Derm Drugs Flashcards
DERMATOLOGY
A unique aspect of dermatological pharmacology is the accessibility of the skin for diagnosis and therapy. Therapeutic agents can reach epidermal keratinocytes as well as immune-competent cells in the skin that are involved in the pathogenesis of cutaneous diseases.
The skin acts as a two-way barrier to prevent adsorption or loss of water and electrolytes. The barrier function is largely carried out by the epidermis, more specifically the outer most layer-the stratum corneum- as evidenced by approximately equal rates of penetration of chemicals through isolated stratum corneum or whole skin.
stratum corneum
The stratum corneum cells are nonviable, having lost nuclei and cytoplasmic organelles. The cells are flattened, and fibrous proteins are aligned into disulfide cross-linked macrofibers and the intercellular spaces are filled with strongly hydrophobic lipids.
The combination of hydrophilic cornified cells in hydrophobic intercellular material is a barrier to both hydrophilic and hydrophobic substances.
PARAMETERS CONTROLLING ABSORPTION
The absorption of a drug into the skin is a function of:
(1) the nature of the drug (drug must be soluble in vehicle, better absorption if drug is lipophilic, molecules over a thousand daltons usually will not be absorbed,)
(2) the behavior of the vehicle ( either hydrating or not)
(3) the status of the skin (in disease states the resistance to absorption is rapidly lost and absorption can be facilitated
GENERAL GUIDELINES FOR TOPICAL THERAPY
(1) Dosage- sufficient amount to cover affected body surfaces in repeated applications.
-30 gm will usually cover an entire adult body once
(2) Regional Anatomic Variation- permeability is generally inversely proportional to the thickness of the stratum corneum (differences in lipid concentration may affect absorption)
drug penetration is higher on the face and between folds of skin
Altered Barrier Function
many dermatological diseases the stratum corneum is abnormal and barrier function is lost. Topical absorption is increased to the point that standard drug doses can result in systemic toxicity—like potent topical steroids
Hydration
drug adsorption is increased with hydration, defined as an increase in the water content of the stratum corneum that is produced by inhibiting transepidermal loss of water.
-methods of hydration include occlusion with an impermeable film, application of lipophilic occlusive vehicles such as ointments, and soaking dry skin before occlusion.
Vehicle
topical therapy is delivered by various vehicles, most frequently soaks, lotions, solutions, creams, and ointments, progressing in that order from least to most hydrating.
- in general, acute inflammation is treated with aqueous drying preparations, and chronic inflammation is treated with hydrating preparations.
-soaks are the easiest method of drying acute preparations.
-lotions (powder in water suspensions) and solutions (medications dissolved in a solvent) are ideal for hairy and areas between folds
creams or oil-in-water emulsions are absorbable and the most cosmetically acceptable to the patient.
- ointments, water in oil emulsions, are the most effective for dry scaly eruptions, but are greasy therefore often undesirable.
Age
children have a greater ratio of surface area to mass than adults, and a given amount of topical drug results in a greater systemic dose
TOPICAL ANTIBIOTICS
(1) Triple antibiotic ointment (TAO) (Neosporin)-----otc Contains: Neomycin, bacitracin, and polymyxin B (2) Neosporin G-Rx Contains: Neomycin & Gramicidin (3) Mupirocin (Bactroban) Rx (4) Providone-iodine (Betadine) otc Available as: cream, spray, scrub, solution (5) Hexachlorophene (Phisohex) Rx Available as: solution Bad: CNS toxicity (6) Chlorhexidine (Hibiclens) otc Available as : solution
uses
(1) minor cuts, scrapes, and burns: TAO, Neosporin G
(2) wound cleaning or scrub : Providone-iodine, chlorhexidine, and hexachlorophene
(3) Impetigo due to S. pyrogenes : Mupirocin
TOPICAL CLUCOCORTICOSTEROIDS
Many inflammatory skin diseases respond to topical administration of glucocorticoids.
Guidelines: (1) Absorption varies among different body areas; the steroid to be used.
(2) the steroid to be used is chosen on the basis of its potency
(3) the site of involvement ( ex: usually hydrocortisone or weak potency used on the face—tachyphylaxis can occur)
(4) the severity of the skin disease
(5) Usually, a more potent agent is used initially, followed by a less potent agent
AGENTS
High potency: Betamethasone dipropionate (Diprolene)
Intermediate potency: Triamcinolone acetate (Aristocort A)
Low potency: Hydrocortisone (Hytone)
USES & toxicity
USES
From contact dermatitis (short-term) to Systemic Lupus erythematosus (long-term)
TOXICITY
-higher potency topical glucocorticoids have both local and systemic toxicity
-LOCAL- include skin atrophy, acneiform eruptions, hypopigmentation in pigmented skin.
-SYSTEMIC – suppression of the hypothalamic-pituitary-adrenal axis and growth retardation in small children
Adjuncts for dermatitis – H1 blockers and sometimes oral glucocorticoids.
RETINOIDS
Retinoids include the natural compounds and synthetic derivatives of retinol that exhibit vitamin A activity
Retinoids influence a wide variety of biological activities, including cellular proliferation and differentiation, inflammation, and sebum production
Retinoids actions are mediated through nuclear acid receptors (RARs) which are members of the thyroid/steroid superfamily of receptors. These receptors bind to retinoids and DNA and function as transcription factors that enhance initiation of transcription.
Tretinoin
topical preparation used in the treatment of acne
A primary effect of tretinoin is the reduction of the hyperkeratinization that leads to microcomedone formation, the initial lesion in acne.
-therapeutic response may take up to four months
-adverse effects of tretinoin include erythema, peeling, burning, and stinging, these effects often decrease spontaneously with time.
-photosensitivity occurs, with a resulting greater potential for sunburn
-if given orally it is teratogenic, topical administration has not been associated with birth defects, however tretinoin should not be used in pregnancy
