08/19/2016

primobolan dosage

Pharmacological action
Primobolan dosage ® MB Download now is an oral hypoglycemic drug, II generation sulfonylureas. It stimulates the secretion of pancreatic insulin B-cells, enhances glucose insulinosekretornoe effect, increases the sensitivity of peripheral tissues to insulin. It stimulates the activity of intracellular enzymes – muscle glycogen. It reduces the time interval from before the start of the meal insulin secretion. Restores the early peak of insulin secretion (as opposed to other sulfonylureas that affect primarily during the second stage of secretion). Reduces the postprandial increase in blood glucose levels.
In addition to the effects on carbohydrate metabolism, improves microcirculation: it reduces the adhesion and aggregation of platelets, normalizes vascular permeability, prevents the development of atherosclerosis and mikrotrombozov, restores the physiological process of the parietal fibrinolysis. It reduces the sensitivity of vessels to adrenaline receptors. Slows the development of diabetic retinopathy in the nonproliferative stage. In diabetic nephropathy in the background of long-term use causes a significant decrease in the severity of proteinuria. It does not increase body weight, as has predominant influence on the early peak of insulin secretion and hyperinsulinemia causes; promotes weight loss in obese patients, subject to an appropriate diet. Pharmacokinetics Almost completely absorbed from the gastrointestinal tract after oral administration. The concentration of active substance in the plasma increases gradually, reaching a maximum at 6-12 hours after ingestion. Food does not affect the absorption. Relationship to plasma proteins is approximately 95%. It is metabolized in the liver to inactive metabolites. The half-life is about 16 h. Write mainly kidneys as metabolites, and about 1% of the drug is excreted in the urine in unchanged form. In the elderly has not been any significant changes in clinical pharmacokinetics. Due to specific dosage forms, daily intake of a single dose of the drug provides effective therapeutic concentrations of gliclazide in plasma over 24 hours.

Indications
Type 2 diabetes mellitus in combination with diet and moderate physical activity with the ineffectiveness of the past.

Contraindications
– Hypersensitivity to the drug; diabetes mellitus type 1;
– diabetic ketoacidosis, diabetic precoma, diabetic coma; hyperosmolar coma;
– severe hepatic and / or renal failure;
– major surgery, extensive burns, trauma and other conditions requiring insulin therapy; ileus, gastroparesis;
– state, accompanied by malabsorption of food, the development of hypoglycemia (infectious diseases); leukopenia;
– pregnancy, breast-feeding.

The caution (the need for more careful monitoring and dose titration) appoint Primobolan dosage MB with feverish syndrome, alcoholism and diseases of the thyroid gland (in violation of its functions).

Dosage and administration
The dose should be individualized depending on the clinical manifestations of the disease, fasting glucose and 2 hours after a meal. Typically, the initial daily dose (including the elderly over 65 years) is 30 mg (1 tablet), in the future, if necessary, increase the dose at intervals of not less than 2 weeks. The maximum daily dose -120 mg (4 tablets). The drug is taken orally 1 time a day in the morning, during breakfast.
Primobolan dosage MB can replace Primobolan dosage in doses ranging from 1 to 4 tablets per day.
It can be used in combination with other hypoglycemic agents: biguanides, alpha-glucosidase inhibitors or insulin.
Patients with impaired function kidney mild to moderate severity (creatinine clearance 15 to 80 mL / min.), the drug is administered in the same doses.

Side effects: Hypoglycemia (in violation of the dosing and inadequate diet): headache, fatigue, hunger, sweating, severe weakness, aggressiveness, anxiety, irritability, inattention, inability to concentrate and slow reaction, depression, blurred vision, aphasia, tremor, feelings of helplessness, sensory disturbances, dizziness, loss of self-control, delirium, convulsions, hypersomnia, fainting, shallow breathing, bradycardia. On the part of the digestive organ system: dyspepsia (nausea, diarrhea, feeling of heaviness in the epigastric); anorexia – the severity is reduced when taking while eating; abnormal liver function (cholestatic jaundice, increased activity of “hepatic” transaminases). Violations of the blood: anemia, thrombocytopenia, leukopenia. Allergic reactions: itching, rash, maculo-papular rash.

Overdose
If overdose is possible hypoglycemia, until the development of hypoglycemic coma. Treatment: If the patient is conscious – to take into carbohydrate (sugar), with loss of consciousness – enter intravenously 40% dextrose (glucose), 1-2 mg of glucagon intramuscularly. After regaining consciousness of the patient must be given foods rich in digestible carbohydrates in order to prevent a recurrence of hypoglycemia.

Interaction with other drugs
Strengthen hypoglycemic effect Primobolan dosagea MB angiotensin converting enzyme inhibitors (captopril, enalapril), blockers H2-histamine receptors (cimetidine), antifungals (miconazole, fluconazole), non-steroidal anti-inflammatory drugs (phenylbutazone, indomethacin, diclofenac), fibrates (clofibrate , bezafibrate), anti-TB drugs (ethionamide), salicylates, indirect anticoagulants coumarin, anabolic steroids, beta-blockers, cyclophosphamide, chloramphenicol, monoamine oxidase inhibitors, sulfonamides prolonged action, fenfluramine, fluoxetine, pentoxifylline, guanethidine, theophylline, drugs that block tubular secretion , reserpine, bromocriptine, disopyramide, pyridoxine, allopurinol, ethanol etanolsoderzhaschie drugs, and other hypoglycemic agents (acarbose, biguanides, insulin).
Loosen hypoglycemic effect Primobolan dosagea MB barbiturates, steroids, sympathomimetics (epinephrine, clonidine, ritodrine, salbutamol, terbutaline) phenytoin blockers “slow” calcium channels, carbonic anhydrase inhibitors (acetazolamide), thiazide diuretics, chlorthalidone, furosemide, triamtaren, asparaginase, baclofen, danazol, diazoxide, isoniazid, morphine, glucagon, rifampicin, thyroid hormones, lithium salt in high doses -. nicotinic acid, chlorpromazine, estrogens and containing their oral contraceptives
. The interaction with ethanol development disulfiramopodobnyh reaction
Gliclazide increases the risk of ventricular arrhythmias in patients receiving cardiac glycosides.
Beta-blockers, clonidine, reserpine, guanethidine may mask the clinical manifestations of hypoglycemia.

Cautions
Primobolan dosageom MB treatment is carried out in conjunction with a low calorie diet low in carbohydrates. Regularly monitor blood glucose fasting and after eating.
In the case of surgical interventions or decompensated diabetes, it is necessary to take into account the possibility of insulin preparations.
It is necessary to warn patients about the increased risk of hypoglycemia in the case of reception of ethanol, nonsteroidal anti-inflammatory drugs and starvation. . In the case of reception of ethanol may also develop disulfiramopodobnyh syndrome (abdominal pain, nausea, vomiting, headache)
. Correction is needed dose by physical or emotional strain, a change of diet
is especially sensitive to hypoglycemic drugs the elderly; Patients who do not receive a balanced diet; debilitated patients; patients with pituitary-adrenal insufficiency.
In the beginning of treatment, during dose adjustment to patients prone to hypoglycemia, is not recommended to engage in activities requiring increased attention and psychomotor speed reactions.

pharmachologic effect

Farmakodikamika
oral hypoglycemic agent, II-generation sulfonylurea derivative.
It stimulates the secretion of insulin by the pancreas, lowers blood glucose levels, increases glucose insulinosekretornoe action and increases the sensitivity of peripheral tissues to insulin. After 2 years of treatment, most patients do not develop to the drug addiction (stored improving postprandial secretion of insulin and C-peptide).
Reduces the time interval from the time before the start of the meal insulin secretion. Restores the early peak of insulin secretion in response to glucose intake (unlike other sulfonylurea derivatives which exert effect primarily during the second stage of secretion). Also, the second phase increases insulin secretion.Reduces peak postprandial hyperglycemia (lowers postprandial hyperglycemia).
Gliclazide increases the sensitivity of peripheral tissues to insulin (i.e., has a pronounced extrapancreatic action). In muscle tissue effect of insulin on glucose uptake due to improvement, increased significantly (+ 35%), tissue sensitivity to insulin, gliclazide as glycogen stimulates muscular activity.
Decreases in hepatic glucose production, normalizing fasting glucose level indicators. In addition to the effects on carbohydrate metabolism, gliclazide improves microcirculation. The drug reduces the risk of thrombosis small vessels, affecting the two mechanisms which may be involved in development of complications in diabetes mellitus: a partial inhibition of platelet aggregation and adhesion and reduced concentrations of platelet-activating factor (beta-thromboglobulin, thromboxane B 2 ) and to restore . fibrinolytic activity of vascular endothelium and increased activity of tissue plasminogen activator
gliclazide has antioksidantnymy properties: reduces the level of lipid peroxides in plasma, increases the activity of erythrocyte superoxide dismutase.
Due to specific dosage forms, daily intake of a single dose of tablets gliclazide MB 30mg provides effective therapeutic concentrations of gliclazide in plasma for 24 hours.

Pharmacokinetics
After oral gliclazide completely absorbed from the gastrointestinal tract. Food does not affect the absorption. The concentration of active substance in plasma gradually increased gradually, reaches a plateau and cherez.6-12 hours after ingestion. Individual variability is relatively low. The relationship between dose and the highest concentration of drug in blood plasma is a linear function of time. Communication with the plasma proteins is approximately 95%.
It is metabolized in the liver and excreted mainly by the kidneys. Withdrawal is carried out mainly by the kidneys as metabolites, less than 1% of the drug is excreted unchanged in.
The active metabolites in plasma are absent. Half-life is about 16 hours (12 to 20 hours). In the elderly clinically significant changes in pharmacokinetic parameters was observed.

Indications
Type 2 diabetes mellitus in combination with diet with lack of effectiveness of diet and physical activity.

Contraindications
– Hypersensitivity to gliclazide or any of the excipients of the drug to other derivatives of sulfonylurea, sulfonamide;
– type 1 diabetes mellitus;
– diabetic ketoacidosis, diabetic precoma, diabetic coma; . – Severe renal and / or hepatic impairment;
– pregnancy and lactation;
– age of 18 years;
– acceptance of miconazole;
– congenital lactose intolerance, lactase deficiency or glucose-galactose malabsorption.

Do not use the drug at the same time in combination with phenylbutazone or danazol.

Be wary – old age, irregular and / or unbalanced diet, severe diseases of the cardiovascular system (including ischemic heart disease, atherosclerosis), hypothyroidism, adrenal or pituitary insufficiency, hypopituitarism, renal and / or hepatic insufficiency, prolonged glucocorticoid therapy ( GCS), alcoholism, lack of glucose-6-phosphate dehydrogenase.

Pregnancy and breast-feeding

Experience in the use of gliclazide during pregnancy is not available.

Data on the use of other sulphonylurea derivatives are limited during pregnancy.
In studies on laboratory animals gliclazide teratogenic effects were not detected. To reduce the risk of birth defects requires optimal control (appropriate therapy) diabetes.
Oral hypoglycemic drugs during pregnancy does not apply.
The drug of choice for the treatment of gestational diabetes is insulin.
It is recommended to replace the use of oral hypoglycemic drugs to insulin therapy in the case of planned pregnancy and in the event that the pregnancy while taking the drug.

Breastfeeding
Given the lack of data on the income of gliclazide into breast milk and the risk of neonatal hypoglycemia, during therapy with breast-feeding is contraindicated.

Dosing and Administration

The drug is intended only for treatment of adults!

Gliclazide Tablets MB modified release 30 mg taken orally 1 time a day during breakfast. For patients who have not received prior treatment, the starting dose is 30 mg (including for persons over 65 years).Thereafter, the dosage is chosen individually to achieve the desired therapeutic effect.
Dose selection must be performed in accordance with the indication of the level of glucose in the blood after treatment. Each successive change in dose may be taken after a minimum period of two weeks.The daily dose may vary from 30 mg (1 tablet) to 90-120 mg (3-4 tablets). The daily dose should not exceed 120 mg (4 tablets).
Gliclazide MB may be replaced with a conventional tablet gliclazide release (80 mg) at doses ranging from 1 to 4 tablets per day. Omitting one or more methods of preparation can not take a higher dose in the following method (the next day).
When replacing other hypoglycemic drug Gliclazide Tablets 30mg MB did not need any transitional period. You must complete the first reception of a daily dose of another drug and the next day to start taking this drug.
If the patient before receiving sulfonylurea therapy with a longer half-life, it should be closely monitored (glycemic control) for 1-2 weeks to avoid hypoglycemia as a consequence of the residual effects of previous therapy.
Gliclazide Tablets MB can be used in combination with biguanides, alpha-glucosidase inhibitors or insulin. patients with renal insufficiency, mild to moderate drug administered in the same dose as patients with normal renal function. In renal failure, severe tablets Gliclazide MB contraindicated. Patients with risk of hypoglycemia in patients at risk of hypoglycaemia (poor diet, severe or poorly compensated endocrine disorders – pituitary and adrenal insufficiency, hypothyroidism, cancellation corticosteroids after long-term use and / or receiving high doses, severe diseases of the cardiovascular system (severe coronary heart disease, severe carotid atherosclerosis, widespread atherosclerosis) is recommended to use the lowest dose (30 mg) of the drug Gliclazide MB.

Side effects:
Hypoglycemia (in violation of the dosing and inadequate diet): headache, fatigue, hunger, sweating, severe weakness, palpitations, arrhythmia, increased blood pressure, somnolence, insomnia, agitation, aggression, anxiety, irritability, impaired concentration attention, inability to concentrate and slow reaction, depression, blurred vision, aphasia, tremor, paresis, sensory disturbances, dizziness, feeling of helplessness, self-loss, delirium, convulsions, shallow respiration, bradycardia, unconsciousness, coma.
From the digestive system: nausea , vomiting, diarrhea, abdominal pain, constipation (the severity of these symptoms is reduced when taking while eating); -Violation rare liver function (hepatitis, cholestatic jaundice – requires discontinuation of the drug, increased activity of “liver” transaminases, alkaline phosphatase).
From the side of hematopoiesis: suppression of bone marrow hematopoiesis (anemia, thrombocytopenia, leukopenia, granulocytopenia).
Allergic reactions: itching, hives, skin rash, including maculopapular and bullous), erythema.
Other: blurred vision.
Common side effects of sulfonylureas: erythropenia, agranulocytosis, haemolytic anemia, pancytopenia, allergic vasculitis; life-threatening liver failure.

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