All about lisinopril: use, indications and release form

Instructions for use of Lisinopril

In the process of developing hypertension, stimulation of the renin-angiotensin-aldosterone system (RAAS), which is responsible for the concentration of water, electrolytes and vascular tone, plays an important role.
Various structural mechanisms are involved in the regulation of vascular tone:

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

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

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

There are two main theories in the development of hypertension:

1. Dysfunction of nervous regulation. Occurs against the background of insufficiency of hormonal mechanisms influencing the tone of arterioles, previous kidney diseases, age-related changes in blood vessels, endocrine disorders during menopause.
2. Imbalance between pressor and depressor influences. An increase in the tone of the vascular wall occurs against the background of depletion of the depressor effects of the kidneys.

As a result of the above violations, the following occurs:

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

Volume overload of the vascular bed develops due to the accumulation of Na ions in the plasma and the vessel wall, which entails its swelling, the lumen narrows and the peripheral 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 smaller quantities (relative hypovolemia). In response to this, the heart is forced to contract stronger and more often (as a result of activation of the SNS). Norepinephrine also causes spasm of the smooth muscles of 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, JGA releases renin into the bloodstream, which, under the action of angiotensin-converting enzyme (ACE), forms a substance that persistently constricts blood vessels - angiotensin II.

Mechanism of action of angiotensin II:

• interacts with special receptors on the myocytes of the blood 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 functioning of the medullary layer of the adrenal glands (even more adrenaline enters the bloodstream) and cortical layer (secretion of aldosterone, which increases the retention of Na and water by the kidneys;
• independently activates the absorption pathways of Na and water in the tubules, bypassing the participation of aldosterone.

What kind of drug is this and what does it help with?

Lisinopril is an antihypertensive drug with a long-term effect, belonging to the group of angiotensin-converting enzyme inhibitors (ACE inhibitors). The drug is a representative of class III (a 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 the highly active angiotensin-II.

Actions of Lisinopril:

• stimulation of renin production and reduction of angiotensin;
• bradykinin breakdown;
• blocking aldosterone production;
• vasodilation (expansion) of arterioles and veins;
• correction of pre- and afterload on the myocardium;
• reduction of Na retention by the kidneys;
• prevents worsening dilatation of the left ventricular (LV) cavities;
• regression of LV hypertrophy phenomena;
• decreased proliferation (growth) of smooth muscle cells in the walls of blood vessels;
• stabilization of heart rhythm (improved myocardial trophism, increased concentration of K+ and Mg+ ions in plasma);
• nephroprotection by improving blood flow in the kidneys;
• capable of reducing platelet aggregation (stimulates the secretion of prostaglandin E2, prostacyclin, endothelium-relaxing factor);
• Slowing the progression of atherosclerosis;
• Antioxidant effect;
• Optimizing glucose metabolism.

Lisinopril is the only representative of the 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 safely used in patients with decreased liver function (as it is a ready-made active drug).

Lisinopril is hydrophilic; this means that for its transportation throughout the body there is practically no need to form compounds with albumin in the blood. This allows the drug to be prescribed to patients with hypoalbuminemia and combined with medications that require transport proteins (cardiac glycosides, anticoagulants, antiarrhythmics).

This medicine increases the compliance of elastic-type vascular walls (including the aorta). Lisinopril also blocks the release of protein molecules into the urine in patients with diabetes, 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 qualities, the drug practically does not dissolve and is not deposited in adipose tissue, therefore it is more preferable for use in 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 detected in the blood after 6-7 hours. The half-life is 12 hours. The decrease in blood pressure begins 60 minutes after taking the tablet. The effect of treatment stabilizes after 1 month of systematic use.

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: why is the medicine prescribed?

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 hypertension of I and II severity.

Indications for use:

• primary and secondary forms of arterial hypertension (especially with a long history);
• chronic circulatory failure with LV systolic dysfunction;
• acute coronary syndrome (with systolic pressure above 100 mmHg);
• prevention of recurrent cardiovascular accidents in patients after AMI;
• insulin-dependent form of diabetes mellitus type II, 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 being tied to meals. The best clinical effect is achieved with systematic use of the drug at the same time.

Arterial hypertension.

The initial dosage is 2.5 mg/day. To achieve a stable effect, you need to take the drug for 2-4 weeks. And only after this, 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 dose of 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 SAT <100 mmHg, 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).

In case of clinically significant renal dysfunction, the dose of Lisinopril should be calculated taking into account creatinine levels. Maximum - no more than 20 mg/day.

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

To better stabilize blood pressure, it is advisable to combine Lisinopril with diuretics (Hydrochlorothiazide, Indopamide).

Contraindications for use and symptoms of overdose

Contraindications to the use of Lisinopril:

1. Absolute: Pregnancy and 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 (SAT below 70 mmHg).
10. Cardiogenic shock.

If you suspect poisoning with Lisinopril, you must immediately stop treatment, induce vomiting, take a sorbent, lay the patient horizontally with the head and legs raised, and 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 use of the drug.

Possible adverse reactions:

1. Arterial hypotension (often the “first dose effect”), dizziness with a sudden change in body position, palpitations, general malaise, blurred vision; In patients with AMI, II-III degree AV block and cardiogenic shock may develop within 24 hours from the onset of the attack.
2. Acute renal failure, dysuric manifestations, anuria, edema.
3. Decreased sexual desire, gynecomastia.
4. Dry obsessive cough, shortness of breath, decreased bronchial obstruction, “burnt tongue” syndrome.
5. Indigestion, epigastric discomfort, nausea, loss of appetite, distortion of taste.
6. Skin rashes, redness, itching, angioedema (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.

Side effects

Classification of the frequency of side effects: very often (≥1/10); often (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000); very rare (<1/10,000), including isolated reports.

Side effects of candesartan are mild and transient. The frequency of side effects does not depend on the dose of the drug and the age of the patient.

From the nervous system: often - dizziness, headache, weakness.

From the cardiovascular system: often - a pronounced decrease in blood pressure.

From the respiratory system: often - respiratory infections, pharyngitis, rhinitis, cough.

From the digestive system: very rarely - nausea, increased activity of liver transaminases, impaired liver function or hepatitis.

From the urinary system: often - impaired renal function, including renal failure in predisposed patients.

From the musculoskeletal system: very rarely - back pain, arthralgia, myalgia.

From the hematopoietic system: very rarely - leukopenia, neutropenia, thrombocytopenia and agranulocytosis.

Laboratory indicators: very rarely - hyperkalemia, hyponatremia, increased creatinine concentration in the blood, hyperuricemia, slight decrease in hemoglobin.

Allergic reactions: very rarely - angioedema, skin rash, itching, urticaria.

Other: exacerbation of gout, “flushes” of blood to the skin of the face.

Lisinopril analogs

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

Substitutes (synonyms) for Lisinopril in Russia

• Lisinopril-Ratiopharm;
• Diroton (Hungary);
• Diropress (Germany, Slovenia);
• Iruzid (Croatia);
• Ko-Diroton (Poland, Hungary);
• Lysigamma (Germany);
• Rileys-Sanovel (Türkiye);
• Scopril (Macedonia);
• Equator (Hungary, Russia).

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

There are also many medications on the market that combine Lisinopril with other groups of antihypertensive substances:

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

Such combinations were created to simplify the regimen and reduce the number of tablets, which increases the likelihood of systematic use of the drug.

Overdose

Symptoms: excessive decrease in blood pressure, dizziness, tachycardia. Isolated cases of drug overdose (up to 672 mg of candesartan cilexetil) have been described, resulting in the recovery of patients without serious consequences.

Treatment: if there is a pronounced decrease in blood pressure, the patient should be placed in a supine position with his legs raised; further - carry out measures aimed at increasing the volume of blood volume (administration of 0.9% sodium chloride solution intravenously). If necessary, sympathomimetic drugs can be prescribed. It is recommended to carry out symptomatic therapy under the control of vital functions of the body. Hemodialysis is ineffective.

conclusions

Lisinopril is a long-acting ACE inhibitor that is highly effective. The drug is considered the “gold standard” in the treatment of hypertension and circulatory failure (together with diuretics, statins, angiotensin-II antagonists and Ca2+ channel blockers). 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 antihypertensive effect reaches a plateau no earlier than 10-14 days from the start of treatment.

Before using the drug, you must carefully read the instructions! Lisinopril should not be taken without a doctor’s prescription, and you should not replace it with an analogue yourself.

Drug interactions

The use of candesartan concomitantly with drugs containing aliskiren is contraindicated in patients with diabetes mellitus or moderate to severe renal failure (GFR <60 ml/min/1.73 m2).

The simultaneous use of candesartan with hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinyl estradiol/levonorgestrel), glibenclamide, nifedipine and enalapril has been studied; no clinically significant pharmacokinetic interaction was observed.

Candesartan is slightly metabolized in the liver (via the CYP2C9 isoenzyme). There was no effect on the CYP2C9 and CYP3A4 isoenzymes; the effect on other cytochrome P450 isoenzymes is currently unknown.

Antihypertensive drugs potentiate the antihypertensive effect of candesartan. Experience with the use of other drugs acting on the RAAS shows that the simultaneous use of the drug and potassium-sparing diuretics (spironolactone, eplerenone, triamterene, amiloride), potassium preparations, salt substitutes containing potassium, or other drugs that can increase the concentration of potassium in the blood serum ( for example, heparin) can lead to the development of hyperkalemia.

With the simultaneous use of lithium preparations and ACE inhibitors, cases of transient increases in the concentration of lithium in the blood serum and the development of toxic effects have been observed. A similar effect is possible with the simultaneous use of lithium drugs and angiotensin II receptor antagonists, which requires periodic monitoring of the concentration of lithium in the blood serum during the combined use of these drugs.

With simultaneous use of ARA II and NSAIDs, including selective COX-2 inhibitors and non-selective NSAIDs (for example, acetylsalicylic acid at a dose of more than 3 g / day), the antihypertensive effect of candesartan may be reduced.

Double blockade of the RAAS

As with ACE inhibitors, simultaneous use of ARB II and NSAIDs increases the risk of decreased renal function, including the development of renal failure, which leads to hyperkalemia in patients with impaired renal function. This combination should be used with caution, especially in elderly patients. All patients should receive sufficient fluids; it is necessary to monitor renal function at the beginning of therapy and thereafter.