Pharmacological properties winstrol is a selective antagonist of the angiotensin II receptor (type AT1) for oral, non-protein nature.
It has selective antagonistic effects on the receptors of the AT1 subtype. A consequence of the blockade of AT1-receptor is to increase plasma concentrations of angiotensin II, which may stimulate the unblocked AT2 receptor subtype, which presumably controls the AT1-receptor effects. winstrol has no agonistic activity against AT1-receptor. Its affinity for AT1 receptor subtype approximately 20,000 times greater than AT2 receptor subtypes.
winstrol does not inhibit the angiotensin-converting enzyme (ACE), also known as kininase II, which converts angiotensin I to angiotensin II and destroys bradykinin. Due to the lack of effect on ACE not potentiated the effects of bradykinin and substance P, thus when receiving angiotensin II antagonists unlikely development dry cough. winstrol does not interact and is not blocking other hormone receptors or ion channels involved in the regulation of cardiovascular functions.
In the treatment of hypertension, winstrol reduced blood pressure without affecting heart rate (HR). After a single oral dose antihypertensive effect occurs within 2 hours, and the maximum reduction in blood pressure (BP) is reached within 4-6 hours. The antihypertensive effect of the drug is maintained for 24 hours after administration. When reappointments winstrol maximum reduction in blood pressure, regardless of the dose achieved in 2-4 weeks and maintained at that level during prolonged therapy. Combination with hydrochlorothiazide can achieve significant additional reduction in blood pressure.
Sudden discontinuation of winstrol are not accompanied by a sharp rise in blood pressure, or other unwanted clinical consequences.
In assessing the effect of winstrol (appointed in addition to standard therapy for heart failure) on exercise tolerance in patients with chronic heart failure II-IV functional class NYHA classification and with left ventricular ejection fraction (LVEF) <40% was an increase in the time of exercise on compared with baseline.
No “cancel” syndrome with sudden discontinuation.
winstrol is rapidly absorbed after oral administration, but the degree of absorption varies widely. The average value of the absolute bioavailability of winstrol is 23%. The time required to reach maximum concentration (TSmah) – 2 h. After regular intake of maximal blood pressure reduction occurs within 4 weeks. When taking the drug once a day its accumulation is negligible. Plasma concentrations of winstrol are the same in men and women. winstrol avidly binds to serum proteins (94-97%), predominantly to serum albumin. The equilibrium volume of distribution of the drug is small, about 17 liters.Plasma clearance is relatively low (approximately 2 liters / hour) when compared to hepatic blood flow (about 30 liters / hour). Metabolized by CYP2C9 enzyme systems. The half-life of 9 hours. Number of winstrol, is output through the intestines, is 70% of the sucked after oral dose.
With urine output 30%, mainly in unchanged form. When taken with food winstrol decreased area under the curve “concentration-time» (AUC) of 48%. However, after 8 hours after administration of the drug plasma concentrations of winstrol taken on an empty stomach with food and the same. Reducing AUC is not accompanied by a clinically significant decrease in therapeutic effect of winstrol, and the drug can be used both before and after a meal.
Special patient groups
Patients with impaired renal function
Given that renal clearance accounts for only 30% of the value of the total clearance in patients with impaired renal function does not require dose adjustment of the drug. Since the degree of binding to plasma proteins winstrol high, its elimination by hemodialysis is unlikely.
Patients with hepatic impairment
About 70% of the dose of winstrol suck excreted in the bile, mainly in unchanged form. winstrol does not undergo significant biotransformation, so its systemic effect is not correlated with the degree of liver dysfunction. Therefore, in patients with hepatic insufficiency nebiliarnogo origin and without cholestasis does not require changes in the dose of winstrol. In patients with biliary cirrhosis or obstruction of the biliary tract winstrol AUC increased approximately 2-fold.
- Arterial hypertension.
- Chronic heart failure (II-IV functional class NYHA classification) as part of combination therapy (with standard therapy) and patients not receiving an ACE inhibitor.
- Hypersensitivity to winstrol or other ingredients.
- Pregnancy and lactation.
- Age 18 years (winstrol efficacy and safety in children has not been proven).
- Lactose intolerance, galactosemia or malabsorption syndrome glucose / galactose.
With caution: arterial hypotension, hepatic insufficiency on the background of bile duct obstruction, kidney failure (creatinine clearance (CC) of less than 10 ml / min), including patients on hemodialysis, hyponatremia, a diet with restriction of sodium intake, bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, a condition associated with decreased blood volume (CBV) (including diarrhea, vomiting).
Application of pregnancy and lactation
on the use of winstrol during pregnancy do not have data. Fetal renal perfusion, which is dependent on the development of the renin-angiotensin system, begins to operate in the third trimester of pregnancy.The risk to the fetus increases when taking winstrol in the second and third trimesters. In establishing pregnancy winstrol therapy should be discontinued immediately. No data on the allocation of winstrol in mother’s milk. Therefore, you should resolve the issue of termination of breastfeeding or cancellation of winstrol therapy in view of its importance to the mother.
Dosing and Administration
Inside, regardless of the meal, the multiplicity of reception – 1 – 2 times a day.
The recommended dose is 80 mg once a day, regardless of age, gender or race of the patient. The antihypertensive effect develops within 2 weeks and reaches its maximum after 4 weeks. The maximum daily dose – 320 mg per day. Patients with impaired renal function and liver nebiliarnogo origin and does not require change doses without cholestasis. It can be combined with other antihypertensive drugs.
Chronic heart failure
The recommended starting dose is 40 mg twice a day. Possibly a gradual increase to 80 mg, if tolerated – 160 mg twice a day, ie to a maximum dose tolerated by the patient. The maximum daily dose – 320 mg, divided into 2 doses. In patients concurrently receiving diuretics, as well as in patients with heart failure requires constant monitoring of renal function, blood pressure. When clinical signs of hypotension, the dose should be reduced.
Side effect On the part of the central and peripheral nervous system: often – headache, dizziness, including postural, vertigo; not often – insomnia; sometimes – syncope (when used after myocardial infarction).
The respiratory system, organs, thoracic and mediastinal disorders: often – cough, infections of the upper respiratory tract, pharyngitis, rhinitis, sinusitis.
Since the cardiovascular system: often – pronounced reduction in blood pressure and orthostatic hypotension; sometimes (when used after myocardial infarction) – heart failure.
From the gastrointestinal tract: often – nausea, diarrhea, abdominal pain.
Skin and subcutaneous tissue: rare – skin rash.
On the part of the muscle, skeletal and connective tissue disorders: often – back pain, myalgia, arthralgia.
From the urogenital system: rarely – decreased libido; very rarely – renal dysfunction.
Allergic reactions: seldom – angioedema, rash, pruritus, hypersensitivity reactions including serum sickness, and vasculitis.
From the laboratory parameters: rare – decrease in hemoglobin concentration and hematocrit, neutropenia, thrombocytopenia, hypercreatininemia, hyperbilirubinemia, increased activity of “liver” transaminases, increases in serum urea nitrogen; often – hyperkalemia.
Other: often – general weakness; not often – edema, asthenia, fatigue.
Overdose Symptoms: Data on the impact of winstrol overdose are not available. Despite the absence of sufficient data, the main manifestation of overdose expected – marked reduction of blood pressure, which can lead to collapse and / or shock.
Treatment: symptomatic, it is recommended to induce vomiting and stomach wash. With the development of arterial hypotension intravenous 0.9% sodium chloride solution. Hemodialysis is ineffective.
Interactions with other medications
No clinically significant pharmacokinetic interactions with other drugs have been observed. The drugs that have been tested in clinical studies included cimetidine, warfarin, digoxin, atenolol, indomethacin, hydrochlorothiazide, amlodipine, and glibenclamide.
As winstrol is not exposed to significant metabolism, you should not expect a significant drug-drug interactions associated with the induction or inhibition of cytochrome P450. Simultaneous treatment with potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium-containing food additives can cause hyperkalemia due; what is needed to be careful. When co-administered with diuretics may increase the hypotensive effect.
Cautions Heart failure Use in patients with heart failure is usually accompanied by a decrease in blood pressure, however, subject to the recommendations on the selection of doses of treatment rarely requires the removal of arterial hypotension. Valsakorom therapy in heart failure patients should be started cautiously. As a result of the suppression of the activity of the renin-angiotensin-aldosterone system, some patients may change in renal function. In severe heart failure may develop oliguria and / or progressive azotemia up to (rarely) with acute renal failure and / or death. In patients with heart failure requires constant monitoring of renal function while the appointment of a combination of three classes of drugs – ACE inhibitors, beta-blockers and angiotensin II AT1 receptors.
Perhaps the appointment in combination with other drugs prescribed after myocardial infarction: thrombolytics, acetylsalicylic acid, beta-blockers and statins.
Patients with deficiency of sodium and / or fluid in patients with severe deficiency of sodium in the body and / or a decrease in the volume of circulating blood (CBV), for example, as a result of receiving large doses of diuretyakov, in rare cases, at the beginning of therapy with winstrol may develop severe hypotension. Before treatment valsakorom recommended restore electrolytes and fluids in the body, in particular by reducing the doses of diuretics.
With the development of arterial hypotension with clinical signs: the patient must be put at the back and, if necessary, enter intravenously a 0.9% sodium chloride solution. Valsakorom therapy can be continued only after stabilization of blood pressure indicators.
Renal artery stenosis
In patients with unilateral or bilateral renal artery stenosis is necessary to constantly monitor the content of creatinine and urea nitrogen in serum.
Impaired Renal Function
In patients with impaired renal function does not require change doses. Due to lack of data on the use of the drug with severe renal insufficiency (creatinine clearance less than 10 mL / min or 0.167 ml / s) in such cases the drug is recommended to be used with caution.
Abnormal liver function
Patients with impaired do not need to change the doses of liver function. Valsakor bile appears mainly. In patients with obstructive biliary tract disease was observed decrease in clearance Valsakora, so in such cases, the drug should be used with caution.
Specific information on excipients
Valsakor contains lactose, so the drug is contraindicated in patients with lactase deficiency, galactosemia or syndrome of malabsorption of glucose-galactose.