Lisinopril – an inhibitor of the angiotensin-converting enzyme (ACE) of prolonged action, intended for the treatment of arterial hypertension, and the prevention of the development of its complications. A feature of the drug is that it is not metabolized in adipose tissue, which allows it to be used effectively in overweight patients.
History of creation
Lisinopril is a representative of the II generation of ACE inhibitors. The original drug Privil (Privinil) is manufactured by MSD, but not represented in Russia. Lisinopril – a worthy replacement for captopril, obtained in 1975. Despite the fact that the third generation of ACE inhibitors recently appeared, lisinopril under various trade names is widely used in clinical practice in Russia and abroad.
Pharmachologic Effect
An ACE inhibitor, reduces the formation of angiotensin II from angiotensin I. A decrease in the content of angiotensin II leads to a direct decrease in the release of aldosterone. Reduces the degradation of bradykinin and increases the synthesis of prostagladins. Reduces the OPSS, blood pressure, preload, pressure in the pulmonary capillaries, causes an increase in IOC and an increase in myocardial tolerance to stress in patients with CHF. Expands arteries to a greater extent than veins. Some effects are attributed to effects on tissue RAAS.
With prolonged use, hypertrophy of the myocardium and the walls of resistive arteries is reduced. Improves blood supply to ischemic myocardium. ACE inhibitors prolong life expectancy in patients with CHF, slow down the progression of left ventricular dysfunction in patients who have had a myocardial infarction without clinical manifestations of HF. The beginning of the action – after 1 hour. The maximum effect is determined after 6-7 hours, the duration – 24 hours. With arterial hypertension, the effect is noted in the first days after the start of treatment, a stable action develops in 1-2 months.
Pharmacokinetics
Absorption – 30% (6-60%); bioavailability – 25%. Poorly bound to plasma proteins. Permeability through the hemato-encephalic barrier and placental barrier is low. Cmax – about 90 ng / ml, TCmax – 7 hours. Metabolism is practically not exposed and excreted by the kidneys unchanged. T½ – 12 hours.
Indications
Arterial hypertension (in monotherapy or in combination with other antihypertensive drugs). Chronic heart failure (as part of combination therapy for the treatment of patients taking cardiac glycosides and / or diuretics). Early treatment of acute myocardial infarction (as part of combination therapy). Diabetic nephropathy (reduction of albuminuria in patients with type 1 diabetes mellitus with normal blood pressure and patients with type 2 diabetes with arterial hypertension).
Contraindications
Hypersensitivity, including to other ACE inhibitors, angioedema in the history, including the use of ACE inhibitors, hereditary angioedema, or idiopathic edema, pregnancy, lactation, age up to 18 years (efficacy and safety have not been established).
With Caution
Aortic stenosis, cerebrovascular diseases (including cerebrovascular insufficiency), coronary heart disease, coronary insufficiency, severe autoimmune systemic diseases of the connective tissue (including systemic lupus erythematosus, scleroderma), bone marrow hematopoietic oppression, diabetes mellitus, hyperaemia, and heart disease. arteries, stenosis of the artery of a single kidney, condition after kidney transplantation, renal failure, azotemia, primary aldosteronism, GOKMP, and hypotension, salt-restricted diet, conditions associated with decreased BCC (including diarrhea, vomiting), old age.
Dosing Regimen
Inside, 1 time per day in the morning, regardless of the meal, preferably at the same time. Essential hypertension: initial dose – 10 mg / day, maintenance dose – 20 mg / day. The maximum daily dose is 40 mg. For the full development of the effect may require 2-4 weeks, which should be considered when increasing the dose. If the use of the drug in the maximum dose does not cause a sufficient therapeutic effect, then the additional prescription of another antihypertensive drug is possible. In patients who received pre-diuretics, it is necessary to cancel them for 2-3 days before the start of the drug. If it is impossible to cancel diuretics, the initial dose of buy lisinopril online should be no more than 5 mg / day.
Renovascular hypertension or other conditions with increased activity of the renin-angiotensin-aldosterone system: the initial dose is 2.5-5 mg / day under the control of blood pressure, kidney function, and serum potassium concentration. Maintenance dose is set depending on the value of blood pressure. In chronic renal failure, the dose is determined depending on 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 hemodialysis – 2.5 mg / day. Maintenance dose is determined depending on blood pressure (under the control of kidney function, the concentration of K + and Na + in the blood). Chronic heart failure (simultaneously with diuretics and / or cardiac glycosides): the initial dose is 2.5 mg / day, with a gradual increase of 2.5 mg in 3-5 days to 5-10 mg / day. The maximum daily dose is 20 mg. If possible, the dose of diuretic should be reduced before starting lisinopril.
Acute myocardial infarction (as part of combination therapy in the first 24 hours with stable hemodynamic parameters): in the first 24 hours – 5 mg, then 5 mg after 1 day, 10 mg after two days and then 10 mg 1 time per day. The course of treatment is 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 less), a lower dose of 2.5 mg is prescribed. In the case of lowering blood pressure (systolic blood pressure is less than or equal to 100 mm Hg), the daily dose of 5 mg, if necessary, is temporarily reduced to 2.5 mg. In the case of a prolonged pronounced decrease in blood pressure (systolic blood pressure below 90 mm Hg. Art. More than 1 hour), treatment with the drug is stopped.
Diabetic nephropathy: the initial dose is 10 mg / day, which, if necessary, is increased to 20 mg / day in order to achieve diastolic blood pressure values below 75 mm Hg. Art. in the sitting position for patients with diabetes mellitus type 2 and below 90 mm Hg. Art. in the sitting position in patients with type 1 diabetes.
Side Effects
The most common side effects are dizziness, headache, fatigue, diarrhea, dry cough, nausea.
On the part of the cardiovascular system: marked reduction in blood pressure, chest pain, rarely – orthostatic hypotension, tachycardia, bradycardia, exacerbation of symptoms of HF, impaired AV conduction, myocardial infarction, heart palpitations.
From the side of the central nervous system: emotional lability, confusion, paresthesias, drowsiness. On the part of the blood-forming organs: leukopenia, neutropenia, agranulocytosis, thrombocytopenia, anemia (decreased Hb, hematocrit, erythropenia). On the part of the respiratory system: shortness of breath, bronchospasm.
On the part of the digestive system: dryness of the oral mucosa, anorexia, dyspepsia, changes in taste, abdominal pain, pancreatitis, jaundice (hepatocellular or cholestatic), hepatitis.
On the part of the skin: increased sweating, alopecia, photosensitivity.
On the part of the urogenital system: renal dysfunction, oliguria, anuria, acute renal failure, uremia, proteinuria, reduced potency.
Allergic reactions: angioedema of the face, extremities, lips, tongue, epiglottis and / or larynx, skin rashes, urticaria, pruritus, fever, positive antinuclear antibodies test, increased ESR, eosinophilia, leukocytosis, very rarely – intestinal angioedema,
Other: asthenia, myalgia, arthralgia/arthritis, vasculitis, jerky muscles of the limbs and lips. Laboratory indicators: hyperkalemia, hyponatremia, rarely – increased activity of “liver” enzymes, hyperbilirubinemia, hypercreatininemia, increased serum urea concentration.
Overdose. Symptoms: marked reduction in blood pressure, dryness of the oral mucosa, drowsiness, urinary retention, constipation, anxiety, irritability. Treatment: symptomatic therapy, in / in 0.9% NaCl solution, if necessary – vasopressor drugs, control of blood pressure, water and electrolyte balance. Hemodialysis is effective.
Special Instructions
Special care is required when prescribing patients with bilateral renal artery stenosis or arterial stenosis of a single kidney (an increase in the concentration of urea and creatinine in the blood is possible), in patients with IHD or cerebrovascular disease, with decompensated CHF (arterial hypotension, myocardial infarction, stroke). In patients with CHF, arising hypotension can lead to a deterioration in renal function.
A pronounced decrease in blood pressure during treatment most often occurs with a decrease in circulating blood volume caused by diuretic therapy, restriction of salt intake, dialysis, diarrhea or vomiting. Treatment with lisinopril in acute myocardial infarction is carried out against the background of standard therapy (thrombolytics, ASA, β-blockers).
Compatible with the on / in the introduction of nitroglycerin or with TTC nitroglycerin. When using blood pressure lowering drugs in patients with extensive surgery or during anesthesia, lisinopril can block the formation of angiotensin II, secondary to compensatory renin release.
Before surgery (including dental surgery), the surgeon / anesthetist should be informed about the use of an ACE inhibitor.
Based on the results of epidemiological studies, it is assumed that the simultaneous administration of ACE inhibitors and insulin, as well as oral hypoglycemic drugs, may lead to the development of hypoglycemia. The greatest risk of development is observed during the first weeks of combination therapy, as well as in patients with impaired renal function. Patients with diabetes require careful glycemia control, especially during the first month of treatment with an ACE inhibitor.
Before starting treatment, it is necessary to compensate for the loss of fluid and salt. Risk factors for the development of hyperkalemia include diabetes mellitus, diabetes mellitus and the simultaneous use of potassium-sparing diuretics (spironolactone, triamterene or amiloride), K + drugs or salt substitutes containing K +. Periodic monitoring of plasma K + concentrations is recommended.
In patients taking ACE inhibitors during desensitization to the hymenoptera, it is extremely rare that a life-threatening anaphylactoid reaction may occur. It is necessary to temporarily discontinue treatment with an ACE inhibitor before starting a course of desensitization. Anaphylactoid reactions may occur while simultaneously performing hemodialysis using high-flow membranes (including AN 69). Consideration should be given to using a different type of membrane for dialysis or another antihypertensive drug.
Safety and efficacy of lisinopril in children has not been established. Use during pregnancy is contraindicated, with the exception of cases when it is impossible to use other drugs or they are ineffective (the patient must be informed of the potential risk to the fetus).
Interaction
Slows down the excretion of drugs Li +. Nonsteroidal anti-inflammatory drugs (including selective COX-2 inhibitors), estrogens, adrenomimetics reduce the hypotensive effect. With simultaneous use with potassium-sparing diuretics and K + drugs, hyperkalemia is possible. Combined use with β-blockers, BMKK, diuretics and other antihypertensive drugs increases the severity of the antihypertensive effect. Antacids and colestyramine reduce absorption in the gastrointestinal tract. With the simultaneous use of ACE inhibitors and gold preparations (sodium aurothiomalate), a symptom complex is described, including facial flushing, nausea, vomiting, and lowering blood pressure. Insulin and oral hypoglycemic drugs – the risk of hypoglycemia.