Drugs acting on skin and mucous membrane

1. Dr. Mushtaq Ahmed
Associate Professor, Pharmacology
Punjab Institute Of Medical Sciences, Jalandhar, Punjab

3. 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

4. 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

5. • 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.

6. Modes of treatment of skin disorders
• Topical
• Systemic
• Intralesional
• Controlled ultraviolet (UV) radiations
 UV radiations are toxic & can cause sunburn even cancer of skin

7. Factors governing rate of absorption of
Topical drugs
• Thickness of skin
• Conc. of drug in vehicle
• Degree of hydration
 Absorption varies in normal skin, damaged skin &
exfoliation of skin
 Transdermal patches → Clonidine (HT), hyoscine
(motion sickness) & nitroglycerine (angina pectoris)

8. 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

9. Drugs Based On
Action

10. 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

11. Powders
• Because of soothing & cooling effect → reduce
friction by absorbing moisture
• Adhere poorly to skin → reduces their usefulness
Greases
• Petroleum jelly & polyethylene
glycol are protective
Ointment
• Maintain the hydration of stratum corneum
Vehicles contd.

12. 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 phase
Creams
• Oil in water (o/w) type eg. Vanishing/aqueous cream
• Water in oil (w/o) type eg. Cold cream
Vehicles contd.

13.  Shake lotions (lotion +powder)
• Cause cooling of skin due to evaporation of
water
 Newer Vehicles
• Collodions
• Liposomes
• Microparticle
• Transferosomes
Vehicles contd.

14. Skin Preparations
Topical preparations are used for local effect
However, 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

15.  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.

16.  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.

17.  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.

18.  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

19.  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

20. Sunscreens
• Required to prevent sun burn, aging and skin cancer
Classification of sunscreens based on:
1. Physical Action: Titanium dioxide, zinc oxide &
calamine
They are opaque to all wavelength and reflect them
2. Chemical structure:
- PABA & its esters eg. Padimate O
- Benzophenones: Avobenzone, oxybenzone,
mexenone (highly effective against UVA)
- Cinnamates eg. Octyl methoxycinnamate
- Salicylates eg. Octisalate
- Octocrylene

21. 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

22. 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

23. Keratolytic Agents
• Used to remove warts and corns, calluses &
verrucae
• Mild keratolytic
 Resorcinol and sulphur
• Strong keratolytic
Salicylic acid, silver nitrate and trichloroacetic
acid
Some other keratolytic agents:
• Lactic, Glycolic & salicylic acid
• Propylene glycol
• Trichloroacetic acid
• Silver nitrate
• Urea

24. 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

25. 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

26. 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

27. 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

28. Drugs Based On
Disease/Symptoms

29. Pruritus
• Itching – symptom of many skin diseases
• Treatment depends upon cause of pruritus
Drugs
• Systemic
- Antihistaminics
- Glucocorticoids
• Topical
- Corticosteroids e.g. in eczema
- Emollient cream, menthol,camphor, phenol,
calamine, tar & others

30. 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

31. 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

32. 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.

33. 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

34. 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

35. 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)

36. Ectoparaciticides
Scabies & 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

37. 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

38. Acne Vulgaris
 A common skin disorder seen in
adolescents (boys & girls)
 Is due infection of pilosebaceous unit
by the bacteria Propionibacium acnes
 Changes in acne
1. Plugging of hair follicle
2. Accumulation of sebum
3. Growth of Propionibacium acnes
4. Inflammation

39. Acne Vulgaris contd.
 The treatment aims at:-
1. Correction of follicular abnormality
2. Reducing sebum production
3. Controlling infection and
4. Reducing Inflammation
 Topical Agents
o Retinoids
 Tretinoin, Adaplene, Tazarotene
- Normalize the maturation of follicular epithelium & reduce
inflammation

40. Acne Vulgaris contd.
 Topical Agents
o Antibacterials
o Reduce the population of Propionibacium acnes
 Erythromycin (2-3%), Clindamycin (1%), Benzoyl peroxide (5%)
- Combination with retinoids – more effective
 Other topical agents
o Sulfacetamide & it combination
with sulfur, Metronidazole and
Azelaic acid

41. Acne Vulgaris contd.
 Systemic Agents
o 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
conditions
o Retinoids
o Vit A analogues are called retinoids
o Have imp. Role in vision, cell proliferation & differentiation,
growth of bone etc.

42. Acne Vulgaris contd.
 Retinoids
 First generation
o Retinol, tretinoin, isotretinoin, alitretinoin
 Second generation
o Etretinate, acitretin
 Third generation
o Tazarotene, bexarotene
 Retinoid receptors
o Retinoic acid receptors (RARs) – subtypes ᾳ, β, ϒ
o Retinoid X receptors (RXRs) - subtypes ᾳ, β, ϒ
o Out of the above receptors mainly β and ϒ receptors of X receptors
are present in human skin
1st & 2nd Gen. retinoids lack receptor specificity – more S/E than 3rd gen.
Oral agents – teratogenicity : avoid during pregnancy

43. Acne Vulgaris contd.
 Antibacterials
 Tetracycline, erytromycin,
metronidazole & co-trimoxazole
o Reduce p. acnes colonization & also
reduce inflammation
 Hormone and hormone antagonists
 Oestrogen/ oral contraceptive pills,
cypoterone acetate & corticosteriods
o Are preferred in case of adult onset
acne, premenstrual flares of acne

44. 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

45. Psoriasis
 Aim of treatment
• To dissolve the keratin & inhibit the further
proliferation of cells
 Topical Agents
o Coal tar
• Mainly used with UVB – antimitotic effect
• Used as solution, gel & shampoo
• ADR: folliculitis, irritation, allergic reaction
o 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
Photothera
py
Systemic
Method of Treatment

46.  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.

47. 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