Description
Losartan Pharmacodynamics
Hypotensive drug, is a specific angiotensin II (type AT1) receptor antagonist. Does not inhibit kininase II, an enzyme that degrades bradykinin. Reduces total peripheral vascular resistance (TPR), blood concentrations of norepinephrine and aldosterone, blood pressure (BP), pressure in the “small” circulatory circle; reduces post-load, has a diuretic effect. Prevents the development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure (CHF).
After a single dose, the antihypertensive effect (systolic and diastolic BP decreases) reaches a maximum after 6 hours, then gradually decreases within 24 hours. The maximum antihypertensive effect develops 3-6 weeks after the start of the drug.
Plasma concentrations of losartan and its active metabolite and the antihypertensive effect of losartan increase with increasing dose. Since losartan and its active metabolite are angiotensin II receptor antagonists (ARA II), they both contribute to the antihypertensive effect.
Indications
Arterial hypertension.
Reduction of cardiovascular risk and mortality in patients with arterial hypertension and left ventricular (LV) hypertrophy, manifested by the combined reduction of cardiovascular mortality, stroke and myocardial infarction; type 2 diabetes with proteinuria (reduced risk of hypercreatininemia and proteinuria); CHF (if treatment with angiotensin-converting enzyme (ACE) inhibitors is not effective).
Contraindications .
Hypersensitivity to any drug component, severe liver function abnormalities (more than 9 points by Child-Pugh scale) (no experience of use), pregnancy, breast-feeding, age less than 18 years old (effectiveness and safety of use are not established), concomitant use with aliskiren or aliskiren-containing drugs in patients with diabetes mellitus and/or impaired renal function (glomerular filtration rate (GFR) less than 60 ml/min/1.73 m2), lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome (the drug contains lactose).
Dosage and administration.
- Orally, regardless of the meal, the frequency of administration – once a day.
- In arterial hypertension, the average daily dose is 50 mg. If necessary, the daily dose may be increased to a maximum daily dose of 100 mg once daily.
- Reduction of cardiovascular risk and mortality in patients with arterial hypertension and LV hypertrophy: the initial dose is 50 mg once daily, further it is recommended to prescribe hydrochlorothiazide in low doses or increase the dose to 100 mg once daily (depending on the degree of BP reduction).
- Type 2 diabetes mellitus with proteinuria: the initial dose is 50 mg once a day with further increase to 100 mg/day (taking into account the degree of BP reduction).
- CHF: The initial dose for patients with CHF is 12.5 mg once daily. Typically, the dose is doubled at weekly intervals (i.e., 12.5, 25, 50 mg/day) to an average maintenance dose of 50 mg/day, 100 mg/day to a maximum (for this indication only) dose of 150 mg/day, depending on individual tolerance.
- Special patient groups:
- When administered to patients receiving high doses of diuretics, the initial dose should be reduced to 25 mg/day.
- Patients with a history of liver dysfunction should be prescribed lower doses of LOZARTAN.
Initial dose adjustment is not necessary in elderly patients as well as in patients with - impaired renal function (including those on dialysis).
- Lozartan may be coadministered with other hypotensive drugs (drugs).
