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

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Presentation on theme: "Topical Preparations: Products which are designed for application to the skin - either by simply spreading them over the skin or by rubbing them in. Dermatological."— Presentation transcript:

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2 Topical Preparations: Products which are designed for application to the skin - either by simply spreading them over the skin or by rubbing 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. 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.

3 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.  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.

4 Anti-inflammatory action of corticosteroids PHARMACOLOGY FOR HEALTHCARE PROFESSIONALS

5 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 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

6  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  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

7 Advantages of topical corticosteroids 1.Wide spectrum against skin diseases 2.Rapid action in small amounts 3.Ease of use (topical application) 4.Absence of pain or odor 5.Relative lack of sensitization 6.Prolonged stability 7.Compatibility with almost all commonly used topical medications 8.Rare systemic untoward systemic side effects 1.Wide spectrum against skin diseases 2.Rapid action in small amounts 3.Ease of use (topical application) 4.Absence of pain or odor 5.Relative lack of sensitization 6.Prolonged stability 7.Compatibility with almost all commonly used topical medications 8.Rare systemic untoward systemic side effects

8 Factors affecting the effectiveness of topical corticosteroids 1. Drug potency 1. Active form (e.g. prednisone & prednisolone), Binding to a glucocorticoid receptor 2. 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 1. Drug potency 1. Active form (e.g. prednisone & prednisolone), Binding to a glucocorticoid receptor 2. 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

9 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 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

10 Factors affecting trans-dermal absorption of corticosteroids 1. Site of steroid application. (See the next diagram) 2.Hydration 3.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 corticosteroids 8.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. 1. Site of steroid application. (See the next diagram) 2.Hydration 3.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 corticosteroids 8.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.

11 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 mm Eyelids Thin

12 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 ( %).  Dexamethasone (0.1%, 0.04%). B. Low efficacy corticosteroids: (Mild to moderate)  Who: infant, child, adult  Potency: 2-25 times as hydrocortisone  Sites: Face, folds, genitals,  Examples:  Betamethasone valerate (0.01%)  Triamcinolone acetonide (0.025%) 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 ( %).  Dexamethasone (0.1%, 0.04%). B. Low efficacy corticosteroids: (Mild to moderate)  Who: infant, child, adult  Potency: 2-25 times as hydrocortisone  Sites: Face, folds, genitals,  Examples:  Betamethasone valerate (0.01%)  Triamcinolone acetonide (0.025%)

13 Classification of topical steroids according to their potency C. Intermediate efficacy corticosteroids: Moderately potent  Potency: Up to 100 times as hydrocortisone  Who: Adult & Child & Extensive area of the skin  Examples:  Hydrocortisone valerate (0.2%) (Betnovate)  Betamethasone valerate (0.1 %).  Triamcinolone acetonide (0.1 %). (Kenacort) D. High efficacy corticosteroids: Potent  Who: Adults  Potency: Up to 150 times as hydrocortisone  Areas: Localized thick lesions  Examples:  Betamethasone dipropionate (0.05%) (diprolone)  Triamcinolone acetonide (0.5%).  Flucinolone acetonide (0.2%). C. Intermediate efficacy corticosteroids: Moderately potent  Potency: Up to 100 times as hydrocortisone  Who: Adult & Child & Extensive area of the skin  Examples:  Hydrocortisone valerate (0.2%) (Betnovate)  Betamethasone valerate (0.1 %).  Triamcinolone acetonide (0.1 %). (Kenacort) D. High efficacy corticosteroids: Potent  Who: Adults  Potency: Up to 150 times as hydrocortisone  Areas: Localized thick lesions  Examples:  Betamethasone dipropionate (0.05%) (diprolone)  Triamcinolone acetonide (0.5%).  Flucinolone acetonide (0.2%).

14 Classification of topical steroids according to their potency E. Highest efficacy corticosteroids: (Very Potent)  Who: Adult  Potency: Up to 600 times hydrocortisone  Areas: 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 efficacy 2.Use the less potent corticosteroids e.g. 1% hydrocortisone on scrotum, groin, axillae, eyelids, face. Why? E. Highest efficacy corticosteroids: (Very Potent)  Who: Adult  Potency: Up to 600 times hydrocortisone  Areas: 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 efficacy 2.Use the less potent corticosteroids e.g. 1% hydrocortisone on scrotum, groin, axillae, eyelids, face. Why?

15 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 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

16 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). 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).

17 Dermatological disorders responsive to topical corticosteroids B. Less responsive disorders: 1.Discoid lupus erythematosus 2.Psoriasis of palms and soles 3.Necrobiosis lipoidica diabeticorum 4.Sarcoidosis 5.Lichen striatus 6.Vitiligo 7.Granuloma annulare C. Least responsive disorders: (Intra lesion injection required): 1.Kelosis 2.Hypertrophic scars 3.Hypertrophic lichen planus 4.Alopecia areata 5.Acne cysts 6.Prurigo nodularis B. Less responsive disorders: 1.Discoid lupus erythematosus 2.Psoriasis of palms and soles 3.Necrobiosis lipoidica diabeticorum 4.Sarcoidosis 5.Lichen striatus 6.Vitiligo 7.Granuloma annulare C. Least responsive disorders: (Intra lesion injection required): 1.Kelosis 2.Hypertrophic scars 3.Hypertrophic lichen planus 4.Alopecia areata 5.Acne cysts 6.Prurigo nodularis

18 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  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

19 Topical steroids: Adverse effects I. 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 I. 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

20 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.Tachyphylaxis 8.Hypo-pigmentation. 9.Hyper-trichosis. (Excessive abnormal hair growth) 10.Glaucoma & cataract. (when used around the eye) 11.Allergic contact dermatitis. (leg ulcers, stasis ) 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.Tachyphylaxis 8.Hypo-pigmentation. 9.Hyper-trichosis. (Excessive abnormal hair growth) 10.Glaucoma & cataract. (when used around the eye) 11.Allergic contact dermatitis. (leg ulcers, stasis )

21 Contraindications to topical corticosteroids 1. Untreated skin infections (bacterial, fungal, or viral) 2.Acne rosacea 3.Peri-oral dermatitis 4.Potent corticosteroids are contra-indicated in widespread plaque psoriasis. Why? Questions for revision: 1.What are the precautions of using topical corticosteroids in children and infants? 2.On which basis you choose the dosage form of corticosteroids? e.g. occlusion 3.How frequent you apply the topical corticosteroids per day. Why? 4.What is your opinion about using topical steroids in pregnancy and lactation? 1. Untreated skin infections (bacterial, fungal, or viral) 2.Acne rosacea 3.Peri-oral dermatitis 4.Potent corticosteroids are contra-indicated in widespread plaque psoriasis. Why? Questions for revision: 1.What are the precautions of using topical corticosteroids in children and infants? 2.On which basis you choose the dosage form of corticosteroids? e.g. occlusion 3.How frequent you apply the topical corticosteroids per day. Why? 4.What is your opinion about using topical steroids in pregnancy and lactation?

22 How can you minimize the side effects of topical steroids? 1.Potency: use the least potent steroid whenever possible 2.Frequency: ≱ Once or Twice daily 3.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 occlusion 8.Once the lesion responded, reduce or stop the steroid & maintain on a mild one 9.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. 1.Potency: use the least potent steroid whenever possible 2.Frequency: ≱ Once or Twice daily 3.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 occlusion 8.Once the lesion responded, reduce or stop the steroid & maintain on a mild one 9.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.

23 Intralesional corticosteroids Definition: Injection of small amounts of corticosteroids into coetaneous lesions (Relatively insoluble steroids) Examples: Triamcinolone acetonide, triamcinolone diacetate, betamethasone acetatephosphate) 2.5 mg/ml Advantages: 1.High concentration 2.Prolonged depot (3-4 weeks) 3.No systemic side effects Treated diseases : Acne cysts, Alopecia areata, keloids, nail disorders, Prurigo nodularis Methods : 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: 1.No systemic. Why? 2.Local: Atrophy, hypo-pigmentation, hair growth, infection, ulceration. Definition: Injection of small amounts of corticosteroids into coetaneous lesions (Relatively insoluble steroids) Examples: Triamcinolone acetonide, triamcinolone diacetate, betamethasone acetatephosphate) 2.5 mg/ml Advantages: 1.High concentration 2.Prolonged depot (3-4 weeks) 3.No systemic side effects Treated diseases : Acne cysts, Alopecia areata, keloids, nail disorders, Prurigo nodularis Methods : 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: 1.No systemic. Why? 2.Local: Atrophy, hypo-pigmentation, hair growth, infection, ulceration.


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