Ramipril
Symptoms of arterial hypotension
In patients with uncomplicated arterial hypertension, symptoms of arterial hypotension are rare. In patients with hypertension taking ramipril, the likelihood of developing arterial hypotension increases with a decrease in the volume of circulating blood (for example, as a result of diuretic treatment, restriction of salt intake, dialysis, diarrhea, or vomiting), and severe forms of renin-dependent hypertension. Symptoms of arterial hypotension were observed in patients with heart failure, regardless of whether it is combined with renal insufficiency. This is most often observed in patients with more severe heart failure who are forced to take high doses of "loop" diuretics who have hyponatremia or functional renal failure.
Patients with an increased risk of hypotension need close monitoring in the initial period of treatment and in the selection of a dose.This also applies to patients with coronary artery disease or cerebrovascular disease, in whom a significant fall in blood pressure can lead to myocardial infarction or cerebral circulation impairment.
In the case of arterial hypotension, the patient should be placed on his back, legs raised and, if necessary, an intravenous infusion of sodium chloride solution. Transient hypotensive reaction is not a contraindication for the subsequent administration of the drug.
In some patients with heart failure who have normal or low blood pressure, ramipril may cause an additional decrease in systolic blood pressure. This effect can be foreseen, therefore it is usually not a basis for discontinuing treatment. If hypotension is symptomatic, it may be necessary to reduce the dose or stop treatment.
Aortic and mitral stenosis / hypertrophic cardiomyopathy Like other ACE inhibitors, ramipril requires caution for patients with aortic stenosis or difficulty in ejection from the left ventricle (eg, in aortic stenosis or hypertrophic cardiomyopathy).In some cases, the hemodynamic picture may make it unacceptable to take a fixed combination of ramipril and gydrochlorothiazide.
Primary aldosteronism (Conn's disease)
The use of fixed combinations of ramipril and hydrochlorothiazide is contraindicated, since patients with primary aldosteronism are not sensitive to antihypertensive agents, the action of which is based on the suppression of the renin-angiotensin system. Impaired renal function
In patients with heart failure at the beginning of treatment with ACE inhibitors, impaired renal function may be observed. In such situations, cases of acute renal failure, usually transient, are described.
In some patients with narrowing of both renal arteries or with stenosis of the artery of a single kidney, ACE inhibitors increase the level of urea in the blood and creatinine in the serum; usually these changes occur after discontinuation of medication. The likelihood of this is especially high in renal failure. In the presence of renovascular hypertension, the risk of severe arterial hypotension and renal failure is high.In such patients, treatment should be started under close medical supervision with small doses, which must be accurately matched. Because diuretics can contribute to the clinical dynamics described above, during the first weeks of treatment with ramipril, their intake should be discontinued and the kidney function needs careful monitoring.
In some patients with arterial hypertension without an obvious renal vessel disease, taking ramipril, especially against diuretics, causes an increase in the level of urea in the blood and creatinine in the serum; these changes tend to be minor and transient. The probability of their occurrence is higher in patients already suffering from impaired renal function. In such cases, it may be necessary to reduce the dose and / or stop taking the diuretic and / or ramipril.
Condition after kidney transplantation
In connection with the lack of experience with the use of ramipril in patients who have recently undergone kidney transplantation, ramipril it is not recommended to take such patients.
Increased Sensitivity / angioedema
Angioedema of the face, extremities, lips, tongue, vocal cords and / or larynx rarely develops in patients receiving ACE inhibitors, including ramipril. During treatment, angioedema may develop at any time. In this case, the taking of ramipril should be stopped immediately, the appropriate treatment should be carried out and the patient should be monitored; Before releasing the patient, you should make sure that all the symptoms of the edema are eliminated. Even in cases where edema is limited to the tongue and signs of breathing are not present, patients may need long-term follow-up, since treatment with angstamines and corticosteroids may not be sufficient. In rare cases death of patients due to angioedema of the larynx or tongue is documented.
If swelling spreads to the tongue, vocal cords, or larynx, it is very likely that the airway is blocked, especially in patients who have previously undergone surgery on the respiratory system. In such cases it is necessary to take emergency therapy (see Overdose section). It can include the administration of epinephrine (adrenaline) and / or maintenance of airway patency. The patient should be under careful medical supervision until the symptoms disappear completely and persistently.
Patients who have a history of angioedema, not associated with an inhibitor of ACE, may be at increased risk of angioedema in Response to an ACE inhibitor.
Anaphylactoid reactions in patients receiving hemodialysis treatment
There are reports of anaphylactoid reactions in patients on hemodialysis using membranes with high hydraulic permeability (for example, AN 69) with simultaneous use of ACE inhibitors. In such cases, another type of membrane or other antihypertensive medication should be considered. Anaphylactoid reactions in the apheresis of low density lipoproteins (LDL)
In rare cases, life-threatening anaphylactoid reactions develop in patients taking an ACE inhibitor against a background of low-density lipoprotein (LDL) apheresis with dextrin sulfate. Such reactions can be avoided if temporarily refraining from taking an ACE inhibitor before each apheresis procedure.
Desensitization
In patients taking ACE inhibitors against the background of desensitizing therapy (for example, the venom of Hymenoptera), long anaphylactoid reactions develop.If such patients refrained from taking ACE inhibitors for the time of desensitization, no reactions were observed, but a random injection of ACE provoked an anaphylactoid reaction.
Liver failure
FROM the use of ACE inhibitors is associated with the development of a rare syndrome that begins with cholestatic jaundice or hepatitis and passes into transient liver necrosis, sometimes with a fatal outcome. The mechanism of development of this syndrome is not clear. If patients taking ramipril, jaundice develops or the activity of "liver" enzymes increases significantly, the drug must be canceled, leaving the patient under the supervision of a doctor until the symptoms disappear.
Neutropenia / agranulocytosis
It has been reported that patients taking ACE inhibitors may develop neutropenia / agranulocytosis, thrombocytopenia and anemia. With normal kidney function and in the absence of complications, neutropenia develops rarely. Neutropenia and agranulocytosis are reversible and pass after discontinuation of the ACE inhibitor. Caution should be exercised when appointing ramipril to patients suffering from connective tissue diseases with vascular manifestations undergoing treatment with antidepressants taking allopurinol or procainamide, as well as a combination of these factors, especially against a background of impaired renal function. Some of these patients develop severe infections, which are not always accompanied by intensive antibiotic therapy. If the treatment of such patients is used ramipril, it is recommended to periodically check the number of white blood cells, and patients should be warned about the need to report any signs of infection.
Race
ACE inhibitors often cause the development of angioedema in patients of the Negroid race as compared to patients of other race.
Like other ACE inhibitors, ramipril may be less effective in lowering blood pressure in black patients than in other races, possibly due to a higher incidence of low renin in a population of black patients suffering from hypertension.
Cough
It was reported that the administration of ACE inhibitors may be accompanied by a cough. It is characteristic that the cough is dry and persistent; it passes after the drug is discontinued. The fact that the cough is caused by the intake of an ACE inhibitor should be considered as a differential diagnostic feature.
Surgery / general anesthesia
In patients undergoing surgery or general anesthesia with drugs that reduce blood pressure, ramipril can block the increase in the formation of angiotensin II under the influence of compensatory release of renin. If it is assumed that arterial hypotension develops by this mechanism, it can be corrected by increasing the volume of circulating blood. _
Hyperkalemia
In some patients taking ACE inhibitors, including ramipril, there is an increase in potassium in the serum. The risk group for hyperkalemia includes patients suffering from renal insufficiency or diabetes mellitus, taking potassium-sparing diuretics, or potassium-containing salt substitutes, as well as those who take other medicines that increase potassium levels in the serum (eg, heparin). If the reception of the above drugs against the background of treatment with an ACE inhibitor is considered necessary, regular monitoring of serum potassium levels is recommended (see Interaction).
Patients with diabetes mellitus
In patients with diabetes mellitus, who take hypoglycemic drugs for ingestion or insulin, you must carefully monitor blood sugar levels during the first month of treatment with an ACE inhibitor (see Interactions).
Lithium
It is usually not recommended to combine lithium and ramipril (see Interaction). Potassium-containing food additives, potassium-sparing diuretics or potassium-containing substitutes
Although serum potassium levels in clinical studies of ACE inhibitors usually remained within normal limits, some patients still developed hyperkalemia. The risk of hyperkalemia is associated with a number of factors, including renal insufficiency, diabetes mellitus, and simultaneous use of potassium-sparing diuretics (for example, spironolactone, triamterene or amiloride), as well as potassium-containing food additives or salt substitutes. The use of potassium-containing food additives, potassium-sparing diuretics or potassium-containing substitutes can lead to a significant increase in potassium levels in the serum, especially in patients with impaired renal function.
During the reception of ramipril on the background of potassium-releasing diuretics, hypokalemia caused by their intake may be weakened.
Guiduochlorooctiazide Impaired renal function
In patients with kidney disease, thiazides can cause azotemia. Taking medicines against a background of impaired renal function can lead to cumulative effects. If kidney failure improves, characterized by an increase in non-protein nitrogen, the need for therapy should be carefully assessed and the possibility of stopping diuretics should be considered.
Impaired liver function
Patients with a violation or progressive impairment of liver function, thiazides should be administered with caution, since even minor fluctuations in the water-electrolyte balance can cause hepatic coma.
Metabolic and endocrine effects
Thiazide therapy can reduce glucose tolerance. With diabetes, it may be necessary to choose a dose of insulin or oral hypoglycemic agents. Thiazide therapy can cause a manifestation of latent diabetes mellitus.
With therapy, thiazide diuretics are associated with an increase in cholesterol and triglyceride levels.In some patients receiving thiazide diuretics, there may be an increase in the level of uric acid or the manifestation of gout.
Gout
In some patients, thiazide therapy may increase the level of uric acid and / or cause gout. but ramipril can increase the excretion of uric acid, thereby weakening the degree of increase in the level of uric acid under the influence of hydrochlorothiazide. Violations of the water-electrolyte balance
Any patient receiving treatment with diuretics should periodically determine the content of electrolytes in the blood serum.
ThiazidY, including hydrochlorothiazide, can cause a violation of the water-electrolyte balance (gipokaliemiyu, hyponatremia and hypochloremic alkalosis). Harbinger violations of water or electrolyte balance are dry mouth, thirst, weakness, lethargy, drowsiness, anxiety, myalgia or muscle spasms, muscle fatigue, arterial hypotension, oliguria, tachycardia and gastrointestinal disorders such as nausea and vomiting.
Although the use of thiazide diuretics and may lead to the development of hypokalemia, with the simultaneous administration of ramipre can reduce the severity of hypokalemia caused by diuretics.The likelihood of hypokalemia is highest in cirrhosis, in patients with elevated diuresis, in inadequate oral administration of electrolytes, as well as in the treatment of corticosteroids and ACTH (see Interaction). In hot weather, it is possible to develop hyponatremia in patients with peripheral edema. The lack of chlorides is usually minor and does not need treatment.
Thiazides can reduce the excretion of calcium ions in the urine, resulting in a slight periodic increase in the level of calcium in the blood, even in the absence of obvious violations of calcium metabolism. Explicit hypercalcemia may indicate latent hyperparathyroidism. The administration of thiazides should be discontinued until the results of the parathyroid gland function are obtained. It has been shown that thiazides increase the renal excretion of magnesium, which can lead to a decrease in the level of magnesium in the blood.
Neutropenia / agranulocytosis
It is necessary to stop taking a combination of fixed doses of ramipril and hydrochlorothiazide in case of occurrence or suspicion of neutropenia (the number of neutrophils is less than 1000 / mm3).
Anti-doping tests
Hydrochlorothiazide, which is part of this drug, can give a positive reaction in the anti-doping control.
Other
Regardless of the history of allergy or bronchial asthma, patients may develop hypersensitivity reactions. The possibility of exacerbation of systemic lupus erythematosus was reported.
Lactose intolerance
This medication contains lactose monohydrate.
It should not be prescribed to patients with a rare hereditary impairment of tolerance to galactose, hereditary lactose deficiency or a syndrome of glucose-galactose absorption impairment.