Glucocorticosteroids

Group of substances that belongs to the most frequently used drugs. Its effect is based on its broadly effective antiphlogistic and immunosuppressive properties. Due to a wide range of targets (inhibition of arachidonic acid, prostaglandins, leukotrienes, thromboxane, PAF, TNF-alpha, Il-1, Il-2, Il-6, plasminogen activator, etc.), the substance is highly effective, inhibition of T-cell activation, stimulation of apoptosis of eosinophilic granulocytes and certain subtypes of T-lymphocytes, stabilization of lysosomal membranes in neutrophilic granulocytes and others) they have a wide range of medical uses.

For the classification of glucocorticoids see below. Glucocorticosteroids, inhaled; glucocorticoids, topical; glucocorticoids, systemic.

Since serious side effects are often observed during long-term use which cannot be avoided, use requires careful risk-benefit analysis.

Cortisol is the most important endogenous glucocorticoid in humans. It belongs to the steroid hormones and is synthesized in the NNR. Daily production at 20 mg. Circadian rhythm with maximum in the early morning hours (70% of daily production). Minimum at midnight. Increase in production in the presence of stressors. Cortisol inhibits the release of CRH from the hypothalamus and ACTH from HVL. In the blood it is bound to plasma proteins to 90-95%. High-affinity binding to the specific transport protein "cortisol binding protein" (approx. 80%) or low-affinity binding to albumin (approx. 10-15%). Cortisol is broken down in the liver by reduction and excreted in a glucuronidated form.

Due to lipophilicity, glucocorticoids can penetrate freely through the membranes of cells. In the cytosol binding to glucocorticoid receptors. Their conformational change leads to activation with dissociation of the HSP complex (heat shock protein) and translocation into the cell nucleus. There binding to specific DNA sequences in the regulatory region of glucocorticoid-dependent genes.

• Type I mechanism: Classical mechanism of action of steroid hormones. Increase in transcription rate of metabolically and cardiovascularly relevant genes.
• Type 2 mechanism: Decrease in transcription rate of immunologically relevant genes, e.g. for IL-2.

Immunosuppressive or antiphlogistic long-term therapy
:General: Dosages mostly physiological: i.e. suppression of the adrenal control circuit, NW due to glucocorticoid-specific effects!

Synthetic non-fluorinated preparations with absent or low mineralocorticoid effects (e.g. prednisolone) are preferable. Favourable: prednisolone (e.g. Decortin H) or prednisone (Decortin), methylprednisolone (e.g. Urbason).

Limited favourable: cloprednol (Syntestan). Too high initial doses are needed if the HWZ is too short (also high price). In patients prone to RR rise and oedema, use of glucocorticoids with weaker mineralocorticoid action such as fluocortolone (e.g. Ultralan) and triamcinolone acetonide (Volon A).

Other indications:

• Substitution therapy: Mostly hydrocortisone (e.g. Hydrocortisone Hoechst).
• Short-term therapy: methylprednisolone (Urbason), prednisolone (Decortin H); prednisone (Decortin); cloprednol (Syntestan).
• High-dose therapy (1000 mg prednisolone i.v. for 3 consecutive days) for certain forms of scleroderma (see Scleroderma, Circumscribed).
• Topical use: see below hydrocortisone, triamcinolone acetonide (Triamgalen); mometasone furoate (Ecural); prednicarbate (Dermatop); amcinonide (Amciderm); clobetasol propionate (Dermoxin).
• Systemic therapy for cerebral edema: dexamethasone initial 12 mg i.v., then 4 mg every 6 hrs i.v., p.o. if preventive.
• Emergency therapy: Prednisolone, e.g. in anaphylactic shock, 250-1000 mg i.v.
• Pregnancy: prednisolone 0.3 mg/kg bw, side effects are not expected if duration of therapy < 4 weeks. At high dose or long duration of therapy, fetal growth should be evaluated by ultrasound. Adrenal insufficiencies should be taken into account. A 3.4-fold increased risk of oral clefts is reported in the literature. In summary, according to current knowledge, the use of prednisolone in various maternal diseases is supported, but information about the risks should be provided in advance.

In case of prolonged internal/external therapy: striae cutis distensae, steroid atrophy, steroid purpura, telangiectasia, pigmentary shifts, hypertrichosis, formation of comedones, steroid acne. S.a.u. Rubeosis steroidica, see stippled skin below.

Contact allergy: Contact allergies are reported with an incidence of 0.5 to 6%. Type I immediate reactions are rarer. After systemic administration, these manifest themselves as an anaphylactic reaction or as a deterioration of an anaphylactic reaction. Type IV allergies are perceived as "veiled" "eczema reactions" (frequently also in polyvalent treated ulcers) (see glucocorticoid epicutaneous test series)

After ocular administration, conjunctivitis or eyelid dermatitis may occur.

After nasal application, in addition to local contact dermatitis, there may be scattering reactions, nasal obstruction, chronic rhinitis, itching, burning, stomatitis, angioedema of the lips.

Bronchoconstriction is possible by inhalation. Airborne reactions have also been observed.

1. Ambros-Rudolph CM (2006) Dermatoses of pregnancy. J Dtsch Dermatol Ges 4: 748-759
2. Basedow S et al.(2011) Immediate and delayed hypersensitivity to corticosteroids.J Dtsch Dermatol Ges 9:885-888.
3. Wurpts G (2018) Contact allergy to glucocorticoids. Allergo J 27: 13-15