It reduces the degradation of bradykinin and increases the synthesis of prostaglandins. Reduces the total peripheral vascular resistance (SVR), blood pressure (BP), preload, pressure in the pulmonary capillaries, causing an increase in cardiac masteron prop output (IOC) and increase tolerance to myocardial stress in patients with chronic heart failure (CHF). Artery expands to a greater extent than veins. Some effects are explained by the influence on the tissue renin-angiotensin-aldosterone system (RAAS). With prolonged use reduces myocardial hypertrophy and arterial wall of the resistive type. It improves blood flow to ischemic myocardium. ACE inhibitors prolong the life expectancy of patients with chronic heart failure, slow the progression of left ventricular dysfunction (LV) function in patients with myocardial infarction without clinical symptoms of heart failure (HF). The beginning of the antihypertensive action – after 1 hour.Maximal effect was observed after 6-7 h. Antihypertensive effect lasts for 24 hours. The duration of the effect is also dependent on the dose. When hypertension effect noted in the first days after the start of treatment, stable effect develops in 1-2 months.
The mean extent of absorption of lisinopril is approximately 25%, with large inter-individual variability (6-60%). Food does not affect the absorption of lisinopril.
Maximum plasma concentration is 90 ng / ml reached after 6 hours. Bioavailability – 25%. Weakly bound to plasma proteins. Permeability through the blood brain barrier and the placental barrier – is low. The metabolism of virtually exposed and excreted by the kidneys unchanged. The half-life is 12 hours in patients with chronic heart failure, cirrhosis of the liver, patients older absorption and clearance of lisinopril reduced..
Impaired renal function leads to an increase in AUC (area under the curve “concentration in plasma – time”) and half-life of lisinopril, but these changes are clinically significant only when the glomerular filtration rate is less than 30 ml / min.
Pharmacokinetics in particular groups of patients
in patients with chronic heart failure absorption and clearance lisinopril reduced bioavailability is 16%.
In patients with renal impairment (creatinine clearance less than 30 mL / min), the concentration of lisinopril is several times higher than the concentration in the blood plasma of healthy volunteers and marked increase in the time to reach maximum concentration in the plasma and an increase in half-life.
elderly patients concentration of lisinopril in the plasma increased on average by 60% and the area under the curve “concentration-time” 2 times greater than in younger patients.
patients with cirrhosis of lisinopril reduced bioavailability by 30% and the clearance is reduced by 50% compared with patients with normal liver function.
– Essential and renovascular hypertension (AH) (as monotherapy or in combination with other antihypertensive agents);
– Chronic heart failure (CHF) (in combination therapy);
– early treatment of acute myocardial infarction in combination therapy (in the first 24 hours with stable hemodynamics to maintain these indicators and prevention of left ventricular dysfunction and heart failure);
– diabetic nephropathy (reduction of albuminuria in patients with type 1 diabetes with normal blood pressure and patients with type 2 diabetes with hypertension).
– Hypersensitivity to lizinoprilu, other ACE inhibitors, and drug components;
– Angioedema in history, including during treatment with ACE inhibitors;
– hereditary angioedema or idiopathic angioedema edema
– age of 18 years (effectiveness and safety have not been established);
– lactose intolerance, lactase deficiency, glucose-galactose malabsorption.
aortic stenosis, hypertrophic obstructive cardiomyopathy, bilateral renal artery stenosis, stenosis of the artery only kidney condition after kidney transplantation, severe renal impairment (creatinine clearance (CC) of less than 30 ml / min.), Primary hyperaldosteronism, hypotension, inhibition of bone marrow hematopoiesis, hyponatremia (increased risk of hypotension in patients who are at malosolevoy or salt-free diet), hypovolemic state (including diarrhea, vomiting), systemic connective tissue disease (including systemic lupus erythematosus, scleroderma), diabetes, hyperkalaemia , ischemic heart disease, cerebrovascular disease (including cerebrovascular insufficiency), severe chronic heart failure, hemodialysis using dialysis membranes vysokoprotochnyh (AN69®), advanced age.
Pregnancy and lactation
Use of the drug Lisinopril during pregnancy is contraindicated. In establishing the drug pregnancy should be stopped as soon as possible. ACE inhibitors in the II and III trimester of pregnancy has adverse effects on the fetus (subject to marked reduction of blood pressure, renal failure, hyperkalemia, hypoplasia of the skull bones, fetal death). Data about the negative effects of the drug on the fetus when used during the I trimester there. For newborns and infants who have been exposed to ACE inhibitors in utero, it is recommended to monitor for early detection of significant decrease in blood pressure, oliguria and hyperkalemia.
During the period of treatment with the drug should be abolished breastfeeding (no data on the penetration of lisinopril passes into breast milk).
Dosing and Administration
Inside, 1 time per day in the morning, regardless of the meal, preferably at the same time.
Essential hypertension: an initial dose – 10 mg / day maintenance dose – 20 mg / day, maximum daily dose – 40 mg . Stable antihypertensive effect develops in 1-2 months, which should be considered when increasing the dose. If use of the drug at the maximum dose does not cause a sufficient therapeutic effect, it is possible additional purpose other antihypertensive agents.
Patients receiving pre diuretics, you must cancel them for 2-3 days prior to the start of the drug. If unable to cancel diuretics initial dose of lisinopril should not exceed 5 mg / day.
Renovascular hypertension or other conditions with increased activity of the RAAS: the initial dose – 2.5-5 mg / day under the control of blood pressure, kidney function, potassium blood serum. The maintenance dose is set depending on the magnitude of blood pressure.
In chronic renal failure (CRF) is determined by the dose depending on creatinine clearance (CC): with CC 30-70 ml / min – 5.10 mg / day, with CC – 10-30 ml / min – 2.5-5 mg / day, less than 10 ml / min, including patients on dialysis – 2.5 mg / day. The maintenance dose is determined depending on the pressure (controlled by the kidneys, potassium and sodium content in the blood).
CCF (simultaneously with diuretics and / or cardiac glycosides): initial dose – 2.5 mg / day, with a gradual increase of 2.5 mg every 3-5 days maintenance daily dose of 5-10 mg / day. The maximum daily dose – 20 mg. If possible, the dose of diuretic should be reduced before you start taking lisinopril.
Elderly patients are often observed a more pronounced long-term antihypertensive effect, which is associated with a decrease in the rate of excretion of lisinopril (it is recommended to start treatment with 2.5 mg / day – ½ tablets of 5 mg).
Acute myocardial infarction (in combination therapy in the first 24 hours with stable hemodynamics) in the first 24 hours – 5 mg, and then 5 mg a day,
10 mg every two days and then 10 mg 1 time per day. The course of treatment -. At least 6 weeks
at the beginning of treatment or during the first 3 days after acute myocardial infarction in patients with low systolic blood pressure (120 mmHg or lower) prescribe a lower dose – 2.5 mg. In case of reduction of blood pressure (systolic blood pressure less than or equal to 100 mm Hg) a daily dose of 5 mg, if necessary, temporarily reduced to 2.5 mg. In the case of long pronounced reduction in blood pressure (systolic blood pressure below 90 mm Hg for more than 1 hour) treatment with the drug is stopped.
Diabetic nephropathy: an initial dose – 10 mg / day, which, if necessary, increased to 20 mg / day to achieve diastolic blood pressure values below 75 mm Hg measured in the “sitting” for patients with type 1 diabetes and below 90 mmHg in the “sitting” in patients with type 2 diabetes.
The most common side effects: dizziness, headache, fatigue, diarrhea, dry cough, nausea. Cardio – vascular system : marked reduction of blood pressure, chest pain, orthostatic hypotension, tachycardia, bradycardia, new or worsening symptoms of heart failure, violation of atrioventricular conduction, myocardial infarction, palpitations. On the part of the central nervous system : emotional lability, impaired concentration, paraesthesia, somnolence, jerking of the limbs and lips, fatigue, asthenic syndrome, confusion. From the side of hematopoiesis : leukopenia, neutropenia, agranulocytosis, thrombocytopenia, anemia (decreased concentration, hemoglobin, hematocrit, erythropenia). The respiratory system : dyspnea, dry cough, bronchospasm. From the digestive system : dryness of the oral mucosa, anorexia, dyspepsia, taste changes, abdominal pain, pancreatitis, jaundice (hepatocellular or cholestatic), hepatitis. For the skin : increased sweating, alopecia, photosensitivity, pruritus. With the genitourinary system : renal failure, oliguria, anuria, acute renal failure, uremia, proteinuria , reduced potency. Allergic reactions : angioneurotic edema of the face, extremities, lips, tongue, epiglottis and / or throat, skin rash, hives, fever, positive test results antinuclear antibodies, increased erythrocyte sedimentation rate, eosinophilia, leukocytosis, intestinal angioedema. Other : . myalgia, arthralgia / arthritis, vasculitis With simultaneous use of ACE inhibitors and gold preparations (sodium aurothiomalate) intravenously, describes a symptom, including facial flushing, nausea, vomiting, and hypotension. Laboratory indicators : hyperkalemia, masteron prophyponatremia, increased activity of “liver” transaminases, hyperbilirubinemia, hypercreatininemia, increasing concentrations of urea.
Symptoms: marked reduction of blood pressure, dryness of the oral mucosa, drowsiness, urinary retention, constipation, fluid and electrolyte balance, renal failure, shortness of breath, tachycardia, palpitations, bradycardia, dizziness, anxiety, irritability.
Treatment: gastric lavage reception activated carbon, giving the horizontal position of the patient with elevated legs, replenishment of circulating blood volume – intravenous 0.9% sodium chloride solution or other plasma solutions, if necessary – vasopressor drugs, monitoring of the cardiovascular and respiratory systems, blood pressure, bcc , urea, creatinine, fluid and electrolyte balance. In the case of bradycardia resistant -. The use of artificial pacemaker
Hemodialysis is effective.
Interaction with other drugs
With simultaneous use of potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium supplements, salt substitutes containing potassium – increases the risk of hyperkalemia, especially in patients with impaired renal function. Therefore, they can jointly appoint only on the basis of individual decisions the doctor for regular monitoring of potassium serum levels and renal function.
In an application with beta-blockers, blockers “slow” calcium channel blockers, diuretics and other antihypertensive agents enhancement of the antihypertensive effect of the drug.
Lisinopril can be used in conjunction with beta-blockers, acetylsalicylic acid (in doses less than 300 mg / day), thrombolytics, nitrates.
while the use of vasodilators, barbiturates, phenothiazines, tricyclic antidepressants, ethanol – increased antihypertensive action of the drug.
in an application with non-steroidal anti-inflammatory drugs (NSAIDs) (including selective cyclooxygenase-2 inhibitors), estrogens and adrenostimulyatorov – reduced antihypertensive effect of lisinopril.
in an application with drugs lithium – slower excretion of lithium (increased cardiotoxic and neurotoxic effects of lithium).
at the same time use with antacids and colestyramine -. reduced absorption in the gastrointestinal tract
drug increases neurotoxicity salicylates, reduces the effect of hypoglycemic agents for oral administration, norepinephrine (noradrenaline), epinephrine (adrenaline) and protivopodagricakih preparations enhances the effects (including spin), cardiac glycosides effect peripheral muscle relaxants, reduces excretion of quinidine.
reduces the effect of oral contraceptives. At the same time taking methyldopa increased risk of hemolysis.
The combined use with selective serotonin reuptake inhibitors can lead to severe hyponatremia.
The combined use with allopurinol, procainamide, cytostatics may cause leukopenia.
With the simultaneous use of ACE inhibitors and gold preparations (sodium aurothiomalate) intravenously, describes a symptom, including facial flushing, nausea, vomiting, and hypotension.
Marked reduction in blood pressure often occurs with a decrease in circulating blood volume caused by diuretic therapy, reducing the amount of salt in the diet, hemodialysis, diarrhea or vomiting. In patients with chronic heart failure with simultaneous renal failure or without her, perhaps marked reduction in blood pressure. It is most often diagnosed in patients with severe stage of chronic heart failure as a result of application of high doses of diuretics, hyponatremia or impaired renal function. In these patients, treatment should start under close medical supervision (with caution in selection of dosage and diuretics).Such rules must be followed in the appointment of patients with ischemic heart disease, cerebrovascular insufficiency, in which a sharp decrease in blood pressure can lead to heart attack or stroke. Prior to treatment, if possible, should be to normalize the concentration of sodium and / or fill the volume of circulating blood, carefully controlled initial dose effect on the patient. Treatment of symptomatic hypotension includes bed rest, and, if necessary, on / in the liquid (saline infusion). Transient hypotension is not a contraindication to treatment with lisinopril, however, may require the temporary cancellation of his or dose reduction.
Treatment with Lisinopril is contraindicated in case of cardiogenic shock and acute myocardial infarction, if vasodilator appointment can significantly worsen the hemodynamic parameters, such as when the systolic BP less than 100 mm Hg. v.
In patients with acute myocardial infarction decreased renal function (creatinine concentration in plasma is more than 177 umol / l and / or proteinuria greater than 500 mg / 24 h) is a contraindication for use of the drug Lisinopril. In the case of renal insufficiency during lisinopril therapy (serum creatinine concentration in the blood plasma to more than 265 mmol / l, or twice the baseline), the doctor has to decide the need for treatment discontinuation.
In bilateral renal artery stenosis and renal artery stenosis sole kidney, as well as with hyponatremia and / or reducing the volume of circulating blood or circulatory failure, hypotension caused by the intake of the drug Lisinopril may lead to a decrease in renal function and the subsequent development of reversible (after discontinuation of the drug), acute renal failure. A slight temporary increase in the concentration of urea and creatinine in the blood can be observed in cases of impaired renal function, especially against the background of simultaneous treatment with diuretics. In cases of a significant reduction in renal function (creatinine clearance less than 30 ml / min) require careful monitoring of renal function.
Angioneurotic edema of the face, extremities, lips, tongue, epiglottis and / or the larynx is rare in patients treated with ACE inhibitors, including the drug Lisinopril, It may occur at any time during treatment. In this case, treatment with lisinopril as soon as possible and stop patient monitoring set up to complete regression of symptoms. In cases where only the face and lips originated edema, a condition often goes untreated, however, possible to assign antihistamines. Angioedema with laryngeal edema can be fatal. When covered by the language, the epiglottis, or larynx airway obstruction may occur, so it is necessary to immediately carry out the appropriate therapy (0.3-0.5 ml of epinephrine solution (epinephrine) 1: 1000 subcutaneous administration of corticosteroids, antihistamines) and / or measures to ensure airway patency.
in patients with a history already had angioedema not associated with previous treatment with ACE inhibitors, the risk of its development during treatment with an ACE inhibitor can be increased.
An anaphylactic reaction is observed and in patients on hemodialysis using vysokoprotochnyh dialysis membranes (AN69®), which simultaneously receive lisinopril. In such cases it is necessary to consider the possibility of using other types of dialysis membranes or other antihypertensive agents. You may experience anaphylactic reactions during low-density lipoprotein apheresis dextran sulfate.
In some cases, desensitization to Hymenoptera venom (wasp, bee, etc..), Treatment with ACE inhibitors was accompanied by hypersensitivity reactions. Such can be avoided by previously temporarily interrupt receiving ACE inhibitors.
In patients with extensive surgery or during general anesthesia, ACE inhibitors (such as lisinopril) can block the formation of angiotensin II. Reduction in blood pressure associated with this mechanism of action, adjusted increase in circulating blood volume. Before surgery (including dental) must notify the surgeon / anesthetist on the use of Lisinopril drug.
Use of the recommended doses of the drug in elderly patients may be associated with an increased concentration of lisinopril in the blood, so the titration requires special attention and is carried out, depending on renal function and blood pressure of the patient.
However, so in the elderly and younger patients Lisinopril antihypertensive effect of the drug is masteron prop expressed in the same degree.
By the use of ACE inhibitors coughing was observed. Cough dry, long, which disappears after discontinuation of treatment with ACE inhibitors. In the differential diagnosis of cough should be considered, and cough caused by the use of ACE inhibitors.
In some cases, there is hyperkalemia. The risk for the development of hyperkalemia factors include renal failure, diabetes, intake of potassium drugs or drugs that increase potassium in the blood (eg heparin), especially in patients with impaired renal function. During the period of drug treatment requires regular monitoring of blood potassium ion plasma glucose, urea, lipids.
During the period of treatment is not recommended to drink alcohol, as alcohol increases the antihypertensive effect of the drug.
Caution must be exercised during exercise, hot weather (risk of dehydration and excessive reduction of blood pressure due to a decrease in blood volume).
Since it is impossible to eliminate the potential risk of agranulocytosis, requires periodic monitoring of blood picture.
based on the results of epidemiological studies suggest that concomitant use of ACE inhibitors and insulin and hypoglycemic agents for oral administration may lead to hypoglycemia. The greatest risk of observed within the first weeks of combination therapy, and in patients with impaired renal function. In patients with diabetes requires careful glycemic control, especially during the first month of treatment with an ACE inhibitor. ACE inhibitors may lead to the development of cholestatic jaundice with progression to fulminant hepatic necrosis, so you need to stop taking the drug with an increase in activity of “liver” transaminases and the occurrence of symptoms of cholestasis.