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It has local anti-inflammatory effect due to inhibition of neutrophil lipoxygenase and the synthesis of prostaglandins and leukotrienes. Retards migration, degranulation, phagocytosis of neutrophil, as well as immunoglobulin secretion by lymphocytes. Antibacterial activity against Escherichia coli and some cocci (shown in the colon).
It has antioxidant activity (due to the ability to bind to free oxygen radicals and destroy them). It features well-tolerated, reduces the risk of relapse in Crohn’s disease, especially in dianabol patients with ileitis and long duration of the disease.

Pharmacokinetics
Approximately 30-50% of the dose is absorbed mainly in the small intestine. Mesalazine undergoes acetylation in the intestinal mucosa, in the liver and, to a small extent – by enterobacteria to form M-acetyl-5-aminosalicylic acid. Communication with plasma proteins – 43%, and N-acetyl-5-aminosalicylic acid – 73-83%.Mesalazine and its metabolite do not penetrate the blood-brain barrier and penetrate into breast milk.
Cumulative properties are in healthy volunteers after dosing at a dose of 1500 mg / day. It accumulates in chronic renal failure (CRF). Mesalazine and its metabolites are excreted by the kidneys and intestines.

Indications
Ulcerative colitis, Crohn’s disease (prevention and treatment of exacerbations).

Contraindications:
Hypersensitivity, blood diseases, gastric ulcer and duodenal ulcers, bleeding diathesis, severe renal / hepatic insufficiency, during lactation, the last 2-4 weeks of pregnancy, children’s age (12 years) and children weighing less than 50 kg.

Precautions
Pregnancy (I term), hepatic and / or renal failure, deficiency of glucose-6-phosphate dehydrogenase.

Pregnancy and lactation
It is known that mesalazine crosses the placental barrier, however, limited experience with the drug in pregnant women does not allow to evaluate the possible side effects. Use in pregnancy is only possible if the intended benefits to the mother outweigh the potential risk to the fetus. Mesalazine is excreted in breast milk at a concentration lower than in the blood of women, while the metabolite – acetyl mesalazine – is detected in a similar or higher concentration. If necessary, use during lactation should decide the issue of termination of breastfeeding.

Dosing and Administration
The tablets of the prolonged action of mesalazine is recommended to take a whole, without chewing, after meals, drinking plenty of fluids.

ULCERATIVE COLITIS

Step exacerbation
Adults: dose adjusted individually, normally – to 4 g of mesalazine per day in divided doses.
Children: dose adjusted individually, normally – mesalazine 20-30 mg per 1 kg of patient body weight per day in divided doses.

Supportive therapy
Adults: dose adjusted individually, normally mesalazine 2 g per day in divided doses.
Children: Dose selected individually, mesalazine typically 20-30 mg per 1 kg of patient body weight per day in divided doses.

CROHN’S DISEASE

Step acute and maintenance therapy
Adults: dose adjusted individually, normally – to 4 g of mesalazine per day in divided doses.
Children: Dose selected individually, mesalazine typically 20-30 mg per 1 kg of body weight per day in divided doses.

Side effect From the digestive system: nausea, vomiting, heartburn, diarrhea, loss of appetite, abdominal pain, increased activity of “liver” transaminases, hepatitis, pancreatitis. Cardio-vascular system:palpitation, tachycardia, increase or decrease in blood pressure, chest pain, shortness of breath. From the nervous system: headache, tinnitus, dizziness, polyneuropathy, tremor, depression. From the urinary system: proteinuria, haematuria, oliguria, anuria, crystalluria, nephrotic syndrome. Allergic reactions: skin rash, itching, dermatitis, bronchospasm. From the side of blood: anemia (hemolytic, megaloblastic, aplastic), leukopenia, agranulocytosis, thrombocytopenia, hypoprothrombinemia. Other: weakness, mumps, photosensitivity, lupus-like syndrome, oligospermia, alopecia, reducing production of tear fluid.

 

Overdose
A single dose of less than 150 mg / kg – an overdose of mild, 150-300 mg / kg – moderate, more than 300 mg / kg – heavy.
Symptoms: easy to moderate – symptoms “salitsilizma” (nausea, vomiting, tinnitus , blurred vision, dizziness, severe headache, general malaise, fever – a bad prognostic sign for adults). Heavy -giperventilyatsiya light of central origin, respiratory alkalosis, metabolic acidosis, confusion, drowsiness, collapse, convulsions, anuria, bleeding. Initially, central hyperventilation leads to respiratory alkalosis – shortness of breath, dyspnea, cyanosis, cold clammy sweat; with increased toxicity increases paralysis and respiratory uncoupling of oxidative phosphorylation causes respiratory acidosis.
Chronic overdose dianabol of the concentration determined in plasma, he does not correlate with the degree of severity of intoxication. The greatest risk of chronic intoxication observed in elderly patients when administered within a few days more than 100 mg / kg / day. Children and elderly patients salitsilizma initial signs are not always visible, so it is advisable to periodically determine the concentration of salicylates in the blood level above 70 mg% indicates moderate or severe poisoning; above 100 mg% – on extremely severe, prognostically unfavorable. In moderately severe poisoning requiring hospitalization for 24 hours.
Treatment: provocation of vomiting, the appointment of activated charcoal and laxatives, regular monitoring of blood acid-base composition (CBS) and electrolyte balance; depending on the metabolic state – the introduction of sodium hydrogencarbonate, sodium citrate or sodium lactate solution. Raising reserve alkalinity increases the excretion of mesalazine by alkalinization of urine. Urinary alkalization level shown at salicylates% above and 40 mg is provided on / in infusion of sodium bicarbonate (88 mEq of 1 L of 5% dextrose solution at a rate of 10-15 ml / hr / kg); restoration of circulating blood volume (CBV) and induction of diuresis is achieved by introducing sodium bicarbonate in the same doses and dilution, which is repeated 2-3 times. Caution must be exercised in elderly patients in whom an intense infusion of fluid can lead to pulmonary edema. We do not recommend the use of acetazolamide for alkalinization of urine (may cause acidemia and increase the toxic effects of salicylates). Hemodialysis is shown in greater 100-130 mg% in patients with chronic poisoning, 40 mg% or less when indicated (refractory acidosis, progressive deterioration severe CNS disease, renal failure and pulmonary edema) at the level of salicylates. When pulmonary edema – an artificial lung ventilation (ALV) mixture enriched with oxygen.

Interaction
Enhances hypoglycemic effect of sulfonylurea derivatives, ulzerogennosti corticosteroids, methotrexate toxicity. It reduces activity of furosemide, spironolactone, sulfonamides, rifampicin. It enhances the effect of anticoagulants. Increases efficiency of uricosuric drugs (blockers of tubular secretion). It slows down the absorption of cyanocobalamin.

Specific guidance
is advisable regular blood count (before, during, and after treatment) and urine, monitoring of renal excretory function. Patients who are “slow acetylators” have an increased risk of side effects. There may be urine stains and tears in the yellow-orange staining of soft contact lenses.
In case of missing of the drug missed dose should be taken at any time or in conjunction with the next dose.
If you missed a few doses, that is not stopping the treatment, contact your doctor. If you suspect that the development of an acute intolerance syndrome mesalazine should be abolished.
Patients should avoid driving, as well as the performance of work requiring high concentration dianabol and speed of psychomotor reactions.

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