Skin Pharmacology

Pharmacology

·        Topical treatment ® ¯systemic side effects

·        Penetration of drugs into the skin depends on: 

o  Barrier function (¯ with age and disease)

o  Nature of the vehicle (greasy better)

o  Interaction of the drug and vehicle

o  Hydration

o  Patient compliance (especially if sticky, smelly or staining)

·        Types of vehicles:

o  Liquids: solutions, emulsions (oil in water or water in oil), emulsion, suspension

o  Semi-solids: ointments (no water), gels, creams, pastes

o  Greases: oils, waxes, mineral greases (eg vasoline), macrogols

Treatments

·        Coal tar: in psoriasis, sometimes eczema.  Therapeutic agent unknown

Topical Steroids

·        Double the concentration doesn‟t necessarily double the efficacy

·        Potency related to receptor binding.  Modulates messenger RNA production

·        Anti-inflammatory effects involve a wide range of mediators

·        Side effects:

o   Epidermal thinning

o   Melanocytic inhibition 

o   Reduction in collagen synthesis and ground substance ® striae and intradermal haemorrhage

o   Vascular effects: initial vasoconstriction ® rebound vaso-dilation ® oedema, inflammation

o   Inhibition of pituitary-adrenal axis if excessive use or potent

·        Grouped into 4 classes according to “potency” – based on vasoconstrictor assays not efficiency

Antifungals

·        Griseofulvin

o   Only one till recently

o   Poorly absorbed orally, carried to skin through sweat

o   Fungistatic 

o   Rapidly cleared from the skin ® have to continue till condition cleared

o   Headaches and nausea common

o   Only effective against dermatophytes, not yeasts (eg candida)

o   Lamisil and itraconazole: effective against fungi + yeasts

·        Itraconazole (= Triazole)

o   Fungistatic

o   Absorption dose dependent, take with a fatty meal

o   Persists in skin for 4 weeks and in nails for up to 6 months after 3 month course

o   P450 interaction

o   GI side effects in 7 %

·        Terbinafine (=allylamine)

o   Fungicidal

o   Well absorbed orally

o   Adverse effects in 10%, no P450 effect

·        Use:

o   Cochrane review: no evidence that topical antifungals are of value in fungal toenail infections

o   Skin infections of the feet: allylamines better than azoles, but much more expensive

Retinoids

·        Retinol (vitamin A): metabolised by the liver to retinal, then oxidised to retinoic acids. b carotine can also be converted into retinol 

·        A hormone: binds to nuclear receptors

·        Modifies the expression of a variety of genes involved in cell growth and differentiation

·        Induces epidermal hyperplasia and desquamation (efficacy without peeling unlikely) 

·        Thins the stratum corneum, ­ dermal capillaries, etc etc, promotes hair growth

·        Isotretinoin (=Roaccutane, Oratane, 13 cis retinoic acid) 

o   Lipophilic (Þ take with food)

o   Teratogenic: contraception till 1 month afterwards

o   Side effects: dry skin, mucosa, photo-sensitive, aching muscles, headaches

·        Acitretin (=neotigason)

o   Inhibits formation of retinoic acid from retinol.

o   Used in Psoriasis

o   Teratogenic for 2 – 3 years afterwards, also reduces efficacy of oral contraceptives

o   Plus dry skin, mucosa, photo-sensitive, aching muscles, headaches