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It suppresses kininase II – an enzyme that catalyzes a reaction for conversion of angiotensin I to angiotensin II. Reduces the total peripheral vascular resistance (SVR), the blood concentration of adrenaline and aldosterone blood pressure (BP), the pressure in the pulmonary circulation; reduces afterload, it has a diuretic effect.Prevents liquid anavar the development of myocardial hypertrophy, improves exercise tolerance in patients with chronic heart failure patients. Losartan inhibits the angiotensin converting enzyme (ACE) -kininazu and II, respectively, does not prevent the destruction of bradykinin, so side effects associated with the bradykinin-mediated (e.g. angionevrotiches cue swelling) rarely occur. After a single oral hypotensive effect (reduced systems bolic and diastolic blood pressure) reaches a maximum after 6 hours, then for 24 hours gradually reduced. The maximum antihypertensive effect develops within 3-6 weeks after starting the drug. In patients with hypertension of diabetes without concomitant with proteinuria (greater than 2 g / night) applying the drug significantly reduces proteinuria, urinary albumin and immunoglobulin G. It stabilizes the urea level in blood plasma. No effect on autonomic reflexes and has no effect on long norepinephrine concentration in blood plasma. Losartan to 150 mg per day did not affect the level of triglycerides, total cholesterol and high density lipoprotein (HDL) in the serum of patients with arterial hypertension. At the same dose, losartan does not affect the blood glucose level on an empty stomach.

Absorption When administered losartan is well absorbed, and thus subject to metabolism in the “first pass” through the liver by carboxylation with the participation of isoenzyme of cytochrome CYR2S9 with the formation of the active metabolite. Systemic bioavailability of losartan – about 33%. The maximum concentration of losartan and its active metabolite are achieved in the blood serum after about 1 hour, 3-4 hours after oral administration, respectively. Food does not affect the bioavailability of losartan. Distribution Over 99% of losartan and its active metabolite is bound to plasma proteins, mainly albumin. The volume of distribution of losartan – 34 l. Losartan practically does not penetrate the blood-brain barrier. Metabolism Approximately 14% of losartan administered to a patient intravenously or by mouth, is converted to the active metabolite. Excretion Plasma clearance of losartan is 600 ml / min and the active metabolite – 50ml / min. Renal clearance of losartan and its active metabolite is 74 ml / min and 26 ml / min, respectively. When administered approximately 4% of the dose is excreted by the kidneys in an unmodified form, and about 6% is excreted by the kidneys in the form of the active metabolite. Losartan and its active metabolite is characteristic linear pharmacokinetics when administered at doses up to 200 mg. After oral administration, plasma concentrations of losartan and its active metabolite decline with a finite period polieksponentsialno poluvyvede-of losartan about 2 hours, and the active metabolite – about 6-9 hours. Before the drug at a dose of 100 mg per day or losartan nor the active metabolite bradley martyn bench press was not significantly cumulate in the blood plasma. Losartan and its metabolites are excreted through the intestines and kidneys. In healthy volunteers after oral administration of the labeled isotope C14 losartan, about 35% of the radiolabel found in the urine and 58% in feces.

Pharmacokinetics in particular groups of patients in patients with alcoholic liver cirrhosis and mild-moderate concentration of losartan was 5 times, and the active metabolite – 1.7 times higher than in healthy volunteers – men. If creatinine clearance (CC) higher than 10 ml / min. losartan plasma concentration does not differ from that of normal kidney function. Patients who require hemodialysis, area under the curve value of “concentration – time” (AUC) is approximately 2 times higher than in patients with normal renal function. Neither losartan or an active metabolite thereof is not removed from the body by hemodialysis. Concentrations in plasma of losartan and its active metabolite in elderly hypertensive males do not differ significantly from the values of these parameters in young men with hypertension. The values of the plasma concentrations of losartan in women with hypertension in 2 times higher than the corresponding values in men with hypertension. The concentrations of the active metabolite in both men and women do not differ. This pharmacokinetic difference has no clinical significance.

INDICATIONS

  • Arterial hypertension;
  • Chronic heart failure (in a combination therapy, in case of intolerance or failure of therapy with ACE inhibitors);
  • Reducing the risk of cardiovascular disease (including stroke) and mortality in patients with hypertension and left ventricular hypertrophy;
  • Diabetic nephropathy with hypercreatininemia and proteinuria (urinary albumin ratio and creatinine of more than 300 mg / d) in patients with type 2 diabetes and concomitant hypertension (reduction in the progression of diabetic nephropathy to terminal chronic renal failure).

CONTRAINDICATIONS

  • Hypersensitivity to the drug;
  • Pregnancy and lactation;
  • Age 18 years (effectiveness and safety have been established).

With caution: arterial hypotension, decreased blood volume, fluid and electrolyte balance, bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, renal / hepatic failure.

Pregnancy and lactation Data on the use of losartan during pregnancy does not. However, it is known that drugs that act directly on the renin-angiotensin-aldosterone system, when used in the II and III trimester of pregnancy can cause developmental defects or even death of the developing fetus. Therefore, in the event of pregnancyliquid anavar receiving the drug should be discontinued immediately. In the appointment during lactation should decide to discontinue breast-feeding or discontinue therapy drug.

DOSAGE AND ADMINISTRATION The drug LOZAP® taken orally, regardless of food intake, the multiplicity of reception – 1 times a day. When arterial hypertension the average daily dose is 50 mg. In some cases, to achieve greater therapeutic effect, the dose was increased to 100 mg in one or two doses per day. The initial dose for patients with chronic heart failure is 12.5 mg 1 time per day (1 tablet LOZAP® 12.5 mg). Typically, the dose is increased at weekly intervals (i.e., 12.5 mg / day, 25 mg / day and 50 mg / day) to an average maintenance dose of 50 mg 1 time per day, depending on patient tolerability of the drug. In appointing drug in patients receiving high doses of diuretics , the initial dose should be reduced to LOZAP® 25 mg (? 50 mg tablets LOZAP®) one time per day. No need to adjust the dose of elderly patients. reducing the risk of developing cardiovascular diseases ( including stroke) and mortality in patients with hypertension and left ventricular hypertrophy: the initial dose is 50 mg once a day. Further hydrochlorothiazide may be added in low doses and / or dosage formulation LOZAP® increased to 100 mg per day in one or two doses. Patients with accompanying type 2 diabetes with proteinuria: LOZAP® administered in an initial dose – 50 mg every 1 day with a further dose escalation to 100 mg / day (based on the degree of reduction of blood pressure) in one or two steps.Patients with liver disease history, dehydration, during hemodialysis and in patients older than 75 years is recommended to lower initial dose – 25 mg 1 time per day (50 mg tablets LOZAP®?).

Paediatric use Safety and efficacy in children under 18 years of age have not been established.

SIDE EFFECTS Side effects of losartan is usually transient and did not require discontinuation of therapy. When applying losartan treatment of essential hypertension in controlled studies, the side effects of any incidence of dizziness only differed from the placebo more than 1% (4.1% vs. 2.4%). Dose-dependent effect of orthostatic characteristic of antihypertensive agents when the use of losartan observed in less than 1% of patients.

Adverse events occurring with a frequency of less than 1%: Since the cardiovascular system : orthostatic hypotension (dozozavi-pendent), epistaxis, bradycardia, arrhythmia, angina pectoris, vasculitis, myocardial infarction. On the part of the digestive tract: anorexia, dryness of the oral mucosa mouth, toothache, vomiting, flatulence, gastritis, constipation, hepatitis, abnormal liver function. For the skin: dry skin, erythema, ecchymosis, fotosensibili-tion, increased sweating, alopecia. Allergic reactions: urticaria, skin rash, itching, angioedema (including laryngeal, and swelling of the tongue, causing airway obstruction and / or swelling of the face, lips, throat). From the hematopoietic system: sometimes – anemia (a slight decrease in hemoglobin concentration and hematocrit, an average of 0.11 g and 0% , 09 volume%, respectively, rarely – having clinical significance), thrombocytopenia, eosinophilia, Henoch-Schönlein purpura. From the musculoskeletal system: . arthralgia, arthritis, pain in the shoulder, knee, fibromyalgia On the part of the central nervous system and sensory organs : anxiety, sleep disturbance, drowsiness, memory disorders, peripheral neyropa-ment, paresthesia, gipostezii, tremor, ataxia, depression, fainting, tinnitus, taste disturbance, blurred vision, conjunctivitis, migraine. With the genitourinary system: urgency on urination, urinary tract infections, renal dysfunction, decreased libido, impotence. Other: gout. Laboratory findings: common: hyperkalemia (potassium level in the blood plasma of more than 5.5 mmol / l); sometimes – raising and residual urea nitrogen or creatinine in blood serum; very rarely – a moderate increase in activity of “liver” enzymes: aspartate aminotransferase (AST) and alanine transferase (ALT), hyperbilirubinemia.

Overdose Symptoms: marked reduction of blood pressure, tachycardia, due to parasympathetic (vagus-term) stimulation may develop bradycardia. Treatment: forced diuresis, symptomatic therapy;Hemodialysis is not effective.

INTERACTION WITH OTHER DRUGS may be assigned to other antihypertensive agents. Synergistic effect of beta-blockers and sympatholytic. The combined use of losartan with a diuretic has an additive effect. There was no pharmacokinetic interaction of losartan with gidrohlorotia-zidom, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin. According to fluconazole and rifampicin reduce the level of the active metabolite in the blood plasma. The clinical significance of these interactions is unknown. As with other agents that inhibit angiotensin II or its effects, the combined use of losartan potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium salts and formulations containing potassium, increases the risk of hyperkalemia. Nonsteroidal liquid anavar anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 (COX-2), can reduce the effect of other diuretics and antihypertensives. In a joint application of angiotensin II receptor antagonists and lithium may increase the concentration of lithium in the blood plasma. Given this, it is necessary to weigh the benefits and risks of combined use of losartan with lithium salts. If necessary to use in conjunction preparations, it is necessary regularly to monitor the concentration of lithium in the blood plasma.

Cautions should be carried out to correct dehydration destination LOZAP® drug or to start treatment with the drug at a lower dose. Drugs that affect the renin-angiotensin system may increase the concentration of urea in the blood and serum creatinine in patients with bilateral renal artery stenosis or stenosis unique-term kidney. Patients with cirrhosis losartan concentration in plasma is significantly increased, and therefore the presence of a history of liver disease should be administered in lower doses. During treatment should regularly monitor the concentration of potassium in the blood, especially in elderly patients with renal impairment. Effects on ability to concentrate: losartan does not affect the ability to drive or operate machinery. supplements like steroids buy testosterone online uk buy steroid needles