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

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