Pharmacological action Benazepril Hcl
ACE inhibitor. Is a prodrug, which after hydrolysis in the body is transformed into an active substance that inhibits ACE and violates the education of angiotensin II. Thus, the reduced vasoconstrictor action of angiotensin II and its stimulating effect on aldosterone production of adrenal glands. Causes a decrease in PR and blood pressure, reduces afterload. In addition, some causes varicose veins, reduces preload. Maximum antihypertensive effect is attained within a week a course of benazepril.
Pharmacokinetics Benazepril Hcl
Absorption from the gastrointestinal tract – 37%. Benazepril is rapidly converted to pharmacologically active metabolite – benazeprilat. Time to achieve Cmax in blood plasma and benazeprila benazeprilata is 30 min and 60-90 min, respectively. Bioavailability benazeprilata – about 28%. Reception after a meal slows absorption, but the amount of suction and is converted into an active metabolite benazeprila unchanged.
Plasma protein binding (mainly – to albumin) and benazeprila benazeprilata is about 95% and does not change with age. Benazeprilata Vd at steady state – nearly 9 liters. In the dose range from 5 to 20 mg, the magnitude of AUC and Cmax benazeprila and benazeprilata roughly proportional to dose. When applied in a wider range of doses (2-80 mg) were observed small but statistically significant deviation from the proportional dose-dependent, due to saturable binding benazeprilata with ACE.
Benazepril did not accumulates. Benazeprilat accumulates to a small extent; AUC when the Css of approximately 20% more than after the first dose. T1 / 2 benazeprilata – 10-11 hours Css in plasma is reached within 2-3 days. Benazepril is largely metabolized by enzymatic hydrolysis, mainly in the liver. Two successive metabolites are conjugates atsilglyukuronidnye benazeprila and benazeprilata.
Benazeprilat excreted by the kidneys and the gall to patients with normal renal function is dominated by renal excretion. In the urine of benazeprila – less than 1%, benazeprilata – about 20% of the administered dose. Deriving from the plasma benazeprila ends after 4 h. Excretion benazeprilata two-phase flows: T1 / 2 of the initial phase – about 3 hours, of course – about 22 hours availability of the final phase launch indicates strong binding benazeprilata with ACE.
In patients with hypertension Css benazeprilata in plasma depends on the daily dose.
In patients with chronic heart failure due to a slowing excretion of active substance, as compared with healthy people or patients with hypertension, Css benazeprilata in blood plasma is slightly higher.
With severe renal insufficiency (creatinine clearance below 30 ml / min) excretion benazeprilata slows and as a consequence, cumulative effect is possible. Benazepril and benazeprilat derived from plasma even in patients with end-stage renal failure, pharmacokinetic parameters in these cases are the same as in patients with severely impaired renal function. Extrarenal clearance (eg, metabolic or excretion in bile), partially offset by decreases in renal clearance.
Statement Benazepril Hcl
Hypertension.
Dosing regimen Benazepril Hcl
Average daily dose – 10-20 mg; multiplicity of purpose 1.2 The maximum daily dose is 40 mg.
Side effect Benazepril Hcl
CNS and peripheral nervous system: headache, fatigue, dizziness.
With the respiratory system: dry cough, rhinitis.
From the digestive system: nausea, diarrhea, abdominal pain.
From the laboratory parameters: increase in the concentration of urea and creatinine in serum, hyperkalemia, neutropenia.
Other: muscle pain, allergic skin reactions.
Contraindications Benazepril Hcl
Hyperkalaemia, bilateral renal artery stenosis or stenosis of the artery a single kidney with progressive azotemia, condition after kidney transplantation, primary hyperaldosteronism, hereditary angioedema, hypersensitivity to benasepril.
Application of pregnancy and breastfeeding
Benazepril is contraindicated in pregnancy.
Established that the benazepril and benazeprilat excreted in breast milk, but their maximum concentration is 0.3% of the concentration in blood plasma and therefore the number of benazeprila entering the systemic circulation, baby slightly. However, despite the very low probability of adverse effects in a child who is breastfed, the use of benazeprila during lactation (breastfeeding) is not recommended.
Cautions Benazepril Hcl
With careful use in patients with severe renal impairment, diabetes mellitus, marked coronary and cerebral atherosclerosis.
Drug Interactions Benazepril Hcl
With the simultaneous application of potassium-sparing diuretics (including spironolactone, triamterene, amiloride), potassium preparations, salt substitutes and food supplements containing potassium may develop hyperkalemia (especially in patients with impaired renal function), because ACE inhibitors reduce the content of aldosterone, which leads to a delay of potassium in the body against loss of potassium excretion or additional income in the body.
With the simultaneous application of diuretics, beta-blockers increased antihypertensive effect benazeprila.
With the simultaneous use of ACE inhibitors and NSAIDs, the risk of renal dysfunction and hyperkalemia.
