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equipoise

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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Drugs that activate liver enzymes such as phenobarbital, phenytoin and rifampin may increase the clearance of corticosteroids, which may require increasing doses of the drug to get the desired effect.
Such drugs as troleandomycin and equipoise definition ketoconazole may inhibit the metabolism of corticosteroids and to reduce its clearance. In this case the dose of corticosteroids to be reduced to avoid overdose phenomena.
Corticosteroids may enhance clearance of acetylsalicylic acid in the received high doses for long periods, which can lead to reduced serum salicylate or salicylates increase the risk of toxicity when canceling corticosteroids. Patients with gipoprotrombinemiey appoint acetylsalicylic acid in combination with corticosteroids should be cautious.
exert diverse effects on the action of oral anticoagulants. It is reported as an enhancement, and to reduce the effect of anticoagulants, taken in conjunction with hydrocortisone. To maintain the desired anticoagulant effect needs constant determination of coagulation parameters.

special instructions

  1. When high doses of hydrocortisone for a period longer than 48 – 72 hours, may develop hypernatremia. In this case it is recommended to replace another example methylprednisolone sodium succinate, which causes minor or no causes sodium retention.
  2. Patients who may be exposed to stress on the background of Sequipoise definition therapy showed an increase in the dose before, during and after the stressful situation. These patients should be under strict medical supervision because of the possible development of adrenal insufficiency.
  3. The therapy GCS some infections can occur in the form of worn, 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 or helminths which are localized in different systems the human body, can 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 occur not heavy, but in some cases it is possible for severe and even fatal. The higher doses of corticosteroids are used, the higher the probability of infectious complications.
  4. The use of hydrocortisone sodium succinate 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 corticosteroids administered to patients with latent tuberculosis or positive tuberculin skin test, treatment should be under strict medical supervision, because the possible reactivation of the disease. During prolonged therapy with these patients should receive appropriate prophylactic treatment.
  5. Patients receiving treatment with corticosteroids at the doses that have an immunosuppressive effect, is contraindicated the introduction of live or live equipoise definition 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.
  6. Introduction of hydrocortisone can lead to increased blood pressure, water retention and to the salts in the body and an increased excretion of potassium. You may need to limit salt intake from food and supplemental assignment potassium preparations. All corticosteroids increase calcium excretion.
  7. Since patients receiving parenteral therapy with corticosteroids, in rare cases may develop anaphylactoid reactions (eg, bronchospasm), should take appropriate preventive measures, especially if this patient have a history of allergic reactions to any drugs prior to administration of the drug.
  8. At long daily therapy corticosteroids in children may be a delay of growth, so this dosing regimen should be administered to children only when there are serious indications. Acute myopathy most often develops in the application of high doses of corticosteroids in patients with impaired neuromuscular transmission (eg, myasthenia gravis with), or in patients while receiving treatment by peripheral muscle relaxants (eg, pancuronium). 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 equipoise definitioncan only occur through a number of weeks or even a few years.

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Appropriate studies on the action of corticosteroids human reproduction were not carried out, so 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.  Should be used during pregnancy only if absolutely indicated.
Can easily penetrate through the placenta. Children born to mothers treated during pregnancy large doses of corticosteroids should be carefully examined for signs of adrenal insufficiency. Effect of corticosteroids on the course and outcome of birth is not known.
Allocated into breast milk, so if you need destination equipoise resultsdrug during breast feeding breast-feeding should be discontinued.

Dosing and Administration
The drug may be administered  in the form of injection or in / infusion, but in emergencies preferably start treatment with I / injection. After the period of acute or parenterally administered drug dosage forms with more prolonged action, or oral form of preparation. Drug treatment starts with the on / in within 30 seconds (e.g., 100 mg) and 10 min (eg 500 mg or more). High doses of corticosteroids should be prescribed only until the stabilization of the patient, but not longer than for 48 – 72 hours. The initial dose is 100 – 500 mg or more, depending on the severity of the patient’s condition.
Dose repeatedly assigned every 2, 4 or 6 hours, depending on the response of a patient’s body and the clinical picture of the disease. Babies should be administered a lower dose (but not less than 25 mg / 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. Preparation of solutions preparations for parenteral administration should be inspected visually for change the color or appearance of the particles. Use equipoise results only clear solution. Bottle for in / in or / m injection solution is prepared by adding to the vial (observing the rules of antiseptics) not more than 2 ml of bacteriostatic water for injection or an aqueous sodium chloride solution for injection to the bacteriostatic additive.

  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.

For in / in or / m injection further dilution equipoise results is required. For I / infusion first solution is prepared as described above, then the resulting solution was added to 100 – 1000 ml of 5% aqueous dextrose (or saline or 5% dextrose in saline, if the patient does not need to limit the amount of sodium) . If it is desirable to introduce a small amount of liquid can be added 100 – 3000 mg of hydrocortisone (as hydrocortisone sodium succinate) to 50 ml of the above solution. The resulting solutions are stable for 4 hours and may be administered in / directly or via a second drip.

Side effect Note: the following side effects are typical for all equipoise resultswith parenteral use, not only for this product. The violation of water-electrolyte balance: sodium retention in the body; congestive heart failure in patients with the appropriate disposition; arterial hypertension; fluid retention; potassium loss; hypokalemic alkalosis; . increased excretion of calcium Musculoskeletal: steroid myopathy; muscle weakness; osteoporosis; pathological fractures; Compression fractures of the vertebrae; aseptic necrosis of the epiphysis of long bones; . ruptures of tendons, especially the Achilles tendon Gastrointestinal:peptic ulcer with possible perforation and hemorrhage; gastric bleeding; pancreatitis; esophagitis; perforation of the intestine; raising alanintransaminazy , aspartate transaminase  and alkaline phosphatase in the serum (usually these changes are minor, not associated with any clinical syndromes and reversible upon discontinuation of treatment). Adverse events in the appointment of high doses of corticosteroids for a short period of time are rare, but may develop peptic ulcers. . It can be shown the appointment of prophylactic antacid therapy Dermatological: slow wound healing; petechiae and ecchymosis; thinning of the skin and reduction of strength; Kaposi’s sarcoma. It is reported that in patients treated with corticosteroids, there was a Kaposi’s sarcoma.

If you cancel the equipoise resultsmay occur clinical remission. Metabolic: negative nitrogen balance due to protein catabolism. Neurological: increased intracranial pressure with papilledema; pseudotumor of the brain; convulsions; mental disorders, including euphoria, insomnia, mood instability, personality changes, depression; acute psychotic symptoms; strengthening of the already existing emotional instability or propensity to psychotic reactions.Endocrine: menstrual irregularities; development of Cushing’s syndrome; suppression of pituitary-adrenal axis; reduced glucose tolerance; manifestation of latent diabetes mellitus; increased need for insulin or oral hypoglycemic agents in patients with diabetes, growth retardation in children. Ophthalmic: posterior subcapsular cataracts; increased intraocular pressure; . exophthalmos Immunological: erased the clinical picture of infectious diseases; activation of latent infections, including tuberculosis reactivation: the emergence of infections caused by opportunistic pathogens, any localization occurring in an easy manner, and with the possibility of death; hypersensitivity reactions, including anaphylaxis and anaphylactoid reactions (eg, bronchospasm, laryngeal edema, urticaria); . suppression of reactions during skin tests Other: the solvent contains benzyl alcohol, which may cause “suffocation syndrome”equipoise results with fatal outcome in preterm infants.

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equipoise dosage

Maximum pharmacologic activity of corticosteroids appears not at the peak plasma concentration, and after him, therefore, the effect of equipoise dosage is primarily due to their . effect on enzyme activity .  After the / m of the maximum plasma concentration of the drug is achieved in approximately 30 – 60 minutes. about 40 – 90% of hydrocortisone is bound to plasma proteins. Most hydrocortisone associated with one of the globulin (transcortin) and only a small amount – from albumin. Free unbound fraction hormone defines its biological activity and bound fraction serves as a reserve. Hydrocortisone metabolism occurs primarily in the liver. Within 24 hours of the organism is excreted in urine 22 – 30% / m or / in the introduction of the drug. The drug is almost completely eliminated from the body within 12 hours, so to maintain high drug concentrations in the blood it is necessary to introduce / m or / every 4 – 6 hours.

Indications

    1. Endocrine diseases
      • Primary or secondary adrenocortical insufficiency (-gidrokortizon selecting drugs or cortisone, if necessary, their synthetic analogs may be used in combination with a mineralocorticoid, especially in pediatric patients)
      • Acute adrenocortical insufficiency (the choice of drugs – hydrocortisone or cortisone, it may be necessary in the simultaneous appointment of mineralocorticoid)
      • In the preoperative period, in the case of serious injury or serious illness, in patients with established or suspected adrenal insufficiency
      • Shock, which is not amenable to treatment by conventional methods when possible presence of adrenal insufficiency
      • Congenital adrenal hyperplasia
      • Subacute thyroiditis
      • Hypercalcemia equipoise dosage on the background of cancer
    2. Rheumatic diseases (as adjunctive therapy for short-term elimination of the acute condition or exacerbation)
      • Acute and subacute bursitis
      • Acute gouty arthritis
      • Acute nonspecific tenosynovitis
      • Ankylosing spondylitis
      • Epicondylitis
      • Post-traumatic osteoarthritis
      • Psoriatic arthritis
      • Rheumatoid arthritis, including juvenile rheumatoid arthritis (in some cases may require maintenance therapy with low doses)
      • Synovitis of osteoarthritis
    3. Systemic diseases of connective tissue (in acute or in some cases as maintenance therapy)
      • Acute rheumatic heart disease
      • Systemic dermatomyositis (polymyositis)
      • Systemic lupus erythematosus
    4. skin diseases
      • Bullous dermatitis herpetiformis
      • exfoliative dermatitis
      • granulosarcoid
      • Pemphigus
      • Severe erythema multiforme (Stevens-Johnson syndrome)
      • Severe psoriasis
      • Severe seborrheic dermatitis
    5. Allergic conditions (in the case of severe or incapacitating conditions for which conventional therapy is ineffective)
      • Acute noninfectious laryngeal edema
      • Atopic dermatitis
      • Bronchial asthma equipoise dosage
      • Contact dermatitis
      • Hypersensitivity reactions to medicines
      • Seasonal and perennial allergic rhinitis
      • serum sickness
      • Post-transfusion reactions such as urticaria
    6. Eye diseases (severe acute and chronic allergic and inflammatory processes in the eye lesions).
      • Allergic conjunctivitis.
      • Allergic corneal marginal ulcers
      • Inflammation of the anterior segment
      • Chorioretinitis.
      • Diffuse posterior uveitis and choroiditis.
      • Ocular form of Herpes zoster.
      • Iritis and iridocyclitis.
      • Keratitis.
      • Optic neuritis.
      • Sympathetic ophthalmia.
    7. Diseases of the gastrointestinal tract (to remove the patient from the critical state).
      • Ulcerative colitis (systemic therapy)
      • Regional enteritis (systemic therapy)
    8. Diseases of the respiratory tract
      • inhalation pneumonia
      • berylliosis
      • Fulminant and disseminated pulmonary tuberculosis combined with appropriate antituberculous chemotherapy
      • Loeffler’s syndrome, is not amenable to treatment by other means
      • Symptomatic sarcoidosis
    9. Hematologic disorders
      • Acquired (Autoimmune) Hemolytic Anemia
      • Congenital (erythroid) hypoplastic anemia
      • Erythroblastopenia (red cell anemia)
      • Idiopathic thrombocytopenic purpura in adults (only on / in the c / m administration is contraindicated)
      • Secondary thrombocytopenia in adults.
    10. Cancer (as a palliative therapy)
      • Acute leukemia in children
      • Leukemias and lymphomas in adults
    11. Edematous syndrome – To stimulate diuresis and remission of proteinuria in patients with nephrotic syndrome without uremia; nephrotic syndrome, idiopathic type or lupus erythematosus.
    12. Emergencies
      • Shock, which developed as a result of adrenal insufficiency, or resistant to standard therapy, with the possible presence of adrenal insufficiency.
      • Acute allergic reactions after adrenaline purpose (status asthmaticus, anaphylactic reactions, insect bites, etc.).

Corticosteroids may be effective in the treatment of traumatic and surgical hemorrhagic shocks, for which standard therapy is ineffective .

  1. Other indications equipoise dosage for use
    • Trichinosis with nervous system lesion or infarction
    • Tuberculous meningitis with subarachnoid block or the threat of the unit (in conjunction with appropriate antituberculous chemotherapy).

 

Contraindications

  • Systemic fungal infections
  • Hypersensitivity to any components of the drug in history

Do not use the drug in patients with acute and subacute myocardial infarction, as the use of corticosteroids 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.
The drug is supplied in dvuhemkostnyh bottles , not recommended for use in neonates as the solvent contains benzyl alcohol.

 

With careful preparation should be applied in the following cases:

  • with the defeat of the eye caused by the herpes simplex virus, because it can lead to corneal perforation;
  • for ulcerative colitis, if there is a threat of perforation, 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.

 

Use during pregnancy and breast-feeding
In a number of animal studies equipoise dosage have shown that administration of high doses of corticosteroids to pregnant females can lead to deformities in the fetus. steroider kob

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The metabolism of ibuprofen occurs predominantly in the liver. Excreted by the kidneys as metabolites (unchanged output is not more than 1%), to a lesser extent – in the bile.
Capsules sustained release “Solpafleks” yield increase the half-life of ibuprofen as compared with its conventional dosage forms provide extended duration of the drug to 12 hours.

Indications
capsule “Solpafleks” used to relieve joint, equipoise for sale muscle pain, back pain, back pain, sciatica, pain in damaged ligaments, headache, including migraine, dental pain, painful menstruation, feverish conditions, for colds, flu, rheumatoid arthritis, osteoarthritis.

Contraindications:
hypersensitivity, peptic ulcer and duodenal ulcer (in the acute stage), ulcerative colitis, optic nerve disease, amblyopia, impaired color vision, liver cirrhosis with portal hypertension, “Aspirin asthma” (provoked by taking aspirin or other. NSAIDs), heart insufficiency, edema, hypertension, hemophilia, anticoagulation, leukopenia, hemorrhagic diathesis, hearing loss, vestibular pathology, deficiency of glucose-6-phosphate dehydrogenase; pregnancy (III trimester), children up to 12 years.

Be wary – if hyperbilirubinemia, pregnancy, lactation; gastric ulcer and duodenal ulcer (in history), gastritis, enteritis, colitis; with liver and / or kidney failure, blood diseases of unknown etiology.

Dosage and administration Adults, elderly and children over 12 years: 1 – 2 capsules 2 times a day. Do not take more than 4 capsules in 24 hours. The capsules do not use in children under 12 years. The capsules should be swallowed with water. Do not chew or dissolve capsules! If you can not swallow the capsule, its contents can be poured into a tablespoon of soft cold food, such as yogurt and swallow without chewing. The course of treatment without consulting a doctor should not exceed 10 days. If you have forgotten in time to take medication, take it, as soon as remembered about it, provided that it took only a few hours. Otherwise, skip this intake and take the next dose at the usual time. If symptoms persist, consult a doctor.

Side effects of
drug is usually no side effects at the recommended doses. On the part of the gastrointestinal tract may include nausea, vomiting, abdominal pain, heartburn, anorexia, diarrhea, flatulence, equipoise for sale.Rarely in the nervous system are observed: headache, dizziness, hearing loss, tinnitus, insomnia, agitation, drowsiness, depression. In extremely rare cases, by the cardiovascular system: heart failure, tachycardia, increased blood pressure; on the part of the urinary system – edema, renal dysfunction. Allergic reaction – skin rash, itching, hives, angioedema. Sometimes it may increase sweating. With prolonged use at high doses -. Ulceration of the mucosa of the gastrointestinal tract, bleeding and blurred vision
if the drug caused a change in your normal state, stop taking the capsules “Solpafleks” and see a doctor immediately.

Overdose
Do not exceed the indicated dosage. If you exceed the dose, call your doctor or the nearest medical facility. Bring a package of the drug.
Overdose symptoms – abdominal pain, nausea, vomiting, lethargy, sleepiness, depression, headache, tinnitus, metabolic acidosis, coma, acute renal failure, decreased blood pressure, bradycardia, tachycardia, atrial fibrillation, respiratory arrest. First aid -promyvanie stomach (just an hour after ingestion), activated carbon, alkaline water.

Interactions
In therapeutic doses of ibuprofen does not enter into meaningful interactions with commonly used medications.
Inducers of enzymes of microsomal oxidation in the liver (phenytoin, ethanol, barbiturates, ziksorin, rifampin, phenylbutazone, tricyclic antidepressants) increase equipoise for sale the production of hydroxylated active metabolites, increasing the risk of severe intoksitkatsy. Inhibitors of microsomal oxidation – reduce the risk of hepatotoxicity.
Reduces hypotensive activity vasodilators natriuretic -furosemida and hydrochlorothiazide.
Reduces the uricosuric drugs, increases the effects of anticoagulants, antiplatelet agents, fibrinolytic agents (increased risk of bleeding), side effects mineralokortikosteroidov, glucocorticosteroids (risk of gastrointestinal intestinal bleeding), estrogens, ethanol; It enhances the hypoglycemic effect of sulfonylureas. Antacids and cholestyramine reduce the absorption. It increases the blood concentration of digoxin, drugs lithium and methotrexate.

Special instructions
for prolonged use is necessary to monitor patterns of peripheral blood and functional state of the liver and kidneys. When gastropathy symptoms should seek medical attention.
If necessary, the definition of 17-keto steroids equipoise for sale drug should be discontinued 48 hours prior to the study.
While receiving the drug should refrain from drinking alcohol. Running low dose t3 clen cycle trying to lose bodyfat isn’t a real hot idea imo.