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)
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.
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
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
Notas do Editor
Trichloroacetic acid, silver nitrate, podophyllum : are also keratolytic agents