The majority of indications for the use of corticosteroids due to their anti-inflammatory, immunosuppressive and anti-allergic properties. The dose corresponding to 4 mg of methylprednisolone has the same antiinflammatory effect as 20 mg of hydrocortisone.
Methylprednisolone deca durabolin price has only negligible mineralocorticoid activity (equivalent to 200 mg methylprednisolone deoxycorticosterone 1 mg).
Influence of carbohydrate and protein metabolism
GCS exert catabolic action on proteins. The released amino acids are converted into hepatic gluconeogenesis and glycogen into glucose. Consumption of glucose in peripheral tissues is reduced, which may lead to hyperglycaemia and glycosuria, especially coal at risk of developing diabetes.
Effects on lipid metabolism
corticosteroids possess lipolytic activity, which manifests itself primarily in the extremities. GCS also have lipogeneticheskoe action that is most pronounced in the chest, neck and head. All this leads to a redistribution of body fat.
Maximum pharmacologic activity of corticosteroids appears not at the peak plasma concentration, and after him, therefore, the effect of drugs is primarily due to their effect on the activity of enzymes.
Pharmacokinetics. Absorption methylprednisolone occurs primarily in the proximal small intestine, where it is approximately two times larger than the distal. Communication methylprednisolone proteins (albumin and transcortin) – about 40 – 90%.
Metabolism of methylprednisolone in the liver and qualitatively similar to cortisol metabolism. The main metabolites – 20p and 20p-gidroksimetilprednizolon-hydroxy-6a-metilprednizon.
. Excretion Metabolites are mainly in the urine in unbound form as well as in the form of glucuronides and sulfates which are produced primarily in the liver and partially – in the kidneys. Methylprednisolone – glucocorticosteroids with an intermediate duration of action. Due to the intracellular activity revealed a pronounced difference between the half-life of methylprednisolone from plasma (approximately 3.3 hours), and half-life of the organism as a whole (about 12-36 hours). Pharmacotherapeutic effect persists even when it is not determined in the blood level of the drug.
INDICATIONS FOR USE Apply strictly prescribed by a doctor to avoid complications.
- Primary and secondary adrenocortical insufficiency (the drug of choice -gidrokortizon or cortisone, if necessary, synthetic analogs may be used in combination with a mineralocorticoid, of particular importance is the addition of mineralocorticoid in pediatric patients).
- Congenital adrenal hyperplasia
- Chronic and subacute thyroiditis
- Hypercalcemia of malignancy
not endocrine diseases
1. Diseases of the musculoskeletal system (including rheumatic) (as adjunctive therapy for short-term elimination of the acute condition or exacerbation)
- Psoriatic arthritis
- Rheumatoid arthritis, including juvenile rheumatoid arthritis (in some cases may require maintenance therapy with low doses)
- Ankylosing spondylitis
- Acute and subacute bursitis
- Acute nonspecific tenosynovitis
- Acute gouty arthritis
- Postgravmatichesky osteoarthritis
- Synovitis of osteoarthritis
2. Systemic diseases of connective tissue (in acute or in some cases as maintenance therapy)
- Acute rheumatic heart disease
- Systemic lupus erythematosus
- Systemic dermatomyositis (polymyositis)
- polymyalgia rheumatica
- giant cell arteritis
3. Skin diseases
- Bullous dermatitis herpetiformis
- Severe erythema multiforme (Stevens-Johnson syndrome)
- exfoliative dermatitis
- Severe psoriasis
- Severe seborrheic dermatitis
4. Allergic reactions (severe incurable condition in which conventional therapy is ineffective)
- Seasonal or perennial allergic rhinitis
- serum sickness
- Bronchial asthma
- Hypersensitivity reactions to medicines
- Contact dermatitis
- Atopic dermatitis
5. Eye diseases (severe acute and chronic allergic and inflammatory processes in the eye lesions)
- Allergic corneal marginal ulcers
- Ocular herpes zoster
- Inflammation of the anterior segment of the eye
- Diffuse posterior uveitis and choroiditis
- transferred ophtalmia
- Allergic conjunctivitis
- Optic neuritis
- Iritis and iridocyclitis
6. Respiratory diseases
- Symptomatic sarcoidosis
- Loeffler’s syndrome, is not amenable to treatment by other means
- Lightning or disseminated pulmonary tuberculosis combined with appropriate antituberculous chemotherapy
- inhalation pneumonia
7. Hematologic Disorders
- Idiopathic thrombocytopenic purpura in adults
- Secondary thrombocytopenia in adults
- Acquired (Autoimmune) Hemolytic Anemia
- Erythroblastopenia (red cell anemia)
- Congenital (erythroid) hypoplastic anemia
8. Cancer (as a palliative therapy)
- Leukemias and lymphomas in adults
- Acute leukemia in children
9. edema syndrome
- To stimulate diuresis and remission of proteinuria in patients with nephrotic syndrome without uremia, nephritic syndrome or idiopathic type or caused by systemic lupus erythematosus.
10. Diseases of the gastrointestinal tract (to remove the patient from the critical state)
- Ulcerative colitis
- regional enteritis
11. Nervous System
- Exacerbation of multiple sclerosis
- cerebral edema caused tumor
12. Other indications for use
- Tuberculous meningitis with subarachnoid block or the threat of the unit (in conjunction with appropriate antituberculous chemotherapy)
- Trichinosis with nervous system lesion or infarction
13. Organ transplants
- Hypersensitivity to any component of the drug in history.
- Systemic fungal infections
WITH CARE drug should be used in the following cases: gastric and duodenal ulcer disease, esophagitis, gastritis, acute or latent peptic ulcer, intestinal anastomosis (in the near history), ulcerative colitis, with the threat of perforation or abscess, diverticulitis; dibet diabetes and predisposition to it; hyperlipidemia; myasthenia gravis, osteoporosis, hypothyroidism, hyperthyroidism, acute psychosis, acute and subacute myocardial infarction, congestive heart failure, hypertension, severe liver dysfunction (especially accompanied by hypoalbuminemia) or kidney disease, open-angle glaucoma, herpes simplex (eye shape), chicken pox, measles, strongyloidiasis, AIDS, HIV – infection; active and latent tuberculosis, severe bacterial or viral infections (increases the risk of superinfection, masking symptoms), it is permissible to use the drug only on the background of specific therapy.
DOSAGE AND ADMINISTRATION
The initial dose may be 4 mg to 48 mg per day of methylprednisolone, depending on the nature of the disease. In less severe disease usually sufficient use of lower doses, although individual patients may require higher doses. High doses may be required in such diseases and conditions such as multiple sclerosis (200 mg / day), brain edema (200-1000 mg / day), and organ transplantation (up to 7 mg / kg / day). If after a reasonable period of time not received a satisfactory clinical effect, the drug should be discontinued and the patient to assign another type of therapy.
Babies dose determined by the physician taking into account the body weight or surface. When adrenal insufficiency – inside the 0.18 mg / kg or 3.33 mg / m² per day in 3 divided doses, other testimony – at 0,42-1,67 mg / kg or 12.5-50 mg / m² .m per day in 3 divided doses.
It should be emphasized that the required dose can vary and should be individualized, depending on the nature of the disease and the patient’s response to therapy. Recommended the gradual abolition of the drug after prolonged therapy. If the treatment received good effect, it is necessary to pick up a sick individual maintenance dose by gradually reducing the initial dose at regular intervals until such time until it finds the lowest dose that allows to maintain the achieved clinical effect. Keep in mind that constant monitoring of the drug dosing regimen.
There may be situations in which the required dose correction, for example, changes in clinical status due to the onset of remission or exacerbation of the disease, the patient’s individual response to the drug, as well as the impact on the patient stressful situations not directly related to the underlying disease for which treatment is directed; in the latter case it may be necessary to increase the dose of the drug for a certain period of time, depending on the patient.
Alternating therapy – is a dosing regimen in which twice the daily dose of corticosteroids administered every other day in the morning. The goal of this therapy is to achieve in the patient receiving the drug for a long time, the maximum clinical effect, while minimizing certain undesirable effects such as suppression of pituitary-adrenal axis, Cushing’s syndrome, the abolition of GCS syndrome and growth retardation in children.
Violation of water and electrolyte balance: Sodium retention, congestive heart failure in patients with the appropriate predisposition, high blood pressure, fluid retention, potassium loss, hypokalemic alkalosis.
Musculoskeletal: steroid myopathy, muscle weakness, osteoporosis, pathologic fractures, vertebral compression fractures, aseptic necrosis of the epiphysis of long bones, tendon rupture, particularly the Achilles tendon.
Gastrointestinal: peptic ulcer with possible perforation and hemorrhage, gastric hemorrhage, pancreatitis, esophagitis, perforation of the intestine.
After treatment there was an increase GCS alanintransaminazy level (ALT), aspartate transaminase (ACT) and alkaline phosphatase in serum. Typically, these changes are minor, not associated with any clinical syndrome and are reversible upon discontinuation of treatment.
Dermatologic: slow wound healing, petechiae and ecchymosis, thinning of the skin and reduction of strength.
Metabolic: negative nitrogen balance due to protein catabolism.
Neurological: increased intracranial pressure, cerebral pseudotumor, mental illness, seizures.
Endocrine: menstrual irregularities, hirsutism, the development of Cushing’s syndrome, suppression of pituitary-adrenal axis, decreased carbohydrate tolerance, the emergence of latent diabetes mellitus, increased requirements for insulin or oral hypoglycemic agents in patients with diabetes, growth retardation in children.
Ophthalmic: posterior subcapsular cataracts, increased intraocular pressure with the risk of damage to the optic nerve, exophthalmos
Immunological: erased the clinical picture of infectious diseases, activation of latent infections, the occurrence of infections due to opportunistic pathogens, hypersensitivity reactions, including allergic systemic reactions, may suppress reactions during skin tests. Other: withdrawal of GCS.
The clinical syndrome of acute drug overdose not described. Reports of acute toxicity is extremely rare with an overdose of Valium. There is no specific antidote. Frequent reception repeated (daily or several times a week) for a long time may lead to the development of Cushing’s syndrome and other complications, prolonged therapy characteristic SCS. Treatment is symptomatic. Methylprednisolone is deca durabolin price displayed during dialysis.
INTERACTION WITH OTHER DRUGS
The following examples of drug interactions may have important clinical implications. The combined use of methylprednisolone and cyclosporine is mutual inhibition of metabolism, therefore, likely that the side effects associated with the use of each of these drugs as monotherapy, when used together can occur more frequently (in the combined use of these drugs cases of seizures have been observed).
The therapeutic effect is reduced under the influence of methylprednisolone inducers of microsomal liver enzymes ( ephedrine, theophylline, phenobarbital, phenytoin, rifampin ), which may require increasing doses of the drug to produce the desired effect.
Oleandomycin, ketoconazole. estrogensoderzhaschie oral contraceptives may inhibit the metabolism of corticosteroids and reduce their clearance, to increase half-life, the therapeutic and toxic effects of methylprednisolone. In this case, to avoid overdose phenomena, it is necessary to reduce the dose of methylprednisolone.
Methylprednisolone may increase the clearance of acetylsalicylic acid , the received high doses for long periods, which can lead to reduced serum salicylate or salicylates increase the risk of toxicity when canceling methylprednisolone. In a joint application with salicylates increases the risk of gastropathy. Patients with gipoprotrombinemiey appoint acetylsalicylic acid in combination with corticosteroids should be with caution.
Methylprednisolone has an impact on the effect of oral anticoagulants . It reported on enhancing or reducing the effect of anticoagulants, taken together with methylprednisolone. To maintain the desired anticoagulant effect needs constant determination of coagulation parameters.
Because of the emerging hypokalemia increases the toxicity of cardiac glycosides (arrhythmias).
Thiazide diuretics, carbonic anhydrase inhibitors, corticosteroids and other amphotericin B increase the risk of hypokalemia, sodium-containing drugs – swelling and increase blood pressure.
Alcohol and NSAIDs increase the risk of gastrointestinal ulceration and bleeding. In combination with NSAIDs for the treatment of arthritis may reduce the dose of methylprednisolone due to the addition of the therapeutic effect.
In combination with paracetamol increases the risk of hepatotoxicity (liver enzyme induction and the formation of toxic metabolites of paracetamol).
Methylprednisolone reduces the effect of hypoglycemic agents.
Co-administration of antacids reduces absorption of methylprednisolone.
High-dose methylprednisolone reduce the effectiveness of growth hormone .
Androgens in kombinitsii with methylprednisolone increase the risk of otekov.Metilprednizolon reduces the effectiveness of vaccines (live vaccines against the backdrop of methylprednisolone may cause disease).
Mitotane and other inhibitors of the function of the adrenal cortex may condition the need to increase the dose.
Antithyroid drugs and thyroid hormones: methylprednisolone clearance is reduced in hypothyroidism and hyperthyroidism increases, so the dose of methylprednisolone should be selected based on the functional test results.
Methylprednisolone accelerates metabolism of isoniazid, mexiletine, resulting in reduced plasma concentrations of drugs, especially at the “fast” acetylators.
- Because GCS therapy complications depend on the dose and duration of treatment, the need to make a decision on such treatment in each case based on the analysis of risk / benefit ratio, and determine the treatment duration and frequency of administration.
- It is necessary to apply the lowest dose that provides adequate therapeutic effect, if necessary, dose reduction should be gradual.
- The therapy of GCS may develop a variety of mental disorders from euphoria, insomnia, mood instability, personality changes and severe depression to acute psychotic symptoms. In addition, it may increase the already existing emotional instability or propensity to psychotic reactions.
- Patients who may be exposed to stress on the background of SCS therapy, shows an increase in the dose before, during and after the stressful situation.
- Patients receiving treatment with corticosteroids at the doses that have an immunosuppressive effect, is contraindicated the introduction of live or live attenuated vaccines, but it is possible to introduce killed or inactivated vaccines, but the reaction to the introduction of such vaccines may be reduced. Patients receiving treatment with corticosteroids at doses that do not produce an immunosuppressive action, immunization can be carried out by the appropriate indications.
- Amid GCS therapy of infection can occur some obliterated, moreover, may develop a new infection. In the application of corticosteroids may be reduced resistance to infection, and also reduced the body’s ability to localize the infection process. The development of infections caused by various pathogens, such as viruses, bacteria, fungi, protozoa and helminths, which are located in various human organ systems, may be associated with the use of corticosteroids, both as monotherapy and in combination with other immunosuppressive agents acting on cellular immunity, humoral immunity, or neutrophil function. These infections can easily occur, however, in some cases, possibly severe course, and even death. Moreover, the higher doses of corticosteroids are used, the higher the probability of infectious complications.
- Use of the drug Medrol in active tuberculosis should be restricted to cases of fulminant and disseminated tuberculosis when corticosteroids are used to treat the disease in conjunction with appropriate antituberculous chemotherapy. If the drug deca durabolin price is prescribed to patients with latent tuberculosis or positive tuberculin skin test, treatment should be under strict medical supervision as possible reactivation process. During prolonged treatment with corticosteroids, such patients should receive appropriate prophylactic treatment.
- The drug should be used with caution in lesions of the eye caused by the herpes simplex virus, because it is possible corneal perforation.
- Prolonged use of corticosteroids may result in posterior subcapsular cataracts, glaucoma with possible lesions of the optic nerve and provoke the accession of secondary ocular fungal or viral infection.May develop allergic reactions (eg, angioedema).
- Medium and high doses of cortisone or hydrocortisone can cause high blood pressure, retention of sodium and water, and increased potassium excretion. These effects are less likely with the use of synthetic corticosteroids (including methylprednisolone), except when used in high doses. It is necessary to limit consumption of salt with food and the appointment of potassium preparations. All corticosteroids increase calcium excretion.
- Osteoporosis is a common and, at the same time, rarely diagnosed side effect, developing long-term use of high doses of corticosteroids.
- The children receiving the drug for a long time every day several times a day, there may be a delay of growth, so this dosing regimen should be used only if absolutely indicated. Application of alternating therapy usually avoids or minimizes this side effect.
- Manifestations of secondary adrenal insufficiency, which develops against the background of SCS therapy can be minimized by gradual reduction of the dose. This type of relative insufficiency may occur within a few months after the end of treatment, so any stress during this period should be to re-appoint corticosteroids. At the same time may be impaired secretion of mineralocorticoid, and therefore the need to concomitant administration of electrolytes and / or mineralocorticoid.
- It noted a more pronounced effect of corticosteroids in patients with hypothyroidism and liver cirrhosis.
- There is no consensus about the likelihood of the development of peptic ulcers during treatment Valium. SCS therapy can mask the symptoms of peptic ulcers, and therefore may cause perforation or bleeding without the expressed painful syndrome.
- GCS should be used with caution in nonspecific ulcerative colitis, if there is a risk of perforation gastrointestinal wall, the development of an abscess or other purulent infection, as well as in diverticulitis, in the presence of fresh intestinal anastomoses, with active or latent peptic ulcer, renal insufficiency, hypertension, osteoporosis, myasthenia gravis.
- Cases of development of Kaposi’s sarcoma in patients treated with corticosteroids (clinical remission may occur when their cancellation).
- Carcinogenic and mutagenic effect of the drug and its adverse effect on the reproductive function have not been established.
Pregnancy and breast-feeding
In a number of animal studies have shown that administration of high doses of corticosteroids females can lead to deformities in the fetus. Since the relevant studies of the effect of GCS on human reproduction has not yet been carried out, the use of these drugs in pregnancy, nursing mothers or women of childbearing age requires an assessment of the likely positive effect of the drug compared to the potential risk to the mother, fetus or embryo. GCS should be used during pregnancy only if absolutely indicated.
SCS can easily penetrate through the placenta. Children born to mothers who have received substantial doses of corticosteroids during pregnancy should be carefully examined in order to identify possible symptoms of adrenal hypofunction. Effect of corticosteroids on the course and outcome of birth is unknown.