Description
Lisinopril-Alsi Pharmacodynamics
Angiotensin-converting enzyme (ACE) inhibitor, reduces the formation of angiotensin II from angiotensin I. Decreased angiotensin II leads to a direct reduction in aldosterone release. Reduces bradykinin degradation and increases prostaglandin synthesis. Reduces total peripheral vascular resistance (TPR), blood pressure (BP), preload, pulmonary capillary pressure, causes an increase in the minute blood volume and increases myocardial tolerance to exercise in patients with chronic heart failure. Dilates arteries more 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. It improves the blood supply to the ischemic myocardium.
ACE inhibitors increase life expectancy in patients with chronic heart failure (CHF), slow the progression of left ventricular dysfunction in patients with acute 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 When lisinopril is abruptly withdrawn, no marked increase in BP has been observed.
Lisinopril reduces albuminuria. It does not affect blood glucose concentration in patients with diabetes mellitus and does not lead to increased incidence of hypoglycemia.
Indications
– Arterial hypertension (in monotherapy or in combination with other antihypertensive agents);
– Chronic heart failure (as part of combined therapy for the treatment of patients taking foxglove drugs and/or diuretics);
– Early treatment of acute myocardial infarction (in the first 24 hours with stable hemodynamic parameters to maintain these parameters and prevent left ventricular dysfunction and heart failure);
– Diabetic nephropathy (reduction of albuminuria in patients with type 1 diabetes with normal blood pressure, and in patients with type 2 diabetes with arterial hypertension).
Contraindications
– Hypersensitivity to any of the components of the drug, to lisinopril or other ACE inhibitors, history of angioedema, including history of ACE inhibitors, hereditary Quincke’s edema;
– Under 18 years of age (efficacy and safety not established);
– Pregnancy;
– Breast-feeding period;
– Concomitant use with aliskiren and drugs containing aliskiren in patients with diabetes mellitus and/or moderate or severe renal dysfunction (glomerular filtration rate (GFR) less than 60 ml/min/1.73 m2 body surface area);
– Concomitant use with angiotensin II receptor antagonists (APA II) in patients with diabetic nephropathy;
– The tablets contain lactose; therefore, the drug should not be taken by patients with rare hereditary diseases, such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption.
Dosage and administration
- Orally, regardless of meals. In patients with arterial hypertension who are not receiving other hypotensive agents, 5 mg once daily is prescribed. If there is no effect, the dose is increased every 2-3 days by 5 mg to an average therapeutic dose of 20-40 mg/day (an increase in dose over 40 mg/day usually does not lead to further BP reduction). The usual daily maintenance dose is 20 mg. The maximum daily dose is 40 mg. In clinical trials in patients with arterial hypertension, maximum daily doses of lisinopril were 80 mg and in patients with chronic heart failure, 35 mg. In order to provide the dosing regimens described below, lisinopril preparations from other manufacturers should be prescribed in the dosage form “2.5 mg tablets” or “5 mg tablets” with a rice if a dose of 2.5 mg is required.
- The full effect usually develops in 2-4 weeks from the beginning of treatment, which should be taken into account when increasing the dose. If the clinical effect is insufficient, the drug may be combined with other hypotensive agents.
- If the patient received prior treatment with diuretics, the intake of such drugs should be discontinued 2-3 days before the start of lisinopril. If this is not feasible, the initial dose of lisinopril should not exceed 5 mg per day. In this case, after the first dose, medical supervision for several hours is recommended (maximum action is achieved after about 6 hours), as a marked decrease in BP may occur.
- In renovascular hypertension or other conditions with increased activity of renin-angiotensin-aldosterone system it is reasonable to administer also low initial dose – 2.5-5 mg per day, under increased medical supervision (BP control, renal function, serum potassium concentration). The maintenance dose, while continuing close medical supervision, should be determined depending on the dynamics of BP.
- In renal failure, due to the fact that lisinopril is excreted via the kidneys, the initial dose should be determined according to creatinine clearance, then, according to the response, the maintenance dose should be set under frequent monitoring of renal function, serum potassium, sodium levels.
