ACE inhibitor, reduces the formation of angiotensin II from angiotensin I. Reduction of angiotensin II leads to a direct reduction of aldosterone release. It reduces the degradation of bradykinin and increases the synthesis of prostaglandins. It reduces the total peripheral vascular resistance, blood pressure (BP), preload, pressure in the pulmonary capillaries, causing an increase in cardiac output and increase tolerance to myocardial stress in patients with chronic heart failure. Artery expands to a greater extent than veins. Some effects are explained by the influence on the tissue renin-angiotensin system. With testosterone suspension results 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 in patients with myocardial infarction without clinical manifestations of heart failure. The antihypertensive effect begins in about 6 hours and is maintained for 24 hours. Duration of the effect is also dependent on the dose. Onset of action -. 1 hour maximum effect is determined after 6-7 hours.When hypertension effect noted in the first days after the start of treatment, stable effect develops in 1-2 months. With a sharp lifting of the drug was observed pronounced increase in blood pressure. In addition to lowering blood pressure lisinopril reduces albuminuria. Patients with hyperglycemia promotes the normalization of the function of the damaged glomerular endothelium. Lisinopril not affect the blood glucose concentration in diabetic patients and leads to increased incidence of hypoglycemia. Pharmacokinetics suction. After oral administration around 25% of lisinopril absorbed from the gastrointestinal tract. Food does not affect the absorption of the drug. Absorbance is average of 30%, bioavailability -. 29% . The distribution almost does not bind to plasma proteins. The maximum plasma concentration (90 ng / mL) was reached after 7 hours. The permeability of the blood-brain and placental barrier is low. Metabolism. Lisinopril is not biotransformed in the body. Excretion. Excreted by the kidneys unchanged.The half-life is 12 hours. Pharmacokinetics in specific patient groups In patients with chronic heart failure Absorption clearance lininoprila reduced. In patients with renal insufficiency, the concentration of lisinopril several times higher than plasma concentrations in the volunteers, and increased time observed maximum plasma concentration and increase half-life. elderly patients drug concentration in plasma and area under the curve in a 2-fold greater than in younger patients.
Arterial hypertension (as monotherapy or in combination with other antihypertensive agents), chronic heart failure (in a combination therapy for the treatment of patients taking drugs digitalis and / or diuretics), early treatment of acute myocardial infarction (during the first 24 hours with stable hemodynamics to maintain these indicators and prevention of left ventricular dysfunction and heart failure), diabetic nephropathy (insulin-dependent reduction of albuminuria in patients with normal blood pressure and insulin dependent patients with hypertension).
: Hypersensitivity to lizinoprilu or other ACE inhibitors, angioedema in history, including the use of ACE inhibitors, hereditary angioedema, age 18 years (effectiveness and safety have been established).
Precautions : severe renal impairment, a bilateral renal artery stenosis or stenosis of the artery only kidneys with progressive azotemia, condition after kidney transplantation, renal failure, azotemia, hyperkalemia, aortic stenosis, hypertrophic obstructive kardiomipatiya, primary aldosteronism, hypotension, cerebrovascular disease ( including cerebrovascular insufficiency), ischemic heart disease, coronary insufficiency, autoimmune systemic diseases of connective tissue (including scleroderma, systemic lupus erythematosus); inhibition of medullary hematopoiesis; sodium restricted diet; hypovolemic states (including through diarrhea, vomiting); elderly age.
Pregnancy and lactation
The use of 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, 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, should be closely monitored for timely detection of significant decrease in blood pressure, oliguria and hyperkalemia.
Lisinopril crosses the placenta. No data on the penetration of Lisinopril passes into breast milk. For the period of drug treatment should be abolished breastfeeding.
Dosing and Administration
Inside, regardless of meals. When hypertension patients are not receiving other antihypertensive drugs, prescribed 5 mg 1 time per day. If no effect dose is increased every 2-3 days on average to 5 mg of a therapeutic dose of 20-40 mg / day (an increase of more than 40 mg / day usually will not lead to further reduction in blood pressure). The usual daily maintenance dose – 20 mg. The maximum daily dose – 40 mg.
The full effect usually develops within 2-4 weeks of starting treatment, which should be considered when increasing the dose. When there is insufficient clinical effect of the drug can be combined with other antihypertensive agents.
If the patient has received prior treatment with diuretics, the use of these drugs should be discontinued for 2-3 days prior to the application Lizigammy. If this is not feasible, then Lizigammy initial dose should not exceed 5 mg per day. In this case, after the first dose is recommended medical supervision for several hours (maximum action is reached after about 6 hours), since it may be a marked reduction in blood pressure. If renovascular hypertension or other conditions with increased activity of the renin-angiotensin-aldosterone system appropriate to appoint as lower initial dose – 2.5-5 mg a day, under increased medical supervision (control of blood pressure, the kidneys, the concentration of potassium in blood serum). Maintenance dose, continuing strict medical control should be determined depending on the dynamics of AD. In renal failure because the lisinopril excreted through the kidneys, the initial dose should be determined according to the creatinine clearance, then according to the reaction, should establish a maintenance dose of a conditions of frequent monitoring of renal function, potassium, sodium in serum.
At the reception of hypertension shows a long-term maintenance of 10-15 mg / day treatment. In chronic heart failure – begin with 2.5 mg 1 time per day, with a consequent increase in the dose of 2.5 mg every 3-5 days to normal, maintenance a daily dose of 5-20 mg. The dose should not exceed 20 mg per day. In the elderly often observed more pronounced prolonged hypotensive 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). Acute myocardial infarction (in combination therapy) On the first day – 5 mg orally, followed by 5 mg every other day, 10 mg every two days and then 10 mg 1 time per day. In patients with acute myocardial infarction drug use for 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..) It is necessary to 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. Art.), A daily dose of 5 mg may be, 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. Art. 1 hour), treatment should be stopped Lizigammoy. Diabetic nephropathy in patients with insulin-dependent diabetes mellitus used Lizigammy 10 mg 1 time per day. The dose may, if necessary, be increased to 20 mg 1 time per day in order to achieve values below the diastolic blood pressure of 75 mm Hg. Art. in a sitting position. Patients with insulin-dependent diabetes mellitus is the same dosage, in order to achieve values below the diastolic blood pressure of 90 mm Hg. Art. in a sitting position.
The most common side effects: testosterone suspension results dizziness, headache (in 5-6% of patients), fatigue, diarrhea, dry cough (3%), nausea, vomiting, orthostatic hypotension, skin rashes, chest pain (1-3% ). Other side effects (frequency <1%): the part of the immune system: (0.1%), angioedema (face, lips, tongue, larynx or epiglottis, the upper and lower limbs). Since the cardiovascular system: marked reduction of blood pressure , orthostatic hypotension, renal dysfunction, disorders, heart palpitations heart rhythm. On the part of the central nervous system: fatigue, drowsiness, convulsive twitching of the muscles of the limbs and lips. From the hematopoietic system: leucopenia, neutropenia, agranulocytosis, thrombocytopenia, long-term treatment – a slight decrease in hemoglobin concentration and hematocrit, erythropenia.Laboratory indicators: hyperkalemia, azotemia, hyperuricemia, hyperbilirubinemia, increased activity of “liver” enzymes, especially when there is a history of kidney disease, diabetes, and renovascular hypertension. rare side effects (less than 1% ): Since the cardiovascular system: heart rate; tachycardia; myocardial infarction; cerebrovascular stroke in patients with an increased risk of disease, as a result of pronounced reduction in blood pressure. On the part of the digestive tract: dry mouth, anorexia, dyspepsia, changes in taste, abdominal pain, pancreatitis, hepatocellular or cholestatic jaundice, hepatitis.For the skin: hives, increased sweating, itching, alopecia. From the urinary system: renal failure, oliguria, anuria, acute renal failure, uremia, proteinuria. On the part of the immune system: the syndrome, including the acceleration of erythrocyte sedimentation rate (ESR), arthralgia and appearance antinuclear antibodies. On the part of the central nervous system: asthenic syndrome, mood lability, confusion, reduced potency. Other: myalgia, fever, disturbance of fetal development.
Symptoms (occur when receiving a single dose of 50 mg): marked reduction of blood pressure; dry mouth, drowsiness, urinary retention, constipation, anxiety, irritability.
. Treatment: symptomatic therapy, intravenous fluids, controlling blood pressure, fluid and electrolyte balance and normalize the last
Lisinopril can be removed from the body by hemodialysis.
Interaction with other medicinal products
require special care while applying the drug with: potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium, Vice salts containing potassium (increased risk of hyperkalemia, especially with impaired renal function, so they can jointly appoint only . based on the individual judgment of the prescribing physician with regular monitoring of potassium serum levels and renal function
Caution can be applied together: a diuretic: the additional administration of a diuretic to a patient receiving Lisinopril, as a rule, comes an additive antihypertensive effect – the risk of significant decrease in blood pressure;
- with other antihypertensive agents (additive effect);
- with non-steroidal anti-inflammatory drugs (. indomethacin, etc.), estrogens and adrenostimulyatorov – reduced antihypertensive effect of lisinopril;
- with lithium (lithium excretion may be reduced, so you should regularly monitor the concentration of lithium in blood serum);
- with antacids and colestyramine – reduce absorption in the gastrointestinal tract. Alcohol enhances the effect of the drug.
Lisinopril reduces potassium excretion from the body in the treatment of diuretic.Cautions Symptomatic hypotension is most often pronounced decrease in blood pressure occurs with a decrease in fluid volume caused by diuretic therapy, reduction of salt in food, dialysis, diarrhea or vomiting. In patients with chronic heart failure with simultaneous renal failure or without her, perhaps marked reduction in blood pressure. It is 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 Lizigammoy 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 testosterone suspension results lead to heart attack or stroke. Transient hypotensive response is not a contraindication to receiving the next dose of the drug. in applying Lizigammy, in some patients with chronic heart failure but with normal or low blood pressure, there may be a decrease in blood pressure, which is usually not a cause for discontinuation of treatment. Before treatment Lizigammoy at Wherever possible, normalize the concentration of sodium and / or compensate for the lost volume of liquid carefully control action starting dose Lizigammy to the patient. in the case of renal artery stenosis (especially in bilateral stenosis or in the presence of artery stenosis single kidney) and circulatory failure due to lack of sodium and / or liquid Lizigammy use may lead to renal dysfunction, acute renal failure, which is usually irreversible after discontinuation of the drug. in acute myocardial infarction The application of standard therapy (thrombolytics, acetylsalicylic acid, beta-blockers). Lizigammu may be used in conjunction with intravenous or using therapeutic transdermal nitroglycerin systems. Surgery / general anesthesia In extensive surgical interventions, as well as the use of other drugs that cause a decrease in blood pressure, lisinopril, blocking the formation of angiotensin II of, can cause pronounced unpredictable blood pressure reduction . in elderly patients the same dose results in a higher concentration of drug in the blood, so extra care is required when determining the dose. Because you can not rule out the potential risk of agranulocytosis, requires periodic monitoring of blood picture. In applying the drug in a dialysis polyacryl-nitrile membrane can occur anaphylactic shock, it is recommended that a different type of dialysis membrane or appointment of other antihypertensive agents.