Subject: Pharmacology Topic: Dermatologic Pharmacology 1 Lecturer: Dra.

Dela Cruz Date of Lecture: 19/7/11 Transcriptionist: ior and yhtak Editor: ted failon Pages: 7

Routes of Administration 1. Topical applied directly to the skin for systemic absorption and consequence systemic effect Transdermal Patch o Outer: covering; waterproof o Inner: for slow release of drug to circulation o Middle: medicine reservoir

DRUG DELIVERY IN DERMATOLOGIC DISEASES: 1. through intact stratum corneum 2. through sweat ducts 3. through sebaceous follicle

Characteristics of Topical drugs: 1. Low molecular mass (600da) 2. Adequate solution in oil and water 3. High partition coefficient Major Steps in Percutaneous Absorption : Semisolid Preparation: o Ointment, cream, gel, etc. 2. Intralesional direct contact with underlying pathologic process no first pass metabolism a drug depot that slowly releases the active ingredient of the drug 1. Establishment of a concentration gradient, which provides the driving force for drug movement across the skin 2. Release of drug from the vehicle (partition coefficient) 3. Drug diffusion across the layers of the skin (diffusion coefficient) Factors that Affect Percutaneous Absorption: 1. Dosage amount of drug should be sufficient to cover affected body surface approximately 30 g is required to cover the whole body surface Sufficient contact time 3. Systemic Oral: capsules, tablets syrup, oral suspension Parenteral: IV, IM, SC

SY 2011-2012

2. Regional Anatomic Variation permeability is generally inversely proportional to the thickness of stratum corneum drug penetration is higher on the face, in intertriginous areas or skin sites with opposing surfaces e.g. axilla, groin and inframammary areas (This areas have thin stratum corneum) vulnerable to drug related toxicity 3. Integrity of the skin intact skin provides a formidable barrier for passage of drugs disrupted epidermal layer allows drug to readily pass (compromised barrier function) e.g. inflammation Abnormal stratum corneum (i.e. psoriasis)

markedly influence ability of drug to penetrate the outer layers of the skin 6. Age drug penetration is generally greater in infants and in elderly because they have thinner stratum corneum children have a greater ratio of surface area to mass than adults, so greater systemic absorption of topical drugs 7. Lipid Solubility of Drug lipid soluble compounds diffuse through lipids within the stratum corneum Dermatologic Vehicles 1. Dimethyl sulfoxide (DMSO) penetrate deeply into the skin without damaging it and carry other compounds deeper into the biologic system predominantly used vehicle for topical analgesics, anti-inflammatory and anti-oxidant 2. Propylene glycol vehicle for organic compounds also an effective Humectant and increases the water content of the stratum corneum Keratolytic at 40-70% concentration

4. Hydration increase in the water content of the stratum corneum due to inhibition of transepidermal loss of water increases drug penetration hydration causes swelling of the stratum corneum making it more permeable to drug molecules Methods of Hydration: 4.1. Occlusion with an Impermeable film 4.2. Application of Lipophilic Occlusive vehicles e.g. Ointments

3. Urea also possess hygroscopic property makes cream and lotion less greasy 4. Liposomes are concentric spherical shells of phospholipids in an aqueous medium that may enhance percutaneous absorption penetrate compromised epidermal barriers more efficiently variations in size, charge and lipid content can influence liposome function

(AN EXAMPLE OF OCLUSIVE DRESSING) 5. Vehicle solvent through which most drugs for topical administration is incorporated

5. Microgels are polymers that may enhance solubilization of certain drugs to enhance penetration and decrease irritant effects

Characteristics of an Ideal Dermatologic Vehicle: 1.Easy to apply and remove 2.Non-irritating, inexpensive 3.Odorless, non greasy 4.Cosmetically pleasing 5.Active drug must be stable in the vehicle 6.Active drug must be readily released once in contact with the skin Types of Dermatologic Preparation 1. Powder Talc, Starch consist of very fine particle size, which covers a large surface area of the body absorb moisture and reduce friction soothing and cooling effect adhere poorly to the skin 2. Ointment semisolid preparation intended for external application to the skin or mucous membranes creates and oily residue increase hydration of stratum corneum occlusive effects prolong and enhance drug penetration not suitable for weeping lesions useful in chronic, dry lesions anhydrous nature does not require preservatives Typical ointment bases: 1.Petrolatum 2.Polyethylene glycol 3.Lanolin good skin penetration and adherence to surfaces NOT for wet lesions

Three different types of emollient 1. Oil in water emulsion cream 2. Water in oil emulsion ointment 3. Water free preparation fatty ointment provides a layer of oil on the surface of the skin to slow water loss and thus increase the moisture content of the stratum corneum also known as: Moisturizer Lubricant Vanishing cream employed as protective and as skin softening agent also serve as vehicles for more active drugs

(AN EXAMPLE OF AN EMOLIENT) 5. Lotion usually applied to external body surfaces e.g. skin with bare hands used to soften and smoothen skin or used to deliver medications to the skin less viscous than cream or ointment medicated lotions may contain: Antibiotics Antifungals Corticosteroids Antiseptics Skin Whitening Antipruritics applied thinly on external body surface such as the skin, scalp cover a larger body surface area applied to the skin more frequently without rubbing 6. Gels sticky, jelly-like semisolids or solids prepared from high molecular weight polymers in an aqueous or alcoholic base liquefies upon contact with the skin

3. Creams classified as water-in-oil or oil-in-water formulations less messy and less occlusive than ointments dry quickly contain water so prone to bacterial or fungal contamination drying effect preferred form for exudative dermatoses and for use under wet dressings for wet lesions 4. Emollient substances in liquid form that soften and soothe the skin component of lipstick, lotion and other cosmetic products essential component is lipid

Two Kinds of Gels: 1. Alcoholic gels hand sanitizers best suited for acute exudative, pruritic eruptions 2. Non-alcoholic gels hair gels, sunscreens more-lubricating best suited for dry scaly lesions in the scalp 7. Liniment viscous liquids containing substances possessing analgesic, soothing or stimulating properties should be rubbed when applied to the skin to release active drug should not be applied to broken skin similar viscosity as lotion

9. Humectants substances that diffuse into the stratum corneum and attract water substances that promote water retention due to their hygroscopicity e.g. glycerine, urea, pyrrolidone carboxylic acid (PCA), sorbitol 10. Collodion liquid preparations consisting of a solution of proxylin in a mixture of ether and alcohol painted on the skin and allowed to dry to leave a flexible film over the site of application used to seal minor cuts and wounds or as a means to hold a dissolved drug in contact with the skin for prolonged periods

(TREAT WITH A COLLODION) 11. Paste stiff preparations containing a high proportion of finely powdered solids such as Zinc oxide, calcium carbonate or starch forms an unbroken, relatively water impermeable film on the skin surface less occlusive and messy than ointments suitable for subacute or chronic dermatoses useful for local application of irritating drugs Corticosteroids Mode of administration: 1. Local Topical Intralesional 2. Systemic Oral Intramuscular Intravenous

8. Astringent forms a protein precipitate which serve as a protective coat allowing new tissues to generate underneath check oozing discharge or bleeding in skin and mucous membrane by coagulating protein commonly used to reduce extent of weeping dermatitis e.g. Zinc oxide Burrows solution

Corticosteroid Mechanism of action:

Class 1 Betamethasone dipropionate cream, ointment 0.05% (in optimized vehicle)* Clobetasol propionate cream, ointment Diflorasone diacetate ointment 0.05% Halobetasol propionate ointment 0.05% Class 2 Amcinonide ointment 0.1% Betamethasone dipropionate ointment 0.05%* Desoximetasone cream, ointment 0.25%, gel 0.05% Diflorasone diacetate ointment 0.05% Fluocinonide cream, ointment, gel 0.05% Halcinonide cream, ointment 0.1% Class 3 Betamethasone dipropionate cream 0.05%* Betamethasone valerate ointment 0.1% \ Diflorasone diacetate cream 0.05% Fluticasone proprionate 0.005% Mometasone furoate 0.1% Triamcinolone acetonide ointment 0.1%, cream 0.5% Class 4 Amcinonide cream 0.1% Desoximetasone cream 0.05% Fluocinolone acetonide cream 0.2%* Fluocinolone acetonide ointment 0.025%* Flurandrenolide ointment 0.05%, tape 4 mg/cm2 Hydrocortisone valerate ointment 0.2% Triamcinolone acetonide ointment 0.1% Mometasone furoate cream, ointment 0.1% Class 5 Betamethasone dipropionate lotion 0.05%* Betamethasone valerate cream, lotion 0.1% Fluocinolone acetonide cream 0.025% Flurandrenolide cream 0.05% Hydrocortisone butyrate cream 0.1% Hydrocortisone valerate cream 0.2% Triamcinolone acetonide cream, lotion 0.1%* Triamcinolone acetonide cream 0.025% Class 6 Aclometasone dipropionate cream, ointment 0.05% Desonide cream 0.05% Fluocinolone acetonide cream, solution 0.01%*

** Remember that steroids and lipid soluble drugs utilizes a transcription factor type of hormone receptor to enter the nucleus. (type 4 receptor)

Corticosteroids: Anti-inflammatory inhibition of Phospholipase A2 Immunosuppression classification of Topical Corticosteroids in order of decreasing potency more potent steroid is used initially followed by a less potent agent twice daily application is sufficient more frequent application does not improve response Classification of Topical Corticosteroids: (GIVE IMPORTANCE TO DRUGS WITH ASTERISK AS THEY ARE THE PROTOTYPE DRUGS) Class 1 - Highest Potency Clobetasol propionate 0.05% Betamethasone dipropionate in optimized vehicle 0.05% Class 2 - High Potency Fluocinonide 0.05% Betamethasone dipropionate 0.05%

Class 7 Dexamethasone sodium phosphate cream 0.1% Hydrocortisone cream, ointment, lotion 0.5%, 1.0%, 2.5%* Methylprednisolone aceponate cream, ointment 1 mg/g Prednisolone cream 5 mg/g Topical Corticosteroids Selection Criteria: 1.Type of skin lesions 2.Location of the skin lesions 3.Severity of skin lesions 4.Age of the patient 5.Duration of treatment Comparative Indications of Topical Corticosteroids Low-Med Potency Type of lesion Thin, acute High Potency

Creams preferred for acute and subacute dermatoses used in moist skin and in intertriginous areas preferred for weeping or wet lesions Lotions preferred for lesions: in hairy areas involving large body surface areas Topical Corticosteroids (Site of the Skin Lesions) face and intertriginous areas (axilla, groin, perineum, and inframammary area) has thin stratum corneum susceptible to local and systemic adverse effects recalcitrant lesions of the face or intertriginous areas may require more potent corticosteroids or a longer duration of treatment Topical Corticosteroids (Special Considerations) use the lowest potency corticosteroid that is effective, especially in infants and children use of topical corticosteroids under plastic wrap, tight-fitting clothing, or under diapers may increase absorption several fold apply very thinly Systemic Corticosteroids used for severe dermatologic conditions such as: allergic contact dermatitis to plants e.g. poison ivy life-threatening vesicolobullous dermatoses e.g. -pemphigus vulgaris -bullous pemphigoid usually given in the morning to coincide with circadian rhythm of endogenous steroid secretion chronic administration predispose to greater side effects with chronic therapy, need to taper dose gradually before stopping treatment ** It is best to give corticosteroids in the morning to coincide with the endogenous cortisol that our body produces.

Chronic, hyperkeratotic, lichenified, endurated recalcitrant lesion in face and intertrigneous areas Palms and soles Smaller areas

Site

areas with thin stratum corneum

Extent or size of lesion Age of patient Duration of treatment

Large areas

Young and elderly longer

Adults

not > 3 weeks; longer for recalcitrant lesions

Topical Corticosteroids (Preparation) Ointment is the most effective preparation for treating thick, fissured, lichenified skin lesions choice for dry dermatoses the occlusive nature enhances corticosteroid penetration

Local Adverse Effect: -impaired wound healing -brusing -skin thinning -striae (also known as stretch marks) END OF TRANSCRIPTION To this end we always pray for you, that our God will make you worthy of His calling and may fulfill every resolve for good and every work of faith by His power, so that the name of our Lord Jesus may be glorified in you, and you in Him, according to the grace of our God and the Lord Jesus Christ. 2 Thessalonians 1:11-12