GLUCOCORTICOID DRUGS


APPLICATION IN DERMATOLOGY

Glucocorticoids are applied externally in the form of ointments, creams, gels, lotions for a number of skin diseases. They have a local anti-inflammatory, anti-allergic effect, eliminate swelling, redness, itching. When external use of glucocorticoids is very important, depending on the location and nature of the lesion, to choose the optimal dosage form, each of which has some features (Table 1).

Table 1. Features of the action of dosage forms for external use.

Dosage Form Indications Disadvantages and advantages
Ointment It is used for dry, scaly, irritated skin. It promotes maceration in the case of moist and intertriginous processes. Oily; the active substance is released slowly.
Cream Preferred for intertriginous processes. Cosmetically more convenient. May cause dryness and irritation, especially if the skin is damaged.
Lotion Preferred in exudative processes. Convenient for use on hairy parts of the body.  

Classification

Preparations of glucocorticoids for external use are traditionally divided into several groups, depending on the strength of the local anti-inflammatory action. Moreover, there are some, not having fundamental importance, differences between the classifications considered in different literary sources. According to the above classification (Table 2), the drugs are divided into 4 groups.

Table 2. Classification of glucocorticoids for external use.

Group Generic name Trade names
Very strong Clobetasol propionate 0.05% Dermovate
Halcinonide 0.1% Halciderm
Strong Betamethasone valerate 0.1% Betnovate, Celestoderm-V
Budesonide 0.0375% Alupent
Halometasone monohydrate 0.005% Sicotran
Hydrocortisone 17-butyrate 0.1% Laticort, Locoid
Mometasone furoate 0.1% Elocom
Dexamethasone 0.025% Esperon
Triamcinolone acetonide 0.1% Polcortolone ointment, Ftorocort
Triamcinolone acetonide 0.025 and 0.1% Triacortum
Flumetasone pivalate 0.02% Locacorten, Lorinden
Fluocinolone acetonide 0.025% Synalar, Synaflan, Flucinar
Fluticasone propionate 0.05% Cutivate
Medium strength Prednisolone 0.25% Depersolon
Prednisolone 0.5% Prednisolone ointment
Prednicarbate 0.25% Dermatop
Fluocortolone 0.025% Ultralan
Light Hydrocortisone acetate 0.1%, 0.25%, 1%, 5% Hydrocortisone

Fluorinated glucocorticoids ("very strong" and "strong" drugs), which are poorly absorbed from the skin surface and have a local effect, have the most powerful effect. Their disadvantage is the more frequent development of local undesirable reactions in comparison with other drugs (see below).

Drugs belonging to groups III and IV (Prednisolone, Hydrocortisone Acetate and others) are characterized by a greater ability to absorb from the area of application, therefore their local effect is weaker and the probability of developing systemic adverse reactions is higher.

The strength of the drug also depends on the type of dosage form (ointment> cream> lotion) and concentration.

One of the modern principles of systematization of glucocorticoid drugs for external use is to divide them into four generations, differing in the characteristics of the action. The first generation is Hydrocortisone Acetate, which has the most gentle effect. The second is Prednisone, which has an average severity effect.

The third generation is represented by an extensive amount of fluorinated glucocorticoids, which have a "strong" or "very strong" local action. The fourth group includes “strong” glucocorticoids, which do not contain in their structure a fluorine atom — Hydrocortisone-17-butyrate, Mometasone Furoate, and also a preparation of moderate degree of activity — Prednicarbate.

Created in recent years, fourth-generation drugs are recognized as the most preferred because they successfully combine the positive properties of their predecessors: they have high activity, comparable to the strength of the action of fluorinated glucocorticoids, and minimal undesirable local action characteristic of Hydrocortisone acetate.

Mometasone furoate (Elocom - cream, ointment, lotion) belongs to the fourth generation glucocorticoids. It is superior to hydrocortisone, dexamethasone and betamethasone in its ability to block the formation of cytokines (interleukin-1 and interleukin-6), which play an important role in skin inflammation, in particular, in psoriasis.

In controlled clinical trials, mometasone has a higher efficacy in psoriasis and atopic dermatitis compared with Hydrocortisone and Betamethasone. The drug is well tolerated, does not cause skin atrophy. Mometasone has a prolonged effect, so it is applied once a day. Due to its improved tolerability, it is suitable for use in children and the elderly.

Hydrocortisone 17-butyrate (Laticort, Locoid), unlike Hydrocortisone acetate, is poorly absorbed from the area of application, therefore the probability of systemic action is extremely small. At the same time, like fluorinated glucocorticoids, it has a powerful local effect, but, unlike the latter, rarely causes local undesirable reactions and may have wider application.

Prednicarbate (Dermatop) is a glucocorticoid with an average degree of activity and is characterized by a mild, sparing local action. It almost does not cause systemic adverse reactions. Local effects are very rare. It can be applied on large surfaces and applied to the skin with the most sensitive (face, groin). In controlled clinical studies, high efficacy and good tolerability of Prednicarbate in children from 2 months to 16 years old and elderly are shown, therefore the drug is recommended primarily for use in these age groups.

Indications

Psoriasis, eczema, neurodermatitis, contact dermatitis, sun dermatitis, seborrheic dermatitis, atopic dermatitis, lichen planus, red discoid lupus erythematosus.

Rules of application

1. Before using glucocorticoid drugs, it is necessary to establish the diagnosis accurately.

2. It is recommended to begin treatment with the use of a drug with weak activity (Table 2), in the absence of an effect, switch to a stronger one within 2-3 weeks, and after reaching the effect, use the weak glucocorticoid again.

3. Preparations with very strong activity (Clobetasol propionate, Halcinonide) should be used only for lichenoid eczema and discoid lupus erythematosus.

4. The drug is applied to clean skin (after a bath or shower) 2 times a day, in a thin layer, do not rub or massage. The procedure is recommended in a glove. Mometasone Furoate and Fluticasone propionate, which have a prolonged effect, are applied 1 time per day, which is convenient for diseases requiring prolonged use of glucocorticoids (eczema, psoriasis).

5. After applying the drug to enhance the therapeutic effect (as a rule, with psoriasis), it is possible to use occlusive dressings for a short time, not more than 2 days.

6. The process of release of the active substance from the ointment is usually more slowly than from the cream, so in chronic processes it is preferable to use ointment.

7. When the lesion is located on the scalp, it is recommended to use a gel or lotion.

8. If an infection is suspected, combination glucocorticoids for external use containing antimicrobial components should be used (see below).

Undesirable reactions

1. From the skin:

2. Accession or dissemination of infection.

3. Systemic action (with prolonged use, application to large areas of the body, often in children and with the use of occlusive dressings).

4. Withdrawal syndrome (usually requires the resumption of the use of local drugs glucocorticoids).

Contraindications

Features of use in children

In children with local application of glucocorticoids, a higher predisposition to their systemic action is observed than in adults (including suppression of the function of the hypothalamic-pituitary-adrenal system, development of Cushing's syndrome, growth and developmental delay), as more children.

Therefore, preparations of glucocorticoids should be used in limited areas, especially in newborns, if possible, in a short course. In children under 1 year old, only ointment with Hydrocortisone (no more than 1%) or fourth-generation glucocorticoid Prednicarbate should be used, up to 5 years - ointment of medium strength and 17-butyrate hydrocortisone.

Combined drugs

Combined ointments and creams are being produced, which, along with glucocorticoids, include other components (Table 3). Their composition may contain antibiotics (Neomycin and others), drugs that combine antifungal and antibacterial activity (Miconazole, Triclosan, etc.), antifungal and anti-trichomonas action (Natamycin), antiseptics, salicylic acid, local anesthetics, vitamin-like compounds, antihistamines.

Some features of the composition of the drug may indicate the presence in its trade name of an additional letter. For example, Flucinar N includes the antibiotic Neomycin, Sinalar C - the antifungal agent Clioquinol, Lorinden A - Salicylic acid. In other cases, the combined drugs have special trade names (Localen, Triderm).

Preparations containing antimicrobial components are recommended to be used in case of bacterial or fungal infection adherence, suspicion of it and with a high probability of its development (oozing processes, irritant lesions, anogenital and senile itching). It should be borne in mind that neomycin, when applied externally, can be absorbed and have an oto- and nephrotoxic effect; therefore, it is not necessary to use the dosage forms containing it for a long time and on large surfaces.

Salicylic acid has a kerato and squamolytic effect, promotes the penetration of glucocorticoids through an overly horny epidermis, restores the protective covering of the skin, and has a weak antiseptic effect. Therefore, drugs, in which it is included, it is advisable to apply for diseases accompanied by increased keratinization of the epidermis, desquamation, hyperkeratosis, mozolelost, such as lichen eczema, old cases of psoriasis, ichthyosis and others.

Table 3. Combined preparations of glucocorticoids for external use.

Glucocorticoid Tradename Other components
Betamethasone Vipsogal Gentamicin (1)
Salicylic acid
Panthenol (2)
Diprogent Gentamicin
Diprosalic Salicylic acid
Triderm Gentamicin
Clotrimazole (1,3)
Celestoderm-V with Garamycin Gentamicin
Halometasone Sicorten Plus Triclosan (1,3)
Hydrocortisone acetate Oxycort Oxytetracycline (1)
Hydrocortisone 17-Butyrate Pimafucort Neomycin (1)
Natamycin (2,4)
Sibicort Chlorhexidine (5)
Diflucortolone Travocort Isoconazole (1,3)
Prednisolone Mycosolon Miconazole (1,3)
Aurobin Triclosan
Lidocaine (6)
Panthenol
Dermosolon Iodine Chlorine Oxyquinoline (1,3)
Triamcinolone Polcortolon TC Tetracycline 1 (1)
Flumethasone Locasalen Salicylic acid
Lorinden A Salicylic acid
Lorinden C Iodine Chlorine Oxyquinoline
Fluocortolonum Ultraproct Clemizole (7)
Cinchocainum (6)
Fluocinolone acetonide Synalar C Cliochinolum (1,3)
Synalar N Neomycinum
Flucinar N Neomycinum
Notes:
1 - antibacterial action;
2 - vitamin-like compound (pantothenic acid);
3 - antifungal action;
4 - antitrichomonad action;
5 - antiseptic;
6 - local anesthetic;
7 - antihistamine.

APPLICATION OF GLUCOCORTICOIDS IN OPHTHALMOLOGY AND otorhinolaryngology

The use of glucocorticoids in ophthalmology is based on their local anti-inflammatory, antiallergic, antipruritic action. They prevent the expansion of capillaries, reduce their permeability, inhibit the migration of leukocytes, the release of kinins, reduce the deposition of fibrin, collagen, the formation of scar tissue. Their use reduces pain, burning, tearing and photophobia.

Indications are various inflammatory diseases of the eye tissue of non-infectious etiology, including after injuries and operations (iritis, iridocyclitis, scleritis, keratitis, uveitis, severe conjunctivitis and others).

The most preferred special preparations of glucocorticoids for topical administration are solutions, suspensions, and ointments (Table 4). They have a more pronounced local anti-inflammatory effect than glucocorticoids used in such situations, inside or parenterally.

The most effective "ophthalmologic" drugs are Fluorometholone and Prednisolone Acetate.

In severe cases, glucocorticoids can be administered subconjunctivally. Dexamethasone and Betamethasone phosphate are used for this, and injections of the second drug are less painful. There is evidence of the possibility of subconjunctival administration of Betamethasone phosphate / dipropionate (diprospan).

Glucocorticoids are contraindicated in acute infectious diseases of the eye. If necessary, apply combined preparations containing antibiotics.

Table 4. Glucocorticoids for topical use in ophthalmology.

A drug Salt / ether Tradename Concentration Dosage Form The degree of reduction of corneal inflammation
Dexamethasone Alcohol Maxidex 0.1%
Suspension 40%
Phosphate Decadron 0.1% Solution 19%
0.05% Ointment 12%
Fluorometholone --
--
Efflumidex 0.1%
0.25%
Suspension
Suspension
31%
35%
Acetate Flarex 0.1% Suspension 48%
Prednisolone Acetate Econopred 0.12% Suspension 34%
Econopred Plus 1.0% Suspension 52%
Phosphate Inflamaze 0.12% Solution 23%
Inflamaze Forte 1.0% Solution 28%

Undesirable reactions

Despite the fact that glucocorticoids, when applied topically, unlike systemic administration, do not increase, but on the contrary, inhibit the formation of chamber moisture, they can also cause an increase in intraocular pressure (most of all Dexamethasone, at least Fluorometholone) and lead to the development of glaucoma . Exophthalmos may occur. Sometimes a serious complication is posterior subcapsular cataract. In case of diseases accompanied by thinning of the cornea, its perforation is possible.

Combined drugs

In the ophthalmologic and otorhinolaryngological practice, a number of combined preparations are used, which include, in addition to glucocorticoids, antibiotics (Table 5). They combine anti-inflammatory and bactericidal action, and more preferred are drugs that include glucocorticoid Betamethasone, which has less effect on intraocular pressure (Garazon).

In ophthalmology, these drugs are used in inflammatory and allergic diseases of the eye, if present or suspected bacterial infection (staphylococcal Blepharoconjunctivitis and microbe-allergic keratoconjunctivitis, keratitis, episcleritis, dacryocystitis, iridocyclitis, eye injuries, etc.).

In otolaryngology, indications for use of the combined drugs are acute and chronic external otitis; eczema of the external auditory canal; seborrheic dermatitis; contact dermatitis, complicated by secondary infection; allergic and vasomotor rhinitis, complicated by secondary infection.

Precautionary measures. It is not recommended to use the same vial of the drug for the treatment of otitis media, rhinitis and eye diseases in order to avoid the spread of infection. It is impractical to use these drugs for the treatment of otitis media, which requires systemic (oral, parenteral) use of antibiotics. The drug Maxitrol, containing two ototoxic antibiotics (Neomycin and Polymyxin B), can be used only in short courses.

Table 5. Combined drugs of glucocorticoids for use in ophthalmology and otorhinolaryngology.

Name Composition Dosage Form Dosage
Garasone Betamethasone
Gentamicin
Eye / ear drops Eyes: 1-2 drops 3-4 times a day; in the acute stage, 2 drops every 1-2 hours, followed by contraction.
Ears: 3-4 drops 2-4 times a day or a tampon is laid for 24 hours, which is moistened every 4 hours with the preparation.
Eye ointment 3-4 times a day in a conjunctival sac; in the acute stage - every 2 hours.
Sofradex Dexamethasone
Neomycinum
Gramicidin
Eye / ear drops Eyes: 1-2 drops 4-6 times a day; in the acute stage more often. Ears: 2-3 drops 3-4 times a day.
Eye / Ear Ointment It is placed 1-2 times a day in the conjunctival sac or ears.
Hycomycin-Teva Hydrocortisone
Neomycinum
Eye / ear drops / nose drops 2-3 drops every 1-4 hours in the eye, ear, or every half of the nose; after the inflammation subsides, 1-2 drops 3-4 times a day.
Eye / Ear Ointment / Nose Ointment It is laid 1-3 times a day.
Maxitrol Dexamethasone
Neomycinum
Polymyxinum B
Eye drops 1-2 drops 4-6 times a day; in the acute stage, 2 drops every 1-2 hours
Eye ointment It is laid 3-4 times a day.

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