Download - Drugs acting on skin
Drugs Acting On Skin And Mucous Membrane
Dr. Mushtaq AhmedAssociate Professor, Pharmacology
Punjab Institute Of Medical Sciences, Jalandhar, Punjab
SKIN IF IT’S DRY, WET IT IF IT‘S WET, DRY IT
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
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
• 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.
Modes of treatment of skin disorders
• Topical
• Systemic
• Intralesional
• Controlled ultraviolet (UV) radiations
UV radiations are toxic & can cause sunburn even cancer of skin
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)
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
Drugs Based On Action
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
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.
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.
Shake lotions (lotion +powder)• Cause cooling of skin due to evaporation of
water Newer Vehicles
• Collodions
• Liposomes
• Microparticle
• Transferosomes
Vehicles contd.
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
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.
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.
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.
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
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
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
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
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
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
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
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
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
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
Drugs Based On Disease/Symptoms
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
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
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
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.
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
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
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)
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
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
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
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
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
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.
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
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
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
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
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.
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
SKIN IF IT’S DRY, WET IT IF IT‘S WET, DRY IT
THANK YOU