Pharmacological action Ramipril
Ramipril ACE inhibitor. Is a prodrug, from which the body produces the active metabolite ramiprilat. It is believed that the mechanism of antihypertensive action is related to competitive inhibition of ACE, which leads to a decrease in the rate conversion of angiotensin I to angiotensin II, which is a potent vasoconstrictor substance. As a result, reduce the concentration of angiotensin II is a secondary increase in plasma renin activity by removing the negative feedback of renin release and a direct reduction in aldosterone secretion. Thanks to the vasodilator action reduces PR (afterload), wedge pressure in the pulmonary capillaries (preload) and pulmonary vascular resistance, increases cardiac output and exercise capacity.
The hypotensive effect of ramipril develops in about 1-2 hours, reaching a peak within 3-6 hours, lasts at least 24 hours
Pharmacokinetics Ramipril
If ingestion absorption is 50-60%, the food does not affect the extent of absorption, but it slows absorption. Cmax achieved within 2-4 h. In the liver, is metabolized to the active metabolite ramiprilata (6 times more active ACE inhibition than ramipril), an inactive diketopiperazine and glyukuroniziruetsya. All metabolites are formed, except ramiprilata, pharmacological activity have not. Plasma protein binding of ramipril for – 73%, ramiprilata – 56%. Bioavailability after oral administration of 2.5-5 mg ramipril – 15-28% for ramiprilata – 45%. After daily administration of ramipril 5 mg / day sustained concentration in plasma achieved ramiprilata to 4 day.
T1 / 2 for ramipril – 5.1 h in the phase distribution and elimination of a drop in the concentration of serum ramiprilata occurs with T1 / 2 – 3 h, followed by a transitional phase with a T1 / 2 – 15 hours long and the final phase with very low concentrations ramiprilata in plasma and T1 / 2 – 4-5 days. T1 / 2 increased in chronic renal failure. Vd ramipril – 90 liters, ramiprilata – 500 liters. Kidneys eliminate 60% of the bowel – 40% (mostly as metabolites). When kidney function is the excretion of ramipril and its metabolites is slowed down proportionally reduce the spacecraft, with abnormal liver function slows down the conversion to ramiprilat; heart failure ramiprilata concentration increases 1.5-1.8 times.
Statement Ramipril
Arterial hypertension, chronic heart failure, post myocardial infarction (especially with symptoms of heart failure).
Dosage regimen Ramipril
Taken orally. Initial dose – 1.25-2.5 mg 1-2 times / day. If necessary, you can gradually increase the dose. The maintenance dose is determined individually, depending on the indications for the use and effectiveness of treatment.
Side effect Ramipril
Cardio-vascular system: hypotension, rarely – chest pain, tachycardia.
CNS: dizziness, weakness, headache, rarely – sleep disorders, mood.
On the part of the digestive system: diarrhea, constipation, loss of appetite, rarely – stomatitis, abdominal pain, pancreatitis, cholestatic jaundice.
The respiratory system: dry cough, bronchitis, sinusitis.
Urinary system: rarely – proteinuria, increased serum creatinine and blood urea (mainly in patients with impaired renal function).
From the hemopoietic system: rarely – neutropenia, agranulocytosis, thrombocytopenia, and anemia.
From the laboratory parameters: hypokalemia, hyponatremia.
Allergic reactions: skin rash, angioedema and other hypersensitivity reactions.
Other: rarely – muscle cramps, impotence, alopecia.
Contraindications Ramipril
Expressed by the human liver and kidney, bilateral renal artery stenosis or stenosis of the artery of a sole kidney, the state after a kidney transplant, primary hyperaldosteronism, hyperkalemia, aortic stenosis, pregnancy, lactation (breastfeeding), children and teens up to 18 years, increased sensitivity to ramipril and other ACE inhibitors.
Pregnancy and breastfeeding
Ramipril is contraindicated during pregnancy and lactation (breastfeeding).
Cautions
In patients with concomitant renal impairment, the dose selected individually in accordance with the values of QC. Before treatment, all patients should be a study of kidney function. In the course of treatment with ramipril regularly monitored renal function, electrolyte composition of blood levels of liver enzymes in the blood and peripheral blood (especially in patients with diffuse diseases of connective tissue in patients receiving immunosuppressants, allopurinol). Patients who have a deficiency of fluid and / or sodium before treatment is necessary to correct fluid and electrolyte disturbances. During treatment with ramipril can not be held hemodialysis using polyacrylonitrile membranes (increased risk of anaphylactic reactions).
Drug Interactions
With the simultaneous use of potassium-sparing diuretics (including spironolactone, triamterene, amiloride), potassium preparations, salt substitutes and food supplements containing potassium may develop hyperkalemia (especially in patients with impaired renal function), because ACE inhibitors reduce the content of aldosterone, resulting in a delay of potassium in the body against the limitations of potassium excretion or additional income in the body.
With the simultaneous use of NSAIDs may decrease the antihypertensive effect of ramipril, renal failure.
While the use of loop or thiazide diuretics increased antihypertensive effect. Severe hypotension, particularly after the first dose of the diuretic, apparently, is due to hypovolemia, which leads to a transient increase of the hypotensive effect of ramipril. There is a risk of hypokalemia. The risk of renal dysfunction.
When applied simultaneously with the means of providing the hypotensive effect, may increase the hypotensive effect.
While the use of immunosuppressive tsistostatikami, allopurinol, procainamide may increase the risk of leucopenia.
When applied simultaneously with insulin, sulfonylureas hypoglycemic agents, metformin may develop hypoglycemia.
While the use of allopurinol tsistostatikami, immunosuppressants, procainamide may increase the risk of leucopenia.
While the use of lithium carbonate may increase the concentration of lithium in blood serum.
