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The mechanism of action consists in the alkylation of DNA and RNA. The inhibition of DNA synthesis caused by carbamoylation DNA polymerase and other DNA repair enzymes, and damage to the DNA template. The drug can also slow down key enzymatic anavar reviews processes by changing the structure and function of many proteins and enzymes. Lomustine acts late GI phase and early S-phase of the cell cycle.The highest sensitivity to lomustine from cells in stationary growth phase (determinant activity in solid tumors with low proliferative pool)After oral administration, rapidly and almost completely absorbed from the gastrointestinal tract. The maximum plasma concentration of drug attained within 1 -4 hours. Relationship to plasma proteins – 50%. Penetrates through the blood-brain barrier and into breast milk. In the cerebrospinal fluid is determined by more than 50% of plasma concentrations. It is metabolized in the liver with the formation of active metabolites (oksimetildiazoniya and isocyanate). Oksimetildiazony ionized and converted into ions metildiazoniya, which is transformed into a more stable tautomeric form (diazomethane) or decomposes into nitrogen and metilkarbonievy ion. The half-life of the active metabolites ranges from 16 to 48 hours. Write mainly kidneys as metabolites, less than 5% – through the intestines.

Indications for use
lomustine is used in monotherapy or combination therapy of the following diseases:

 

  • primary and metastatic brain tumors after surgery and / or radiotherapy;
  • lymphoma (Hodgkin’s disease) as second line therapy;
  • stomach and intestinal cancer, small cell lung cancer, kidney cancer, multiple myeloma, malignant melanoma.Contraindications
    : Hypersensitivity to lomustine, other derivatives of nitrosoureas or component parts of the drug.
    Pregnancy and lactation.
    Precautions – myelosuppression (including with concurrent radiation or chemotherapy, toxicity); chicken pox (including recently transferred or after contact with sick), herpes zoster and other acute infectious diseases of viral, fungal or bacterial origin; cachexia, intoxication, renal and / or hepatic failure, respiratory failure, treatment with cytostatics and radiotherapy history. 

    Side Effects On the part of hematopoiesis: thrombocytopenia develops after 4 weeks, leukopenia after 5-6 weeks after treatment and may last 1 – 2 weeks. Typically, thrombocytopenia is more severe than leukopenia. Less often observed anemia and granulocytopenia. Lomustine may cause cumulative myelosuppression, and after receiving repeated doses may experience more pronounced bone marrow suppression or myelosuppression duration can be greater. On the part of the digestive system: nausea and vomiting (within 3-6 hours after taking lomustine usually lasts up to 24 hours), anorexia. The frequency and duration of these side effects may be reduced by the use of prophylactic antiemetic drugs, as well as through the appointment of lomustine to patients on an empty stomach. Rarely – diarrhea, stomatitis, elevated liver enzymes and bilirubin. On the part of the respiratory system: rarely – cough, respiratory failure, concomitant occurrence of infiltration and / or pulmonary fibrosis (noted in 6 months or a longer period after the initiation of treatment with cumulative doses . preparation of more than 1100 mg / m² has been reported one case of pulmonary toxicity at anavar reviews a cumulative dose of 600 mg / m²). From the nervous system: confusion, lethargy, ataxia, a disorder of articulation of speech, fatigue. From the urinary system: urinary retention, swelling of feet or lower extremities, azotemia, decrease in the size of the kidneys (usually at high cumulative doses of the drug under conditions of prolonged treatment with lomustine and other drugs nitrosoureas). On the part of the reproductive system: azoospermia (in some cases, irreversible), amenorrhoea. others: rare – alopecia, irreversible defeat optic nerve leading to blindness (in conjunction with radiation therapy of the brain). It was reported on acute leukemia and bone marrow dysplasias as a result of treatment nitrosourea drugs.

    Drug overdose
    In case of overdose should be expected to increase the severity of side effects – inhibition of bone marrow hematopoiesis, disorders of the gastrointestinal tract, and the deterioration of liver function, and neurological disorders. The antidote is not known. Treatment is symptomatic.

    Interaction with other medicaments
    Medicaments cause myelosuppression as well as other cytostatic and radiotherapy can exacerbate leukopenia and thrombocytopenia caused lomustine. The combined use of lomustine with amphotericin B increases the risk of nephrotoxicity, lower blood pressure and bronchospasm.
    The case of a significant strengthening of leucopenia and neutropenia in a joint application lomustine and cimetidine.
    Increased toxicity may occur while taking lomustine and theophylline. Phenobarbital, activating microsomal enzymes may enhance the metabolism of lomustine. Patients receiving lomustine, attenuation may occur defense mechanisms of the body, which may cause a decrease in the formation of antibodies when administered antiviral vaccines. This state lasts from 3 months to 1 year after the last cycle of chemotherapy. Particular caution should be observed in the case of the use of vaccines containing live viruses.

    Cautions
    lomustine should be used under the supervision of physicians experienced with antineoplastic drugs.
    A systematic (not less than 1 time per week) to monitor patterns of peripheral blood during therapy and for 6 weeks after the end of treatment, as well as periodic monitoring of laboratory parameters of liver function and kidney.
    in thrombocytopenia and leukopenia in debilitated patients may experience bleeding and severe infection.
    Prior to initiation of therapy and during treatment should be assessed lung function. Patients with initially reduced vital capacity of the lungs more susceptible to pulmonary toxicity of lomustine.
    It is not recommended to use the drug anavar reviews more than 1 time in 6 weeks.
    Men and women of childbearing age should be during treatment and for at least 6 months after, use reliable methods of contraception .
    Do not open the capsule (powder is an irritant), avoid contact of the powder on the skin and mucous membranes.

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