Perindopril acts through its active metabolite, perindoprilat. Eliminates the vasoconstrictor action of angiotensin II of, increases the concentration of bradykinin and vasodilatory prostaglandins trenbolone acetate price (ACE converts the inactive angiotensin I to angiotensin II, providing vasoconstriction, as well as causing the degradation of bradykinin, and prostaglandins 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 ACE activity is accompanied by a rise in the circulating and tissue kallikrein-kinin system and prostaglandins system.
Helps restore the elasticity of the large arteries (reduced formation of excessive amounts of subendothelial collagen), lowers blood pressure in the pulmonary kapyllyarah, 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 (BP) in the position of “lying” and “standing”), filling pressure of the left and right ventricles, total peripheral vascular resistance (SVR); increases minute volume of blood (IOC) and cardiac index, does not increase the heart rate (HR) (in patients with chronic heart failure (CHF) is moderately slows heart rate), strengthens the regional blood flow in the muscles. It increases concentration of high density lipoprotein, in 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 it causes a significant reduction in the severity of clinical signs of heart failure, increases exercise tolerance (according to bicycle stress test), trenbolone acetate price while 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”.
Absorption – 25%, bioavailability – 65-70%. The time to maximum concentration (Tcmah) -1ch perindopril, perindoprilat – 3-4 hours.
Equilibrium concentration (Css) is created for 4 days.
In the process of metabolism of 20% is transformed into an active metabolite – perindoprilat (receiving perindopril after a meal reduces the proportion of perindoprilat formed -essential clinical significance has not); remainder – 5 inactive compounds. The half-life (T1 / 2) of perindopril -1ch.
Communication perindoprilat plasma proteins – insignificant with ACE – less than 30% (depending on concentration). The volume of distribution of free perindoprilat – 0.2 l / kg. Perindoprilat excreted by the kidneys, T1 / 2 free fraction metabolite -. 3-5 hours Dissociation of perindoprilat bound to ACE, 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. Status “effective” Css achieved by the end of 4 days.
Excretion of perindoprilat is slowed in elderly patients and in patients with chronic heart and kidney failure (in recent dose adjustment should be made depending on the level trenbolone acetate price of creatine kinase). 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.
Chronic heart failure.
: Hypersensitivity to perindopril and other components of the drug or other ACE inhibitors, angioedema in history against a background of ACE inhibitor therapy, hereditary or idiopathic angioedema, pregnancy, lactation, age 18 years (effectiveness and safety have been established).