Basic Pharmacology Mod 5: Dermatologic Pharmacology PDF

BASIC PHARMACOLOGY 09/04/2024. MOD 5: DERMATOLOGIC PHARMACOLOGY...

BASIC PHARMACOLOGY 09/04/2024. MOD 5: DERMATOLOGIC PHARMACOLOGY Dr. Baxeley Joy N. Villanueva, MD, DPBA Trans Groups: 1B, 2B I. LAYERS OF THE SKIN Stratum Responsible for the bulk of cellular The skin is divided into 3 main layers — epidermis, Basale division. dermis, and hypodermis. A. EPIDERMIS B. DERMIS The outermost layer that acts as a protective barrier. Contains blood vessels, nerves, and hair follicles. Composed of 5 main layers. Provides mechanical strength and flexibility to the skin. Cells within the dermis that are targets of drugs include: NON-LIVING LAYER LIVING LAYER ○ Mast cells: permanent residents and producers of inflammatory mediators Stratum Stratum Lucidum ○ Infiltrating immune cells: producing cytokines Corneum Stratum Granulosum Superficial capillary plexus: found between epidermis Stratum Spinosum and dermis which is the site of the majority of the Stratum Basale systemic absorption of cutaneous drugs. There are a large number of lymphatics in the dermis. Strata Granulosum, Spinosum, & Basale: are the leading layers C. HYPODERMIS OR SUBCUTANEOUS TISSUE of the epidermis because they Subcutaneous tissue that is the innermost layer. have metabolically active cells Provides insulation, cushioning, and serves as an energy reservoir. LAYER FUNCTION II. ROUTES OF DRUG ADMINISTRATION IN DERMATOLOGICAL DISEASES “Horny layer” Major barrier to percutaneous A. TOPICAL absorption of drugs and to the loss Absorbed through the skin of water from the body. Stratum Commonly used to treat local problems rather than A drug may partition into the stratum Corneum systemic corneum and form a reservoir that Examples are lotion, ointment and cream will diffuse into the rest of the skin even after topical application of drug has ceased. B. INTRALESIONAL Drug administered directly into the specific lesion or area of the skin Where dead cells containing For inflammatory lesions, warts, neoplasms Stratum keratohyalin are located. NO systemic absorption Lucidum Found only in thick skin (palms, Advantages: soles) of the feet. ○ Direct contact with underlying pathological process Where the extracellular lipids are ○ Bypasses hepatic first-pass metabolism extruded from the epidermis, ○ Drug depot effect forming extracellular lipids that are important transport pathways. C. SYSTEMIC Where the cell envelope is formed, Oral route making it resistant to proteolysis and Parenteral route — intradermal, intravenous, Stratum alkali. intramuscular, subcutaneous Granulosum Site of filaggrin synthesis Filaggrin: an intracellular molecule that enhances keratin packing, D. NON-PHARMACOLOGIC THERAPY promotes water retention, Using electromagnetic spectrum applied by many contributes to the acid pH of the sources such as lasers, visible and infrared light, etc. skin, and has natural moisturizing function. III. DRUG DELIVERY FOR TOPICAL MEDICINES Contains cells that actively A. TRANSEPIDERMAL PATHWAY Stratum synthesize most epidermal Drug is delivered through the stratum corneum Spinosum proteins, especially keratin. Pharmacology - Mod 5 Dermatologic Pharmacology 1 of 13 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  In the epidermal and dermal layers, drugs may also 1. INTERCELLULAR MICROPATHWAY reach the sweat glands and their ducts. Hydrophilic drugs Permeation to the dermis brings the drugs in contact Passage of drugs between the corneocytes with lymphatics and cutaneous vessels, carrying arterial Route wherein drug is delivered between the cells of and venous blood. the stratum corneum These vessels provide an absorptive route into the general circulation. 2. TRANSCELLULAR MICROPATHWAY Permeation to the hypodermis may also occur. Lipophilic drugs D. FACTORS AFFECTING PERCUTANEOUS Through the cytoplasm of dead keratinocytes and ABSORPTION intercellular lipids Occurs primarily through intercellular pathway — with Route wherein drug passes across the corneal cellular transcellular and appendageal routes playing a much layer smaller role Rate-limiting step: passage through the stratum B. TRANSAPPENDAGEAL/FOLLICULAR PATHWAY corneum Through the hair follicle (follicular), sebaceous, and eccrine glands 1. PHYSICAL FACTORS Route if it’s in to the concavity of a hair follicle with its associated sebaceous glandular cells and arrector pili Drug concentration: high drug concentration increases muscle percutaneous absorption Occlusion: application of a plastic wrap to hold the drug and its vehicle in close contact with the skin is effective in maximizing efficacy Vehicle: an appropriate vehicle maximizes the ability of the drug to penetrate the outer layers of the skin. Exposure time: longer time of contact with the skin also increases percutaneous absorption 2. BIOLOGICAL FACTORS Percutaneous absorption differs between children and elderly Skin age: intact skin provides a formidable barrier for passage of drugs Barrier function: disrupted epidermal layer allows drug to readily pass resulting to increased systemic toxicity Absorption of Topical Drug Into the System. (e.g., as inflammation, an abnormal stratum corneum like in the case of psoriasis) C. ABSORPTION OF TOPICAL DRUG INTO THE SYSTEM Anatomical sites: percutaneous absorption can be increased or decreased depending on the anatomical sites of the skin 3. PHYSICOCHEMICAL FACTORS Percutaneous absorption is increased due to: ○ Hydration — hydrated skin increases percutaneous absorption ○ High partition coefficient ○ High solubility in water and oil ○ Small particles of drug ○ Low molecular weight ○ Presence of heat E. PREFERABLE CHARACTERISTICS OF TOPICAL DRUGS Low molecular mass (≤ 500 Da or Dalton) Adequate solubility in both oil and water A high partition coefficient: drug will selectively partition from the vehicle in the stratum corneum Absorption of Topical Drug Into the System. Except for very small particles, water-soluble ions and polar molecules do NOT penetrate significantly through After the application of the drug to the surface of the skin intact stratum corneum via the stratum corneum, evaporation and structural or compositional alterations may occur that affect the F. REGIONAL ANATOMIC VARIATIONS drug’s bioavailability. The thinner the stratum corneum, the higher the drug Stratum corneum limits drug diffusion into the lower concentration. layers and then into the body. Drug penetration is greater in the face, postauricular Absorptive routes can be intercellular, transcellular, or area, and intertriginous/flexural areas (e.g., axilla, transappendageal. groin, inframammary areas). Melanocytes and Langerhans cells are accessible in the lower epidermis. Pharmacology - Mod 5 Dermatologic Pharmacology 2 of 13 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  ○ Active drug must be readily released once in contact with the skin A. POWDER B. OINTMENT C. CREAM D. GEL E. LOTION F. SOLUTION G. PASTE Absorption Percentages of Different Body Parts. H. POULTICE/CATAPLASM G. AGE V. DERMATOLOGIC DRUGS Children ○ Greater ratio of surface area to mass than adults: A. CORTICOSTEROIDS same amount of topical drug → systemic exposure Preterm infants have markedly impaired barrier function until the epidermis keratinizes completely Elderly: thinner and poorly hydrated stratum corneum may impede drug delivery H. SKIN HYDRATION Phenomenon when water content of skin exceeds the normal state Swelling of the stratum corneum → more permeable to drug molecules ○ Increase intracellular water → diffusion of water molecules → intercellular space becomes larger → drug penetration Promotes transdermal absorption of drugs Skin hydration mainly increases the penetration of non-polar, fat-soluble molecules ○ Little effect on the penetration of polar molecules ○ Encapsulation method or applying of ointment on MOA of Corticosteroids. the skin reduces the evaporation of skin moisture ○ The covering effect of applying ointment Have immunosuppressive and anti-inflammatory increases endogenous hydration of stratum properties corneum and increases skin penetration MOA: acts by binding to glucocorticoid receptors → inhibiting phospholipase A2 → inhibits arachidonic acid I. DOSAGE AND APPLICATION FREQUENCIES synthesis → decreased cascade of release of Topical agents often applied 2x daily inflammatory mediators such as prostaglandins, For some drugs, once-daily application of a larger leukotrienes, and cytokines dose may be equally effective as more frequent Modes of administration applications of smaller doses ○ Locally: topical, intralesional Stratum corneum may act as drug reservoir ○ Systemic: intramuscular, intravenous, oral Intermittent pulse therapy: treatment for several days or weeks alternating with treatment-free periods 1. TOPICAL CORTICOSTEROIDS ○ May prevent development of tachyphylaxis which A more potent steroid is used initially, followed by a is the loss of effectiveness due to giving successive less potent agent doses of drugs ○ 2x a day of application is sufficient ○ More frequent application DOES NOT improve IV. DERMATOLOGIC VEHICLES response. Inactive part of a topical preparation that brings a In general, only non-fluorinated glucocorticoids drug into contact with the skin should be used on the face or in occluded areas such as Markedly influence the ability of a drug to penetrate the the axillae or groin. outer layers of the skin ○ Fluorinated compounds can cause perioral Ideal Characteristics: dermatitis and rosacea. ○ Easy to apply and remove ○ Non-irritating and non-allergenic ○ Cosmetically pleasing ○ Active drug must be stable in the vehicle Pharmacology - Mod 5 Dermatologic Pharmacology 3 of 13 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  SELECTION CRITERIA OF TOPICAL CORTICOSTEROIDS LOW TO CRITERIA MEDIUM HIGH POTENCY POTENCY Chronic, Rosacea. Type of Thin, acute hyperkeratotic, Lesion lichenified, indurated 1.1 Potency of Selected Topical Corticosteroids Topical steroids have been grouped into seven classes Recalcitrant lesion in in order of decreasing potency Areas with thin face and intertriginous Most potent drugs are classified in class 1 while the Site stratum areas; palms and soles least classified are in class 7. corneum (fixed stratum corneum) POTENCY OF SELECTED TOPICAL CORTICOSTEROIDS Extent of Size of Large areas Smaller areas DRUG CLASS GENERIC NAME, FORMULATION Lesion Clobetasol propionate cream, ointment Age of Young and Adults 0.05% Patient elderly MOST 1 Potent Betamethasone dipropionate cream, ointment (in optimized vehicle) 0.05% Not > 3 weeks; Duration of Longer Longer for recalcitrant Treatment Fluocinonide cream, ointment 0.05% lesions 2 Betamethasone dipropionate ointment 0.05% 2. INTRALESIONAL CORTICOSTEROIDS Insoluble preparations of: Betamethasone dipropionate cream ○ Triamcinolone acetonide 3 0.05% ○ Triamcinolone hexacetonide Betamethasone valerate ointment 0.1% Solubilized gradually → prolonged duration of action Fluocinolone acetonide ointment 3. SYSTEMIC CORTICOSTEROIDS 0.025% 4 Used for severe or extensive dermatological illnesses Mometasone furoate cream, ointment 0.1% such as: ○ Allergic contact dermatitis in plants (e.g., poison Triamcinolone acetonide lotion cream ivy) 5 0.1% ○ Vesiculobullous dermatoses (e.g., pemphigus Hydrocortisone valerate cream 0.2% vulgaris, bullous pemphigoid) ○ Vasculitis Fluocinolone acetonide cream, solution ○ Autoimmune connective tissue diseases 6 0.01% ○ Neutrophilic dermatoses (e.g., pyoderma Desonide cream 0.05% gangrenosum) LEAST Usually given in the morning to coincide with the Potent circadian rhythm of endogenous secretion of steroids Hydrocortisone cream, ointment, lotion 7 Fewer side effects are seen with alternate-day dosing 0.5%. 1% and 2.5% If required for chronic therapy: ○ Steroids are TAPERED EVERY OTHER DAY as 1.2 Selection Criteria of Topical Corticosteroids soon it is practical. The steroid is selected based on its potency, type of lesion, site of involvement, extent of site of the 4. ADVERSE EFFECTS OF CORTICOSTEROIDS lesion, age of patient, and duration of treatment. Systemic effects are mainly due to chronic use LOCAL SYSTEMIC Pharmacology - Mod 5 Dermatologic Pharmacology 4 of 13 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  Decrease colonization of Propionibacterium Atrophy Acute Adrenal Insufficiency acnes/Cutibacterium acnes Shiny and Result from overly rapid Decrease inflammation depressed, often withdrawal of wrinkled skin corticosteroids after 3. ANTI-ACNE AGENTS “Cigarette chronic use paper”-appearing Most severe skin complication of steroid 3.1 Retinoids Prominent withdrawal Comprise of natural and synthetic compounds that telangiectasia Suppression of HPA exhibit vitamin A-like biological activity or bind to May develop to axis nuclear receptors for retinoids purpura or Functions include regulation of cell proliferation and ecchymosis differentiation Corticoid rosacea Growth retardation in Central facial children distribution of pustules and papules Retinoids. Perioral dermatitis, Immunosuppression Mechanism of Action steroid acne, Due to the inhibitory ○ Exert their effect on gene expression by activating hypopigmentation, and effects of corticosteroids two families of nuclear receptors on the epidermis hypertrichosis (towards the immune ○ Activates retinoic acid receptors (RARs) and system and retinoid X receptors (RXRs) inflammatory response) ○ Form heterodimers that subsequently bind specific DNA sequences called retinoic acid response Increased intraocular Cataract formation elements (RAREs) pressure Cataracts are a ○ Activate transcription of genes → produce both well-established pharmacological effects and side effects complication of glucocorticoid therapy Related to dosage and duration of therapy Children appear to be particularly at risk Allergic contact Gastritis, ulcer formation, dermatitis and gastrointestinal bleeding Risks mildly increased by steroids Overgrowth of skin Others: Metabolism of topical retinoids. fungi and bacteria Hypertension Hyperglycemia (can 3.1.1 Retinoids Based on Generations lead to delayed wound healing and overt RETINOIDS BASED ON GENERATIONS diabetes) Myopathy Retinol (Vitamin A) Behavioral changes Tretinoin (all-trans retinoic acid or Osteoporosis First Vitamin A acid) Osteonecrosis (AKA Gen Isotretinoin (13-cis-retinoic acid) avascular or aseptic Alitretinoin (9-cis-retinoic acid) necrosis) a.k.a. Aromatic Retinoids Second B. AGENTS FOR ACNE Acitretin Gen Etretinate 1. ACNE VULGARIS Optimizes receptor selective binding Believed to result from a combination of these following Includes: processes: Third ○ Tazarotene ○ Sebaceous gland hyperplasia Gen ○ Bexarotene ○ Follicular hyperkeratosis ○ Adapalene ○ Cutibacterium acnes colonization (previously known as the Propionibacterium acnes) Fourth Trifarotene: further optimizes receptor ○ Inflammation Gen selective binding 2. GOALS OF ACNE TREATMENT Correct abnormalities of follicular maturation Decrease sebum production Pharmacology - Mod 5 Dermatologic Pharmacology 5 of 13 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited. 3.1.2 Retinoids Based on Retinoid Receptor Selectivity Suicidal RETINOIDS BASED ON RETINOID RECEPTOR ideation SELECTIVITY (Isotretinoin) Teratogenicity RAR-Selective RXR-Selective Retinoids Retinoids 4. ANTIBACTERIAL AGENTS FOR ACNE Cellular Cellular apoptosis Action differentiation and 1 Benzoyl peroxide (topical) proliferation 2 Clindamycin Acne Kaposi Psoriasis sarcoma 3 Doxycycline Use Photoaging Mycosis Fungoides 4 Erythromycin Tretinoin Bexarotene 5 Metronidazole Example Adapalene Alitretinoin Tazarotene 6 Sodium sulfacetamide Mucocutaneous & Physiochemical Side 4.1 Benzoyl Peroxide musculoskeletal changes Effects symptoms First line agent for mild to moderate acne with no inflammation 3.1.3 Retinoids Based on Route of Administration Antimicrobial activity against P. RETINOIDS BASED ON ROUTE OF ADMINISTRATION MOA acnes Peeling and comedolytic effects Route Topical Systemic Dry skin Non-inflammatory Severe, Adverse Peeling (comedonal acne): recalcitrant Effects Skin irritation topical retinoids are nodular acne the first line agents Psoriasis for this type of acne Cutaneous Available in many over-the-counter acne treatment Indication Inflammatory acne: T-cell products combined with other lymphoma An oxidant and may rarely cause bleaching of the hair or agents colored fabrics Photoaging ○ Fine wrinkles 5. KERATOLYTICS ○ Dyspigmentation Substances that reduce hyperkeratosis through a variety of mechanisms: Tretinoin: first line Isotretinoin ○ Breaking of intercellular junctions agent for moderate (oral) ○ Increasing stratum corneum water content Example acne Acitretin ○ Increasing desquamation Adapalene Bexarotene Tazarotene KERATOLYTIC MECHANISM OF ACTION Erythema Mucocutaneous Solubilization of intercellular Desquamation effects cement, reducing corneocyte Burning or stinging Myalgia Salicylic Acid adhesion & softening the stratum sensation Arthralgia corneum Photosensitivity Alopecia reaction Nail fragility Increased Dissociation of the chemical into Hydrogen serum lipids water and reactive oxygen species Peroxide Side Elevation of (ROS), which results in skin cell death Effect serum transaminases Propylene Increase water content of stratum Hypothyroidism Glycol corneum & enhances desquamation Leukopenia Pseudotumor Increases skin absorption and cerebri (in Urea retention of water leading to combination increased flexibility & softness of skin with tetracyclines) 6. PHARMACOLOGIC TREATMENT OF ACNE BY SEVERITY Pharmacology - Mod 5 Dermatologic Pharmacology 6 of 13 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  ○ Hypercalcemia SEVERITY TREATMENT ○ Hypercalciuria ○ Perilesional irritation Topical antibacterials (Benzoyl ○ Mild photosensitivity Peroxide) Generally applied 2x daily often in combination with MILD If not effective, use topical topical corticosteroids antibiotics (Clindamycin, Erythromycin) D. SUNSCREENS Topical antibiotics + topical vitamin A derivatives (Tretinoin, MODERATE Adapalene, or Tazarotene) If no response, use oral antibiotics (Minocycline or Doxycycline) SEVERE Oral antibiotics + Isotretinoin C. DRUGS FOR PSORIASIS 1. PSORIASIS An autoimmune disease characterized by hyperproliferation of keratinocytes in the epidermis Typically appears as silvery, scaly plaques that are non-pruritic and commonly found on the flexural areas (elbows, knees), back, scalp. 2. TREATMENT OF PSORIASIS Diagram showing electromagnetic spectrum of visible and When choosing a treatment for psoriasis, consider its UV radiation and biologic effects on the skin. severity whether it’s confined locally or extensively spread already. 1. SOLAR UV RADIATION Solar UV radiation can be subdivided into: TREATMENT OF PSORIASIS ○ UVA ○ UVB SEVERITY TREATMENT EXAMPLE ○ UVC The three types of UV radiation are classified according Steroids: topical, Fluocinonide, to their wavelength — the shorter the wavelength, the high potency Triamcinolone, more harmful the radiation Betamethasone, However, shorter wavelength UV radiation is less Clobetasol capable of penetrating the skin. Ambient sunlight: predominantly made up of UVA and Local Immunomodulators Pimecrolimus, UVB Tacrolimus UV RADIATION Vitamin A Derivative Tazarotene TYPE INDICATIONS Vitamin D Analogue Calcipotriene Shortest wavelength UV light Most damaging UVC Completely filtered in the Anti-TNF inhibitors Etanercept, atmosphere and doesn’t reach the Adalimumab, earth’s surface Infliximab Long wavelength Extensive Vitamin A Derivative Acitretin Penetrates deeply, reaching well into the dermis Methotrexate LAST RESORT Responsible for immediate tanning (Except for effect psoriatic arthritis) Recent studies strongly suggest that Adverse Effect: it may also enhance development of LUNGS & LIVER UVA = Aging skin cancers Remains constant all year long Accounts for up to 95% of UV 2.1 Calcipotriene radiation reaching the earth Vitamin D Analogue Causes skin aging Used for Plaque Psoriasis Can penetrate glass, requiring MOA: inhibit keratinocyte proliferation and increases protection both indoors and out keratinocyte differentiation Adverse Effects Pharmacology - Mod 5 Dermatologic Pharmacology 7 of 13 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  5. CLASSIFICATION BY ACTIVE INGREDIENT Medium wavelength Almost completely absorbed by ACTIVE MECHANISM EXAMPLE the epidermis with comparatively INGREDIENT OF ACTION little reaching the dermis Responsible for delayed tanning or Work by Benzophenones burning (or sunburn) absorbing UV ○ Oxybenzone Enhances skin aging UVB = Burns rays ○ Dioxybenzone Significantly promotes development ○ Sulisobenzone of skin cancer Dibenzoylmethane More intense than UVA rays ○ Avobenzone Strongest in the summer but Anthralates filtered by glass ○ Meradimate Most all sunscreens work to block Camphors UVB rays ○ Ecamsule ORGANIC Aminobenzoates 2. ACTIVE INGREDIENTS OF SUNSCREEN (CHEMICAL ○ PABA** SUNSCREEN) ○ Padimate O Sunscreens provide temporary photoprotection from Cinnamates the acute and chronic effects of sun exposure ○ Cinoxate ○ Octinoxate MAJOR ACTIVE INGREDIENTS OF SUNSCREEN Salicylates ○ Trolamine ORGANIC AGENTS INORGANIC AGENTS salicylate** ○ Homosalate “Chemical blockers” “Physical blockers” ○ Octisalate Absorb UV radiation in Contain particulate Octocrylene the UVB or UVA ranges materials that act by Ensulizole and then converts it to scattering or reflecting heat energy visible, UV, and infrared Provide Zinc oxide radiation to reduce its UVA, UVB, Titanium dioxide transmission to the skin and visible *Aggregation of these light particles on the skin 3. SUN PROTECTOR FACTOR (SPF) protection tends to leave a INORGANIC Ratio of the minimal dose of incident sunlight that Protect whitish hue on the (PHYSICAL will produce erythema (sunburn) on skin with the skin from skin. SUNSCREEN) sunscreen in place to the dose that evokes the same the sun by reaction on skin without the sunscreen deflecting Primarily a measure of UVB protection or But does NOT provide information regarding UVA blocking coverage the sun’s With the new guidelines released by FDA, UVA rays protection is now assessed using the critical wavelength method There is a risk of allergic and photoallergic skin “BROAD SPECTRUM”: products with critical reactions with PABA**. wavelength of greater than or equal to 370nm For trolamine salicylate**, the risks include wavelength anticoagulant effects and salicylic toxicity. It is better to choose sunscreens with broad spectrum Will absorb more than 92% of coverage for more efficient protection. SPF 15 incident UVB radiation E. AGENTS FOR PIGMENTATION DISORDERS SPF 30 AND May absorb 96.7% and 97.5% of 1. HYDROQUINONE SP40 UVB radiation respectively Indicated for gradual bleaching of hyperpigmented skin in conditions such as melasma, freckles, and The higher the SPF, the greater the protection from solar lentigines. sun-induced skin damage. MOA: inhibits tyrosinase enzymes → interferes with the biosynthesis of melanin → decreased melanocyte 4. APPLICATION pigment production Sunscreens should be applied liberally 15 to 30 ○ Causes degradation of melanosomes and minutes prior to sun exposure and reapplied at least destruction of melanocytes by production of every 2 hours reactive oxygen radicals If activities involve swimming or sweating Adverse effects: Dermatitis and Ochronosis ○ Water-resistant sunscreens are recommended Lightens the skin temporarily ○ Reapply every 40 or 80 mins depending on More than 4% of hydroquinone must not be used labelling because it can induce carcinogenesis About 1 ounce (5-6 teaspoons) of sunscreen is Concomitant application of SPF 15 to 30 sunscreens recommended to cover the entire body and meticulous photoprotection are essential to Pharmacology - Mod 5 Dermatologic Pharmacology 8 of 13 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  minimize sun-induced exacerbation of 1. MINOXIDIL hyperpigmentation. Topical Minoxidil (such as Rogaine), is effective in reversing the progressive miniaturization of terminal scalp hairs associated with androgenic alopecia in BOTH male and female MOA: unknown ○ Believed to shorten the telogen (resting) phase of hair cycle ○ Stimulates and prolongs the anagen (growth) phase of the hair cycle leading to longer and increased numbers of hairs ○ Enhances follicular size thereby producing thicker hair shafts Adverse effects: allergic and irritant contact Melasma. dermatitis Available as a non-prescription TOPICAL foam or 2. METHOXSALEN solution A psoralen used for the repigmentation of vitiligo and Vertex balding is more responsive to therapy than also for psoriasis treatment frontal balding. MOA: must be photoactivated by UVA to produce a Effect is not permanent — cessation of treatment will beneficial effect lead to hair loss in 4 to 6 months ○ Psoralen Plus UVA (PUVA) radiation: method of Minimal percutaneous absorption in normal scalp — photoactivation by UVA to form a DNA product monitor possible systemic effects on blood pressure inhibiting DNA replication in cardiac patients ○ Inhibits cell proliferation and promotes cell differentiation of epithelial cells Adverse effects for long-term therapy: cataracts, skin cancer Topic or oral preparations Minoxidil (Rogaine). Vitiligo. 2. FINASTERIDE Used to treat androgenic alopecia in males ONLY F. TRICHOGENIC AGENTS Also used in higher doses for benign prostatic Used to treat Androgenic alopecia hypertrophy ○ Male and female pattern baldness MOA: 5α-reductase inhibitor that blocks the ○ Most common cause of hair loss at 40 years old conversion of testosterone to dihydrotestosterone ○ Genetically inherited trait ○ Responsible for androgenic alopecia in Common Trichogenic Agents used genetically predisposed men ○ Minoxidil Adverse effects ○ Finasteride ○ Decreased libido, ejaculation disorders, and erectile dysfunction — resolve in most men who remain on therapy and in all men who discontinue finasteride ○ Each of these occurs in less than 2% of patients ○ Risk of hypospadias developing in a male fetus — pregnant women should not be exposed either by use or by handling crushed tables Treatment for 3-6 months for hair growth and prevention of hair loss Requires continuous treatment Oral preparation Androgenic Alopecia. Pharmacology - Mod 5 Dermatologic Pharmacology 9 of 13 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  Chickenpox Penciclovir for (Varicella-Zoster virus or mucocutaneous HSV VZV) Condyloma acuminatum Podophyllin Podofilox Molluscum contagiosum Verrucae Finasteride (Propecia). (Human Papillomavirus or HPV) G. ANTIFUNGALS 1. TOPICAL AGENTS Best initial therapy if NO hair or nails are involved EXAMPLES Keratolytic Whitfield’s Ointment (Benzoic Acid + Salicylic Acid) Imidazole Ketoconazole Clotrimazole Miconazole Allylamine Terbinafine: best initial therapy for tinea capitis & tinea unguium Tolnaftate Examples of Viral Infections. I. ECTOPARASITICIDES 2. SYSTEMIC AGENTS Antifungals 1 Lindane EXAMPLES 2 Permethrin Griseofulvin 3 Malathion Imidazole Ketoconazole: can cause gynecomastia Fluconazole Itraconazole Terbinafine Permethrin cream. Candidiasis. Ectoparasites. H. TOPICAL ANTIVIRALS 1. LINDANE Organochloride compound that induces neuronal VIRAL SKIN INFECTION ANTIVIRAL DRUG hyperstimulation and eventual paralysis of parasites Used as a commercial insecticide as well as topical Herpes simplex (HSV) Acyclovir medication Cidofovir: if Side effect: neurotoxicity Acyclovir-resistant Valacyclovir Pharmacology - Mod 5 Dermatologic Pharmacology 10 of 13 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  Disinfection can be accomplished to kill microorganisms by: ○ Application of chemical agents ○ Use of physical agents Ionizing radiation Dry or moist heat Superheated steam (autoclave, 120° C) Lindane shampoo. 1. HAND HYGIENE Most important means of preventing transmission of 2. PERMETHRIN infectious agents from person to person or from Synthetic derivative of the insecticide pyrethrum regions of high microbial load (mouth, nose, or gut) to which is obtained from Chrysanthemum cinerariifolium potential sites of infection MOA: interferes with insect sodium transport proteins Alcohol-based hand rubs and soap and warm water causing neurotoxicity and paralysis are used to kill or remove bacteria Used for scabies and head lice Skin disinfectants + detergent and water: used Neurotoxicity is rare preoperatively as a surgical scrub for the hands and arms of surgical team members ANTISEPTICS/DISINFECTANTS 1 Alcohol 2 Chlorhexidine 3 Iodophors 4 Chlorine Permethrin (Kwell) Shampoo. 3. MALATHION 2. ALCOHOL Organophosphate that binds acetylcholinesterase in For antisepsis and disinfection lice causing paralysis and death They are rapidly active killing Mycobacterium tuberculosis, vegetative bacteria, many fungi, and inactivating lipophilic viruses Optimum bactericidal concentration: 60%-90% by volume in water MOA: denaturation of proteins Side effect: skin drying — alleviated by adding emollients to the formulation Use of alcohol based hand rubs ○ Reduce transmission of health-care associated pathogens (e.g. COVID-19) ○ In health-care setting, this is the preferred method in hand decontamination (CDC) Malathion lotion and liquid. ○ Ineffective against spores of Clostridium difficile Handwashing with soap and water is J. ANTISEPTICS/DISINFECTANTS required for decontamination of patients with C. difficile Flammable and must be stored in cool well ventilated ANTISEPTIC Disinfecting chemical agents with areas sufficiently low toxicity for host ○ Must be allowed to evaporate before cells that they can be used directly electrosurgery, laser surgery, or cautery on skin, mucous membranes, or Alcohol can damage corneal tissues when applied wounds directly to it Most topical antiseptics interfere ○ Instruments like tonometer that have been with wound healing to some disinfected in alcohol should be rinse with sterile degree water or let the alcohol evaporate before using ○ Cleansing of wounds with soap and water may be less damaging than the application of antiseptic DISINFECTANT Chemical agents or physical procedures that inhibit or kill microorganisms Pharmacology - Mod 5 Dermatologic Pharmacology 11 of 13 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  Common alcohol based rub in operating room. 3. CHLORHEXIDINE Iodophor example. Cationic biguanide with very low water solubility Used in a water based formulation as an antiseptic Active against vegetative bacteria and mycobacteria, ADVANTAGE DISADVANTAGE and has variable activity against fungi and viruses MOA: strongly adsorbs to the bacterial membrane Less irritating Require drying time on → small molecule leakage and precipitation of skin before becoming active cytoplasmic proteins Slower in its action than alcohol Less likely to Although iodophors have a ○ Bactericidal is still equivalent to alcohol due to produce skin broader spectrum of activity residual activity hypersensitivity than chlorhexidine, including Most effective against gram positive (+) cocci sporicidal action, they lack ○ Less active against gram positive (+) and gram persistent activity on skin negative (-) rods Inhibits spore germination Neutralized by anionic and nonionic agents in 5. CHLORINE moisturizers, surfactants, and neutral soap Strong oxidizing agent and universal disinfectant Chlorhexidine Gluconate + 70% Alcohol: preferred 5.25% sodium hypochlorite solution (household agent for skin antisepsis in many surgical and bleach) percutaneous procedures 1:10 dilution of household bleach ○ Rapid action after application ○ 0.525% concentration: 5,000 ppm of chlorine ○ Retained activity after exposure to body fluids ○ Concentration for disinfection of blood spills ○ Persistent activity on the skin (recommended by CDC) Very low skin-sensitizing or irritating capacity Inactivated by blood, serum, feces, and Low oral toxicity because it is poorly absorbed from protein-containing materials alimentary tract ○ Clean surfaces before disinfecting with chlorine Contraindicated for surgery on the middle ear ○ Causes sensorineural deafness CONCENTRATION EFFECT ○ Similar neural toxicity may be encountered during neurosurgery Up to 5,000 ppm Kills bacterial spores 1,000-10,000 ppm Tuberculocidal 500 ppm Kills fungal spores 200-500 ppm Inactivates viruses Chlorhexidine example. 4. IODOPHORS Complexes of iodine with a surface-active agent — polyvinyl pyrrolidone (povidone-iodine) Used as antiseptic or disinfectant (the latter containing more iodine) Retain activity of iodine Kill vegetative bacteria, mycobacteria, fungi, and lipid-containing viruses Sporicidal with prolonged exposure Pharmacology - Mod 5 Dermatologic Pharmacology 12 of 13 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited. DERMATOLOGIC VEHICLE MEANING USES ADVANTAGES DISADVANTAGES Very fine particle size substance which covers a Antifungal or antibacterial Powder large surface area of the body Adhere poorly to skin For infections or irritations Absorbs moisture and reduces friction Semi-solid preparation that usually Occlusive effect prolong and contains oleaginous bases → Chronic, lichenified and dry Greasy Ointment enhance drug penetration provides greater occlusive and lesions Stains clothes Spreads easily on skin emollient effects Evaporates easier Contain water soluble bases that Exudative (wet) dermatoses Non-greasy More prone to microbial Cream