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This acute myopathy is generalized, may affect the eye muscles and the respiratory system, lead to the development tetraparesis. Perhaps the increase in creatine kinase. This improvement or recovery after the abolition of the SCS can only occur through a number of weeks or even a few years. Gastrointestinal:. Peptic ulcer with possible perforation and hemorrhage, gastric hemorrhage, pancreatitis, esophagitis, perforation of the intestine after treatment there was an increase of buy equipoise alanintransaminazy level , aspartate transaminase  and alkaline phosphatase in the blood serum. Typically, these changes are minor, not associated with any clinical syndrome and are reversible upon discontinuation of treatment, dermatological: slow wound healing, petechiae and ecchymosis, thinning and reduction of skin resistance.

Metabolic: negative nitrogen balance due to protein catabolism. Neurological: increased intracranial pressure with papilledema (pseudotumor of the brain), mental disorders, convulsions. The therapy of buy equipoise 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. Endocrine: menstrual irregularities, development of Cushing’s syndrome, suppression of pituitary-adrenal axis, decreased glucose tolerance, manifestation of latent diabetes mellitus, increased need for insulin or oral hypoglycemic agents in diabetes, growth retardation in children. Ophthalmic: posterior subcapsular cataracts, increased intraocular pressure, exophthalmos. Immunologic: erased the clinical picture of infectious diseases, activation of latent infections, the occurrence of infections due to opportunistic pathogens, hypersensitivity reactions, including anaphylaxis with or without circulatory collapse, cardiac arrest, bronchospasm, suppression of reactions during skin tests. The other: a . persistent hiccups (at higher doses) reported that patients treated with corticosteroids, there was a Kaposi’s sarcoma. If you cancel the GCS may occur clinical remission.

 

Overdose
The clinical syndrome of acute drug overdose not described. Reports of acute toxicity is extremely rare with an overdose of Valium. There is no buy equipoise specific antidote. Treatment is symptomatic.Methylprednisolone is displayed during dialysis.

Interaction with other medicinal products
compatibility and stability of solutions of methylprednisolone with a / in the introduction of other drugs that are part of the mixtures for the on / in, depending on the pH, concentration, time, temperature, and the solubility of methylprednisolone. Methylprednisolone is recommended whenever possible administered separately from other medicaments, the form I / bolus injection in / drip infusion, or through a second additional solution IV.
The following examples 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. When the joint application of these drugs cases of seizure were observed.
Preparations activating hepatic enzymes such as phenobarbital, phenytoin, and rifampin may increase the clearance of methylprednisolone, which may require increasing doses of the drug to produce the desired effect. Inhibitors of buy equipoise (such as antibiotics, macrolides, azole antifungals of the group, some calcium channel blockers) may inhibit methylprednisolone metabolism and decrease its clearance.In this case, to avoid overdose phenomena, it is necessary to reduce the dose of methylprednisolone. Methylprednisolone may increase the clearance of acetylsalicylic acid. received high doses for long periods, which can lead to reduced serum salicylate or salicylates increase the risk of toxicity when canceling methylprednisolone. Patients with gipoprotrombinemiey appoint acetylsalicylic acid in combination with corticosteroids should be cautious.
Methylprednisolone has a varied impact on the effect of oral anticoagulants. It is reported as an enhancement, and to reduce the effect of anticoagulants, taken together with methylprednisolone. To maintain the desired anticoagulant effect needs constant determination of coagulation parameters.

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Do not use the drug in patients with equipoise for horses acute and subacute myocardial infarction, since the use of glucocorticosteroids, they may lead to the spread of necrosis focus, slowing the formation of scar tissue and, as a consequence, – to rupture of the heart muscle.

 

Precautions
The drug should be used in patients with eye disease caused by the herpes simplex virus, because it can lead to corneal perforation.
Corticosteroids should be used with caution in nonspecific ulcerative colitis, if there is a perforation of the threat, abscess or other purulent infection, as well as diverticulitis, in the presence of fresh intestinal anastomoses with active or latent peptic ulcer, renal insufficiency, hypertension, osteoporosis, myasthenia gravis.
This formulation contains benzyl alcohol. It was found that benzyl alcohol can cause “suffocation syndrome” fatal in premature infants. The drug is not recommended for use in neonates.

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. However, in a number of clinical studies have shown that the use of corticosteroids during pregnancy apparently does not cause birth defects. In one retrospective study found an increased incidence of babies born with low birth weight in mothers who received corticosteroids.Since studies in pregnant women do not exclude the possible harm corticosteroids, 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. Be used during pregnancy only if absolutely indicated.
Can easily penetrate through the placenta. Although babies born to mothers who have received substantial doses of corticosteroids during pregnancy, adrenal insufficiency is rare, these children 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. Stand in breast milk, so if necessary, the appointment of equipoise for horsesduring lactation breastfeeding should be discontinued.

Dosage and administration
Can be administered as a w / w or w / o Injection, or in / in infusion, but in emergencies preferably start treatment in / injection. Babies should be administered a lower dose (but not less than 0.5 mg / kg / day), but when choosing the dose primarily take into account the severity of the condition and the patient’s response to therapy, and not the age and body weight. As an additional therapy for life-threatening conditions of 30 mg / kg body weight / in for at least 30 min. The introduction of this dose can be repeated every 4-6 hours for a maximum of 48 hours. Pulse therapy in the treatment of diseases for which effective corticosteroid therapy in exacerbations of the disease and / or ineffectiveness of standard therapy.

Preparation of solutions
Preparations for parenteral administration as much as possible should be checked visually for color changes or the appearance of the particles.

  1. Dvuhemkostny vial of equipoise for horses
    1. Click on plastic activator to the solvent fracture in his lower capacity.
    2. To gently swing the vial until the lyophilizate is dissolved.
    3. Remove the plastic disc, covering the center of the plug.
    4. Treat the surface of the stopper corresponding antiseptic.
    5. Puncture needle cork center so that was visible tip of the needle. Turn the vial and syringe Collect the required amount of solution.
  2. Bottle
    1. Aseptically enter the solvent into the vial of lyophilisate.
    2. Only use a special solvent.
  3. Preparation of solutions for intravenous infusion
    1. Prepare a solution as described above. The drug can also be administered in the form of diluted solutions obtained by mixing a starting drug solution with aqueous 5% dextrose, saline, 5% dextrose in 0.45% or 0.9% sodium chloride solution. Prepared solutions are physically and chemically stable for 48 hours.

 

Side effects NOTE: The following side effects are typical for all GCS with parenteral use. Inclusion in this list does not mean that these effects are specific to this drug. The violation of water-electrolyte balance: Sodium retention, congestive heart failure in patients with the appropriate disposition, fluid retention, potassium loss, hypokalemic alkalosis. Cardiovascular: hypotension or hypertension; cardiac arrhythmias; in patients with acute and subacute myocardial infarction -dissemination necrosis, slowing the formation of scar tissue, which can lead to rupture of the heart muscle. There are reports of heart rhythm disturbances and / or the development of circulatory collapse and / or cardiac arrest about after a rapid on / in the high doses of methylprednisolone (0.5 g, introduced in less than 10 minutes). During and after the on / in the high-dose equipoise for horses methylprednisolone have also been reported cases of bradycardia, but they are not necessarily dependent on the speed or duration of infusion. Musculoskeletal: steroid myopathy, muscle weakness, osteoporosis, pathologic fractures, compression fractures of the vertebrae, aseptic necrosis of the epiphysis of long bones , tendon rupture, particularly the Achilles tendon.Acute myopathy most often develops in the application of high doses of corticosteroids in patients with impaired neuromuscular transmission (eg, myasthenia gravis), or in patients while receiving treatment by peripheral muscle relaxants (eg, pancuronium bromide) .

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Then, these complexes enter the cell nucleus, binds (chromatin) and stimulate the transcription  and subsequent synthesis of various enzymes, which explains the effect of corticosteroids for systemic use.  Not only have a significant impact on the inflammatory and immune response, but also affect the carbohydrate, protein and fat metabolism.
Most of the indications for use of equipoisedue to their anti-inflammatory, immunosuppressive and anti-allergic properties. Because of these properties are achieved following therapeutic effects:

  • reducing the number of immunoactive cells near the inflammation focus;
  • reduction in vasodilation;
  • stabilization of the lysosomal membranes;
  • inhibition of phagocytosis;
  • decrease in production of prostaglandins and related compounds.

Methylprednisolone has a strong anti-inflammatory action, and its activity is higher than that of prednisolone, and the ability to cause water retention and sodium ions is reduced compared to prednisolone.Metabolism and mechanism of anti-inflammatory action of methylprednisolone sodium succinate are similar to those for methylprednisolone. For parenteral administration of equivalent amounts of the biological activity of both compounds identical. The on / in the introduction of activity ratio of methylprednisolone sodium succinate and hydrocortisone sodium succinate, designed to reduce the number of eosinophils was not less than 4: 1. This correlates well with data on the relative potency equipoise of methylprednisolone and hydrocortisone when administered orally. A dose of 4 mg of methylprednisolone has the same glucocorticosteroid (anti-inflammatory) effect as 20 mg of hydrocortisone. Methylprednisolone has only negligible mineralocorticoid activity (equivalent to 200 mg methylprednisolone deoxycorticosterone 1 mg).
Exert catabolic action on proteins. The released amino acids are converted into hepatic gluconeogenesis and glycogen into glucose. Glucose uptake in peripheral tissues is reduced, which may lead to hyperglycaemia and glycosuria, especially in patients at risk of developing diabetes.
Maximum pharmacological activity of corticosteroids appears not at the peak plasma concentration, and after it, therefore, the action of corticosteroids is primarily due to their effect on the enzyme activity.

 

In any method of methylprednisolone sodium succinate injection is largely and rapidly hydrolyzed by the action of cholinesterase with the formation of the active form – free methylprednisolone. After the on / in infusion of 30 mg / kg for 20 minutes, or 1 g for about 30-60 min after 15 min methylprednisolone achieved peak plasma concentration (20 ug / ml). After about 25 min after i / v bolus 40 mg methylprednisolone reached its peak in the plasma concentration equal to 42-47 g / 100 ml. When the / m 40 min 120 mg methylprednisolone achieved plasma level equal to 34 g / 100 ml. When the / m achieves a low peak value than on / in. The average maximum plasma concentration C max is reached after 1 hour / m administration of 40 mg of methylprednisolone sodium succinate and is 454 ng / mL.After 12 hours methylprednisolone concentration in plasma decreased to 31.9 ng / ml and after 18 hours -metilprednizolon not detected in the blood. Comparing equipoise the areas under the curve “concentration – time” refers to the equal effectiveness of the drug in / in and / m the introduction of equivalent doses of sodium succinate methylprednisolone.
After the / m of the drug present in the blood plasma for a more extended period than after in / in the introduction, if you have entered the equivalent amount of methylprednisolone. Considering the mechanism of action of corticosteroids, it can be assumed that these differences have minimal clinical significance. The clinical effect is usually seen after 4-6 hours after administration. In the treatment of bronchial asthma first positive results identified after 1-2 h. The half-life of methylprednisolone sodium succinate in blood plasma is 2.3-4 hour, and probably does not depend on the route of administration.Methylprednisolone – glucocorticosteroids with an intermediate duration of action. Its half-life in the human body is 12-36 hours. Due to the intracellular activity revealed a pronounced difference between the half-life of the SSC and plasma half-life of the whole organism. Pharmacotherapeutic effects is maintained even when the drug is no longer in the blood is determined. The duration of anti-inflammatory activity of corticosteroids is approximately equal to the duration of suppression of the hypothalamic-pituitary-adrenal equipoise system.
Methylprednisolone Contact proteins (albumin and transcortin) – about 40 -. 90%
Metabolism of methylprednisolone in the liver, and this process is qualitatively similar to the metabolism of cortisol. The main metabolites are 20β-gidroksimetilprednizolon and 20β-hydroxy-6α-metilprednizon.Metabolites are mainly in urine in free form or in the form of glucuronides and sulfates which are produced primarily in the liver and partially – in the kidneys. After the on / in the methylprednisolone labeled with carbon- 14 C, 75% of the total radioactivity excreted in the urine within 96 hours, and 9% excreted in the feces within 5 days and 20% found in the bile.

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