Cardipril

Cardipril is a medication that slows down the action of angiotensin. Thanks to its use, the volumes of formed angiotensin-2 are reduced, as well as its vasoconstrictor effect and the blocking of bradykinin breakdown, which causes the production of PG and nitrous oxide, are prevented.

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

Indications Cardipril

It is applied in case of such violations:

• increased blood pressure indicators ;
• developed as a result of the active phase of myocardial infarction HF in people with a stable level of hemodynamics;
• CHF;
• having a pronounced nephropathy of a diabetic or non-diabetic nature;
• to prevent the development of myocardial infarction or stroke , and in addition to reduce the likelihood of death from diseases in the field of CVS.

Release form

The release of the drug is realized in capsules with a volume of 1.25, 2.5, as well as 5 or 10 mg - 10 pieces inside the cell packs. Inside the package - 1 or 3 such packs.

Pharmacodynamics

Ramiprilat, which is a metabolic element of ramipril (with a therapeutic effect), slows down the activity of the enzyme dipeptidyl carboxypeptidase-1. Inside 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 breakdown of bradykinin (has vasodilating activity).

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

Pharmacokinetics

Ramipril is absorbed at high speed when taken orally. Thanks to the use of a radioactive label determined inside the urine, it was found that the absorption of the element is at least 56%. There was no significant change in the degree of absorption with the use of drugs with food.

Intraplasma Cmax values are noted after 60 minutes from the moment of ingestion. The half-life of ramipril is approximately 1 hour. Plasma level Cmax of ramiprilat is recorded within 2-4 hours from the moment of ramipril administration. [3]

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

After this activation / exchange of the prodrug, about 20% of orally ingested ramipril remains bioavailable. In the case of oral administration of 2.5 or 5 mg of ramipril, the level of bioavailability of ramiprilat is approximately 45%.

With the introduction of 10 mg of ramipril, which was previously labeled with a radioactive label, about 40% of this label is excreted in feces, and about 60% - along with urine. After oral administration of 5 mg of ramipril in persons with biliary drainage, approximately the same volume of ramipril and metabolic components were excreted along with bile and urine during the first 24 hours.

Approximately 80-90% of metabolic elements inside bile with urine are ramiprilat or its metabolites. Glucuronide and diketopiperazine of the active element make up about 10-20% of the total volume, and unchanged ramipril about 2%.

When tested with animals, it was determined that ramipril is secreted in mother's milk.

The decrease in the plasma level of ramiprilat is implemented in several stages. The half-period of the start distribution and elimination stage is approximately 3 hours. Then the transitional stage begins (with a half-life of about 15 hours), and after that, the final stage, at which the intraplasmic values of ramiprilat are extremely low (the half-life lasts about 4-5 days).

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

Although the drug has a long final stage of excretion, with a single administration of 2.5+ mg of ramipril, its stable parameters inside 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 revealed that the deceleration constant of ramiprilat is 7 mmol / l, and the term for the half-dissociation of the substance with ACE is 10.7 hours, which demonstrates its pronounced activity.

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

Dosing and administration

The medicine is applied internally - every day, at the same time, without reference to the use of food. The tablets are swallowed whole with plain water.

Persons with increased blood pressure values should begin the course with the introduction of 2.5 mg per day. If necessary, the portion can be increased at 2-3 week intervals. The size of the standard maintenance dosage per day ranges from 2.5 to 5 mg; the maximum size is 10 mg.

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

After suffering a myocardial infarction, drug intake begins in the interval 2-9 days from the moment the disorder develops. First, 1.25-2.5 mg of the drug is used 2 times a day, after which the portion is allowed to be doubled - up to 2.5-5 mg. A maximum of 10 mg of the medication can be administered per day.

In the case of nephropathy, 1.25 mg of Cardipril is required per day. This portion is allowed to be increased at 2-3 week intervals, until the 5 mg mark is reached.

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

• Application for children

Cannot be used in pediatrics (under the age of 18).

Use Cardipril during pregnancy

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

During the period of treatment, patients should use reliable contraception. When planning conception, the use of drugs must be abandoned.

If conception occurred during therapy, you should consult your doctor regarding the transfer to alternative methods of treatment.

Contraindications

The main contraindications:

• severe intolerance to the elements of drugs;
• SLE;
• a history of Quincke's edema caused by the use of an ACE inhibitor;
• Quincke's edema, which is hereditary or idiopathic;
• scleroderma;
• suppression of hematopoietic processes inside the bone marrow;
• excessive amount of the element K inside the body;
• stenosis affecting the arteries of both kidneys or the artery of one kidney;
• failure of the liver / kidneys;
• deficiency of the element Na inside the body;
• kidney transplant;
• the initial stage of hyperaldosteronism;
• breast-feeding.

Side effects Cardipril

Among the side signs:

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

Overdose

Among the main symptoms of poisoning are kidney failure, a marked decrease in blood pressure, shock and electrolyte disorders.

With such violations, gastric lavage and the intake of activated carbon are performed. In addition, the patient must be sent to intensive care in order to monitor and maintain the work of important body systems.

A pronounced decrease in blood pressure values requires the introduction of catecholamines and angiotensin-2, and in addition to this, an increase in the volume of Na and fluid. Hemodialysis processes have no effect.

Interactions with other drugs

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

Indomethacin and other NSAIDs can prevent the development of hypotensive effects by suppressing the production of PGs inside the kidneys, and in addition, retaining Na and fluid inside 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 hyperkalemia.

Medicines that suppress bone marrow function, when combined with a medicine, 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 can 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 can potentiate the suppressive effect of ethyl alcohol in relation to NS.

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

Storage conditions

Cardipril must be kept out of the reach of small children and moisture. Temperature level - maximum 30 ° C.

Shelf life

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

Analogs

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