Skin is about 1/6 body weight, complex diffusion barrier Epidermis is keratinized, stratum corneum the principal barrier Dermis is highly vascular, hypodermis and subcutaneous are connective tissues Palms have no follicles and sebaceous glands, but with sweat glands and thick keratin Face, scalp and upper chest, with lots of sebaceous glands Major variable affecting Drug Action
Regional variation, affects drug penetration, e.g., face, axilla, scalp > forearm Concentration gradient Dosing schedule, skin as a drug reservoir Vehicles and occlusion: corneum hydration, enhances absorption They have effects on solubility, release rates, stability, & component interactions Non-specific Effects of Vehicles
Solutions and gels drying effect Greasy ointments pronounce lubricating effect Creams and lotions slight lubricating effect Acne
Obstruction of sebaceous follicles Abnormal keratinization Androgens increase secretion – testosterone & dihydrotestosterone Microbial colonization, propionibacterium acnes Comedogenic acne (white and blackheads) – topical retinoid Papulopustule acne – topical retinoids and benzoyl peroxide, topical/oral antibiotic Cystic acne (suppurative nodules) – oral isotretinoin Benzoyl peroxide Peeling agent, increase skin turnover and clear pores, antibacterial Bleaching, drying side effects
Adapalene Naphthoic acid derivative, comedolytic, antiproliferative, and antiinflammatory Antibiotics Topical clindamycin, erythromycin Bind to 23s ribosomal RNA in the 50S portion of the bacterial ribosome Oral erythromycin, tetracycline, doxycycline, minocycline Photosensitivity, use sunscreen Cellulitis – bacterial infection of the skin, rash, fever, and malaise Antibacterial agents for prevention and treatment of wound infection: bacitracin, polymyxin B, neomycin, gentamycin, against G-ve, e.g., staphylococci, E. Coli, P. aeruginosa Neomycin, frequently causing sensitization, cross sensitized to streptomycin, kenamycin, gentamycin Topical retinoids Related to vitamin A, bind with retinoid receptors 1st generation – retinol, tretinoin, isotretinoin 2nd generation – etritinate, acitretin 3rd generation – tazarotene, bexarotene Comedolytic and anti-inflammatory, normalize follicle cell cycle, prevent hyperkeratinization Isotretinoin Decreases the size and secretion of the sebaceous gland Normalizes follicular keratinization, anti-inflammatory, inhibits P. acnes Absorption increased by high-fat meal Can cause birth defects, strict birth control, not to donate blood Antivirals
Salicyclic acid ointment, podophyllin for common wart 5-iododeoxyuridine (5-IDU), acyclovir for herpes simplex (cold sore) Herpes hominis virues of 2 strains: HSV1 (facial) & HSV2 (genital) Reside in nerve root ganglions, spread sown nerve fibers to affect skin (recurs) Shingles – herpes zoster (chickenpox) virus, painful, fever, malaise, anorexia Unilateral rash following the course of a nerve tract with small blisters Fungal infection
Tinea pedis – often involving interdigital space; tinea cruris – infection of the groin; tinea corporis – affecting the trunk or limbs Candidiasis – less well defined edges, sometimes vesicles Imidazoles, e.g., clotrimazole, miconazole, ketoconazole, econazole Terbinafine, tolnaftate, haloprogin, grieseofulvin Griseofulvin a penicillium mold, may show cross-sensitivity with penicillin Inhibits hyphal cell wall and nucleic acid synthesis Interferes with microtubules and mitosis Candidiasis (thrush) Yeast (Candida albicans); red patches on skin, white in mouth, discharge from vagina Predisposing factors, moist warm skin, dentures, diabetes, serous illness, antibiotics or steroids, pregnancy and O.C. Treat with nystatin ointment, tablet, pessary Binds to ergosterol Dermatitis and Eczema
Eczematous dermatoses, e.g., atopic dermatitis, eczema, contact dermatitis Topical corticosteroids, induce lipocortin anti-inflammatory protein, inhibiting PGs products Inhibits inflammatory cytokines Side effects: atrophy, telangiectasia, suppression of adrenal glands Potency depends on molecular structure, concentration and vehicle Fingertip unit – tip to the first crease of index finger, about 0.5g, ½ unit to one palm Side effects Systemic absorption hydrocortisone 1% but with occlusion about 10% Adrenal suppression, may recover within 1 week of stopping Atrophy and acneiform eruptions, telangiectasia Reduce cellular replication and immune functions Emollient creams/ointments Emulsifying ointment, etc., with humectant, e.g., urea, glycerine, polyethylene glycol Liquid paraffin, isopropyl myristate Emollient bath oil, e.g., oilatum bath oil
Shampoos free of sodium lauryl sulphate Aqueous cream may cause irritation Potassium permanganate soaks for wet eczematous lesions Napkin dermatitis – napkin rash Barrier agents, zinc cream/ointment, titanium Candidal infection, topical imidazole creams Antihistamines Sedating and non-sedating, diphenhydramine aid sleep Antibiotics Systemic cephalexin, errthromycin, tetracyclines Calcineurin inhibitors – tacrolimus, pimecrolimus Inhibit the production of inflammatory cytokine in T cells and mast cells through suppression of phosphatase activity of calcineurin Prevent formation of interleukins, interferon-, TNF- Long term safety? Skin cancer? Not for children less than 2 years More potent than chemically unrelated cyclosporine Psoriasis
Hyperproliferation and abnormal differentiation of epidermis Lymphocyte infiltration, limited neoangiogenesis Topical corticosteroids – tachyphylaxis, rebound reactions may occur and limited its use Calcipotriene (calcipotriol) – synthetic derivative of calcitriol or vit D Binds to vit D receptor, modulates T cells activity Reduce keratinocyte proliferation, normalize differentiation, reduce immune activation Tazarotene – topical retinoid, a synthetic acetylenic retinoid Selectively binds to retinoic acid receptors Side effects – dry skin, pruritus, redness Oral retinoids – acitretin but teratogenic Anthralin (dithranol_ - accumulates in mitochondria, apoptosis of lymphocytes
Tacrolimus, cyclosporine, mycophenolate mofetil – immunosuppressive, suppress inflammation Block T cell activation through inhibition of calcineurin phosphatase Inhibits calcineurin, thus T cell signal transduction Methotrexate – inhibits dihydrofolate reductase thus DNA, RNA, thymidylates, and protein synthesis Weekly oral or injection NSAIDs, vaccines, ethanol (liver toxicity) should be avoided Mercaptopurine/azathioprine PUVA photochemotherapy (psoralens + UVA) – intercalates DNA base pairs, damage cell membrane Risk of skin cancer Biologics Adalimumab, etanercept, infliximab – block TNF-
BASIC KNOWLEDGE FROM CLINICAL PHARMACY 1. Simple Choice . 2 2. Multiple Choice. 8 3. Grouping. 16 4. Relation Analysis . 18 5. Calculations . 22 6. Answer key. 24 BASIC KNOWLEDGE FROM CLINICAL PHARMACY 1 . S i m p l e C h o i c e Choose the only one correct answer by solving the following problems. 1. A. Utilising the pharmacological, medico-biological knowledge of the pharmacist in
For many gardeners a slight air of mystery can surround the use ofgrasses in gardens, but in fact they are deceptively easy to use and arereally no different from most perennial plants. Certainly there aregrasses which are ‘spreaders’, but those mostly offered by specialist nurseriesand good garden centres are clump forming plants that have excellent gardenmanners. Strongly architectura