Cardipril

Cardipril is a drug that slows down the action of angiotensin. Its use reduces the volume of angiotensin-2 formed, and also prevents its vasoconstrictor effect and blocking bradykinin breakdown, which causes the production of PG and nitrous oxide.

The drug reduces cardiac afterload and blood pressure, and also reduces the release of aldestorone and systemic vascular resistance. At the same time, Cardipril helps to reduce resistance inside the renal vessels and improve their blood supply processes. [ 1 ]

Indications Cardipril

It is used in case of such violations:

• increased blood pressure;
• heart failure that develops as a result of the active phase of myocardial infarction in people with a stable hemodynamic level;
• ZSN;
• pronounced nephropathy of diabetic or non-diabetic nature;
• to prevent the development of myocardial infarction or stroke, and in addition to this, to reduce the likelihood of death from diseases in the cardiovascular system.

Release form

The release of the medicinal product is realized in capsules of 1.25, 2.5, and also 5 or 10 mg - 10 pieces inside blister packs. Inside the package - 1 or 3 such packs.

Pharmacodynamics

Ramiprilat, which is the metabolic element of ramipril (with therapeutic effect), slows down the activity of the enzyme dipeptidyl carboxypeptidase-1. In tissues and blood plasma, this enzyme catalyzes the transformation of angiotensin-1 into angiotensin-2 (an active vasoconstrictor), and at the same time blocks the processes of bradykinin breakdown (has vasodilatory activity).

A decrease in the volume of angiotensin-2 formed and a slowdown in bradykinin breakdown leads to vasodilation in relation to blood vessels. Considering that angiotensin-2 also stimulates the processes of aldosterone release, the effect of ramiprilat leads to a weakening of aldosterone release. [ 2 ]

Pharmacokinetics

Ramipril is rapidly absorbed when taken orally. Using a radioactive tracer detected in urine, it was found that the absorption of the element was at least 56%. No significant change in the degree of absorption was observed when the drug was taken with food.

Intraplasmic Cmax values are observed after 60 minutes from the moment of oral administration. The half-life of ramipril is approximately 1 hour. Plasma Cmax levels of ramiprilat are recorded in the period of 2-4 hours from the moment of ramipril administration. [ 3 ]

In the liver, presystemic metabolic processes of the prodrug (ramipril) occur, which leads to the formation of the only metabolic component with medicinal effect - ramiprilat (during hydrolysis, mainly realized in the liver). In addition to this activation with the formation of ramiprilat, the active element of the drug undergoes glucuronidation and is transformed into an ester - ramipril diketopiperazine. Ramiprilat is also subject to glucuronidation, which is transformed into an acid - ramiprilat diketopiperazine.

Following this prodrug activation/exchange, approximately 20% of orally administered ramipril remains bioavailable. When 2.5 or 5 mg ramipril is administered orally, the bioavailability of ramiprilat is approximately 45%.

When 10 mg of ramipril, which had been previously labeled with a radioactive tracer, was administered, about 40% of the tracer was excreted in the faeces, and approximately 60% in the urine. When 5 mg of ramipril was administered orally to individuals with biliary drainage, approximately equal amounts of ramipril and metabolic components were excreted in the bile and urine over the first 24 hours.

Approximately 80-90% of the metabolic elements in the bile with urine are ramiprilat or its metabolites. The glucuronide and diketopiperazine of the active element constitute about 10-20% of the total, and unchanged ramipril - about 2%.

In animal studies, ramipril was found to be excreted in breast milk.

The reduction of plasma ramiprilat levels occurs in several stages. The half-life of the initial distribution and elimination phase is approximately 3 hours. Then the transition phase begins (with a half-life of approximately 15 hours), and then the final phase, during which intraplasmic ramiprilat values are extremely low (the half-life lasts approximately 4-5 days).

The presence of the final stage is associated with the low-speed dissociation of ramiprilate with close but intense binding to ACE.

Although the drug has a prolonged final excretion phase, with a single administration of 2.5+ mg of ramipril, its stable indicators in the plasma are noted after only 4 days. With repeated use, the effective half-life, taking into account the dosage, is 13-17 hours.

In vitro tests have shown that the inhibition constant of ramiprilat is 7 mmol/l and the half-dissociation term of the substance with ACE is 10.7 hours, which demonstrates its pronounced activity.

Protein synthesis of the active ingredient and metabolite is 73% and 56%, respectively.

Dosing and administration

The medicine is taken orally - every day, at the same time, without reference to food intake. The tablets are swallowed whole, washed down with plain water.

People with increased blood pressure should start the course with 2.5 mg per day. If necessary, the dose can be increased with 2-3 week breaks. The size of the standard maintenance dose per day fluctuates in the range of 2.5-5 mg; the maximum size is 10 mg.

People with CHF need to take 1.25 mg of the medication per day. This dose can be increased at 2-3 week intervals until it reaches 10 mg.

After myocardial infarction, the drug intake begins in the period from the 2nd to the 9th day from the moment of the disorder development. At first, 1.25-2.5 mg of the drug is used 2 times a day, after which the dose can be doubled - up to 2.5-5 mg. A maximum of 10 mg of the drug can be administered per day.

In case of nephropathy, 1.25 mg of Cardipril is required per day. This dose can be increased at 2-3 week intervals until reaching 5 mg.

For prevention, 2.5 mg of the drug is administered per day; after 1 week, this dose can be increased to 5 mg. After 3 weeks, the dosage can be doubled again - increased to 10 mg.

• Application for children

Not for use in pediatrics (under 18 years of age).

Use Cardipril during pregnancy

Cardipril should not be used during pregnancy. Before prescribing the drug to patients of reproductive age, they must be examined for possible pregnancy.

During the treatment period, patients should use reliable contraception. If you are planning to conceive, you should stop using the drug.

If conception occurs during therapy, you should consult your doctor about switching to alternative treatment methods.

Contraindications

Main contraindications:

• severe intolerance to the components of the drug;
• SKV;
• history of Quincke's edema caused by the use of ACE inhibitors;
• Quincke's edema, which has a hereditary or idiopathic origin;
• scleroderma;
• suppression of hematopoietic processes within the bone marrow;
• excess amount of element K in the body;
• stenosis affecting the arteries of both kidneys or the artery of one kidney;
• liver/kidney failure;
• deficiency of the element Na in the body;
• kidney transplant;
• initial stage of hyperaldosteronism;
• breast-feeding.

Side effects Cardipril

Side effects include:

• a strong decrease in blood pressure, asthenia, angina pectoris, heart failure, tachycardia, chest pain and arrhythmia;
• dizziness, depression, drowsiness, memory loss, headaches and convulsions, as well as neuropathy, cerebrovascular disorders, tremor, hearing loss with vision, neuralgia and paresthesia;
• proteinuria, oliguria, edema and weakening of renal function;
• thrombocytopenia or pancytopenia, hemolytic anemia, eosinophilia, agranulocytosis and myelodepression;
• diarrhea, anorexia, nausea, hypersalivation, constipation, xerostomia, vomiting, dyspepsia, pain in the epigastric region and dysphagia, as well as pancreatitis, gastroenteritis, hepatitis, problems with liver function and changes in transaminase levels;
• sinusitis, tracheobronchitis, dry cough, pharyngitis, dyspnea, rhinitis, upper respiratory tract infections, laryngitis and bronchial spasm;
• fever, rash, anaphylactoid symptoms, erythema multiforme, urticaria, photosensitivity and Quincke's edema;
• arthralgia, myalgia or arthritis;
• weight loss, increased K values and creatinine and urea nitrogen levels, as well as changes in enzyme activity, bilirubin, sugar and uric acid levels.

Overdose

The main symptoms of poisoning include renal failure, a marked decrease in blood pressure, shock, and electrolyte disturbances.

In such cases, gastric lavage and activated carbon are performed. In addition, the patient must be sent to intensive care to monitor and support the functioning of important body systems.

A marked decrease in blood pressure values requires the administration of catecholamines and angiotensin-2, as well as an increase in the volume of Na and fluid. Hemodialysis processes have no effect.

Interactions with other drugs

The use of the drug together with antihypertensive drugs, diuretic drugs, narcotic analgesics and anesthetics potentiates its antihypertensive activity, while administration with NSAIDs and table salt, on the contrary, reduces it.

Indomethacin and other NSAIDs can prevent the development of the hypotensive effect by suppressing the production of PG in the kidneys, and in addition, by retaining Na and fluid in the body.

The use of drugs in combination with milk, cyclosporine, potassium substances and its additives, as well as with salt substitutes and potassium-sparing diuretics (triamterene and amiloride with spironolactone), increases the risk of developing hyperkalemia.

Medicines that suppress bone marrow function, when combined with the drug, increase the risk of agranulocytosis and neutropenia, which can lead to death.

The introduction of Cardipril with lithium substances increases their blood values.

The drug may potentiate the antidiabetic effect of insulin and sulfonylurea derivatives.

The use of drugs together with allopurinol, procainamide, cytostatics and immunosuppressants potentiates the risk of leukopenia.

The drug may potentiate the suppressive effect of ethyl alcohol on the nervous system.

The combination of the drug and estrogens reduces its antihypertensive activity.

Storage conditions

Cardipril should be stored in a place closed to small children and moisture. Temperature level – maximum 30оC.

Shelf life

Cardipril can be used within 36 months from the date of manufacture of the medicinal product.

Analogues

The analogs of the drug are the substances Polapril, Ramizes, Ramipril and Hartil with Ampril, and in addition Topril with Mipril N and Ramigexal with Ramag N.