Carvedilol

Carvedilol is a non-selective substance that blocks the action of β-adrenoreceptors, and in addition selectively blocks the activity of α-receptors.

It does not demonstrate an internal sympathomimetic effect, reduces the overall load on the atria by selectively blocking α-adrenoreceptors. Performing a non-selective blocking of β-adrenoreceptors leads to inhibition of renal ASD (reduction of the effect of intraplasma renin) and a weakening of blood pressure along with heart rate, and in addition to this cardiac output. Blocking α-receptors helps peripheral vasodilation, which leads to a decrease in vascular resistance.

[1], [2], [3], [4], [5], [6]

Indications Carvedilola

Used for such disorders:

• increased blood pressure (monotherapy or a combination with any other antihypertensive drugs);
• stable angina ;
• failure of the CCC in the chronic stage.

[7], [8], [9], [10]

Release form

The release of drugs produced in tablets with a volume of 12.5 or 25 mg. Inside the cell packaging - 30 such tablets.

[11], [12], [13]

Pharmacodynamics

The combination of such effects as blockade of β-receptor activity and vasodilation leads to the following reactions:

• people with IHD are prevented from developing pain, as well as myocardial ischemia;
• in persons with increased blood pressure, they decrease;
• in patients with blood flow insufficiency and left ventricular dysfunction, there is a decrease in the size of the left ventricle, accompanied by an increase in its fractional release, and an improvement in hemodynamic processes.

The drug has no effect on lipid metabolism.

[14], [15], [16], [17], [18], [19], [20],

Pharmacokinetics

The level of bioavailability of the substance carvedilol is 25%. Сmax values are registered after the expiration of the 1st hour from the moment of oral administration of the drug. The medication has a linear relationship between blood values and the administered portion. The level of bioavailability does not change under the influence of food consumed.

Carvedilol is an element with high lipophilicity. About 98-99% of the component is synthesized with blood protein. The term half-life equals 6-10 hours. Volumes at the 1st intrahepatic passage are 60-75%. The distribution volume is equal to 2 l l / kg. The values of intraplasma clearance - 590 ml per minute.

Carvedilol metabolism processes take place inside the liver during glucuronization oxidation that occurs with the phenol ring. Dimethylation and hydroxylation associated with the aromatic ring leads to the formation of 3 metabolic components, demonstrating β-blocking activity.

During the preclinical phase, it was found that the metabolic element 4'-hydroxy-phenol has enhanced 13 times (compared to carvedilol) activity. Blood levels of metabolic elements are approximately ten times lower than carvedilol levels. The remaining 2 metabolic components (hydroxycarbazole) have intense antioxidant and adreno-blocking properties. The antioxidant effect of degradation products exceeds the effect of carvedilol by 30-80 times.

Elimination of drugs is made with bile (and then with feces). A small part of the drug is eliminated through the kidneys.

Older people have an increased rate of carvedilol (up 50%).

The values of the bioavailability of the substance in patients with hepatic cirrhosis quadrupled, and blood parameters - five times higher than in a healthy person.

In individuals with kidney failure (the KK indicator is ≤ 20 ml per minute) and an elevated blood pressure level, an increase of 40-55% of the blood values of the drug is recorded (compared to people without renal impairment).

[21]

Dosing and administration

Carvedilol is taken orally, without reference to food intake. If the patient has insufficiency of the CAS function, the drug should be taken along with the food (this increases the absorption, allowing you to reduce the likelihood of orthostatic collapse).

With increased values of blood pressure.

Take the medication should be 1-2 times a day. Adults are advised to take 12.5 mg per day during the first 1-2 days. The size of the maintenance portion per day is 25 mg. When the need may be a gradual increase in servings with 14-day breaks (minimum) until reaching the maximum recommended dosage of 50 mg.

Older people should first take 12.5 mg of the drug a day. This portion is enough for later use.

In the case of increased values of blood pressure per day is allowed to take no more than 50 mg of the drug.

In the case of angina with a stable form.

The first 1-2 days of the course should be consumed 25 mg per day (divide the portion into 2 applications). Maintenance portion is 50 mg (in 2 use). During the day, you can take no more than 0.1 g of medicine (for 2 doses).

In the first 1-2 days, elderly people need to take 12.5 mg of drug 1-fold. After that, a transition to a maintenance portion of 50 mg is made (divided into 2 uses). In older patients, this is the maximum portion.

The failure of the CAS, which has a chronic form.

Carvedilol is used as an auxiliary element in standard therapy with the introduction of ACE inhibitors, digitalis drugs, diuretics, and vasodilators. To start taking the drug, it is necessary that the patient remained stable during the last month before proceeding to the use of carvedilol. Also, to take the medication, you need the heart rate to be above 50 beats per minute, and the systolic blood pressure indicator is above 85 mm Hg.

First, take 6.25 mg per day (1 time). If there are no complications, gradually increase the portion with a minimum of 14 days: first, 6.25 mg 2 times a day, then 12.5 mg 2 times, and then 25 mg (2 times).

People with a weight of ≤ 85 kg per day can be administered a maximum of 50 mg (for 2 uses), and for people with a weight of ≥85 kg, 0.1 g (for 2 uses). In the latter case, except for persons with insufficiency of the CAS function. Increase portions produced only under the supervision of a doctor.

At the beginning of treatment, there may be a slight worsening of the manifestations of the disease (especially in individuals taking diuretics in large portions, or in severe form of pathology). It is not necessary to cancel the drug in case of such violations; you should only refuse to increase its portion.

During therapy, the patient should be constantly monitored by a therapist (or cardiologist). Before the increase of the portion, it is required to examine the patient additionally (find out the weight, indicators of liver function, blood pressure with heart rate and stability of the heart rhythm). When registering fluid retention or symptoms of decompensation, symptomatic procedures should be carried out (increasing the amount of diuretic). At the same time, it is not necessary to increase the portion of the drug (at least until the moment when the general state of the patient is stabilized).

In some situations, it is necessary to reduce the dose of the drug or to cancel it for a while (in such cases, dosage titration can be performed).

If the therapy is interrupted, it should be resumed from the minimum portion (1 single dose per day 6.25 mg). Then the dosage is gradually increased, following the above instructions.

With the abolition of the drug requires a gradual decrease in portions in a 1-2-week period.

[27], [28], [29], [30]

Use Carvedilola during pregnancy

Carvedilol is forbidden to prescribe during breastfeeding and pregnancy. Testing with the participation of animals did not confirm the teratogenic effect of drugs, but there were too few clinical tests that investigated the safety of its use in this group of women. The drug can reduce the values of the placental circulation, which can cause fetal death inside the womb or preterm birth. The use of the drug during pregnancy can trigger hypoglycemia in a newborn baby or fetus, and, in addition, hypothermia, severe bradycardia or lung insufficiency and cardiorespiratory complications.

Use of drugs in pregnant women is allowed only in situations where the likely benefits of its administration are more expected than the risk of negative consequences for the child. When taking medication for a pregnant woman, it should be discontinued 2-3 days before the due date of delivery. If this recommendation is not followed, the first 2-3 days should be monitored for monitoring the condition of the newborn.

When testing with the participation of animals, the ability of a molecule with its metabolic elements to excretion with mother's milk was revealed. Therefore, when using drugs during this period, you need to abandon breastfeeding.

[22], [23]

Contraindications

The main contraindications:

• failure of the CCC function in the decompensated phase;
• obstructive diseases affecting the bronchopulmonary system (chronic stage);
• AV block (grade 2–3);
• AND;
• cardiogenic shock;
• bradycardia (heart rate indicators are ≤50 beats per minute);
• allergy signs associated with the active ingredient or other elements of the drug; 
• SSS (this includes sinoauricular cardiac block);
• variant angina;
• untreated pheochromocytoma;
• combination with parenteral injections of verapamil or diltiazem in the vascular region;
• a strong decrease in pressure with systolic blood pressure below 85 mm Hg;
• pathologies affecting peripheral vessels;
• glucose-galactose malabsorption;
• hypolactasia, which is hereditary;
• lack of lactase Lappa.

[24]

Side effects Carvedilola

Among the adverse events:

• damage to hematopoietic function: mild stage of thrombocytopenia;
• metabolic disorders: hypervolemia, -cholesterolemia or -glycemia, fluid retention and peripheral edema. Hyperglycemia usually develops in diabetics;
• CNS disorders: sleep problems, dizziness, syncope, depression, headaches, and paresthesias;
• visual impairment: eye irritation, disorders of visual function and reduction in the production of tears;
• problems affecting the urethra: disorders of the urethra, peripheral edema and kidney function failure;
• disorders of the gastrointestinal tract: diarrhea, nausea, dry oral mucous membranes, pain, affecting the abdominal area, constipation, vomiting and increased transaminase values;
• sexual dysfunction: impotence or swelling, affecting the genitals;
• damage to the CVS function: a disorder of peripheral blood flow processes, bradycardia or orthostatic collapse;
• ODA disorders: pain affecting the limbs;
• problems with respiratory function: dyspnea (obstructive syndrome) in patients with COPD, and nasal dryness of the nasal mucosa;
• manifestations associated with the subcutaneous layers and epidermis: itching, rash, having an allergic nature, urticaria, symptoms similar to psoriasis or lichen planus. If a patient has psoriasis, his epidermal manifestations may worsen;
• other: systemic weakness;
• rare disorders: AV blockade, exacerbation of manifestations of diseases affecting peripheral vessels (intermittent claudication, Raynaud's disease, etc.) or angina pectoris.

The use of Carvedilol can provoke the development of previously latent diabetes mellitus, worsening of the course of existing diabetes, as well as improper regulation of the serum values of sugar.

As a result of titration of drugs, myocardial contractile activity can rarely be reduced.

[25], [26]

Overdose

Overdose can lead to a severe drop in blood pressure, bradycardia, heart failure, vomiting, bronchial spasm, loss of consciousness, respiratory disorders, cardiogenic shock, seizures and cardiac arrest.

When treatment is required to monitor the function of the main systems of the body. Persons with intoxication should be placed in intensive care when needed.

Supporting activities: to prevent severe bradycardia - in / in the introduction of 0.5-2 mg of atropine; maintaining the work of the cardiovascular system - using glucagon (at first in a jet i / v method of 1-10 mg, and then - intravenous infusion of 2-5 mg per hour). Sympathomimetics are also used (dobutamine or isoprenaline with epinephrine), whose portion is determined by the weight of the patient.

In the case of bradycardia, refractory to drug therapy, cardiac electrical stimulation is performed. To eliminate bronchial spasm, β-sympathomimetics are used via IV infusion or inhalation; in addition, it works well in / in the introduction of aminophylline. Convulsions are eliminated by administering diazepam at low speed.

Because carvedilol is synthesized at high speed with blood protein, hemodialysis will be ineffective.

In case of severe intoxication, the supporting procedures are carried out for quite a long time, because the redistribution and excretion of drugs take place slowly. The duration of this course is determined by the patient's condition (until stability is achieved).

[31]

Interactions with other drugs

Antiarrhythmic drugs and Ca antagonists.

After the combined use of carvedilol and diltiazem, amiodarone or verapamil, hypotension or bradycardia sometimes develops. In such patients, it is required to monitor the level of blood pressure and ECG values.

The synergistic effect of the medication and Ca antagonists can lead to cardiac abnormality with abnormality with the appearance of decompensation.

It is necessary to closely monitor patients combining the drug with antiarrhythmic substances of the 1st class or amiodarone. There is evidence of the occurrence of bradycardia, ventricular fibrillation, or cardiac arrest after starting carvedilol by persons using amiodarone.

In the case of parenteral administration of an antiarrhythmic agent, insufficiency of CVS function can be observed (antiarrhythmic drugs of classes Іa or Ic).

There is evidence of the development of bradycardia in the case of a combination of a substance with methyldopa or guanethidine, and in addition, guanfacine, reserpine or MAOI (excluding IMAO-B). With such combinations, you need to track the rhythm of the heartbeat.

It is forbidden to administer the drug with dihydropyridines, because it can lead to CAS insufficiency or a severe fall in blood pressure.

When combined with nitrates, a decrease in blood pressure occurs.

Drug administration with digoxin causes an increase in the equilibrium indices of digitoxin with digoxin (by 13% and 16%). When using such a combination, it is necessary to determine the blood values of digoxin before the start of therapy and by the time the selection of the support portion is completed.

The drug potentiates the antihypertensive activity of drugs from other pharmacological categories (barbiturates, vasodilators, phenothiazines with tricyclics, alcoholic beverages, and α1 receptor antagonists).

Administration in conjunction with cyclosporin requires the determination of its blood values, because they may increase.

Antidiabetic drugs (insulin among them).

The drug is able to level the symptoms of hypoglycemia; in addition, it can enhance the action of hypoglycemic substances and insulin. In this regard, it is required to constantly monitor the serum indicators of sugar in these patients.

With the introduction of drugs along with clonidine and the need to cancel both drugs, you must first cancel Carvedilol, then gradually reduce the amount of clonidine.

In the case of the need for the use of inhalation anesthesia, it is necessary to remember that anesthetics, when combined with the drug, lead to the appearance of negative inotropic and antihypertensive effects.

The therapeutic efficacy of the drug is weakened when combined with substances that trap sodium with a liquid inside the body (anti-inflammatory anesthetic drugs, estrogens and GCS).

Persons using fluoxetine, verapamil, cimetidine with haloperidol, barbiturates, ketoconazole with rifampicin, or erythromycin (substances that slow down or induce the action of the hemoprotein P450 enzymes) must be under medical control, because Carvedilol levels may be increased by injection, due to injection. When using inductors).

Introduction together with ergotamine leads to the development of a strong vasoconstrictor effect.

Combining with substances that block neuromuscular activity leads to a potentiation of the blockade of this effect.

Use in combination with sympathomimetics (α- and β-adrenomimetics) increases the likelihood of increased blood pressure and the development of strong bradycardia.

[32], [33], [34]

Storage conditions

Carvedilol is stored in a dark and closed place from small children. Temperature values - in the range of 15-25 ° C.

[35], [36]

Shelf life

Carvedilol can be used within the 36-month term from the moment of release of the drug.

[37], [38]

Application for children

In persons younger than 18 years of age, Carvedidol is not appointed, because there is no information for this subgroup of treatment regarding its therapeutic efficacy and safety.

[39], [40], [41], [42], [43], [44],

Analogs

Analogues of drugs are substances Corvazan, Dilatrend and Coriol with Acridilol.

[45], [46], [47], [48]

Reviews

Carvedilol receives good reviews from medical specialists - it is considered effective in the treatment of insufficiency of cardiac function, as well as a means of monitoring the processes of AV conduction in the case of atrial fibrillation. In addition, it is allowed to assign it to reduce elevated values of blood pressure, which increases its value as a medication.

[49], [50], [51], [52], [53], [54],