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Sustanon side effects representative of the class of triazole derivatives, is a selective inhibitor of the synthesis of sterols in fungal cells. Blocks the conversion of lanosterol to ergosterol cells of fungi; increases the permeability of the cell membrane. Fluconazole, being highly selective for the cytochrome P450 fungi, practically does not inhibit cytochrome P-450 in humans (as compared to itraconazole, clotrimazole, econazole and ketoconazole less suppresses dependent cytochrome P450 oxidative processes in human liver microsome). It has no androgenic activity.The drug is active in mycosis caused by Candida spp, Cryptococcus neoformans, Microsporum spp , Trichophyton spp .. Blastomyces dermatidis, Coccidioides immitis and Histoplasma capsulatum…Pharmacokinetics Plasma concentrations are directly proportional to the dose. 90% -. I equilibrium concentration achieved by 4-5 day of treatment (when taking one time per day) Applying the first day dose of 2 times the normal daily dose, achieves a plasma concentration of fluconazole of 90% of the equilibrium concentration value the second day. The apparent volume of distribution. approaches to total body water. Plasma protein binding -. 11-12% Fluconazole penetrates well into all body fluids. The horny layer of the epidermis, the dermis and sweat liquid reaches high concentrations that exceed the whey. Patients with fungal meningitis content of fluconazole and in cerebrospinal fluid reaches a 80% level of its concentration in plasma. The permanent value in vaginal secretions are reached at 8 hours after oral administration and are maintained at this value for at least 24 hours. It is an inhibitor of isozyme CYP2C9 liver pharmacokinetics of fluconazole substantially independent of renal function, thus there is an inverse relationship between T 1/2 . KK and half-life (T 1/2 ) of fluconazole is approximately 30 hours fluconazole excreted mainly kidneys.; approximately 80% of the administered dose excreted by the kidneys in unchanged form, 11% – in the form of metabolites. Fluconazole clearance is proportional to creatinine clearance. Fluconazole metabolites in peripheral blood has been detected. After dialysis for 3 fluconazole hourly concentration in plasma decreased by 50%.

– Cryptococcosis: cryptococcal meningitis, cryptococcal infection of the lungs and skin; cryptococcal septicemia; . cryptococcosis relapse prevention in patients with AIDS, organ transplants or other cases of immunodeficiency
– Generalized candidiasis: candidemia, disseminated candidiasis and other forms of invasive Candida infections (abdominal infections, endocarditis, eye, respiratory and urinary tract infections), including patients, receiving a course of cytotoxic or immunosuppressive therapy, as well as the presence of other factors predisposing to the development of candidiasis – treatment and prevention.
– candidiasis of the mucous membranes: oral, including atrophic oral candidiasis associated with wearing dentures, pharynx, esophagus, and non-invasive . bronchopulmonary infection candiduria
– Genital candidiasis: vaginal (acute or chronic recurrent form), candida balanitis.
– Prevention of fungal infections in patients with malignancy who are predisposed to such infections as a result of chemotherapy, cytostatics or radiation therapy; . Prevention of relapse of oropharyngeal candidiasis in patients with AIDS
– Fungal infections of the skin, including tinea pedis, torso, groin; pityriasis versicolor, onychomycosis;
– Deep endemic mycoses, including coccidioidomycosis, paracoccidioidomycosis and histoplasmosis in patients with normal immunity.

– Hypersensitivity to fluconazole, other ingredients or other close structure azole compounds;
– Concomitant use of terfenadine (on the background of continuous use of fluconazole 400 mg per day and above) and cisapride, since both drugs prolong the QT interval and increase the risk of the development of severe cardiac arrhythmias;
– Concomitant use of astemizole;
– lactose intolerance; Lactase deficiency; glucose-galactose malabsorption;
– Lactation.

Liver and / or kidney failure, rash during treatment with fluconazole in patients with superficial fungal infection and invasive / systemic fungal infections, concomitant use of fluconazole with rifabutin or other drugs metabolized by cytochrome P450, concomitant use of terfenadine and fluconazole at a dose of less than 400 mg per day, potentially proaritmogennoe status in patients with multiple risk factors (organic heart disease, electrolyte imbalance, concomitant use of drugs that cause arrhythmias); Patients with intolerance to acetylsalicylic acid and pregnancy.

Pregnancy and lactation
The use of fluconazole during pregnancy is possible only if the potential benefit to the mother outweighs risk to the fetus.
Fluconazole is determined in breast milk in the same concentration as in plasma, so his appointment is contraindicated during lactation.

The drug is taken orally.
When translated from intravenous to receive capsules or vice versa is not necessary to change the daily dose. Use in Adults In cryptococcal infections, the usual dose of fluconazole is 400 mg once a day for the first day of treatment in the future – 200 -400 mg once a day. The duration of treatment for cryptococcal infections depends on the clinical efficacy, confirmed by mycological examination, and usually ranges from 6 to 8 weeks. The recommended duration of treatment for the treatment of cryptococcal meningitis is 10-12 weeks after the negative results of microbiological studies of samples of cerebrospinal fluid. For the prevention of relapse of cryptococcal meningitis in AIDS after completing the full course of primary therapy fluconazole is administered to the patient in a dose of 200 mg per day for a long period. When candidemia, disseminated candidiasis and other invasive Candida infections, the daily dose of fluconazole is 400 mg on the first day and 200 mg on subsequent days. If necessary, the dose may be increased to 400 mg / day. The duration of treatment depends on the clinical efficacy In severe systemic candidiasis – may increase the dose to 800 mg per day. The duration of therapy depends on clinical efficacy. It should be continued for at least 2 weeks after receiving a negative blood culture or after the disappearance of symptoms. In oropharyngeal candidiasis, including patients with narusheniyamiimmuniteta, the usual dose of fluconazole is 50-100 mg once daily for 7-14 days. For the prevention of relapse of oropharyngeal candidiasis in patients with AIDS, after the completion of a full course of primary therapy – 150 mg 1 time per week. If necessary, the treatment can be extended, particularly in severe disorders of immunity. In atrophic oral candidiasis associated with wearing dentures, fluconazole usually administered at 50 mg 1 time per day for 14 days in combination with antiseptic agents for the treatment of the prosthesis. In other Candida infections, eg esophagitis, non-invasive bronchopulmonary infections, candiduria, candidiasis of the skin and the mucous membranes of the daily dose is 50-100 mg for 14-30 days. in severe mucosal candidiasis -. 100-200 mg per day for prevention of fungal infections in patients with malignant tumors of fluconazole dose should be 50 mg once a day for as long as the patient is at high risk due to cytostatic or radiation therapy. vaginal candidiasis – 150 mg dose. To reduce the frequency of relapses is used 1 time per month at 150 mg for 4-12 months, and sometimes may require more frequent application. When balanitis caused by Candida spp., Fluconazole administered a single dose of 150 mg orally. For the prevention of candidiasis recommended dose of fluconazole is 1 50-400 mg once a day depending on the degree of risk of fungal infection. If sustanon side effects you have a high risk of generalized infection, eg in patients with severe or long-anticipated persistent neutropenia, the recommended dose is 400 mg 1 time per day. Fluconazole is administered a few days before the expected occurrence of neutropenia; after increasing the number of neutrophils over 1000 / mm3, treatment was continued for 7 days. When skin mycosis (including candidiasis), including tinea pedis, inguinal skin recommended dose is one 150 mg weekly or 50 mg every 1 day. Duration of therapy in ordinary cases is 2-4 weeks, but with tinea pedis longer therapy may be required (up to 6 weeks). When pityriasis versicolor – 300 mg 1 time per week for 2 weeks, some patients required a third dose of 300 mg per week , while in some cases it is sufficient single dose of 300 mg; Alternative treatment scheme is the use of 50 mg 1 time a day for 2-4 weeks. In onychomycosis the recommended dose is 150 mg 1 time per week. Treatment should be continued until infected nail healthy substitution.For the re-growth of nails on the fingers and feet normally required 3-6 months and 6-12 months, respectively. In deep endemic mycoses may require use of the drug at a dose of 200-400 mg daily for 2 years.The duration of therapy is determined individually; it can be 11-24 months with coccidioidomycosis; Paracoccidioidomycosis 2-17 months at 3-17 months and at histoplasmosis. Pediatric Use The duration of treatment depends on the clinical and mycological effect. In children, the drug should not be applied in a daily dose greater than that of adults. Fluconazole is used every day, once a day. At mucosal candidiasis, fluconazole is recommended dose of 3 mg / kg per day. On the first day loading dose of 6 mg / kg in order to more quickly reach an equilibrium concentration can be administered. For treatment of generalized candidiasis and cryptococcal infection recommended dose is 6-12 mg / kg per day depending on the severity of the disease. For the prevention of fungal infections in children immunocompromised, in whom the risk of infection associated with neutropenia, developing as a result of cytotoxic chemotherapy or radiation therapy, the drug is prescribed for 3-12 mg / kg per day, depending on the severity and duration of preservation-induced neutropenia. in newborns fluconazole appears slower, so in the first 2 weeks of life of the drug administered in the same dose (in mg / kg) as that of the older children, but with intervals of 72 hours. Children aged 3-4 weeks of life, the same dose is administered every 48 hours. Use in elderly patients In the absence of renal dysfunction should follow the usual recommendations for dosing of the drug. For patients with impaired renal function (creatinine clearance <50 mL / min), the dosing regimen should be adjusted as indicated below. Use in patients with renal impairment Fluconazole is excreted mainly by the kidneys unchanged. With a single application changes fluconazole dose is not required. If necessary, the course of treatment for patients (including children) with impaired renal function should initially enter a “shock” dose of 50 mg to 400 mg.

ADVERSE EFFECTS From the digestive system: nausea, vomiting, diarrhea, flatulence, abdominal pain, change in taste, abnormal liver function (hyperbilirubinemia, increased activity of “liver” transaminases, alkaline phosphatase, jaundice, hepatitis, hepatocellular necrosis, including fatal outcome). From the nervous system: headache, dizziness, seizures. From the side of hematopoiesis:leukopenia, thrombocytopenia, neutropenia, agranulocytosis. Allergic reactions: skin rash, erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), anaphylactoid reactions (including angioedema, face edema, urticaria, itching of the skin), bronchial asthma (often in case of intolerance of acetylsalicylic acid). Since the cardiovascular system:an increase in the QT interval duration in the electrocardiogram, flickering / flutter ventricles. Other: renal failure, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia.

Symptoms: nausea, vomiting, diarrhea, and in severe cases may experience seizures, hallucinations, paranoid behavior.
Treatment: symptomatic (gastric lavage, forced diuresis, hemodialysis). After three-hour hemodialysis fluconazole concentration in blood plasma decreases by about 50%.

INTERACTION WITH OTHER DRUGS Anticoagulants: Patients receiving fluconazole and indirect anticoagulants coumarin, careful monitoring of the prothrombin time, as it may be extended. Sulfonylureas:Fluconazole while receiving can extend the half-life sulfonylureas, therefore, in their joint application should be considered the possibility of hypoglycemia. phenytoin: simultaneous administration of fluconazole and phenytoin may be accompanied by an increase in clinically phenytoin concentrations significant degree, which requires lowering the dose. rifampicin: while taking rifampicin and fluconazole reduced the maximum concentration and half-life of the latter, therefore, if necessary combined use should be increased dose fluconazole. rifabutin: co-administration of fluconazole and rifabutin is accompanied by an increase in serum concentration of the latter may develop uveitis. Tacrolimus: in the combined use of fluconazole and cyclosporine is recommended to monitor the concentration of the latter in the blood, because it may increase. Terfenadine: taking into account the emergence of serious, life-threatening arrhythmias in patients taking anti-fungal agents – azole derivatives in conjunction with terfenadine, their co-administration is sustanon side effects contraindicated. cisapride: while receiving fluconazole and cisapride described cases of adverse reactions on the part of the heart, including paroxysms of ventricular tachycardia. Simultaneous administration is contraindicated. Zidovudine: the combined use with fluconazole may increase zidovudine plasma concentrations. Patients receiving this combination should be monitored in order to identify the side effects of zidovudine. Theophylline: receiving fluconazole reduces the average clearance rate: theophylline from blood plasma, therefore, increases the risk of toxic action of theophylline and its overdose. Midazolam: simultaneous administration of fluconazole and midazolam leads to a significant increase in the concentration of the latter in the blood plasma and the risk of development of psychomotor reactions. hydrochlorothiazide: while receiving fluconazole and hydrochlorothiazide increases fluconazole concentration in blood plasma by 40%. tacrolimus: while receiving fluconazole and tacrolimus increases last concentration in blood serum, which is to increase the risk of nephrotoxicity. care must be taken when using fluconazole in patients simultaneously receiving other drugs metabolized by the cytochrome P450 system.

Treatment with fluconazole should continue until clinical remission. Premature discontinuation of treatment leads to relapse.
Since fluconazole excreted mainly by the kidneys, caution should be exercised in patients with renal insufficiency. Long-term treatment with fluconazole dosing should be based on creatinine clearance.
In rare cases, the use of fluconazole was accompanied by toxic effects on the liver, including fatalities, primarily in patients with serious underlying medical conditions. It is necessary to monitor liver function. When you see signs of liver damage, which may be associated with administration of fluconazole, the drug should be discontinued.
In patients receiving the drug in patients observed rare cases of exfoliative cutaneous reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis. AIDS patients, and malignant tumors are more prone to the development of severe skin reactions in the application of many drugs. When the patient during the treatment of superficial fungal sustanon side effects infections of rash, which can be associated with the use of fluconazole, the drug should be discontinued. When a rash in patients with invasive / systemic fungal infections should be carefully monitored and cancel fluconazole when a bullous lesions or erythema multiforme.
Care must be taken while taking fluconazole with rifabutin or other drugs metabolized by the cytochrome P450 system.
It is necessary to monitor the prothrombin time in patients while receiving fluconazole and coumarin anticoagulants indirect. Effects on ability to drive a car or other mechanical means Patients should use caution when driving or road when dealing with technology, as during treatment with fluconazole may occur dizziness.

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