All about lisinopril: application, indications and form of release

Instructions for the use of Lisinopril

In the development of hypertension, an important role is played by the stimulation of the renin-angiotensin-aldosterone system (RAAS), which is responsible for the concentration of water, electrolytes and vascular tone.

Various structural mechanisms are involved in the regulation of vascular tone:

• various parts of the central nervous system (CNS);
• peripheral fibers of the autonomic NS;
• humoral factors (RAAS, sympathoadrenal, calicrein-kinin system);
• prostaglandins - powerful vasoconstrictors (cause vasoconstriction);
• prostacyclins - dilate arterioles.

RAAS is presented in the form of a complex combination of enzymes and hormones, the main components of which are:

• angiotensinogen;
• renin;
• angiotensins I and II;
• receptors on the vascular wall, sensitive to angiotensin-II.

There are two main theories in the development of hypertension:

1. Violation of nervous regulation. It occurs against the background of insufficient hormonal mechanisms of influence on the tone of arterioles, previous renal diseases, age-related changes in blood vessels, endocrine disorders during menopause.
2. Imbalance between pressor and depressor effects. An increase in the tone of the vascular wall occurs against the background of depletion of the depressant effects of the kidneys.

As a result of the above violations, there is:

• overloading by the volume of the vascular bed;
• increased cardiac output (CO);
• hyperstimulation of the sympathetic nervous system (SNS);
• renal dysfunction;
• increase in total peripheral vascular resistance (OPSS).

An overload of the volume of the vascular bed develops due to the accumulation of Na ions in the plasma and the vessel wall, which entails its edema, the lumen narrows and the systemic vascular resistance increases. Na ions increase the sensitivity of the smooth muscle layer of the vessel to angiotensin II and norepinephrine. Through narrowed arterioles, blood enters the organs in a smaller amount (relative hypovolemia). In response to this, the heart is forced to contract harder and more frequently (as a result of SNS activation). Norepinephrine also causes spasm of the smooth muscle of the arterioles, which provokes an even greater increase in blood pressure.

Prolonged spasm of arterioles in the kidneys causes a drop in pressure in the capillaries supplying the juxtaglomerular apparatus (JGA). In order to compensate for hypoxia, JHA releases renin into the bloodstream, which, under the action of an angiotensin-converting enzyme (ACE), forms a substance that persistently constricts the vessels - angiotensin II.

The mechanism of action of angiotensin II:

• interacts with special receptors on the myocytes of the vessels of the kidneys, lungs, liver, aorta, spleen, brain, adrenal glands;
• stimulates the vascular-motor center in the posterior part of the brain;
• increases the secretion of norepinephrine;
• influence on the work of the medullary layer of the adrenal glands (even more adrenaline enters the bloodstream) and cortical (secretion of aldosterone, which increases the retention of Na and water by the kidneys;
• independently activates the pathways of absorption of Na and water in the tubules, bypassing the participation of aldosterone.

What is this drug and what does it help from?

Lisinopril is a long-lasting antihypertensive agent belonging to the group of angiotensin-converting enzyme (ACE) inhibitors. The medication is a representative of the III class (hydrophobic metabolite of Enalapril).

Pharmacological classification of ACE inhibitors

The principle of action is to block the activity of one of the key enzymes of the RAAS, which promotes the conversion of the inert form of angiotensin-I into highly active angiotensin-II.

Actions of Lisinopril:

• stimulation of renin production and decrease in angiotensin;
• disintegration of bradykinin;
• blocking the production of aldosterone;
• vasodilation (expansion) of arterioles and veins;
• correction of pre- and afterload on the myocardium;
• reduction of Na retention by the kidneys;
• prevents the aggravation of dilatation of the cavities of the left ventricle (LV);
• regression of the phenomena of LV hypertrophy;
• decrease in proliferation (proliferation) of smooth muscle cells in the walls of blood vessels;
• stabilization of the heart rate (improvement of myocardial trophism, an increase in the concentration of K ions⁺ and Mg⁺ in plasma);
• nephroprotection by improving blood flow in the kidneys;
• able to reduce platelet aggregation (stimulates the secretion of prostaglandin E₂, prostacyclin, endothelium relaxant factor);
• Slowing the progression of atherosclerosis;
• Antioxidant effect;
• Optimization of glucose metabolism.

Lisinopril is the only representative of an ACE inhibitor that does not undergo metabolic transformations in tissues and is completely eliminated by the kidneys without changing its structure. The drug can be used safely in patients with decreased hepatic function (since it is a ready-made active drug).

Lisinopril is hydrophilic; this means that for its transportation through the body, it is practically not required to form compounds with albumin in the blood. This allows prescribing a medication to patients with hypoalbuminemia, combining it with medications that require transport proteins (cardiac glycosides, anticoagulants, antiarrhythmics).

This drug increases the compliance of the elastic-type vascular walls (including the aorta). Also, Lisinopril blocks the release of protein molecules into the urine in patients with diabetes mellitus, that is, it slows down the progress of latent nephropathy.

Lisinopril has the ability to sensitize tissues to insulin, which gives it an advantage in the treatment of patients with a combination of hypertension and type II diabetes mellitus.

Due to its hydrophilic properties, the drug practically does not dissolve and is not deposited in adipose tissue, therefore, it is more preferable for prescribing to overweight patients.

The bioavailability of Lisinopril ranges from 26-50%, food does not interfere with the absorption of the drug. The maximum concentration of the drug is found in the blood after 6-7 hours. The half-life is 12 hours. The decrease in blood pressure begins 60 minutes after taking the pill. The effect of the treatment stabilizes after 1 month of systematic administration.

This makes it possible to take a Lisinopril tablet once throughout the day and maintain a stable blood pressure level, as well as avoid morning rises in blood pressure.

Indications: what is the medicine prescribed for?

Lisinopril may be the only drug in the diet or a component of complex therapy for cardiovascular pathologies.

According to studies, the use of Lisinopril stabilizes blood pressure levels in 50-80% of patients with AH of I and II severity.

Indications for use:

• primary and secondary forms of arterial hypertension (especially with a long history);
• chronic circulatory failure with systolic LV dysfunction;
• acute coronary syndrome (with systolic pressure above 100 mm Hg);
• prevention of repeated cardiovascular accidents in patients after AMI;
• insulin-dependent type II diabetes mellitus complicated by nephropathy.

How to take and in what dosages?

It is enough to take Lisinopril once a day, optimally in the first half of the day, without becoming attached to food intake. The best clinical effect is achieved if the drug is used systematically at the same time.

Arterial hypertension.

The initial dosage is 2.5 mg / day. To achieve a stable effect, you must drink the drug for 2-4 weeks. And only after that, if necessary, increase the dose to 10-20 mg / day within 1 week.

The usual maintenance dose is 10-20 mg (maximum daily dose is 40 mg).

It is not recommended to exceed the dosage of 40 mg; it is better to additionally prescribe an antihypertensive drug of another group.

Heart failure.

The saturation dose is 2.5 mg / day. Gradually, it is brought to the average therapeutic level - 20 mg / day.

Acute coronary syndrome.

Patients with AMI and ST-segment elevation are recommended to use Lisinopril on the first day after the onset of an anginal attack.

The initial dosage is 5 mg / day, the average therapeutic dosage is 10 mg / day. In case of arterial hypotension, when CAT is <100 mm Hg, the dose of the drug is reduced to 2.5 mg / day.

The duration of the course is 6-7 weeks, then additional studies are required to confirm the presence of indications for further use of the drug (if LV dysfunction is detected, it is recommended to continue treatment at a dosage of 10-20 mg / day).

Nephropathy in patients with diabetes mellitus.

The starting dose of Lisinopril is 10 mg / day (maximum - 20 mg / day).

With clinically pronounced renal dysfunction, the dose of Lisinopril should be calculated taking into account the creatinine values. Maximum - no more than 20 mg / day.

In some clinical cases, it is worth increasing the intervals between doses up to 48 hours.

For better stabilization of pressure indicators, it is advisable to combine Lisinopril with diuretics (hydrochlorothiazide, Indopamide).

Contraindications to both use and symptoms of overdose

Contraindications to the appointment of Lisinopril:

1. Absolute:
   1. Pregnancy and the period of breastfeeding.
   2. Bilateral narrowing of the renal arteries.
   3. Quincke's edema.
   4. Primary hyperaldosteronism.
   5. Intolerance or allergy to any of the components of the drug.
   6. Severe stenosis of the aortic and mitral valves.
   7. Obstructive form of hypertrophic cardiomyopathy (HCM).
   8. Anuria.
   9. Arterial hypotension (CAT below 70 mm Hg).
   10. Cardiogenic shock.
2. Relative:
   1. Diffuse connective tissue pathology (dermatomyositis, systemic lupus erythematosus, polyarthritis nodosa and rheumatoid arthritis, scleroderma).
   2. Hypovolemia.
   3. Combined use with potassium-preserving diuretics (Veroshpiron).
   4. Hyperkalemia.
   5. Terminal stage of chronic renal failure (CRF).
   6. Childhood.

If you suspect Lisinopril poisoning, you must immediately stop treatment, induce vomiting, take a sorbent, lay the patient horizontally with the head and leg ends raised, urgently call an ambulance.

Side effects

In general, Lisinopril is well tolerated by patients - the reactions that occur are mild and do not require discontinuation of the drug.

Possible side reactions:

1. Arterial hypotension (often - "the effect of the first dose"), dizziness with a sharp change in body position, palpitations, general malaise, blurred vision; In patients with AMI, within 24 hours from the onset of an attack, it is possible to develop II-III degree AV block, cardiogenic shock.
2. Acute renal failure, dysuric manifestations, anuria, edema.
3. Weakening of sexual desire, gynecomastia.
4. Dry obsessive cough, shortness of breath, decreased bronchial patency, burnt tongue syndrome.
5. Indigestion, epigastric discomfort, nausea, impaired appetite, distortion of taste.
6. Skin rashes, redness, itching, Quincke's edema (possibly fatal), urticaria, autoimmune reactions.
7. Decrease in the number of red blood cells, platelets, leukocytosis.
8. Sleep disturbance, anxiety, paresthesia, tinnitus, depression.
9. Double vision, sensitivity to light, decreased visual acuity.

Lisinopril's analogs

The original Lisinopril has an affordable price, but there are still many generics on the market (analogues of the drug from different manufacturing countries).

Substitutes (synonyms) for Lisinopril in Russia

• Lisinopril-Ratiopharm;
• Diroton (Hungary);
• Diropress (Germany, Slovenia);
• Iruzid (Croatia);
• Ko-Diroton (Poland, Hungary);
• Lysigamma (Germany);
• Rileis-Sanovel (Turkey);
• Skopril (Macedonia);
• Equator (Hungary, Russia).

Lisinopril is available in the form of tablets of 5, 10 and 20 mg.

There are also many medicines on the market with a combination of Lisinopril with other groups of antihypertensive substances:

• with Amlodipine (Equator, Tenliza);
• with hydrochlorothiazide (Co-Diroton, Lisinopril-H, HL, Lizoretic);
• with Indopamide (Diroton-Plus).

Such combinations were created in order to simplify the intake regimen, reduce the number of tablets, which increases the likelihood of systematic use of the medication.

Conclusions

Lisinopril is a long-acting ACE inhibitor with high efficiency. The drug is considered the "gold standard" in the treatment of hypertension and circulatory failure (together with diuretics, statins, angiotensin II antagonists and Ca blockers²⁺channels). The combined use of Lisinopril and Indapamide reduces the likelihood of recurrent episodes of ischemic stroke by 29%, and intracranial hemorrhage by 50%.

It is worth remembering that the plateau of the antihypertensive effect occurs no earlier than 10-14 days from the start of treatment.

Before using the drug, you must carefully read the instructions! Lisinopril can not be taken without a doctor's prescription, as well as independently replace it with an analogue.