Topically Applied Corticosteroids

Dr Muhammad Raza

Topical Preparations: Products which are designed for application to the skin - either by simply spreading them over the skin or byrubbing them in.• Dermatological preparations: are employed for the

treatment of diseased or injured skin. Diseased, injured or inflamed skin proves more permeable than intact skin.

• Percutaneous topical preparations: are intended for use on intact skin and they produce their effects either locally or systemically.

Topically used corticosteroids The most potent and effective anti-inflammatory

medications available They are the therapy of choice in most inflammatory

diseases, pruritic eruptions (dermatitis), hyperproliferative disorders (psoriasis), infiltrative disorders (sarcoidosis)

Effectiveness of the drugs is due to their anti-inflammatory activity. (Explain the mechanism of action?)

They have the ability to inhibit cell division In dermatologic diseases characterized by increased cell

turnover e.g. psoriasis, the anti mitotic effect of steroids is important factor.

Anti-inflammatory action of corticosteroids

PHARMACOLOGY FOR HEALTHCARE PROFESSIONALS

Analogues of topical steroids and their efficacy

• Hydrocortisone (HC) is the prototype. (Active or not?)• Prednisolone & Methylprednisolone are active as HC• 9-α-flourinated compounds like dexamethasone &

Betamethasone (As hydrocortisone)• Attaching 5-carbon valerate to the 17 hydroxy position

to betamethasone 300 times active as hydrocortisone• Acetonide derivatives of fluorinated steroids potent

topical drugs• 21-derivatives of acetonide 5-fold increase

Intrinsic activity of topical corticosteroids is dependent on chemical modification of the molecule like F at C9, carbon valerate chain at C17 Betamethasone + 5- carbon valerate chain at 17 position > 300 times as active as hydrocortisone

Advantages of topical corticosteroids

1. Wide spectrum against skin diseases2. Rapid action in small amounts3. Ease of use (topical application)4. Absence of pain or odor5. Relative lack of sensitization6. Prolonged stability7. Compatibility with almost all commonly used

topical medications8. Rare systemic untoward systemic side effects

Factors affecting the effectiveness of topical corticosteroids

1. Drug potency1. Active form (e.g. prednisone & prednisolone),

Binding to a glucocorticoid receptor2. Addition of halogen atom (e.g. fluoride)3. Vehicle (Oint., cream, lotion, etc)

4. Added drug (salicylic acid, urea)

2. Percutaneous penetration: See next slide

Percutaneous Drug Absorption

All topical preparations must make their way into the skin before they can exert effects.

• Percutaneous absorption involves: • Dissolution of the drug in its vehicle,• Diffusion of the drug from the vehicle to the surface of the skin, and

• The actual penetration of the drug through the different layers of the skin.

• Percutaneous absorption may be effected by the following routes:

• Transcellular diffusion• Diffusion through channels between the epidermal cells• Diffusion through sebaceous ducts• Diffusion through the hair follicles• Diffusion through the sweat ducts

Factors affecting trans-dermal absorption of corticosteroids

1. Site of steroid application. (See the next diagram)2. Hydration3. Long term occlusion of impermeable film. ( 100 times) ▲4. Inflamed skin. (Health status of skin)5. Dosage form: ointment > cream and lotion.6. Increasing the concentration of applied cortisone.7. Lipophilicity of the corticosteroids8. Solubility of cortisone in the vehicle.9. Intra lesional injection.

In diseases that are very responsive apply low to minimum efficacy corticosteroids.

In less responsive diseases apply high efficacy preparations + occlusion or both, when remission occurs shift to low efficacy corticosteroids.

Absorption of steroids is dependent on the site of their application (the times = the concentration of absorbed steroid relative to the percentage of

concentration of the absorbed hydrocortisone). Skin is thinnest on the eyelids at 0.05 mm and the thickest on the palms and soles at 1.5 mm.

(Sole- Thick)

(Palm- Thick)

(Scrotum-thin)

Back 3 mmEyelids Thin

Classification of topical steroids according to their potency

Hydrocortisone 1% < Betamethasone valerate 0.1% < Clobetasole propionate 0.05%

A. Lowest efficacy corticosteroids: Mild Who: infant, child, adult Areas: Face, folds , genitals, extensive areas of the skin Examples

Hydrocortisone (0.25 - 2.5 %). Dexamethasone (0.1%, 0.04%).

B. Low efficacy corticosteroids: (Mild to moderate)Who: infant, child, adultPotency: 2-25 times as hydrocortisoneSites: Face, folds, genitals, Examples:

Betamethasone valerate (0.01%)Triamcinolone acetonide (0.025%)

Classification of topical steroids according to their potency

C. Intermediate efficacy corticosteroids: Moderately potentPotency: Up to 100 times as hydrocortisoneWho: Adult & Child & Extensive area of the skinExamples:

Hydrocortisone valerate (0.2%) (Betnovate)Betamethasone valerate (0.1 %).Triamcinolone acetonide (0.1 %). (Kenacort)

D. High efficacy corticosteroids: Potent Who: AdultsPotency: Up to 150 times as hydrocortisoneAreas: Localized thick lesionsExamples:

Betamethasone dipropionate (0.05%) (diprolone)Triamcinolone acetonide (0.5%).Flucinolone acetonide (0.2%).

Classification of topical steroids according to their potency

E. Highest efficacy corticosteroids: (Very Potent)Who: Adult Potency: Up to 600 times hydrocortisoneAreas: Resistant & Localized thick lesions (palm)Examples:

» Clobetasole propionate 0.05% (Dermovate)» Betamethasone dipropionate (Diprosone)

• General Notes:1. Begin with high efficacy compound then maintain on that with

less efficacy2. Use the less potent corticosteroids e.g. 1% hydrocortisone on

scrotum, groin, axillae, eyelids, face. Why?

Which preparation? cream or ointment, lotion or gel

• As with moisturizers, the type of steroid formulation most suitable depends on the characteristics of disease and the area of skin affected.

• Lotions and gels are most suitable for hairy areas of skin. • Creams are better for moist, weeping areas of skin, while • Ointments are most suitable for drier, scaly areas

Dermatological disorders responsive to topical corticosteroids

• A. Highly responsive disorders:1- Atopic dermatitis. 2- Seborrheic dermatitis.3- Lichen simplex chronicus. 4- Pruritus ani.5- Later phase of allergic contact & irritant dermatitis.6- Stasis dermatitis.7- Psoriasis (genitalia and face).

Dermatological disorders responsive to topical corticosteroids

B. Less responsive disorders:1. Discoid lupus erythematosus2. Psoriasis of palms and soles3. Necrobiosis lipoidica diabeticorum4. Sarcoidosis5. Lichen striatus6. Vitiligo7. Granuloma annulare

C. Least responsive disorders: (Intra lesion injection required):8. Kelosis9. Hypertrophic scars10. Hypertrophic lichen planus11. Alopecia areata12. Acne cysts13. Prurigo nodularis

Corticosteroids Action

Corticoid depresses formation, release and activity of endogenous mediators of inflammation, including

PGs, kinins, histamine, liposomal enzymes and complement system. Also modifies body's immune response

Leads to: Inhibit. lymphoid proliferation Lyses of either suppressor or helper T cells Monocyte- macrophage system inhibit chemotaxis Inhibit. of IL6 & IL1, IL2, TNF, PAF, leukotriens, PGS. Inhibits the antibody response Decrease amount of antibody

Topical steroids: Adverse effectsI. Systemic: Extremely rare e.g. if TS >50 gm clobetasol propionate or 500 gm of

hydrocortisone/week

1. Potential suppression of pituitary-adrenal axis Occlusion, surface area, amount, duration, concentration, Type (Clobetasol), Infants, children, liver failure

2. Growth retardation in children. 3. Iatrogenic Cushing's syndrome.4. When: Too long, too much, too often, too old, too young, too

extensive, face, folds, genitalia. What are the adverse effects of steroid ê occlusion?

Infection, folliculitis, miliaria, heat change, sunburn, atrophy, striae▼ ▲Occlusive dressings (airtight dressings) absorption of the steroid

and may also the chances of side effects

Topical steroids: Adverse effects

II. Local: Rare if TS used correctly 1. Skin atrophy, striae (stretch marks), telangiectases, 2. Easy bruising and tearing of skin (purpura, ecchymosis). 3. Pustules & Papules. 4. Peri-oral dermatitis (rash around mouth)5. Steroid acne.6. ▲Susceptibility to skin infection, Mask superficial infections, worsen

fungal infections.7. Tachyphylaxis8. Hypo-pigmentation. 9. Hyper-trichosis. (Excessive abnormal hair growth)

10. Glaucoma & cataract. (when used around the eye) 11. Allergic contact dermatitis. (leg ulcers, stasis )

Contraindications to topical corticosteroids

1. Untreated skin infections (bacterial, fungal, or viral)2. Acne rosacea3. Peri-oral dermatitis4. Potent corticosteroids are contra-indicated in widespread

plaque psoriasis. Why?Questions for revision: 5. What are the precautions of using topical corticosteroids in children and

infants?6. On which basis you choose the dosage form of corticosteroids? e.g. occlusion7. How frequent you apply the topical corticosteroids per day. Why?8. What is your opinion about using topical steroids in pregnancy and lactation?

How can you minimize the side effects of topical steroids?

1. Potency: use the least potent steroid whenever possible

2. Frequency: ≱ Once or Twice daily3. Amount: use steroid sparingly by using FTU. How? (1, 2, 3, 6, 7 FTU)4. Duration, not for prolonged periods – change to less potent with recovery

5. Surface area: Broad area—least potent, and least amount, reduce frequency

6. Areas of skin: take care of areas that absorb more (like face and genitalia)7. Occlusion: Precautions with occlusion8. Once the lesion responded, reduce or stop the steroid & maintain on a

mild one9. Never use the steroid as moisturizers

Getting the dose right - the fingertip unit– One fingertip unit (FTU) is the amount of topical steroid that is squeezed out from a standard tube

along an adult's fingertip. (This assumes the tube has a standard 5 mm nozzle) A finger tip is from the very end of the finger to the first crease in the finger.

Intralesional corticosteroidsDefinition: Injection of small amounts of corticosteroids into coetaneous lesions (Relatively

insoluble steroids)Examples: Triamcinolone acetonide, triamcinolone diacetate, betamethasone acetatephosphate) 2.5

mg/mlAdvantages:1. High concentration2. Prolonged depot (3-4 weeks)3. No systemic side effectsTreated diseases: Acne cysts, Alopecia areata, keloids, nail disorders, Prurigo nodularisMethods: Insulin syringe (1ml/30 G), Air powered gun ( pyogenic Infection & Viral

hepatitis). Dose 1mg/injection site of triamcinolone (Conc. 10mg/ml- Dose Vol. 0.1ml)

Adverse efects:4. No systemic. Why?5. Local: Atrophy, hypo-pigmentation, hair growth, infection, ulceration.