drugs acting on skin
DESCRIPTION
Drugs acting on skin and mucous membraneTRANSCRIPT
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Drugs Acting On Skin And Mucous Membrane
Dr. Mushtaq AhmedAssociate Professor, Pharmacology
Punjab Institute Of Medical Sciences, Jalandhar, Punjab
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SKIN IF IT’S DRY, WET IT IF IT‘S WET, DRY IT
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Interesting Facts about SKIN
The largest organ of the body
Very important protective layer of the body
Also important for: - Thermoregulation - Immunity - Biochemical synthesis & - Sensory functions
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Structure & function of skin• Skin has two layers →
EPIDERMIS & DERMIS: beneath dermis there is fatty tissue
• Epidermis, the outer layer contains:-
Keratinocytes (keratin), melanocytes (pigment), Langerhan’s cells (antigen), Merkel cells (sensory)
• Keratin → present in all the layers of epidermis
Abnormal keratin production → psoriasis & icthyotic disorders
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• Superficial keratin layer → stratum corneum • Main function of epidermis → to form stratum
corneum • Stratum corneum (horny layer) is important →
reducing water loss and prevention of absorption of noxious substances
Stratum corneum main barrier for absorption of drugs by topical route
Structure & function of skin contd.
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Modes of treatment of skin disorders
• Topical
• Systemic
• Intralesional
• Controlled ultraviolet (UV) radiations
UV radiations are toxic & can cause sunburn even cancer of skin
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Factors governing rate of absorption of Topical drugs
• Thickness of skin
• Conc. of drug in vehicle
• Degree of hydrationAbsorption varies in normal skin, damaged skin &
exfoliation of skinTransdermal patches → Clonidine (HT), hyoscine
(motion sickness) & nitroglycerine (angina pectoris)
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Drugs• Are categorized based on:
Action
• Vehicles: (powders, greases, ointments, liquids, lotions etc.)
• Skin preparations: (adsorbants & protectives, astringents, escarotics, demulcents, irritants & counter irritants )
• Antibacterials, Antifungals, Antivirals• Sunscreens• Keratolytic agents• Corticosteroids
Disease or symptoms
• Pruritus• Seborrhoea• Alopecia• Leukoderma/Vitiligo• Hyperpigmentation• Scabies/ pediculosis (Ectoparasiticides) • Acne vulgaris• Psoriasis• Atopic dermatitis• Drug induced skin diseases
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Drugs Based On Action
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Vehicles
• Are inert substances which carry the drugs : water content of vehicle very imp.
• They also contain some preservatives
• Monophasic e.g. powders, greases & liquids
• Biphasic e.g. pastes, creams and shake lotions
• Triphasic e.g. cream pastes & cooling pastes Vehicle should be non-irritant & cosmetically suitable First pass metabolism in epidermis & dermis also affects the systemic effect
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Powders • Because of soothing & cooling effect → reduce
friction by absorbing moisture• Adhere poorly to skin → reduces their usefulnessGreases• Petroleum jelly & polyethylene glycol are protectiveOintment• Maintain the hydration of stratum corneum
Vehicles contd.
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Liquids • Clean and keep the lesion/skin cool • High water content of lotions are also called wet
dressings e.g. KMNO4, normal saline Gel & jellies• They are semisolid due to addition of polymers
despite containing liquid phaseCreams • Oil in water (o/w) type eg. Vanishing/aqueous cream• Water in oil (w/o) type eg. Cold cream
Vehicles contd.
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Shake lotions (lotion +powder)• Cause cooling of skin due to evaporation of
water Newer Vehicles
• Collodions
• Liposomes
• Microparticle
• Transferosomes
Vehicles contd.
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Skin Preparations
Topical preparations are used for local effectHowever, TD patches are used for systemic effects
Adsorbants and protectives• Bind to noxious and irritant substances on their
surface – adsorbant action - Dusting powder, Zinc oxide, Calamine, Talc, Boric acid, polyvinyl polymer, Sucralfate
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Astringents
• Tannic Acid - Present in tea, catechu, nutmeg etc. → denaturation of proteins & forms coating - Can be used for bleeding gums (with glycerin) & bleeding piles (as suppository)• Ethanol & methanol - Cause precipitation of proteins and are applied locally for prevention of bed sores
and after shave lotion
Escharotics (chemical cauterizers)• Cause tissue destruction, sloughing & precipitation
of proteins • Used to remove warts, moles, papilloma etc. Phenol, Trichloroacetic acid, silver nitrate, podophyllum
Skin Preparations contd.
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Demulcents: Glycerine & propylene glycol
• When applied topically they produce soothing effect on
denuded mucosa or inflammed skin
• Protect the mucous membrane and skin from air and irritant
substances Emollients: (wax – hard & soft, paraffin, olive oil etc.)
• They produce soothing effect & hydrate
the skin
• Useful for dry scaly skin
Skin Preparations contd.
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Irritants and counterirritants (Nicotinate, salicylate, menthol,
camphor, capsaicin)
• Irritant substances produce local
inflammation, tingling, numbness, cooling
or feeling of warmth, hyperaesthesia and vasodilatation
• Counterirritants also produce local irritation and relieve pain &
inflammation arising from deeper structures
• Used for headache, myalgia, neuralgia, joint pain etc.
Skin Preparations contd.
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Antibacterial Agents• Common bacterial infections affecting skin: - Furuncle, boil, folluculitis, pyoderma, impetigo,
cellulitis etc Antifungal Agents (Benzoic acid)• Common fungal infections- ring worm, oral
thrush, dandruff, athlete’s foot Antiviral Agents • Herpes simplex, herpes zoster
Chemotherapeutic Agents
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Three types of UV rays:• UVA (Long wave): photoaging/ skin aging (collagen damage),
photosesitivity and skin cancer • UVB (medium wave): causes
sunburn sun tan, skin cancer & photo aging (skin aging)
• UVC (short wave): causes skin injury, sunburn of superficial epidermis
Ultraviolet rays & their effect on skin
Protection against UV rays:• Avoid exposure to UV rays• Use sunscreens
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Sunscreens• Required to prevent sun burn, aging and skin cancerClassification of sunscreens based on:1. Physical Action: Titanium dioxide, zinc oxide &
calamine They are opaque to all wavelength and reflect them2. Chemical structure: - PABA & its esters eg. Padimate O - Benzophenones: Avobenzone, oxybenzone, mexenone
(highly effective against UVA) - Cinnamates eg. Octyl methoxycinnamate - Salicylates eg. Octisalate - Octocrylene
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Sunscreens contd.
3. Effectiveness against radiation:• Sunscreens for UVA: - Benzophenones eg. Avobenzone, oxybenzone
• Sunscreens for UVB: - PABA & its esters eg. Padimate O - Cinnamates eg. Octyl methoxycinnamate - Salicylates eg. Octisalate - Octocrylene
Regular use of Sunscreens: reduce risk of actinic keratoses, premature aging and squamous cell carcinoma of skin
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Photosensitivity due to drugs
• Systemic use: BZDs, thiazides, hydralazine, sulfonamides, sulfonylurea, NSAIDs, tetracycline, chloramiphenic
• Topical use: PABA as sunscreen, musk ambrette (used in perfumes), 6 methyl coumarin (after shave lotion)
• Phototoxicity causes severe sun burn
• Photoallergy: reaction persists years after the drug withdrawal
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Keratolytic Agents• Used to remove warts and corns, calluses &
verrucae• Mild keratolytic Resorcinol and sulphur• Strong keratolyticSalicylic acid, silver nitrate and trichloroacetic
acid Some other keratolytic agents:• Lactic, Glycolic & salicylic acid• Propylene glycol• Trichloroacetic acid• Silver nitrate• Urea
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Keratolytic Agents Contd. Salicylic acid• Corneocyte adhesion is reduced by solubilization of
intracellular cement• Removes stratum corneum layer by layer Whitfields ointment (salicylic acid 3% & Benzoic acid 6%)
Lactic and glycolic acid• Corneocyte adhesion is reduced by disrupting ionic
bonds at lowest layer of stratum corneum• Used for xerosis & ichthyosis
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Corticosteroids
• Used by both systemic & topical route depending upon disease and severity
• Have anti-infammatory and immunosuppressant action• Reduce proliferation of keratocytes, fibroblasts and
lymphocytes – antimitotic action• Inhibit migration of inflammatory cells and substances
released due to inflammation
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Topical steroids
Highest efficacy
• Clobetasol propionate 0.05%
• Helobetasol propionate 0.05% High efficacy
• Betamethasone dipropionate 0.05%
• Diflorasone diacetate 0.05%• Fluocinolone acetonide 0.2% &
others
Intermediate efficiacy• Clobetasol butyrate 0.05%
• Hydrocortisone acetate 2.5%
• Fluocortolone 0.025% & others Low efficacy• Hydrocortisone butyrate 0.001%
• Hydrocortisone acetate 0.1%
• Methylprednisolone acetate 0.1%
Systemic Agents: Mainly used for serious conditions not responding to other Rx e.g. pemphigus & exfoliative dermatitis
Use of Topical Steroids: allergic conditions, infections (bacterial/ viral/fungal), pigment disorders, Psoriasis, Eczematous disorders, drug induced disorders etc
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Topical steroids : ADRs
• Infection may spread
• Skin atrophy on long term use
• Local hirsutism
• Depigmentation
• Allergic dermatitis
• On eyelids – enter eye – glaucoma• Rebound exacerbation of disease after abrupt cessation
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Drugs Based On Disease/Symptoms
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Pruritus
• Itching – symptom of many skin diseases• Treatment depends upon cause of pruritusDrugs• Systemic - Antihistaminics - Glucocorticoids• Topical - Corticosteroids e.g. in eczema - Emollient cream, menthol,camphor, phenol,
calamine, tar & others
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Seborrhoea • Is due to over-activity of sebaceous glands and
skin is greasy → acne, baldness and dermatitis Drugs• Selenium sulphide - Reduces epidermal proliferation & scaling • ketoconazole & corticosteroids
Limitation is relapse on discontinuation of the Rx
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Alopecia • Common after age of 40 & about 50% men develop alopecia Drugs• Menoxidil Used topically for the Rx of baldness Possibly acts by ↑ circulation around hair follicles, stimulation
of hair follicle reduces the effect of androgen Thickens the hair shafts, ↑ their no. & length Onset is delayed and takes few months Effect is transient- baldness recurs on discontinuation of drug• ADR: Topical- local itching, burning sensation• On significant absorption systemic S/E i.e. tachycardia,
palpitation, headache & dizziness
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Alopecia Contd. • Drugs• Finasteride, Dutasteride Type II 5-ᾳ reductase inhibitor There are two types of 5-ᾳ reductase – type I in sebacecious
gland & type II present in hair follicles & male genital organ Useful for Rx of baldness, benign hyperplasia of prostrate,
prostatic carcinoma Dose: 1mg OD x 2 yrs … minimum effect to come is about 3
months Therapeutic effect is lost one after discontinuation of drug• ADR:• Decreased libido, erectile dysfunction and reduced ejaculate vol.
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Pigment disorders (leukoderma/vitiligo)• Potent photosensitive drug is used with UV rays for vitiligo &
psoriasis Drugs• Psoralen, Methoxsalen, Trioxsalen Two types of photoreaction i.e. type I & II take place In type I mono & bifunctional adducts are formed in DNA while
in type II sensitized transfer of energy to molecular oxygen ocurs PUVA (Psoralen & UV) facilitates melanogenesis by transferring
melanosomes from melanocytes to epidermal cells ADR: Acute: nausea, blistering & painful erythema Chronic:
actinic keratosis, photoaging, PUVA lentigins & non melenoma skin cancer
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Hyperpigmentation• Demelanising agents lighten the hyperpigmented patches on
skin
Drugs
- Hydroquinone Inhibits tyrosinase decreases formation & increases degradation of melanosomes Used in melasma, chloasma of pregnancy and sun induced
hyperpigmentation - Monobenzone Is toxic to melanocytes – depigmentation is irreversible
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Ectoparaciticides (Scabies & Pediculosis)
Scabies• Caused by Sarcoptes scabiei• Itching a common symptom• Female itch mite burrows into superficial layers of
skin and lays eggs - form papule – itching (highly contagious)
• Drugs are applied topically after a warm scrubbed bath
Drugs: Premethrin, Benzyl benzoate, Benzyl hexachloride BHC, IVERMECTIN (only oral drug)
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EctoparaciticidesScabies & Pediculosis
Premethrin• Delays depolarization – neurological paralysis• Effective against scabies (5% cream) & pediculosis (1%)
• Absorption – minimal through skin, rapidly metabolized to inactive products
• Is safest drug – provides 100% cure For scabies Apply premethrin 5% cream below chin all over the body &
left there for 12 h• For pediculosis Apply premethrin 1% cream or lotion for 10 min & then rinse
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Pediculosis
• Caused by pediculus captitis (head) • Itching a common symptom Drugs: Premethrin, malathion & DDT
• Premethrin is preferred drug• Malathion used in cases not responding to premethrin• DDT - In powder form or solution in kerosine – widely
used as insecticide - Not killing ova – disadvantage - Use declined b/o dev. of resistance
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Acne Vulgaris
A common skin disorder seen in adolescents (boys & girls)
Is due infection of pilosebaceous unit by the bacteria Propionibacium acnes
Changes in acne1. Plugging of hair follicle2. Accumulation of sebum3. Growth of Propionibacium acnes4. Inflammation
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Acne Vulgaris contd. The treatment aims at:-
1. Correction of follicular abnormality
2. Reducing sebum production
3. Controlling infection and
4. Reducing Inflammation Topical Agentso Retinoids Tretinoin, Adaplene, Tazarotene - Normalize the maturation of follicular epithelium & reduce
inflammation
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Acne Vulgaris contd. Topical Agentso Antibacterialso Reduce the population of Propionibacium acnes Erythromycin (2-3%), Clindamycin (1%), Benzoyl peroxide (5%)
- Combination with retinoids – more effective
Other topical agentso Sulfacetamide & it combination with sulfur, Metronidazole and Azelaic acid
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Acne Vulgaris contd. Systemic Agentso Retinoic acid Retinoic acid is vitamin A acid & it possesses vit. A activity in
epithelial tissues No activity in other tissues such as eye & germ tissues Rapidly metabolized - eliminated in bile & urine Not stored unlike retinol Its derivatives i.e. tretinoin & isotrtinoin, are used in other
conditionso Retinoidso Vit A analogues are called retinoidso Have imp. Role in vision, cell proliferation & differentiation,
growth of bone etc.
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Acne Vulgaris contd. Retinoids First generationo Retinol, tretinoin, isotretinoin, alitretinoin Second generationo Etretinate, acitretin Third generationo Tazarotene, bexarotene Retinoid receptorso Retinoic acid receptors (RARs) – subtypes ᾳ, β, ϒo Retinoid X receptors (RXRs) - subtypes ᾳ, β, ϒo Out of the above receptors mainly β and ϒ receptors of X receptors
are present in human skin1st & 2nd Gen. retinoids lack receptor specificity – more S/E than 3rd gen.Oral agents – teratogenicity : avoid during pregnancy
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Acne Vulgaris contd. Antibacterials Tetracycline, erytromycin,
metronidazole & co-trimoxazoleo Reduce p. acnes colonization & also
reduce inflammation
Hormone and hormone antagonists Oestrogen/ oral contraceptive pills,
cypoterone acetate & corticosteriodso Are preferred in case of adult onset
acne, premenstrual flares of acne
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Psoriasis• An immunological disorder• Manifests as localized or
widespread erythematous scaling lesions or plaques
• Increased proliferation, inflammation of epidermis & dermis
• Drugs can decrease the lesions but can not cure
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Psoriasis Aim of treatment• To dissolve the keratin & inhibit the further
proliferation of cells Topical Agentso Coal tar• Mainly used with UVB – antimitotic effect • Used as solution, gel & shampoo• ADR: folliculitis, irritation, allergic reactiono Calcipotriol (active vit D)• By acting on keratinocytes – causes decrease
in proliferation of cultured keratinocytes• By the same mechanism, it produces
antipsoriatic effect• Vit D – effective orally & topically Other drugs ; Anthralin, Tazarotene
Local Intralesional
PhototherapySystemic
Method of Treatment
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Systemic Agents• Is required in extensive and severe disease• Cytotoxic & immunosupressants are used Methotrexate • Is a DHFR inhibitor & suppressing immune component
cells (mainly T-cells) in Skin• Epidermal inflammation & hyperproliferation are
retarded • S/E: bone marrow depression, hepatotoxicity• Other drugs: Hydroxurea, Cyclosporine, Efalizumab,• Liarozole & rambazole- newer agents
Psoriasis Contd.
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Atopic Dermatitis• Is an inflammatory condition of skin – starts
during infancy & childhood – may persist upto adult age
• Allergens & environmental pollutants may cause the disease
• Itchy papules & plaques – characteristics of this condition
• Treatment : Glucocorticoids, antihistaminics, immunosupressive agents
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SKIN IF IT’S DRY, WET IT IF IT‘S WET, DRY IT
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