Lisinopril organic chemistry

General characteristics. Structure:

Active ingredient: 5 mg of lisinopril in the form of a dihydrate.

Vspomogately substances: hydrophosphate calcium dihydrate, starch corn, lactoses monohydrate (sugar milk), povidone (polyvinylpirrolidone middlemolecular medical), talc, calcium stearate (calcium stearate).

The drug intended for lowering of blood pressure.

Pharmacological properties:

Pharmacodynamics. Inhibitor of an angiotensin-converting enzyme (APF), reduces formation of II angiotensin of angiotensin I. Decrease in content of angiotensin II leads to direct reduction of allocation of Aldosteronum. Reduces degradation of bradikinin and increases synthesis of prostaglandins. Reduces OPSS, the ABP, preloading, pressure in pulmonary capillaries, causes increase in minute volume of blood and increase in tolerance of a myocardium to loadings in patients with chronic heart failure. Expands arteries more than veins. Some effects are explained by influence on fabric renin-angiotensin-aldosteronovuyu system. At prolonged use the hypertrophy of a myocardium and walls of arteries of resistive type decreases. Improves blood supply of an ischemic myocardium. In addition to decrease the ABP Lizinopril Organika reduces an albuminuria.

APF inhibitors extend life expectancy at patients with chronic heart failure, slow down progressing of dysfunction of a left ventricle at the patients who had a myocardial infarction without clinical displays of heart failure.

The beginning of action - in 1 h. The maximum effect is defined by 6-7 h, duration - 24 h. At arterial hypertension the effect is noted in the first days after an initiation of treatment, stable action develops in 1-2 months.

Pharmacokinetics. Absorption of-30% (6-60%); bioavailability - 25%. Poorly contacts proteins of a blood plasma. Permeability through a blood-brain barrier and a placental barrier - low. Cmax of Lisinopril the Organic chemistry in a blood plasma makes 90 ng/ml. Time necessary for achievement of Cmax of-7 h.

To metabolism it is practically not exposed and removed by kidneys in not changed look. T1/2 is 12 h.

At patients with chronic heart failure absorption and clearance of Lisinopril Organic chemistry are reduced.

At patients with a renal failure concentration of Lisinopril the Organic chemistry several times exceeds concentration in a blood plasma at volunteers, and increase in time of achievement of Cmax in a blood plasma and increase in T1/2 is noted.

Patients of advanced age have a concentration of drug in a blood plasma and the area under a curve is twice more, than at patients of young age.

Indications to use:

— arterial hypertension (in monotherapy or in a combination with other antihypertensives);

— chronic heart failure (as a part of a combination therapy for treatment of the patients accepting cardiac glycosides and/or diuretics);

— early treatment of an acute myocardial infarction as a part of a combination therapy (in the first 24 h with stable indicators of a hemodynamics for maintenance of these indicators and prevention of dysfunction of a left ventricle and heart failure);

— a diabetic nephropathy (decrease in an albuminuria at patients with a diabetes mellitus of 1 type with the normal ABP and patients with a diabetes mellitus 2 types with arterial hypertension).

Route of administration and doses:

Inside, 1 time a day in the morning, irrespective of meal, preferably at the same time.

At arterial hypertension the patient who is not receiving other antihypertensives apply 5 mg of 1 times a day. In the absence of effect the dose is raised by each 2-3 days on 5 mg to an average therapeutic dose of 20-40 mg/days (increase in a dose usually does not lead over 40 mg/days to further decrease in the ABP). A usual daily maintenance dose - 20 mg. The maximum daily dose - 40 mg. At insufficient therapeutic effect the drug combination with other antihypertensives is possible.

If the patient received preliminary treatment by diuretics, then reception of such drugs needs to be stopped in 2-3 days prior to use of the drug Lisinopril Organic Chemistry.

If it is impossible, then the initial dose of the drug Lisinopril Organic Chemistry should not exceed 5 mg a day. In this case, after reception of the first dose medical control within several hours (the maximum of action is reached approximately in 6 hours) as there can be an expressed decrease in the ABP is recommended.

At renovascular hypertensia or other states with a superactivity renin-angiotensin-aldosteronovoy of system it is reasonable to appoint also low initial dose of 5 mg a day under the strengthened medical control (control of the ABP, function of kidneys, contents of potassium in blood serum). A maintenance dose, continuing strict medical control, it is necessary to define depending on ABP loudspeakers. At a renal failure in view of the fact that Lisinopril the Organic chemistry is removed by kidneys, the initial dose has to be defined depending on the clearance of creatinine (CC). Further selection of doses should be made depending on individual reactions at regular control of function of kidneys, contents of potassium, sodium in blood serum. The initial dose at KK of 30-70 ml/min. makes 5-10 mg/days, 10-30 ml/min. - 5 mg/days, less than 10 ml/min., including the patients who are on a hemodialysis - 2.5 mg/days.

At chronic heart failure: an initial dose - 2.5 mg a day, with gradual increase in 3-5 days to 5-10 mg a day. The maximum daily dose - 20 mg.

Early treatment of an acute myocardial infarction (as a part of a combination therapy): in the first 24 h - 5 mg, then 5 mg in a day, 10 mg in two days and then on 10 mg of 1 times a day. A course of treatment - not less than 6 weeks. In an initiation of treatment or within 3 days after an acute myocardial infarction at patients with the low systolic ABP (120 mm of mercury. or below) appoint a smaller dose - 2.5 mg. In case of decrease in the ABP (systolic the ABP is lower or 100 mm of mercury are equal.) the daily dose in 5 mg if necessary is reduced to 2.5 mg. In case of the long expressed decrease in the ABP (systolic the ABP less than 90 mm of mercury. more than 1 p) treatment by drug should be stopped.

At a diabetic nephropathy (decrease in an albuminuria patients with a diabetes mellitus of 1 type with normal arterial pressure and at patients with a diabetes mellitus have 2 types with arterial hypertension): an initial dose of-10 mg/days which is raised if necessary to 20 mg/days for achievement of target values of diastolic arterial pressure.

Use of lisinopril in other dosage forms - tablets of 2.5 mg or a tablet of 5 mg with risky for providing this mode of dosing is possible.

Features of use:

Symptomatic hypotension: most often the expressed decrease in the ABP arises at decrease in the volume of the circulating blood (VCB), the caused therapy by diuretics, reduction of table salt in food, dialysis, diarrhea or vomiting. At patients with chronic heart failure with a simultaneous renal failure or without it, perhaps expressed decrease in the ABP. Under strict control of the doctor it is necessary to use the drug Lisinopril Organic Chemistry at patients with coronary heart disease, cerebrovascular insufficiency at whom sharp decrease in the ABP can lead to a myocardial infarction or a stroke.

Tranzitorny arterial hypotension is not a contraindication for reception of the following dose of drug.

At use of the drug Lisinopril Organic Chemistry, at some patients with chronic heart failure, but with the normal or reduced ABP, decrease in the ABP can be noted that usually is not the reason for the treatment termination.

Prior to treatment by drug, whenever possible, it is necessary to normalize the content of sodium and/or to fill OTsK, to carefully control action of an initial dose of the drug Lisinopril Organic Chemistry on the patient.

In case of a stenosis of renal arteries (in particular, at a bilateral stenosis or in the presence of a stenosis of an artery of the only kidney), and also at a circulatory unefficiency owing to a lack of ions of sodium and/or liquid, use of the drug Lisinopril Organic Chemistry can lead to a renal failure, an acute renal failure which usually is irreversible even after drug withdrawal.

At an acute myocardial infarction use of standard therapy is shown (trombolitik, acetylsalicylic acid, beta adrenoblockers) Organic chemistry perhaps to apply Lisinopril together with intravenous administration or using therapeutic transdermal systems of nitroglycerine.

Surgical intervention / general anesthesia: at extensive surgical interventions, and also at use of other means causing decrease in the ABP, Lisinopril Organic chemistry, blocking formation of angiotensin II, can cause the expressed not predicted decrease in the ABP.

The Quincke's disease of the person, extremities, lips, language, epiglottis and/or throat was noted seldom at the patients treated by APF inhibitors which can arise during any period of treatment. In that case, treatment by the drug Lisinopril Organic Chemistry needs to be stopped as soon as possible and for the patient to establish observation before full regression of symptoms. The state most often undergoes in cases when there was hypostasis only of the person and lips, without treatment, however, perhaps purpose of antihistamines.

The Quincke's disease with hypostasis of a throat can be lethal. When hypostasis captured language, an epiglottis or a throat, there can be an obstruction of respiratory tracts. Therefore it is necessary to carry out immediately the corresponding therapy (0.3-0.5 ml of solution of Epinephrinum (adrenaline) 1:1000 subcutaneously, introduction of glucocorticosteroids, antihistaminic drugs) and/or measures for ensuring passability of respiratory tracts. At patients who in the anamnesis already had a Quincke's disease which is not connected with the previous treatment by APF inhibitors the risk of its development can be increased during treatment by APF inhibitor. Anaphylactic reaction is noted at the patients who are on a hemodialysis with use of high-flowing dialysis membranes (AN69®) which at the same time accept APF inhibitors. In such cases it is necessary to consider the possibility of use of other type of a membrane for dialysis or other anti-hypertensive means. Emergence of anaphylactic reactions when carrying out an aferez of lipoproteins of low density by means of dextran sulfate is possible. In some cases desensitizations by poison of Hymenoptera, treatment by APF inhibitors was followed by hypersensitivity reactions. Similar can be avoided if it is previously temporary to interrupt reception of APF inhibitors.

At patients of advanced age the same dose results in higher concentration of drug in blood therefore extra care when determining a dose is required.

At use of APF inhibitors cough was noted. Cough dry, long which disappears after the treatment termination by APF inhibitors. At the differential diagnosis of cough, it is necessary to consider also the cough caused by use of APF inhibitors.

On the basis of results of epidemiological researches it is supposed that the concomitant use of APF inhibitors and insulin, and also hypoglycemic means for intake can lead to development of a hypoglycemia. The greatest risk of development is observed within the first weeks of a combination therapy, and also at patients with a renal failure. Careful control of a glycemia is required from patients with a diabetes mellitus, especially during the first month of therapy by APF inhibitor.

The hyperpotassemia was in certain cases noted. Risk factors for development of a hyperpotassemia include a renal failure, a diabetes mellitus, administration of drugs of potassium or the drugs causing increase in content of potassium in blood (for example, heparin), especially at patients with an impaired renal function. During treatment by drug regular control at patients in a blood plasma of potassium ions, glucose, urea, lipids is necessary.

During treatment it is not recommended to take alcoholic beverages as alcohol strengthens hypotensive effect of drug.

As it is impossible to exclude potential risk of emergence of an agranulocytosis, periodic control of a picture of blood is required.

Influence on ability of control of vehicles and mechanisms. There are no data on the Lisinopril influence Organic chemistry on ability to control of vehicles and mechanisms applied in therapeutic doses, however it is necessary to consider that developing of dizziness therefore it is necessary to be careful is possible.

At pregnancy establishment administration of drug Lisinopril Organic chemistry needs to be stopped as soon as possible. Reception of APF inhibitors in II and the III trimester of pregnancy makes an adverse effect on a fruit (the expressed decrease in the ABP, a renal failure, a hyperpotassemia, a hypoplasia of bones of a skull, pre-natal death are possible).

There are no data on negative impacts of drug on a fruit in case of use during the I trimester. For newborns and babies who underwent pre-natal influence of APF inhibitors it is recommended to conduct careful observation for early detection of the expressed decrease in the ABP, an oliguria, a hyperpotassemia.

Lisinopril Organic chemistry gets through a placenta. There are no data on release of Lisinopril Organic chemistry in breast milk. If administration of drug Lisinopril Organic chemistry is necessary in the period of a lactation, then breastfeeding needs to be cancelled.

Side effects:

The most often found side effects: dizziness, a headache (at 5-6% of patients), weakness, diarrhea, dry cough (3%), nausea, vomiting, orthostatic hypotension, skin rash, a stethalgia (1-3%).

Other side effects (frequency <1%):

From immune system: (0.1%) Quincke's disease (face, upper and lower extremities, lips, language, throat or epiglottis).

From cardiovascular system: a heart consciousness, tachycardia, orthostatic hypotension, a myocardial infarction, a cerebrovascular stroke at patients with the increased risk of a disease owing to the expressed decrease in the ABP, a renal failure.

From TsNS: asthenic syndrome, lability of mood, confusion of consciousness, increased fatigue, drowsiness, convulsive twitchings of muscles of extremities and lips.

From system of a hemopoiesis: the leukopenia, a neutropenia, an agranulocytosis, thrombocytopenia are possible; at prolonged treatment - small decrease in hemoglobin and a hematocrit, an erythrocytopenia.

From a digestive tract: dryness of a mucous membrane of an oral cavity, anorexia, dyspepsia, changes of taste, abdominal pain, pancreatitis, hepatocellular or cholestatic jaundice, hepatitis.

From integuments: a small tortoiseshell, the increased sweating, a skin itch, an alopecia.

From an urinary system: renal failure, oliguria, anury, acute renal failure, uraemia, proteinuria.

Laboratory indicators: a hyperpotassemia, an azotemia, a hyperuricemia, a hyperbilirubinemia, increase in activity of hepatic transaminases, especially in the presence in the anamnesis of diseases of kidneys, a diabetes mellitus and renovascular hypertensia.

Others: mialgiya, fever, disturbance of fetation.

Interaction with other medicines:

Slows down removal of drugs of lithium (release of lithium can decrease therefore it is regularly necessary to control concentration of lithium in blood serum).

Non-steroidal anti-inflammatory drugs (including the selection inhibitors of cyclooxygenase-2), are oestrogenic, adrenostimulyator reduce hypotensive effect.

At simultaneous use with kaliysberegayushchy diuretics and drugs of potassium the hyperpotassemia is possible.

The combined use with beta adrenoblockers, blockers of "slow" calcium channels, diuretics, tricyclic antidepressants / neuroleptics and other hypotensive medicines, increases expressiveness of hypotensive action.

Antacids and Colestyraminum reduce absorption in a GIT and sizhat hypotensive effect of Lisinopril Organic chemistry.

The means possessing myelosuppressive action at simultaneous use with Lisinopril Organic chemistry increase risk of development of a neutropenia and/or agranulocytosis.

Allopyrinolum, cytostatics, immunodepressants, procaineamide at simultaneous use with Lisinopril Organic chemistry can lead to development of a leukopenia, besides, Allopyrinolum and procaineamide in combination with Lisinopril Organic chemistry can lead to development of a multiformny erythema.

At simultaneous use of APF inhibitors and drugs of gold intravenously (sodium ауротиомалат) the symptom complex including a hyperemia of the person, nausea, vomiting and decrease in the ABP is described.

At combined use with selective serotonin reuptake inhibitors can lead to the expressed hyponatremia.

At combined use with insulin and hypoglycemic means for intake the risk of development of a hypoglycemia is possible.

The case of development of a heavy hyperpotassemia in the patient with a diabetes mellitus at simultaneous use with lovastatiny is described.

The case of heavy arterial hypotension at simultaneous use with pergolidy is described.

Lisinopril the Organic chemistry strengthens manifestations of a drunkenness. Against the background of effect of alcohol strengthening of hypotensive effect of Lisinopril Organic chemistry is possible.

Narcotic analgetics, anesthetics, hypnagogues in combination with Lisinopril Organic chemistry cause strengthening of hypotensive effect.

The anti-hypertensive effect of Lisinopril Organic chemistry decreases against the background of chloride sodium overconsumption.

Contraindications:

— a Quincke's disease in the anamnesis, including against the background of use of APF inhibitors;

— hereditary Quincke's edema or idiopathic Quincke's disease;

— lactose intolerance, deficit of lactase, syndrome of glyukozo-galaktozny malabsorption;

— pregnancy;

— lactation period;

— age up to 18 years (efficiency and safety are not established);

— hypersensitivity to Lisinopril Organic chemistry or to other APF inhibitors, other components of drug.

With care. The expressed renal failures; a bilateral stenosis of renal arteries or a stenosis of an artery of the only kidney with the progressing azotemia; a state after transplantation of a kidney; renal failure, azotemia; diabetes mellitus; hyperpotassemia; stenosis of the mouth of an aorta; hypertrophic subaortic stenosis; primary hyper aldosteronism; arterial hypotension; cerebrovascular diseases (including insufficiency of cerebral circulation); coronary heart disease; coronary insufficiency; autoimmune general diseases of connecting fabric (including scleroderma, system lupus erythematosus); oppression of a marrowy hemopoiesis; a diet with restriction of table salt; hypovolemic states (including as a result of diarrhea, vomiting); advanced age.

Overdose:

Symptoms: the expressed decrease in the ABP, dryness of a mucous membrane of an oral cavity, disturbance of water and electrolytic balance, a renal failure, breath increase, tachycardia, a heart consciousness, bradycardia, dizziness, a condition of alarm, an acrimony, cough, drowsiness, an urination delay, a lock.

Treatment: symptomatic therapy, intravenous administration of 0.9% of solution of sodium of chloride, if necessary - angiotonic HP, control of the ABP, water and electrolytic balance. The hemodialysis is effective. Gastric lavage, use of enterosorbents and purgatives. In case of steady bradycardia statement of a temporary pacemaker is necessary.

Storage conditions:

To store in the dry, protected from light place at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

On 10 pieces of tablets - planimetric strip packagings (on 2) - packs cardboard.
On 10 pieces of tablets - planimetric strip packagings (on 3) - packs cardboard.
On 10 pieces of tablets - planimetric strip packagings (on 5) - packs cardboard.
On 20 pieces of tablets - banks (on 1) light-protective glass - a pack cardboard.
On 30 pieces of tablets - banks (on 1) light-protective glass - a pack cardboard.
On 50 pieces of tablets - banks (on 1) light-protective glass - a pack cardboard.