Anadrol for sale lipid-lowering agents of the statin group. Selective competitive inhibitor of HMG-CoA reductase – the enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonic acid which is a precursor of sterols, including cholesterol. Triglycerides (TG) and cholesterol in the liver are included in the very low density lipoproteins (VLDL) , enter the plasma and transported to peripheral tissues. Low density lipoproteins (LDL) are formed from VLDL during the interaction with the LDL receptor. Atorvastatin decreases the concentration of cholesterol in blood plasma lipoproteins by inhibiting HMG-CoA reductase inhibitors, cholesterol synthesis in the liver and increase the number of “liver” LDL receptors on the cell surface, which leads to increased trapping and LDL catabolism. Reduces LDL, it causes marked and persistent increase in the activity of LDL receptors. Reduces the concentration of LDL cholesterol in patients with homozygous familial hypercholesterolemia, which usually can not be lipid-lowering therapy means. Reduces total cholesterol concentration by 30-46%, LDL – by 41-61%, apolipoprotein B – by 34-50% and triglycerides – in the 14- 33%; causes an increase in the concentration of HDL-cholesterol and apolipoprotein A. Dozozawisimo reduces the concentration of LDL cholesterol in patients with homozygous hereditary hypercholesterolemia resistant to therapy with other lipid-lowering drugs. Significantly reduces the risk of ischemic complications (including death from the development of myocardial infarction) by 16% the risk of re-hospitalization for angina, accompanied by signs of myocardial ischemia -. 26% is not carcinogenic and mutagenic effects. The therapeutic effect is reached after 2 weeks after initiation of therapy, reaching a maximum of 4 weeks and is maintained throughout the treatment period.
Absorption – high. The time to maximum concentration (TC max ) – 1-2 hours, the maximum concentration (C max ) in women over 20%, AUC (area under the ‘plasma concentration-time “curve) – below 10%;The C max in patients with alcoholic cirrhosis by 16 times, AUC – 11 times higher than normal. Food somewhat reduces the rate and duration of absorption of the drug (25 and 9% respectively) but LDL cholesterol reduction similar to that in the application of atorvastatin without food. The concentration of atorvastatin in the evening application in lower than in the morning (approximately 30%). A linear relationship between dose and degree of absorption of the drug.
Bioavailability – 14% systemic bioavailability of inhibitory activity against HMG-CoA reductase – 30%. The low systemic bioavailability due to first pass metabolism in the mucosa of the gastrointestinal tract (GIT), and the “first pass” through the liver.
The average distribution volume – 381 liters, the connection with plasma proteins -. 98%
is metabolized primarily in the liver under the influence of isozymes CYP3A4, CYP3A5 and CYP3A7 with the formation of pharmacologically active metabolites (ortho and paragidroksilirovannyh derivatives, beta-oxidation products). In vitro and ortho paragidroksilirovannye metabolites have an inhibitory effect on HMG-CoA reductase, comparable to that of atorvastatin. The inhibitory effect of the drug against HMG-CoA reductase inhibitor of approximately 70% determined by the activity of circulating metabolites and persists for about 20-30 hours, due to their presence. The half-life (T½) -. 14 hours
is displayed through the intestine with the bile after hepatic and / or extrahepatic metabolism (not exposed to pronounced enterohepatic recirculation). Less than 2% of an oral dose is determined in urine.
Not output during dialysis due to intensive plasma protein binding.
Renal failure does not affect the concentration of drug in the plasma.
- In combination with a diet to reduce elevated total cholesterol, cholesterol / LDL cholesterol, apolipoprotein B, and triglycerides, and increasing concentrations of HDL cholesterol in patients with primary hypercholesterolemia, heterozygous familial and non-familial hypercholesterolaemia and combined (mixed) hyperlipidemia (type IIa and IIb according to Frederickson);
- In combination with a diet for the treatment of patients with elevated serum triglyceride concentrations (familial endogenous hypertriglyceridemia type IV according to Frederickson) and patients with disbetalipoproteinemiey (type III according to Frederickson), whose diet therapy does not provide adequate effect;
- To reduce the concentration of total cholesterol and cholesterol / LDL cholesterol in patients with homozygous familial hypercholesterolemia, when diet therapy and other non-pharmacological treatments are not sufficiently effective (as an addition to lipid-lowering therapy, including autologous transfusion purified from the blood LDL).
- Diseases of the cardiovascular system (including in patients without clinical manifestations of coronary heart disease but with increased risk factors for its occurrence – old age over 55 years, nicotine addiction, hypertension, diabetes mellitus, peripheral vascular disease, previous stroke, left ventricular hypertrophy, a protein / albuminuria, coronary heart disease in the immediate family), including:against the background of dyslipidemia – secondary prevention to reduce the overall risk of death, myocardial infarction, stroke, rehospitalization for angina and the need for revascularization procedures.
: Hypersensitivity to atorvastatin or to other components of the drug, active liver disease or increased activity of “liver” transaminases (more than 3 times) of unknown origin, hepatic failure (severity A and B on the scale of Child-Pugh), women of reproductive age, not using adequate methods of contraception, children up to 18 years (effectiveness and safety have been established). Lactose intolerance, lactase deficiency and syndrome of glucose-galactose malabsorption.
alcoholism, liver disease history, expressed disturbances of water and electrolyte balance, endocrine and metabolic disorders, hypotension, tyazhelytse acute infections (sepsis), uncontrolled epilepsy, extensive surgery, trauma, skeletal muscle disease.
Use during pregnancy and lactation
Use of the drug Lipoford in women of reproductive age, is only possible when using reliable methods of contraception. The patient should be informed about the possible risk of treatment to the fetus.
The drug Lipoford is contraindicated for use during pregnancy. Since cholesterol and substances synthesized from cholesterol are important for the development of the fetus, the potential risk of inhibition of HMG-CoA reductase inhibitors exceeds anadrol for sale the benefit from the use of the drug during pregnancy. In the application of the mothers in the I trimester of lovastatin (an inhibitor of HMG-CoA reductase inhibitors) with dextroamphetamine are known cases of children born with a bone deformity, tracheo-esophageal fistula, anal atresia. In case of pregnancy during therapy, the drug should be discontinued immediately and the patient advised of the potential risk to the fetus.
If necessary, use during lactation, given the possibility of adverse events in infants, should decide the issue of termination of breastfeeding.
Dosage and administration
Before starting treatment with Lipoford patient should be advised to standard lipid-lowering diet, which he must continue throughout the entire treatment period.
Lipoford taken orally, at any time of the day (but at the same time), regardless of the meal.
Recommended the initial dose – 10 mg 1 time per day. Further, the dose is selected based on the original cholesterol / LDL concentrations, the goals of therapy and individual effect. At the beginning of the treatment and / or during dose increasing Lipoford every 2-4 weeks is necessary to control the concentration of lipids in the blood plasma and the dose adjusted accordingly. Changing the dose should be at intervals of not less than 4 weeks. The maximum daily dose – 80 mg per 1 reception.
In patients with a confirmed diagnosis of coronary heart disease, or at high risk of ischemic complications for treatment is to reduce LDL cholesterol levels below 3 mmol / l (or less than 115 mg / dl) and total cholesterol below 5 mmol / l (or less than 190 mg / dl).
The primary (heterozygous familial and non-family), hypercholesterolemia and mixed hyperlipidemia (type IIa and II b).
Treatment is initiated with a recommended starting dose is 10 mg, which increased after 4 weeks of therapy depending on the patient’s response. The maximum daily dose of 80 mg. Homozygous Familial Hypercholesterolemia. The dose range is the same as for other types of hyperlipidemia. The initial dose is selected individually depending on the severity of the disease. The majority of patients with homozygous familial hypercholesterolemia an optimal effect is observed when using the drug in a daily dose of 80 mg (once). In patients with renal impairment and elderly patients dose adjustment of atorvastatin is required. In patients with impaired hepatic function should be cautious due to the slowing of excretion of the drug. Clinical and laboratory parameters and the detection of significant lesions should be carefully monitored dose should be reduced or treatment should be discontinued.
The frequency of adverse reactions listed below was determined according to the following (World Health Organization):
very often – more than 1/10, often – from more to less than 1/100 1/10, rarely – from more to less than 1/1000 of 1 / 100, rarely – from more to less than 1/10000 1/1000, very rare – from less than 1/10000, including isolated reports.
On the part of the central nervous system: often – headache, fatigue, insomnia; Infrequent – dizziness, drowsiness, nightmares, amnesia, depression, peripheral neuropathy, ataxia, hypoesthesia, paresthesia.From the digestive system: often – nausea, constipation or diarrhea, flatulence, gastralgia, stomach pain; rarely – anorexia or increased appetite, vomiting, hepatitis, pancreatitis, cholestatic jaundice. From the musculoskeletal system: very often – myalgia; arthralgia; rare – myopathy; rarely – myositis, rhabdomyolysis, back pain, leg cramps leg muscles. Allergic reactions: often – itching, rash; rarely – urticaria;very rarely – angioedema, anaphylaxis, bullous lesions, erythema poliformnaya, including Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome). Laboratory findings: rarely – hyperglycemia, hypoglycemia, increased activity cyvorotochnoy creatine phosphokinase (CPK), increased activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Prochie: often – pain in the chest, peripheral edema; rarely – impotence, secondary renal failure, alopecia, tinnitus, increase in body weight, malaise, fatigue, thrombocytopenia.
Treatment: No specific antidote, symptomatic treatment. Hemodialysis is ineffective.
The interaction with other drugs
In an application cyclosporin fibrates, erythromycin, clarithromycin, immunosuppressive, antifungal agents (belonging to azoles), nicotinic acid and nicotinamide, drugs inhibiting metabolism mediated by cytochrome P4503A4 concentration of atorvastatin in plasma (and the risk of myopathy) increases . By assigning these drugs should carefully weigh the potential benefits and risks of treatment, regularly monitor patients to detect pain or weakness in muscles, especially during the first months of treatment and during dose escalation of any drug, periodic determination of CPK activity, although such control does not prevent the development of severe myopathy. Treatment with Lipoford should be discontinued in the event expressed increasing CPK or in the presence of confirmed or suspected myopathy.
Atorvastatin had no clinically significant effect on the concentration of terfenadine in the blood plasma, which is metabolized primarily by cytochrome P4503A4; therefore seems unlikely that atorvastatin can significantly affect the pharmacokinetic parameters of other substrates of cytochrome P4503A4.
With simultaneous use of atorvastatin and erythromycin (500 mg four times a day) or clarithromycin (500 mg, 2 times a day), there upconcentration atorvastatin in plasma.
Antacids reduce the concentration of 35% (effect on the cholesterol content of LDL is not changed).
With the simultaneous use of atorvastatin (10 mg 1 time per day) and azithromycin (500 mg 1 time per day) atorvastatin plasma concentration is not changes.
no clinically significant interactions were observed with concomitant use of warfarin, cimetidine, phenazone.
Concomitant use of atorvastatin with inhibitors of proteases, known as inhibitors of isoenzyme of CYP3A4, accompanied by an increase atorvastatin plasma concentration (while the use of erythromycin, the C max of atorvastatin increased by 40%) .
when using digoxin in combination with atorvastatin 80 mg / day digoxin concentration is increased by about 20%.
Increases concentration (the appointment with atorvastatin 80 mg / day) oral contraceptives containing norethisterone 30% and ethinylestradiol is 20%.
Lipid-lowering effect of the combination with colestipol than that for either agent alone, despite the reduction of atorvastatin concentration of 25% when it is used simultaneously with colestipol.
with simultaneous use of atorvastatin 80 mg or amlodipine 10 mg pharmacokinetics of atorvastatin did not change.
The simultaneous use of drugs, which reduce the concentration of endogenous steroid hormones (including cimetidine, ketoconazole, spironolactone), increases the risk of reduction of endogenous steroid hormones (be careful).
Before starting therapy with Lipoford should try to gain control of hypercholesterolemia by an adequate diet therapy, physical activity, weight loss in obese patients, and the treatment of other conditions.
The use of inhibitors of HMG-CoA reductase inhibitor to lower lipid levels in the blood can lead to a change in biochemical liver function, which should be monitored before treatment and after 6 and 12 weeks after the start of Lipoford preparation and after each dose escalation, and periodically, for example every 6 months.
Elevated “liver” enzymes can be observed mainly in the first three months of preparation. Patients with marked increase in the level of activity of “liver” transaminases should be controlled to the level of enzymes return to normal. It is recommended to cancel the drug or dose reduction with increasing indexes of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) is more than 3 times.
Treatment with Lipoford can cause myopathy (pain and weakness in the muscles in combination with increased CPK activity by more than 10 times compared with the upper limit of normal). Lipoford may cause an increase in serum CK indicators that should be taken into consideration in the differential diagnosis of chest pain. Patients should be warned that they should immediately consult a doctor if unexplained pain or weakness in muscles, particularly if accompanied by malaise or fever.
It is necessary to temporarily suspend the use of atorvastatin in the clinical symptoms develop, involving anadrol for sale the presence of acute myopathy, or if there are factors predisposing to the development of acute renal failure with rhabdomyolysis (severe infections, lowering blood pressure, major surgery, trauma, metabolic, endocrine or severe electrolyte disturbances and nektontroliruemye convulsions). Myopathy risk increases while the use of cyclosporine, fibric acid derivatives, erythromycin, nicotinic acid or azole antifungal agents.
There are reports on the development of atopic fasciitis during treatment with atorvastatin, but contact with the drug intake is possible, but not proven until the present time, the etiology is not known .
Effects on ability to drive and doing other activities that require concentration and speed of psychomotor reactions.
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On the adverse effects of the drug Lipoford on ability to drive and doing other activities that require concentration and speed of psychomotor reactions have been reported. steroiden kaufen
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