Dermatologic Pharmacology PDF

Musculoskeletal and Integumentary System Dermatologic Pharmacology By Abdurazak Jemal Tura (B.Pharm, MSc in Pharmacology, Assistant Professor) Drugs Acting on Skin Variety of drugs applied topically to skin produce effects localized to site of applicatio...

Musculoskeletal and Integumentary System Dermatologic Pharmacology By Abdurazak Jemal Tura (B.Pharm, MSc in Pharmacology, Assistant Professor) Drugs Acting on Skin Variety of drugs applied topically to skin produce effects localized to site of application act by physical/chemical/biological attributes divided into several categories by prominent action Drugs Acting on Skin cont… Demulcents inert substances which sooth inflamed/denuded skin by preventing contact with irritants high molecular weight substances applied as thick colloidal/viscid solutions in water serve as protectives propylene glycol, glycerine, methylcellulose  Drugs Acting on Skin cont… Emollients oily substances which sooth & soften skin form occlusive film over skin, preventing evaporation ✓ restore elasticity of cracked & dry skin ✓ serve as protectives olive oil, arachis oil, sesame oil, cocoa butter, hard/soft paraffin, liquid paraffin, wool fat, bees wax, spermaceti  Drugs Acting on Skin cont… Adsorbants/Protectives inert insoluble solids capable of binding to surface (adsorbing) noxious & irritant substances afford physical protection to skin form a continuous, adherent & flexible occlusive coating (protect damaged tissue) → helps healing magnesium/zinc stearate, calamine, starch, boric acid, polyvinyl polymer, sucralfate gel  Drugs Acting on Skin cont… Astringents substances that precipitate proteins not penetrate cells, affecting superficial layer toughen surface making mechanically stronger & decrease exudation tannic acid/tannins, ethanol & methanol (50-90%) reduce secretion from sweat glands, prevents sweat decomposition by bacteria, reducing body odor ✓ aluminum, zinc & zirconium salts  Drugs Acting on Skin cont… Irritants irritants stimulate sensory nerve endings induce inflammation at site of application produce cooling sensation or warmth, pricking & tingling, hyperesthesia or numbness Drugs Acting on Skin cont… counter-irritants produce superficial inflammation to reduce deeper inflammation irritants that produce a remote effect which tends to relieve pain & inflammation in deeper organs Drugs Acting on Skin cont… Counterirritants massaged to relieve headache, muscular pain, joint pain, pleural/peritoneal pain, colics volatile oils (essential oils) ✓ produces cooling sensation on skin ✓ turpentine oil, clove oil, eucalyptus oil, camphor, menthol, thymol, mustard seeds, capsicum, methyl salicylate, alcohol Drugs Acting on Skin cont… Caustics & Escharotics local tissue destruction & sloughing (shedding) precipitates proteins that exude to form scar remove moles, warts, condyloma, papillomas & keratotic lesions microbes may be killed during cauterization podophyllum resin, silver nitrate, phenol, trichloroacetic acid, glacial acetic acid Drugs Acting on Skin cont… Keratolytics dissolve intercellular substance in horny layer of skin epidermal cells swell, soften & desquamate used on hyperkeratotic lesions like corns, warts, psoriasis, chronic dermatitis, ringworm, athletes foot ❑ Salicylic acid 10–20% solution in propylene glycol dissolve corns applied under polyethylene occlusive dressing causes maceration of skin & acts as a keratolytic mildly antiseptic & antifungal  Keratolytics cont… ❑ Resorcinol antiseptic, antifungal, local irritant, keratolytic 3–10% for eczema, seborrheic dermatitis, ringworm ❑ Urea applied at a level of 5–20% in cream/ointment base humectant (hygroscopic) & water retaining softening & solubilization of keratin o facilitating removal from hyperkeratinized lesions like ichthyosis, lichen planus  Antiseborrheics Seborrheic dermatitis affects sebaceous glands rich areas (scalp, face, trunk) characterized by erythematous, scaling lesions dandruff commonest complaint causal role of yeast Pityrosporum ovale Antiseborrheics cont… Selenium sulfide applied to scalp as a 2.5% lotion or shampoo slows epidermal proliferation & scaling antikeratolytic & fungicidal to P. ovale systemic absorption & toxicity occur if applied to inflamed or damaged skin some individuals develop sensitivity reactions Antiseborrheics cont… Zinc pyrithione reduces epidermal turnover & inhibits P. ovale weekly shampoo (1%) reduces dandruff symptoms not resolve completely often combined with ketoconazole 2% ketoconazole cream/shampoo/scalp gel effective Antiseborrheics cont… Corticosteroids massaged in scalp as a lotion topical steroids highly effective in relieving symptoms of seborrheic dermatitis including dandruff Pityrosporal yeasts reduced in affected skin relapse rates high on discontinuation prolonged use produce atrophy, poor healing, purpura Antiseborrheics cont… Sulfur, resorcinol, coaltar, ammoniated mercury mildly effective minimal antiyeast action: may benefit seborrhoea by keratolytic & antiseptic properties Salicylic acid keratolytic, has mild effect in seborrhoea removes scales & improves other drugs penetration  Melanizing agents increase sensitivity to solar radiation promote repigmentation of vitiliginous skin on photoactivation stimulate melanocytes o induce their proliferation psoralen, methoxsalen, trioxsalen sensitize skin to sunlight, induces erythema, inflammation & pigmentation applied topically & given orally skin sensitization maximal at 1–2 hrs., lasts for 8 hrs.  Drugs for Psoriasis Psoriasis immunological disorder manifesting as localized or widespread erythematous scaling lesions or plaques epidermal proliferation attended by dermal inflammation periodic flareups common drugs can diminish lesions, cannot cure disease therapy prolonged & adjusted to severity of disease Drugs for Psoriasis cont… ▪ topically emollients, keratolytic, antifungals afford symptomatic relief ▪ topical corticosteroids primary drugs effective in mild-to moderate disease patients respond within 3 weeks response hastened when steroid under occlusion therapy started with a potent steroid ▪ systemic corticosteroids or immunosuppressants reserved for severe & refractory Drugs for Psoriasis cont… Calcipotriol effective topically in plaque type psoriasis binds to intracellular vit D receptor in epidermal keratinocytes & suppresses proliferation while enhancing differentiation benefit in psoriasis slow; respond in 4–8 weeks comparable to moderate potency topical steroid with a steroid more effective than either drug alone safe & effective alternative to steroids, expensive Drugs for Psoriasis cont… Tazarotene synthetic retinoid as a topical gel (0.05–0.1%) prodrug hydrolyzed in skin to tezarotenic acid bind to retinoic acid receptor & modify gene function ✓exerts antiproliferative & anti-inflammatory action with topical steroid/calcipotriol benefit refractory cases skin irritation, burning sensation, peeling common minimized by careful application to plaques only teratogenic Drugs for Psoriasis cont… Coaltar crude preparation containing phenolic compounds exposed to light exerts phototoxic action on skin o induces resolution of psoriatic lesions o retards epidermal turnover applied on psoriatic plaques (with salicylic acid) skin irritation, allergy, potential for photosensitivity & carcinogenicity  Drugs for Psoriasis cont… Photochemotherapy (PUVA) psoralen ultraviolet A photoactivated psoralen binds to pyrimidine bases interferes with DNA synthesis & epithelial cell turnover for severely debilitating psoriasis oral methoxasalen followed 1–2 hours later by UVA exposure on alternate days skin cancer, cataracts and immunological damage Demelanizing Agents Hydroquinone lighten hyperpigmented patches on skin a weak hypopigmenting agent inhibits tyrosinase & melanin forming enzymes ↓formation & ↑ degradation of melanosomes regular application (2–6% lotion, cream) for months required in melasma, chloasma of pregnancy skin irritation, rashes & allergy Demelanizing Agents cont… Monobenzone potent demelanizing agent→ destroys melanocytes may cause permanent depigmentation full effect takes 4–6 months; treated areas should be protected from sunlight by a sunscreen use restricted to patients with widespread vitiligo 5% lotion or 20% ointment applied 2–3 times daily Demelanizing Agents cont… Azelaic acid effective in hyperpigmentary disorders inhibits melanin forming enzyme tyrosinase weak demelanizing agent with reversible hypopigmentary action used as a 10%, 20% cream mild & transient local irritation  Sunscreens substances that protect skin from harmful effects of exposure to sunlight Chemical sunscreens absorb UV rays responsible for sunburn & convert into heat w/c released from skin efficacy quantified by sun protection factor (SPF) o ratio of dose of UVB radiation that will produce minimal erythema on protected skin to dose required for same on unprotected skin Sunscreens cont… commercial preparations have a SPF of 15 period for remain effective depends on vehicle adjuncts in vitiligo therapy, drug induced phototoxicity facilitate tanning while preventing sunburn can prevent skin cancer & premature ageing of skin Para-aminobenzoic acid glyceryl mono amino benzoate absorb UVB (290–320 nm) 5% solution in alcohol/propylene glycol or 10% cream Sunscreens cont… Benzophenones (oxybenzone 2–6%) block UVA (320–400 nm) highly protective higher concentrations prevent tanning Cinnamates (octyl methoxy cinnamate) included in sunscreens  Sunscreens cont… Physical sunscreens opaque substances that scatter UV & visible light petroleum jelly, titanium dioxide, zinc oxide & calamine sun shades (prevent penetration into skin) applied as a thick lotion/cream immediate protection after application withhold longer wave lengths which cause photoallergy sunburn & tanning prevented  Drugs for Acne vulgaris Acne vulgaris common skin disease in adolescent boys & girls androgenic stimulation of sebaceous follicles produce excess of sebum get colonized by bacteria & yeast bacterial lipases produce FAs which irritate follicular ducts causing retention of secretions & hyperkeratosis rupture into dermis → inflammation & pustulation Drugs for Acne vulgaris cont… Topical Therapy a) Benzoyl peroxide liberates oxygen (in presence of water) which kills bacteria, anaerobic/microaerophilic high efficacy against Propionibacterium acnes keratolytic & comedolytic properties induces mild desquamation, comedone caps shed production of irritant fatty acids in sebum reduced Drugs for Acne vulgaris cont… b) Retinoic acid potent comedolytic: promotes lysis of keratinocytes, prevents horny cells from binding to each other o comedones, which horny impactions in follicles, cannot form efficacious in acne, response delayed (6–10 weeks) potential to irritate skin Drugs for Acne vulgaris cont… c) Adapalene binds directly to retinoic acid receptor modulates keratinization & differentiation of follicular epithelial cells. exerts anti-inflammatory action; comedone formation suppressed effective less irritating than tretinoin Drugs for Acne vulgaris cont… d) Topical antibiotics clindamycin, erythromycin, tetracyclines less effective against P. acnes than benzoyl peroxide appropriate for cases with inflamed papules not irritate skin but can cause sensitization Drugs for Acne vulgaris cont… e) Azelaic acid aerobic & anaerobic microorganisms, P. acnes present on acne bearing skin inhibited reduces cutaneous bacterial density, free fatty acid content of skin surface lipids and proliferation of keratinocytes Drugs for Acne vulgaris cont… 2. Systemic Therapy indicated in severe cases with cysts & pustules Antibiotics tetracycline, minocycline or erythromycin maintenance doses may be continued for months long-term systemic antibiotic complications o risk of intracranial hypertension after use of tetracyclines for > 2 months Drugs for Acne vulgaris cont… Isotretinoin orally administered retinoid reduces sebum (skin bacteria decrease secondarily) corrects abnormal keratinization of follicles 20 week course of 0.5–1 mg/kg daily brings about remission in most cases of cystic acne relapses occur after variable intervals highly teratogenic Drugs for Acne vulgaris cont… Topical Steroids for a large variety of dermatological conditions anti-inflammatory, immunosuppressive & antiproliferative (for scaling lesions) actions beclomethasone dipropionate 0.025% betamethasone benzoate 0.025% betamethasone valerate 0.12% clobetasol propionate 0.05% dexamethasone sod. phosphat0.1% Drugs for Acne vulgaris cont… General guidelines for use of topical steroids penetration at different sites differs markedly o high at axilla, groin, face, scalp, scrotum o medium at limbs, trunk: o low at palm, sole, elbow, knee absorption into skin depends on nature of lesion o high in atopic & exfoliative dermatitis o low in hyperkeratinized & plaque forming lesions General guidelines for topical steroids cont… choice of vehicle important ▪ lotions & creams better for exudative lesions ✓ allow evaporation, cooling, drying & antipruritic effect ▪ sprays & gels appropriate for hairy regions ▪ ointments form occlusive film ✓ good for chronic, scaly conditions General guidelines for topical steroids cont… occlusive dressing enhances absorption (10 fold),retains moisture & maceration of horny layer o chronic, hypertrophied lesions may be occluded intermittently (12 hours at a time) o continuous occlusion promotes bacterial & fungal absorption greater in infants & young children ✓ milder agents should be used General guidelines for topical steroids cont… routine use of potent steroids not justified o restricted to severe inflammatory conditions, unresponsive eczema, psoriasis o short term or intermittent to prevent adverse effects o sudden discontinuation should be avoided more than 2 applications not afford additional benefit o twice daily application satisfactory General guidelines for topical steroids cont… combination of steroid with antimicrobial ✓ for impetigo, furunculosis, secondary infected dermatoses, napkin rash, otitis externa, intertriginous eruptions General guidelines for topical steroids cont… local adverse effects of topical steroids related to potency & duration of treatment skin of face more susceptible potent halogenated steroids not to be used on face thinning of epidermis hypopigmentation delayed wound healing fungal and bacterial infections General guidelines for topical steroids cont… Systemic adverse effects of topical steroids adrenal pituitary suppression occur if large amounts applied repeatedly infants & children susceptible with proper use, systemic risks minimal  Ectoparasiticides drugs used to kill parasites that live on body surface o lice (Pediculus sp.—wingless insects) o mites (Sarcoptes/Acarus scabiei— arachnids) ✓ minute arthropods infesting human skin & hair  Ectoparasiticides cont… Scabies highly contagious; mite burrows through epidermis, laying eggs which form papules that itch intensely lesions get secondarily infected requiring AMAs finger webs preferred sites of entry soon spread to forearms, trunk, genitals & lower legs members of patient’s family treated concurrently garments & bed linen should be washed in hot water & put in sun to prevent cross infection & re-infection Ectoparasiticides cont… Pediculosis lice thrive on head (P. capitis), body (P. corporis) or pubic region (P. pubis). cause itching, suck blood & transmit typhus & relapsing fever eggs (nits) get attached to hair & clothing by a chitin like cement Ectoparasiticides cont… Drugs used for Ectoparasiticides Permethrin Sulfur Lindane (BHC) Dicophane (DDT) Benzyl benzoate Ivermectin Crotamiton Ectoparasiticides cont… Permethrin broad-spectrum and potent pyrethoid insecticide efficacious & convenient for both scabies & lice neurological paralysis by delaying depolarization toxicity in humans very low after application, persists on skin for days systemic absorption minimal 100% cure rates in scabies & pediculsois Ectoparasiticides cont… few patients may experience mild & transient burning, itching, tingling, erythema or rash for scabies: 5% cream; applied all over body except face & head; washed after 8–12 hours for head lice 1% lotion; massage about 30 g into scalp, washed off after 10 min Ectoparasiticides cont… Lindane (Gamma benzene hexachloride, BHC) broad-spectrum insecticide kills lice & mites by penetrating through chitinous cure rate for headlice (67–92% & scabies (84–92% efficacy lower than permethrin lice & mites can develop resistance to lindane benzyl benzoate addition precludes resistance & improves cure rate to nearly 100% Ectoparasiticides cont… For pediculosis applied to scalp & hair (not to enter eyes), leave for 12–24 hours & washed off if lice still present, treatment repeated after 1 week For scabies rubbed over body (below neck) a scrub bath taken 12–24 hours later repeated only after a week, if mite still present Ectoparasiticides cont… Disadvantages of lindane highly lipid soluble absorbed through skin (from oily vehicles, children) can produce systemic toxicity stimulation, vertigo, convulsion (children), arrhythmias widely distributed in body in fat induce CYP isoenzymes in liver Ectoparasiticides cont… Benzyl benzoate oily liquid with faint aromatic smell popular for treatment of scabies emulsion applied after a cleansing bath 2nd coat applied next day which washed after 24 hrs. treatment not interfered with routine activities achieved 76–100% cure in scabies neurological symptoms occurred in children skin irritation, contact dermatitis Ectoparasiticides cont… For pediculosis applied to scalp, taking care not to enter eyes washed off after 24 hours now a 2nd choice drug for scabies seldom used for pediculosis combination with lindane highly effective Ectoparasiticides cont… Crotamiton effective scabicide, pediculocide & antipruritic lower cure rates (60–88%) in scabies extended 5 day application in children good less prone to cause skin irritation low systemic toxicity despite absorption through skin applied twice at 24 hr interval & washed off day second choice drug for scabies & pediculosis Ectoparasiticides cont… Sulfur 10% ointment scabicide, pediculocide, fungicide, keratolytic dissolve cuticle of itch mite & kill it after a warm scrubbing bath (to open burrows) massaged over all body (below neck) for 3 days, followed by soap water bath on 4th day Rx messy: produces bad odour—socially unacceptable repeated applications required Ectoparasiticides cont… Dicophane (DDT) a popular insecticide (mosquitoes, flies) used in dust or watery suspension form poorly absorbed through skin For pediculosis & scabies applied & washed off after 12–24 hours acts as a neurotoxin for arthropods oily vehicles cause rashes, muscle weakness, tremor. induces microsomal enzymes combination with benzyl benzoate more effective Ectoparasiticides cont… Ivermectin highly effective in scabies & pediculosis orally administered drug for ectoparasitosis single 0.2 mg/kg (12 mg in adults) dose has cured up to 91–100% patients of scabies head/ body lice successfully treated not given to children