Description
Lisinopril Pharmacodynamics
Pharmacological action – antihypertensive, vasodilatory, cardioprotective, natriuretic.
ACE inhibitor, reduces the formation of angiotensin II from angiotensin I. Decreased concentration of angiotensin II leads to a direct reduction of aldosterone release. Reduces bradykinin degradation and increases prostaglandin synthesis.
Reduces total peripheral vascular resistance, blood pressure (BP), preload, pulmonary capillary pressure, causes an increase in minute blood volume and increases myocardial exercise tolerance in patients with chronic heart failure (CHF). Dilates arteries to a greater extent than veins.
Some effects are attributed to effects on the renin-angiotensin-aldosterone system (RAAS). Long-term use reduces myocardial hypertrophy and resistive arterial wall hypertrophy. Endothelial function and blood supply to ischemic myocardium are improved.
ACE inhibitors prolong life expectancy in patients with CHF, slow the progression of left ventricular dysfunction in patients who have had myocardial infarction without clinical manifestations of heart failure.
Onset of action of the drug is within 1 hour, the maximum antihypertensive effect is achieved after 6-7 hours and is maintained for 24 hours. The duration of the effect also depends on the dose taken.
For arterial hypertension, the effect is noted in the first days after treatment start, a stable effect develops after 1-2 months of therapy.
When lisinopril is abruptly withdrawn, no pronounced increase in BP has been observed.
Lisinopril reduces the degree of albuminuria. It does not affect blood glucose concentration in diabetic patients and does not lead to increased incidence of hypoglycemia.
Indications
– Arterial hypertension (in monotherapy or in combination with other hypotensive agents);
– 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 (in the first 24 h with stable hemodynamic parameters to maintain these parameters and prevent left ventricular dysfunction and heart failure);
– Diabetic nephropathy (reduction of albuminuria in patients with diabetes mellitus type 1 with normal BP and in patients with diabetes mellitus type 2 with arterial hypertension)
Contraindications
Hypersensitivity to lisinopril, other drug components or other ACE inhibitors; history of angioedema (including from the use of other ACE inhibitors); hereditary Quincke’s edema and/or idiopathic angioedema; age under 18 years (effectiveness and safety not established); pregnancy and breastfeeding; lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome (the drug contains lactose), concomitant use with aliskiren and drugs containing aliskiren in patients with diabetes and/or moderate or severe renal function impairment (glomerular filtration rate (GFR) less than 60 ml/min/1, 73 m2 of body surface area), concomitant use with angiotensin II receptor antagonists (ARA II) in patients with diabetic nephropathy, concomitant use with neutral endopeptidase inhibitors (such as those containing Sacubitril) due to the high risk of angioedema.
Dosage and administration
- Orally, once in the morning, regardless of the time of meals, with sufficient fluid (e.g. glass of water), preferably at the same time.
- For the 2.5 mg dosing regimen, it is recommended that LYSINOPRIL in 2.5 mg tablets or 5 mg tablets with a ricochet of other manufacturers.
- Arterial hypertension (patients not receiving other hypotensive agents): initial dose is 5 mg/day. If there is no effect, the dose is increased every 2-3 days by 5 mg/day to an average therapeutic dose of 20-40 mg/day (a dose over 40 mg/day usually does not lead to further BP reduction). The usual maintenance dose is 20 mg once daily. Maximum daily dose is 40 mg.
- Therapeutic effect develops 2-4 weeks after the start of treatment, which should be taken into account when increasing the dose. In case of insufficient clinical effect, it is possible to combine the drug with other hypotensive agents.
- If the patient has received prior treatment with diuretics, these drugs should be discontinued 2 to 3 days before starting Lysinopril. If this is not possible, the initial dose should not exceed 5 mg per day. In this case, follow up with a physician for several hours after the first dose (max. activity is reached after about 6 hours) as a pronounced fall in BP may occur.
- In renovascular hypertension or other conditions with increased RAAS activity (hypovolemia, diet with restriction of table salt intake, decompensation of cardiac activity or severe arterial hypotension), the initial dose is 2.5-5 mg per day (BP, renal function, potassium content should be controlled). The maintenance dose, continuing strict regular monitoring, should be determined depending on the dynamics of BP.
- In chronic heart failure, the initial dose is 2.5 mg per day, the dose is gradually increased (by no more than 2.5 mg at intervals of 3-5 days) to a maintenance dose of 5-20 mg, depending on BP. The maximum daily dose should not exceed 20 mg.
- In elderly patients (over 65 years), a more pronounced long-term antihypertensive effect is often observed, which is associated with decreased excretion rate of lisinopril. It is recommended to start therapy with 2.5 mg/day.
- In early treatment of acute myocardial infarction with stable hemodynamic parameters (systolic blood pressure at least 100 mm Hg) the dose is 5 mg in the first day, then 5 mg every other day, 10 mg after two days and then 10 mg per day as maintenance therapy.
- In patients with acute myocardial infarction, the drug should be used for at least 6 weeks.
- At the beginning of treatment or during the first 3 days after myocardial infarction in patients with low systolic blood pressure (120 mm Hg or less) a lower dose of 2.5 mg is used. If systolic blood pressure is lower or equal to 100 mmHg, the daily dose of 5 mg should be temporarily reduced to 2.5 mg, and if blood pressure is lower or equal to 90 mmHg, the drug should not be used.
