parabolan steroid

Pharmacodynamics
Parabolan steroid inhibitor. Inhibition of Parabolan steroid results in a reduction of angiotensin II in the blood plasma, and resulting in reduced secretion of aldosterone. Perindopril acts through its active metabolite, perindoprilat. Eliminates the vasoconstrictor action of angiotensin II of, increases the concentration of bradykinin and vasodilatory prostaglandins (Parabolan steroid converts the inactive angiotensin I to angiotensin II, providing vasoconstriction, as well as causing the degradation of bradykinin and prostaglandin having vasodilating activity); reduces production and release of aldosterone, inhibits the release of noradrenaline from the nerve endings of the sympathetic fibers and the formation of endothelin in the vascular wall. Reducing the formation of angiotensin II is accompanied by increased activity of plasma renin activity (due to inhibition of the negative feedback). Inhibition of Parabolan steroid activity is accompanied by a rise in the circulating and tissue kallikrein-kinin system, wherein the system is also activated prostaglandins.

Helps restore the elasticity of the large arteries (reduced formation of excessive amounts of subendothelial collagen), lowers blood pressure in the pulmonary capillaries, long-term appointment reduces the severity of left ventricular hypertrophy and interstitial fibrosis, normalizes the isoenzyme profile of myosin;normalizes the functioning of the heart.

Reduces preload and afterload (reduces systolic and diastolic blood pressure (blood pressure) in the position of “lying” and “standing”), filling pressure of the left and right ventricles, PR (total peripheral vascular resistance); increases the IOC (minute volume of blood circulation), and cardiac index without changes in heart rate (heart rate) (in patients with heart failure (congestive heart failure), moderately slows heart rate, increases regional blood flow in the muscles).

Increases concentration of HDL (high density lipoprotein) patients with hyperuricemia decreases the concentration of uric acid. Increases renal blood flow, glomerular filtration rate does not change the rate.

In patients with heart failure restanon 250 it causes a significant reduction in the severity of clinical signs of heart failure, increases exercise tolerance (according to bicycle stress test), did not significantly reduce blood pressure. After ingestion average single dose maximum hypotensive effect is achieved after 4-6 h and maintained for 24 hours. The hypotensive effect of stabilization is observed after one month of therapy, and stored for a long time. Discontinuation of treatment is not accompanied by the development of the syndrome of “cancellation”.

Pharmacokinetics
Absorption – 25%, bioavailability – 65-70%. . The time to reach maximum plasma concentration – 1 hour, perindoprilat – 4.3 h 20% metabolism is transformed into the active metabolite -perindoprilat (reception perindopril after meals reduces the proportion perindoprilat formed – has substantial clinical significance in); remainder – 5 inactive compounds. T1 / 2 (half life) -1 h perindopril perindoprilat Communication plasma proteins -. Insignificant with Parabolan steroid – less than 30% (depending on concentration). The volume of distribution of free perindoprilat -0.2 l’kg. Perindoprilat excreted by the kidneys. T1 / 2 of the free fraction of metabolite -3-5 hours. Dissociation of perindoprilat bound to Parabolan steroid, slow. Consequently, the “effective” T1 / 2 of 25 hours. Reassignment perindopril does not lead to its accumulation, and T1 / 2 perindoprilat Repeated dose corresponds to the period of its activity.

Excretion of perindoprilat is slowed in elderly patients and in patients with chronic heart failure and chronic renal failure (chronic renal failure) (the latter dose adjustment should be based on creatinine clearance). Perindopril dialysis clearance is 70 ml / min.

In patients with hepatic cirrhosis the clearance of perindopril reduced 2 times, while the total number remains unchanged formed perindoprilat and correct dosing regimen is not required.

Indications
Hypertension; chronic heart failure.

Contraindications
: Hypersensitivity to perindopril and other components of the drug or other Parabolan steroid inhibitors, angioedema in history against a background of Parabolan steroid inhibitor therapy, hereditary or idiopathic angioedema, pregnancy, lactation, age 18 years (effectiveness and safety have been established).

Precautions:
aortic stenosis, hypertrophic obstructive cardiomyopathy, cerebrovascular diseases (including cerebrovascular insufficiency, coronary heart disease, coronary insufficiency – a risk of excessive blood pressure lowering and concomitant ischemia.

Severe autoimmune systemic connective tissue disease (including systemic lupus erythematosus, scleroderma), inhibition of bone marrow hematopoiesis in patients receiving immunosuppressive drugs (increasing the likelihood of neutropenia).

Renovascular hypertension, a bilateral renal artery stenosis, stenosis of the artery only kidney condition after kidney transplantation (risk of renal dysfunction and agranulocytosis), chronic renal failure (especially accompanied by hyperkalemia), hyperkalemia, diet sodium restriction, a condition associated with decreased blood volume (including diarrhea, vomiting, diuretics), diabetes, advanced age, surgery (general anesthesia).

Dosing and Administration
Inside, in the morning before eating.

The initial dose for the treatment of hypertension is 4 mg / day, if necessary (after 1 month), the dose may be increased to 8 mg / day in one portion

In the appointment of Parabolan steroid inhibitors to patients receiving diuretic therapy, there may be a decrease in the sharp decline in blood pressure, which is recommended for the prevention stop taking diuretics 2-3 days before the expected start of therapy Gipernikom or prescribe a drug at lower doses – 1 mg 2 times a day.

In patients with renovascular hypertension initial dose of 1 mg 2 times a day. If necessary, the dose may subsequently be increased.

In elderly patients, therapy should be initiated with a dose of 2 mg per day, and thereafter, if necessary, to gradually increase it up to a maximum dose of 8 mg per day.

Treatment of patients with heart failure in combination with nekaliysberegayuschim diuretic and / or digoxin is recommended to start under close medical supervision, Gipernik administered in an initial dose of 1 mg 2 times a day, in the morning.

Subsequently, after 1-2 weeks of therapy, the dose may be increased to 4 mg 1 time per day.

In patients with renal impairment, the dose should be adjusted according to the degree of renal failure: depending on the creatinine clearance. When CC 30-60 ml / min – 1 mg 2 times a day; with CC 15-30 ml / min – 2 mg every other day; patients on hemodialysis (creatinine clearance less than 15 ml / min) – 2 mg per day of dialysis.

When QA 60 mL / min to 4 mg per day.

In appointing Gipernika patients with hepatic impairment, dose change is required.

Side effect

From the cardiovascular system: often – an excessive fall in blood pressure and related symptoms, rarely – arrhythmias, angina, myocardial infarction and stroke.

From the urinary system: decrease in renal function, acute renal failure.

From the respiratory system: often – “dry” cough, shortness of breath; rarely – bronchospasm, rhinorrhea.

From the digestive system: often – nausea, vomiting, abdominal pain, change in taste, diarrhea or constipation, dry mouth, decreased appetite, cholestatic jaundice, pancreatitis.

On the part of the central nervous system: often – headache, asthenia, fatigue, dizziness, ringing in the ears, blurred vision, muscle cramps, paresthesias; rarely – depressed mood, insomnia; extremely rare – confusion.

Allergic reactions: often – skin rash, itching; rarely – urticaria, angioedema: rarely – erythema multiforme zkssudativnaya

Laboratory tests: often – hypercreatininemia. proteinuria. ginerkaliemiya; hyperuricemia; rarely (with prolonged use at high doses) – neutropenia. leukopenia, gipogemoglobinemiya, platelet persecution, reduced hematocrit; very rarely – agranulocytosis, pantsitoieniya, increased activity of “liver” enzymes, hyperbilirubinemia, haemolytic anemia (compared to glucose-6-phosphate dehydrogenase deficiency).

Other: increased sweating, sexual dysfunction.

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