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Drugs used in skin disorders

Drugs used in Skin Disorders

Skin

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-

Source: http://www.pharma.hku.hk/pharmacy/bsc/teaching/201112/Year3/handouts/BPHM3004/BP-BPHM3004L13DrugsUsedInSkinDisorders-7Oct11.pdf

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