DERMATOLOGI

C
PHARMACOLO
GY
Andualem Tesfaye (Bpharm, MSc)
Department of pharmacology and toxicology
School of pharmacy
 Drugs can be applied to skin for two purposes:
 To directly treat disorders of the skin
 To deliver drugs to other tissues

 Skin provide site for drug action

 Both topical & systemic medications can be used depending on nature & extent of disease
 Topical preparations Convenient & minimize systemic side effects

 Dermatological preparation:
 Aerosol
 Foam
 Bars
 Lotion
 Ointment
 Powder
 Cream
 Gel
 Oil and paste
 Major variables that determine pharmacologic response to
drugs applied to the skin
 Regional variation in drug penetration
 Concentration gradient
  Increasing the concentration gradient increases the mass of drug transferred
per unit time
 Dosing schedule
 Vehicles and occlusion
PERCUTANEOUS ABSORPTION
ANTIBACTERIAL AGENTS
TOPICAL ANTIBIOTICS IN ACNE
 Currently, four antibiotics are so utilized:
 Clindamycin phosphate
 Erythromycin base
 Metronidazole, and
 Sulfacetamide

 Clindamycin has in vitro activity against Propionibacterium acnes

 10% absorbed, so, possibility of Pseudomembranous colitis

 The hydroalcoholic vehicle and foam formulation (Evoclin),,,,,,and The water-based gel and lotion
formulations (less likely to cause irritation )
 Clindamycin is also available in fixed-combination topical gels with benzoyl peroxide (Acanya,
BenzaClin, Duac), and with tretinoin (Ziana)
 Erythromycin In topical preparations, erythromycin base rather than a salt is
used to facilitate penetration
 MOA of topical erythromycin in inflammatory acne vulgaris is unknown
 Complications……antibiotic-resistant strains of organisms
 Adverse local reactoins,,,,,,,, burning sensation, drying and irritation of the skin

 Topical metronidazole is effective in the treatment of rosacea

 Metronidazole act as an anti-inflammatory agent by direct effect on neutrophil
cellular function
 Adverse local effects of the water-based gel formulation include dryness,
burning, and stinging
 Topical sulfacetamide is available alone as a 10% lotion and as a 10% wash
 Several preparations in combination with sulfur for the treatment of acne vulgaris and
acne rosacea
 Contraindicated
 Hypersensitivity to sulfonamides

 Topical dapsone is available as a 5% gel (Aczone) for the treatment of acne vulgaris.
 The mechanism of action is unknown

 Systemic antibiotics mainly :

 Minocycline,
 Doxycycline
 Erythromycin
ANTIFUNGAL AGENTS
 The treatment of superficial fungal infections caused by dermatophytic fungi may
be accomplished
1. With topical antifungal agents
EXP: clotrimazole, miconazole, econazole, ketoconazole, oxiconazole,
sulconazole, sertaconazole
2. With orally administered agents
EXP:griseofulvin, terbinafine, ketoconazole, fluconazole, and itraconazole …
TOPICAL ANTIFUNGAL PREPARATIONS

TOPICAL AZOLE DERIVATIVES

 The topical imidazoles :clotrimazole, econazole, ketoconazole, miconazole,
oxiconazole, sulconazole, and sertaconazole,
 Have a wide range of activity against
 Dermatophytes (epidermophyton, microsporum, and trichophyton) and
 Yeasts, including Candida albicans and Pityrosporum orbiculare

 Once- or twice-daily application to the affected area for 2–3 weeks superficial
dermatophyte
 ADRs: stinging, pruritus, erythema, and local irritation
 Nystatin and Amphotericin B:
 Only for Candida albicans.
 Available as topical preparations, oral suspension, or vaginal tablets

 Amphotericin B
 Bind to ergosterol present in the cell membrane and forms a micropore thus disrupt the membrane
function and cell death
 It is not absorbed orally

 Half life is ~ 15 days

 Metabolized in liver and excreted in urine and bile

 Relatively safe in pregnancy

 ADR: Fever and chills,nephrotoxicity, anemia, CNS toxicity

ORAL ANTIFUNGAL AGENTS
ORAL AZOLE DERIVATIVES
 Azole derivatives currently available for oral treatment of systemic mycosis include
 Fluconazole
 Itraconazole
 ketoconazole , and others

 Imidazole derivatives act by affecting the permeability of the cell membrane of sensitive cells
 Alterations of the biosynthesis of lipids, especially sterols, in the fungal cell

 Ketoconazole is effective in the therapy of cutaneous infections caused by epidermophyton,

microsporum, and trichophyton
 Nausea or pruritus occurs in approximately 3%,,,,, gnacomasia elevations of hepatic enzyme levels, and
hepatitis,
 Administration of the oral azoles with midazolam, triazolam, or HMG-CoA inhibitors is contraindicated.
 Griseofulvin is effective orally against dermatophyte infections caused by epidermophyton,
microsporum, and trichophyton
 Inhibition of fungal mitosis
 Griseofulvin is most effective in treating tinea infections of the scalp and glabrous (nonhairy) skin
 Requires prolonged treatment:
 4-6 weeks for the scalp.

 6 months for fingernails.

 8-18 months for toenails.

 Relapse almost invariably occurs
 Griseofulvin Adverse effects include:
 Headaches
 Vomiting
 Diarrhea
 Peripheral neuritis
 Occasionally mental confusion

 Terbinafine:
 Recommended for onchomycosis (ringworm of the nail)
 6 weeks for fingernails.
 12 weeks for toenails.
TOPICAL ANTIVIRAL AGENTS

ACYCLOVIR, VALACYCLOVIR, PENCICLOVIR, & FAMCICLOVIR

 Are synthetic guanine analogs
 Inhibitory activity against members of the herpesvirus family, including
herpes simplex types 1 and 2.
 Ointments and creams are useful for recurrent orolabial herpes
simplex infection
IMMUNOMODULATORS

IMIQUIMOD
 Imiquimod is available as 5% cream for the treatment of
 External genital and perianal warts in adults
 Actinic keratoses on the face and scalp, and
 Biopsy-proven primary basal cell carcinomas on the trunk, neck, and extremities

 A lower 3.75% concentration cream is available for the treatment of face and scalp
actinic keratoses.
 MOA:Stimulate peripheral mononuclear cells to release interferon-α and to stimulate
macrophages to produce interleukins-1, -6, and -8, and tumor necrosis factor-α (TNF-α).
 ADRS:Inflammatory reactions, including pruritus, erythema, and superficial erosion.
TACROLIMUS AND PIMECROLIMUS
 Useful for atopic dermatitis
 Are macrolide immunosuppressants that have been shown to be of
significant benefit in the treatment of atopic dermatitis
 Inhibit T-lymphocyte activation and prevent release
of inflammatory cytokines and mast cell mediators
ECTOPARASITICIDES
PERMETHRIN
 Permethrin is toxic to:
 Pediculus humanus
 Pthirus pubis , and
 Sarcoptes scabiei

 Less than 2% of an applied dose is absorbed percutaneously

 Residual drug persists up to 10 days following application.
 It is recommended that permethrin 1% cream rinse (Nix) be applied undiluted to
affected areas of pediculosis for 10 minutes and then rinsed off with warm water
PERMETHRIN
 For the scabies, a single application of 5% cream (Elimite, Acticin) is applied to the body from
the neck down, left on for 8–14 hours, and then washed off
 ADR: transient burning, stinging, and pruritus

OTHER AGENT
 LINDANE (HEXACHLOROCYCLOHEXANE)
 CROTAMITON
 SULFUR
 MALATHION
 BENZYL ALCOHOL
AGENTS AFFECTING PIGMENTATION

 Hydroquinone: topical application skin whitening to reduce the color of skin

 Monobenzone
 May be toxic to melanocytes resulting in permanent
depigmentation.
 Mequinol
 Topical hydroquinone and mequinol usually result in temporary lightening.
 Reduce hyperpigmentation of skin by inhibiting the enzyme tyrosinase which will
interfere with biosynthesis of melanin
 Trioxsalen
 Methoxsalen
 Are psoralens used for the repigmentation of depigmented macules of
vitiligo.
 Must be photoactivated by long-wave-length ultraviolet light (320-400nm)
to produce a beneficial effect.
 They intercalate with DNA
 Can cause cataract and skin cancer
SUNSCREENS AND SUNSHADES
 Sunscreens absorb UV light.
 Examples are para amino benzoic acid (PABA) and its esters

 Sunshades are opaque materials that reflect light

 Titanium dioxide

 Useful in :
 Polymorphous light eruption
 Lupus erythematosus and
 Drug –induced photosensitivity.
DRUGS FOR PSORIASIS
ACITRETIN
 Acitretin (Soriatane), a metabolite of the aromatic retinoid etretinate,

 Is quite effective in the treatment of psoriasis, especially pustular forms.

 It is given orally at a dosage of 25–50 mg/d

 Hepatotoxic and teratogenic

TAZAROTENE
 Is a topical acetylenic retinoid prodrug that is hydrolyzed to its active form by an
esterase.
 The active metabolite, tazarotenic acid, binds to retinoic acid receptors, resulting in
modified gene expression
 The precise mechanism of action in psoriasis is unknown
 But may relate to both anti-inflammatory and antiproliferative actions.
CALCIPOTRIENE & CALCITRIOL
 Synthetic vitamin D3 derivative
 Effective in the treatment of plaque-type psoriasis vulgaris of moderate severity
BIOLOGIC AGENTS:
 Alefacept:
 Immunosuppressive dimer fusion protein of CD2 linked to the Fc
portion of human IgG1.
 Efalizumab:
 Recombinant humanized IgG1 monoclonal antibody.
 Withdrawn :progressive multifocal leukoencephalopathy
 Can cause thrombocytopenia
 Etanercept:
 Dimeric fusion protein of TNF receptor linked to the Fc portion of
human IgG1.
ANTI-INFLAMMATORY AGENTS
 They have anti-inflammatory & immunosuppressive effects
 Used for treating many itchy & inflammatory diseases like eczema & psoriasis
 They inhibit the arachidonic acid cascade, inhibit the production of cytokines & act
on inflammatory cells
 Repeated use can lead to tachyphylaxis
 Different potencies as weak, medium strength, high strength & very high strength.
TOPICAL CORTICOSTEROIDS
 Hydrocortisone.
 Prednisolone and Methylprednisolone.
 Dexamethasone and Betamethasone.
 Triamcinolone.
 Fluocinonide
 The therapeutic effectiveness of topical corticosteroids is based primarily on their anti-
inflammatory activity
 Corticosteroids are only minimally absorbed
 Dermatologic disorders very responsive to steroids:
 Atopic dermatitis.
 Seborrheic dermatitis.
 Lichen simplex chronicus.
 Pruritus ani.
 Allergic contact dermatitis.
 Eczematous dermatitis.
 Psoriasis
 Adverse local effects of topical corticosteroids :
 Atrophy
 Corticoid rosacea
 Pustules, and papules in central facial distribution
 Perioral dermatitis
 Steroid acne
 Alterations of cutaneous infections
 Hypopigmentation
 Hypertrichosis
 Increased intraocular pressure; and
 Allergic contact dermatitis.
TRICHOGENIC & ANTITRICHOGENIC
AGENTS
MINOXIDIL
 Topical minoxidil (Rogaine) is effective in reversing the progressive miniaturization
of terminal scalp hairs associated with androgenic alopecia.
 Vertex balding is more responsive to therapy than frontal balding
 The mechanism of action of minoxidil on hair follicles is unknown
 Cessation of treatment will lead to hair loss in 4–6 months.
 Percutaneous absorption of minoxidil in normal scalp is minimal,
 But possible systemic effects on blood pressure
FINASTERIDE
 Finasteride (Propecia) is a 5α-reductase inhibitor
 Blocks the conversion of testosterone to dihydrotestosterone

 Androgen responsible for androgenic alopecia in genetically predisposed men.

 Oral finasteride
 1 mg/d, promotes hair growth and prevents further hair loss in a significant proportion of
men with androgenic alopecia
 ADRs:
 Decreased libido
 Ejaculation disorders, and
 Erectile dysfunction

BIMATOPROST
 Is a prostaglandin analog
 A 0.03% ophthalmic solution to treat hypotrichosis of the eye lashes
READING ASSIGNMENT
 KERATOLYTIC & DESTRUCTIVE AGENTS
 Salicylic acid
 Propylene Glycole
 Urea
 Nonsteroidal Anti-inflammatory Drugs
 Aminolevulinic Acid

 ANTINEOPLASTIC AGENTS
 ANTIPRURITIC AGENTS
 Doxepine
 Pramoxine