their action in diseases with increased cell turnover (psoriasis).
Only 1% of a dose of hydrocortisone applied to the ventral forearm is absorbed.
Occlusion with a plastic wrap enhances penetration, yielding a tenfold increase in absorption.
Corticosteroid penetration varies and compared with the forearm hydrocortisone is absorbed:
• 0.14 times as well through the plantar foot arch
• 0.83 times as well through the palm
• 3.5 times as well through the scalp
• 6 times as well through the forehead
• 9 times as well through vulvar skin
• 42 times as well through scrotal skin
Intralesional injection of insoluble corticosteroids (eg, triamcinolone preparations) increases their penetration.
Adverse local effects of topical corticosteroids
• Atrophy
• Steroid rosacea
• Steroid acne
• Alterations of cutaneous infections
• Hypopigmentation
• Hypertrichosis
• Increased intraocular pressure
• Allergic contact dermatitis
Keratolytics & Destructive Agents
Keratolytics & destructive agents include:
Salicylic acid
Propylene glycol
Urea
Podophyllum resin & podophyllotoxin
Fluorouracil
Aminolevulinic acid (ALA)
Salicylic Acid
Salicylic acid has been extensively used in as a keratolytic agent.
Its mechanism of action is not understood.
Salicylic acid is keratolytic in concentrations of 3-6%
In concentrations greater than 6%, it can be destructive to tissues.
Propylene glycol
Propylene glycol is used alone as a keratolytic agent in 40-70% concentrations, with plastic occlusion, or in gel with 6% salicylic acid.
It is also an effective humectant and increases the water content of the stratum corneum.
Urea
Urea in a compatible cream vehicle or ointment base has a softening and moisturizing effect on the stratum corneum.
It makes creams and lotions feel less greasy and decreases the oily feel of drugs.
As a humectant, urea is used in concentrations of 2-20%
As a keratolytic agent, it is used in 20% concentration in hyperkeratosis of palms and soles
Concentrations of 30-50% appliedthe nail plate have been useful in softening the nail prior to avulsion.
Podophyllum Resin & Podophyllotoxin
The major use of podophyllum resin is in the treatment of condyloma acuminatum.
A 25% concentration of podophyllum resin in compound tincture of benzoin is used for condyloma acuminatum.
Pure 0.5% podophyllotoxin (podofilox) is used for genitalcondylomas.
Fluorouracil
Fluorouracil is used topically for actinic keratoses.
The response begins with erythema, vesiculation, erosion, superficial ulceration, necrosis, and finally reepithelialization.
Fluorouracil should be continued until the stage of ulceration and necrosis (in 3-4 weeks) and then stopped.
Aminolevulinic Acid (ALA)
Aminolevulinic acid (ALA) is an endogenous precursor of photo-sensitizing porphyrin metabolites.
When topical ALA is applied, protoporphyrin IX (PpIX) accumulates the cell.
Photo-dynamic reaction results in the formation of cytotoxic superoxide and hydroxyl radicals.
A 20% topical solution of ALA is used in the treatment of actinic keratoses.
Antipruritic Agents
Topical doxepin 5% cream may provide significant antipruritic activity in atopic dermatitis.
Its mechanism may relate to the potent H1- and H2-receptor antagonist properties.
Trichogenic & Antitrichogenic Agents
Topical minoxidil is effective in reversing the progressive miniaturization of scalp hairs in androgenic alopecia.
Vertex balding is more responsive to therapy than frontal balding.
The mechanism of action of minoxidil on hair follicles is unknown.
The effect of minoxidil is not permanent, and cessation of treatment will lead to hair loss months.
Finasteride blocks the production of dihydrotestosterone which is responsible androgenic alopecia.
Oral finasteride, 1 mg/d, promotes hair growth and prevents further hair loss in many men androgenic alopecia.
Treatment for at least 3-6 months is necessary.
Eflornithine is an irreversible inhibitor of ornithine decarboxylase that catalyzes the biosynthesis of polyamines.
Polyamines are required for cell division, and inhibition of ornithine decarboxylase affects the rate of hair growth.
Eflornithine is effective in reducing facial hair growth in 30% of women when applied twice daily for 6 months.
