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ACE inhibitor, prevents the conversion of angiotensin I to angiotensin II without a compensatory increase in heart rate. Reduces the production of aldosterone, OPSS, pressure in the pulmonary capillaries, resistance in the pulmonary vessels, does not change the glomerular filtration rate, increases coronary blood flow. With prolonged use of the drug, myocardial hypertrophy is reduced in patients with arterial hypertension, the frequency of arrhythmias during myocardial reperfusion decreases; improves blood circulation ischemic myocardium. Cardioprotective effect due to the effect on the synthesis of prostaglandins, the induction of the formation of nitric oxide in endothelial cells. The drug reduces platelet aggregation. The onset of hypotensive action is 1.5 hours after ingestion, the maximum effect is 5–9 hours, the duration is 24 hours. The drug has no withdrawal syndrome.
Thiazide diuretic, the diuretic effect of which is associated with impaired reabsorption of sodium, chlorine, potassium, magnesium ions, and water in the distal nephron; delays the excretion of calcium ions, uric acid. It has antihypertensive properties; the hypotensive effect develops by reducing the bcc, changing the reactivity of the vascular wall, reducing the pressure of the influence and increasing the depressant effect on the ganglia. Virtually no effect on normal blood pressure. The diuretic effect occurs after 1-2 hours, reaches a maximum after 4 hours and lasts 6-12 hours. The antihypertensive effect occurs after 3-4 days, but it may take 3-4 weeks to achieve the optimal therapeutic effect.
Ramipril and hydrochlorothiazide have an additive effect. Ramipril reduces the loss of potassium ions caused by taking hydrochlorothiazide.
Arterial hypertension (for patients who are recommended combination therapy).
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Dosage and Administration
For oral use. dose is selected individually. The usual dose foradults- 1 tab. Ramazid H2.5 mg / 12.5 mg per day. If necessary, can be increased to 1 tab. Ramazid H 5 mg / 25 mg.
In case of impaired renal function of mild or moderate degree (CC more than 30 ml / min, serum creatinine approximately 3 mg / dL or 265 mcmol / l), the usual dose is recommended. For creatinine clearance less than 30 ml / min, the drug is not recommended.
Since the cardiovascular system: reduction of blood pressure, orthostatic hypotension, orthostatic collapse, tachycardia, rarely - arrhythmia, angina, myocardial infarction. On the part of the genitourinary system: the development or strengthening of symptoms of renal failure, proteinuria, decrease in urine volume, decreased libido.
CNS: cerebral ischemia, stroke, dizziness, headache, weakness, drowsiness, paresthesias, nervous irritability, anxiety, tremor, muscle spasm, mood disorders, when used in high doses - insomnia, anxiety, depression, confusion, fainting .
On the part of the senses: vestibular disorders, taste disorders (for example, metallic taste), smell, hearing and vision, tinnitus.
On the part of the digestive system: nausea, vomiting, diarrhea or constipation, pain in the epigastric region, intestinal obstruction, pancreatitis, hepatitis, cholestatic jaundice, abnormal liver function with the development of liver failure, dry mouth, thirst, loss of appetite, stomatitis, glossitis.
On the part of the respiratory system: "dry" cough, bronchospasm, shortness of breath, rhinorrhea, rhinitis, sinusitis, bronchitis.
Allergic reactions: skin rash, itching, urticaria, conjunctivitis, photosensitization; angioedema of the face, extremities, lips, tongue, pharynx and / or larynx, exfoliative dermatitis, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Layel syndrome), vesicle, serositis, onycholysis, vasculitis, myositis, myalgia, arthralgia, arthritis, eosinophilia.
Other: convulsions, alopecia, hyperthermia, increased sweating.
Laboratory indicators: hypercreatininemia, increased levels of urea nitrogen, increased activity of liver transaminases, hyperbilirubinemia, hyperkalemia, hyponatremia, the appearance of antinuclear antibodies.
Effect on the fetus: dysfunction of the fetus, lowering blood pressure of the fetus and newborns, impaired renal function, hyperkalemia, hypoplasia of the skull bones, oligohydramnios, contracture of the extremities, deformation of the skull bones, hypoplasia of the lungs.
From the water-electrolyte and acid-base balance: the development of hypokalemia and hypochloremic alkalosis is possible (dry mouth, increased thirst, heart rhythm disturbances, changes in mood and psyche, cramps or muscle pain, nausea, vomiting, weakness; with hypochloraemic alkalosis, it is possible development of hepatic encephalopathy or hepatic coma), hyponatremia (confusion, convulsions, apathy, slowing the process of thinking, fatigue, irritability), hypomagnesy (arrhythmias).
On the part of the hematopoietic system: agranulocytosis, thrombocytopenia, hemolytic and aplastic anemia, leukocytopenia.
Since the cardiovascular system: arrhythmia, orthostatic hypotension, tachycardia.
On the part of the digestive system: cholecystitis, pancreatitis, jaundice, diarrhea, sialadenitis, constipation, anorexia, epigastric pain.
Metabolism: hyperglycemia, glycosuria, hyperuricemia, exacerbation of gout.
Allergic reactions: skin rash, purpura, necrotic vasculitis, Stevens-Johnson syndrome, respiratory distress (pneumonitis, non-cardiogenic pulmonary edema), photosensitization; anaphylactic reactions (up to life threatening anaphylactic shock).
- hypersensitivity to ramipril and any other ingredient of the drug or other ACE inhibitors;
- angioedema in history, including associated with previous therapy with ACE inhibitors;
- hemodynamically significant bilateral renal artery stenosis;
- stenosis of the artery of the only kidney;
- condition after kidney transplantation;
- renal failure (CC less than 20 ml / min.);
- hemodynamically significant aortic or mitral stenosis (risk of an excessive decrease in blood pressure, followed by impaired renal function);
- hypertrophic obstructive cardiomyopathy;
- primary hyper aldosteronism;
- pregnancy and lactation;
- age up to 18 years (efficacy and safety have not been established).
Precautions: severe lesions of the coronary and cerebral arteries (risk of reducing blood flow with an excessive decrease in blood pressure), unstable angina, severe ventricular arrhythmias, chronic heart failure stage IV, decompensated pulmonary heart, renal and / or hepatic insufficiency, hyperkalemia, hyponatremia ( including on the background of diuretics and diets with limited salt intake), conditions accompanied by a decrease in blood volume (including diarrhea, vomiting), systemic diseases of tissue, diabetes mellitus, bone marrow blood circulation inhibition, old age.
- hypersensitivity to the drug;
- diabetes mellitus (severe forms);
- chronic renal failure (creatinine clearance less than 20-30 ml / min, anuria);
- refractory hypokalemia;
- pregnancy (1 trimester);
- lactation period.
With care: hypokalemia, hyponatremia, hypercalcemia, coronary heart disease, cirrhosis of the liver, old age.
Strengthens the inhibitory effect of ethanol on the central nervous system. Salt intake with food may reduce the hypotensive effect of ramipril.
With the simultaneous use of ramipril and other drugs that reduce blood pressure (eg, diuretics, nitrates, tricyclic antidepressants, anesthetics) leads to an increase in the hypotensive effect of ramipril.
The simultaneous appointment of ramipril and potassium preparations or potassium-sparing diuretics, it is necessary to control the concentration of lithium in the blood serum - the risk of toxic effects. Ikov can cause hyperkalemia.
Vasopressor sympathomimetics (adrenaline, norepinephrine) can reduce the hypotensive effect of ramipril. In this regard, with simultaneous treatment should be carefully monitored blood pressure levels.
The simultaneous appointment of ramipril and allopurinol, immunosuppressants, corticosteroids, procainamide, cytotoxic drugs increases the likelihood of changes in the peripheral blood picture.
The simultaneous appointment of ramipril and lithium preparations leads to a decrease in the excretion of l
ACE inhibitors can enhance the effect of hypoglycemic agents (for example, insulin or sulfonylurea derivatives), which in some cases can cause hypoglycemia. In this regard, blood sugar levels should be carefully monitored, especially at the beginning of the joint use.
The simultaneous use of ramipril and nonsteroidal anti-inflammatory drugs (for example, acetylsalicylic acid and indomethacin) can weaken the hypotensive effect of ramipril. Additionally, concurrent use may cause hyperkalemia and increase the risk of impaired renal function.
The simultaneous use of heparin and ramipril can cause hyperkalemia.
Anaphylactic and anaphylactoid reactions to the poison of stinging insects (and possibly other allergens) are more pronounced during treatment with ACE inhibitors.
With simultaneous use of glycosides in digitalis with thiazide diuretics, the likelihood of the manifestation of the toxic effects of glycosides (including increased ventricular excitability) increases due to the likely development of hypokalemia and hypomagnesemia.
Drugs that bind intensively to proteins (indirect anticoagulants, clofibrate, NSAIDs) enhance the diuretic effect of hydrochlorothiazide.
The hypotensive effect of hydrochlorothiazide is enhanced by vasodilators, beta-blockers, barbiturates, phenothiazines, tricyclic antidepressants, ethanol. Hydrochlorothiazide enhances the neurotoxicity of salicylates, weakens the effect of oral hypoglycemic drugs, norepinephrine, epinephrine and anti-gout drugs, enhances the cardiotoxic and neurotoxic effects of lithium preparations, the effect of peripheral muscle relaxants, reduces quinidine excretion. With the simultaneous use of methyldopa may develop hemolysis. Kolestiramin reduces the absorption of hydrochlorothiazide.
Hydrochlorothiazide reduces the effect of oral contraceptives.
Pregnancy and Lactation
The drug is contraindicated during pregnancy and lactation.
At the beginning of treatment, renal function should be evaluated. Renal function must be carefully monitored during ramipril treatment, especially in patients with impaired renal function, with renal vascular damage (for example, clinically insignificant renal artery stenosis or hemodynamically significant stenosis of a single kidney artery); heart failure.
The risk of hypersensitivity and allergy-like (anaphylactoid) reactions is increased in patients simultaneously taking ACE inhibitors and undergoing hemodialysis procedures using dialysis membranes AN69. Similar reactions have been identified with low density lipoprotein apheresis using dextran sulfate, so the use of this method should be avoided in the treatment with ACE inhibitors.
During treatment with ramipril in patients with impaired renal function, especially with simultaneous treatment with diuretics, the level of urea and serum creatinine may increase. In this case, the treatment should be continued with lower doses of ramipril or discontinue the drug. In patients with impaired renal function, the risk of hyperkalemia increases.
In patients with impaired hepatic function, ramipril metabolism and the formation of an active metabolite can be slowed down due to a decrease in the activity of “liver” enzymes. In this regard, the treatment of such patients should be initiated only under strict medical supervision.
Care must be taken when prescribing ramipril to patients on a low-salt or salt-free diet (increased risk of arterial hypotension). In patients with reduced circulating blood volume (as a result of diuretic therapy), during dialysis, with diarrhea and vomiting, symptomatic hypotension may develop.
Transient arterial hypotension is not a contraindication to continue treatment after stabilization of blood pressure. In the case of recurrence of severe hypotension, reduce the dose or discontinue the drug.
In patients undergoing extensive surgery or receiving other hypotension-causing agents during general anesthesia, ramipril can block the formation of angiotensin II due to the compensatory release of renin. If the doctor connects the development of arterial hypotension with the mechanism mentioned above, arterial hypotension can be adjusted by increasing the volume of blood plasma.
In rare cases, agranulocytosis, erythrocytopenia, thrombocytopenia, hemoglobinemia, or bone marrow depression are observed during treatment with ACE inhibitors. At the beginning and during treatment, it is necessary to control the number of white blood cells to detect possible neutropenia / agranulocytosis. More frequent monitoring is recommended in patients with renal insufficiency, diseases of the connective tissue (eg, systemic lupus erythematosus or scleroderma) and in patients who are simultaneously taking drugs that affect blood formation. The counting of blood cells should also be carried out in the event of clinical signs of neutropenia / agranulocytosis and increased bleeding.
in patients with arterial hypertension in the treatment of ramipril, an increase in serum potassium level is rarely observed. The risk of hyperkalemia increases with chronic heart failure, simultaneous treatment with potassium-sparing diuretics (spironolactone, amiloride, triamterene) and administration of potassium preparations.
When using ACE inhibitors during desensitization therapy, anaphylactoid reactions (eg, arterial hypotension, shortness of breath, vomiting, skin rash), which can be life-threatening, may occur to aspen or bee venom. Hypersensitivity reactions may occur when insect bites (eg, bees or wasps). If it is necessary to conduct desensitization treatment with bee or wasp venom, it is necessary to cancel ACE inhibitors and continue treatment with suitable drugs from other groups.
During the period of Ramazid N treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and psychomotor speed (dizziness is possible, especially after the initial dose of an ACE inhibitor in patients taking diuretic drugs). Patients are advised to refrain from driving and working with machinery until the answer to treatment is clear.
To prevent K + and Mg2 + deficiencies, potassium-sparing diuretics, K + and Mg2 + salts are prescribed. Requires regular monitoring of plasma levels of potassium, glucose, uric acid, lipids and creatinine.
Symptoms: marked reduction in blood pressure, bradycardia, shock, impaired water-electrolyte balance, acute renal failure, stupor, dry mouth, weakness, drowsiness.
Treatment: give the patient a horizontal position with raised legs, in mild cases of overdose - gastric lavage, the introduction of adsorbents and sodium sulfate (it is desirable to hold activities during the first 30 minutes after taking the drug). With a decrease in blood pressure - in / in the introduction of catecholamines, angiotensin II; in bradycardia - the use of pacemaker. The drug is not displayed during hemodialysis.
- Brand name: Ralef
- Active ingredient: Ramipril, Hydrochlorothiazide
- Manufacturer: Obolensky OP
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