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
Isotretinoin
given orally, used for severe nodular acne and acne unresponsive to oral antibiotics.
Isotretinoin reduces:
(1)sebum synthesis
(2)reduces Propionibacterium acnes (the organism that causes inflammation in acne)
(3) reduces microcomedone formation.
Isotretinoin toxicity
(1) most common are effects on the skin and mucus membranes (mucus membrane dryness, dry eyes, conjunctivitis)
(2) photosensitivity
(3) Hyperlipidemia (25% of patients)
(4) depressive episodes
(5) most serious side-effect is Teratogenicity- occurs if given during the first three weeks of pregnancy, spontaneous abortion occurs in 1/3 of patients. Female patients must have negative pregnancy test before therapy and use two forms of birth control while on Isotretinoin
topical & systemic acne treatment
(1) Topical:
-benzyl peroxide
-erythromycin solutions
-clindamycin solutions
-abrasive scrubs, washes with providone-iodine
(2) Systemic
-erythromycin
-minocycline
-tetracycline
RETINOIC ACID
used for skin peels
SELECTED TREATMENTS of PSORIASIS
Psoriasis is a chronic scaling skin eruption characterized by keratinocyte hyperproliferation. It effects 1% of the population of the U.S. and has a genetic basis. At present time there is no cure for psoriasis.
Etretinate moa
- an aromatic retinoid and is effective for inflammatory types of psoriasis, including pustular and erythrodermic disease.
- long half-life (100 days) accumulates in fatty tissue, (can be found in the plasma 2 to 3 years after D/C
- can be used in combination with ultraviolet radiation therapy
- M.O.A.- not completely understood, however it is known that Etretinate normalizes the expression of keratins
Etretinate toxic
hair loss, sticky skin, easy bruising and liver function abnormalities.
- teratogenic——should not be used in females of child bearing age, if used birth control should be practiced 3 years after D/C
Methoxsalen moa & toxicity
taken orally about 2 hours before ultraviolet radiation
-M.O.A- unknown- however PUVA promotes melanogenesis in normal skin. Pigmentation results from the transfer of melanosomes from melanocytes to the epidermal cells
Toxicity- major side-effects include: nausea, blistering, and painful erythema
-chronic effects occur within the skin: photoaging, and non-melanoma skin cancer—squamous cell carcinomas occur at 10 times the expected frequency
–possible cataract formation
–possible liver dysfunction
TOPICAL PSORIASIS TREATMENTS
(1) GLUCOCORTICOIDS
(2) CALCIPOTRIENE (3) Anthralin
CALCIPOTRIENE
a vitamin D analog
- binds to an intracellular receptor that interacts with DNA to modulate transcription, these receptors are found in human epidermal keratinocytes
- usually more effective than high potency glucocorticoids
Anthralin
- M.O.A-inhibits DNA synthesis (intercalation), mitochondrial inhibition, free radical formation
- staining and irritation of the uninvolved skin
- permanent staining of clothes and bathroom fixtures
- no known systemic toxicity
ANTI- TUMOR NECROSIS FACTOR BIOLOGICALS
Etanercept (Enbrel) Infliximab (Remicade)
Adalimumab (Humira)
Coal tar
(A) M.O.A- thought to inhibit DNA synthesis
(B) poor patient compliance- messy, smelly, staining to clothing
KERATOLYTIC AGENTS
Lactic acid, glycolic acid, and salicylic acid
-treat hyperkeratotic and scaling cutaneous eruptions
DESTRUCTIVE AGENTS- Podophyllin resin
- used in the treatment of genital warts
- irritation and ulcerative local reactions have occurred
- serious neuropathy and death have resulted from the use of large amounts on multiple lesions.
LICE & SCABIES
Head lice, crab lice, and their ova (scabies)
-Lindane- stimulates the nervous system resulting in death of the arthropods-applied topically, lotion, cream, & shampoo
PROTECTIVE AGENTS
Calamine –zinc oxide & ferric oxide
WET DRESSINGS
Domeboro- aluminum sulfate & calcium acetate
For treating colds (really for allergy)
(1) histamine H1 antagonist Chlorpheniramine Brompheniramine Diphenhydramine Loratadine (2) decongestants-caution in some patients Pseudoephedrine (3) topical decongestants Oxymetazoline
For treating cough
Syrups contain alcohol, sugar & dyes
(1) dextromethorphan-antitussive
(2) Codeine-antitussive
(3) guaifenesin-expectorant
Antacids
(1) Magnesium & aluminum hydroxide
(2) Calcium carbonate
(3) Sodium bicarbonate
Antiflatulents
simethicone
Laxatives
(1) Bulk former- metamucil
(2) stool softeners-docusate
(3) stimulants-bisacodyl
(4) PEG-Miralax
