Cardil

Cardil is a drug from a subgroup of substances that block the action of Ca channels, and has antihypertensive, antiarrhythmic and antianginal effects.

The active element of the drug is diltiazem, a benzodiazepine substance that prevents the passage of Ca into the cells of cardiomyocytes, as well as cells of vascular smooth muscles. With a decrease in the current of calcium ions, the smooth muscles of the vascular membrane relax, which makes it possible to increase the vascular lumen, stabilize microcirculation within ischemic areas and reduce the systemic resistance of peripheral vessels. All this contributes to a decrease in blood pressure. [1]

Indications Cardil

It is used for angina pectoris (this includes its variant and stable varieties). The medication is not used to eliminate acute angina attacks.

It can be used with increased blood pressure - for example, in situations where it is impossible to use substances that block the activity of β-adrenergic receptors. Cardil is administered both in monotherapy and in complex treatment.

It is also prescribed in case of arrhythmias - for example, to reduce the rhythm of the heart ventricles during atrial fibrillation.

Release form

The drug is released in the form of tablets - 30 or 100 pieces inside the bottle. The box contains 1 such bottle.

Pharmacodynamics

Antianginal properties of the drug develop after coronary vasodilation and afterload reduction. In the case of stable angina pectoris in persons using the medication, there was an objective (prolongation of the period during which there was no depression of the ST segment during physical exertion) and subjective (a decrease in the number of angina episodes requiring the use of nitrates) improvement in the condition. The severity of the effect of Cardil in people with unstable angina pectoris is, on average, similar to the effect of nifedipine or verapamil, while the frequency of the appearance of negative signs with the use of diltiazem is less than with the introduction of these drugs.

The antihypertensive effect of the drug develops with a decrease in increased blood pressure (diastolic as well as systolic); at normal values of blood pressure, diltiazem does not change it. The use of the drug in persons with hypertension did not lead to the appearance of reflex-type tachycardia, as a reaction to a decrease in blood pressure indicators. [2]

The drug has a weak negative inotropic effect, but when it is administered, there is no decrease in the stroke volume of the heart, as well as the left ventricular ejection fraction. In people with left ventricular hypertrophy, prolonged use of diltiazem leads to regression of the disorder. [3]

In individuals with supraventricular arrhythmias, the drug inhibits the movement of calcium ions within the cells of the sinus and AV node, thereby stabilizing the heart rhythm.

Cardil can be used in monotherapy or in combination with other antihypertensive drugs (among them diuretics and ACE inhibitors). The medication is prescribed to people who cannot use drugs that block the effect of β-adrenergic receptors - with angiopathies of the peripheral type or BA, as well as diabetics.

The drug does not have a negative effect on the lipid blood structure.

Pharmacokinetics

After oral administration, the medication is fully absorbed inside the gastrointestinal tract. Participates in the 1st intrahepatic passage (while the level of absolute bioavailability is 40% in the range of personal variability of 24-74%). Bioavailability indicators are not tied to serving size and do not change with the use of different dosage forms in the spectrum of clinical dosages. Serum values of Cmax of diltiazem are noted after 3-4 hours and are equal to 39-120 ng / ml after 1-time use of 60 mg of drugs.

About 80% of the administered portion of diltiazem is involved in serum protein synthesis (about 40% with albumin). The medicine easily passes into the tissues; the level of the distribution volume is about 5 l / kg.

Equilibrium serum values of diltiazem in the case of regular use of 60 mg of the drug 3 times a day are noted by the 3-4th day of treatment. In the case of using daily portions in the range of 0.12-0.3 g, stable serum values of the substance are in the range of 20-200 ng / ml (the minimum therapeutic level is in the range of 70-100 ng / ml).

Metabolic intrahepatic drug processes occur with the help of CYP3 A4; the drug is a substrate of P-glycoprotein. After the administration of diltiazem, there is a decrease in the effect of the hemoprotein CYP3 A4.

During the 1st stage of the exchange, the processes of deacetylation, as well as O- and N-demethylation, take place. The main metabolic component is deacetyldyltiazem (its serum level is approximately 15-35% of the values of unchanged diltiazem), which has a drug activity similar to the active element, but it is slightly weaker (approximately 40-50% of the effect of diltiazem).

Excretion is carried out mainly in the form of derivatives through the kidneys; the level of systemic clearance is 0.7-1.3 l / kg / hour. Inside urine, 5 unconjugated derivatives of diltiazem are recorded, and some of them also have a conjugated form. Elimination has one-stage kinetics. According to the 3-chamber model, the term half-life is 0.1, 2.1, and 9.8 hours during the initial, middle and final stages of elimination. The general term for elimination half-life is in the range of 4-7 hours.

Dosing and administration

You need to use drugs inside, without crushing the tablets before use. The dosage size is calculated so that it corresponds to the volume of the substance inside the 1st tablet. The mode of administration and portion sizes are selected by the doctor, taking into account the severity and course of the disease, the weight and age of the patient, as well as concomitant treatment.

On average, 0.18-0.24 g of drugs should be used per day; if necessary, an increase to the maximum daily dosage of 0.48 g is allowed. If negative symptoms develop during an increase in the portion, the volumes of diltiazem should be reduced. If the required control over the blood pressure level with the introduction of the maximum daily dosage of the drug (0.48 g) is not established, but this portion is well tolerated, other antihypertensive substances (for example, diuretics or ACE inhibitors) should be additionally used.

The initial portion of the drug per day should be 60 mg with 3-4 administrations. Later, taking into account the therapeutic efficacy and the general clinical picture, it can increase or decrease. For most patients, to control blood pressure values and prevent angina attacks, a 3-time administration of 0.12 g per day is sufficient.

Elderly persons should first apply 3-4 times 30 mg of the substance. It is possible to increase the portion in this group of patients only under the supervision of a doctor and in the absence of complications from the administration of diltiazem.

People with hepatic dysfunctions need to use Cardil very carefully - they have more careful monitoring of blood pressure and ECG readings, and at the same time, a lower initial dosage is prescribed (3-4 times a day of 30 mg).

• Application for children

It is forbidden to use the medication in pediatrics.

Use Cardil during pregnancy

The medication is not used during pregnancy. During planning or the onset of conception when using diltiazem, you need to consult with your doctor about choosing an alternative treatment.

If you need to use Cardil during breastfeeding, you need to stop using HB before starting the introduction of drugs.

Contraindications

It is contraindicated to use in case of intolerance to diltiazem or additional elements of drugs.

Cannot be used for cardiac conduction disorders, including AV block (stage 2-3; except for situations when the patient has a pacemaker) and SSSU.

It is forbidden to prescribe medicine to people with low blood pressure (with systolic marks below 90 mm Hg), severe bradycardia (heart rate less than 50 beats / minute) and decompensated heart failure.

In addition, it is not used in the active phase of myocardial infarction (proceeding with complications), WPW syndrome and cardiogenic shock associated with poisoning with digitalis substances.

Side effects Cardil

Possible side symptoms include:

• problems with the activity of the CVS: bradycardia, sinus or AV block (stage 1; more rarely - 2-3rd), CHF, decreased blood pressure, suppression of the sinus node activity and paradoxical worsening of angina pectoris, and besides this tachycardia and palpitations, arrhythmia, syncope, extrasystole, facial hyperemia, loss of consciousness and peripheral edema;
• dysfunction of the gastrointestinal tract: nausea, weight gain, impaired appetite, xerostomia, vomiting, stool disorders, dyspeptic symptoms, gingivitis and gingival hyperplasia;
• lesions of the subcutaneous layer and epidermis: SS, urticaria, pruritus, lupus erythematosus, TEN, exanthema and petechiae, and in addition, Quincke's edema, vasculitis, exfoliative dermatitis and photosensitivity;
• disorders of hepatobiliary activity: hyperglycemia, increased activity of intrahepatic enzymes and hepatitis of the granulomatous type;
• problems with the blood system: thrombocyto- or leukopenia, as well as prolongation of the bleeding period;
• dysfunction of the central nervous system: confusion, personality changes, amnesia, depression, paresthesia and hallucinations, and in addition, drowsiness, tremors, ear noise, sleep disturbances, gait disturbances and drowsiness;
• Others: myalgia, eosinophilia, dyspnoea, lymphadenopathy, taste and olfactory disorders, eye irritation or amblyopia, nasal congestion or bleeding, polyuria, pain affecting bones or joints, nocturia, gynecomastia, erectile dysfunction, and increased creatine kinase values.

Epidermal manifestations caused by the introduction of diltiazem disappear on their own, without canceling the use of drugs. But if epidermal disorders continue to persist for a long time, the option of discontinuing Cardil should be considered.

Overdose

With the introduction of excessively large portions of the drug, the potentiation of the intensity of the negative symptoms that are characteristic of diltiazem may occur. After the introduction of 900-1800 mg of the drug, moderate or severe poisoning is observed. Severe poisoning occurs with a single injection of 2600 mg of drugs in the elderly and 5900 mg in younger adults. The use of 10.8 g of Cardil caused extremely severe poisoning.

Signs of intoxication appear on average after 8 hours after drug administration. Among the main manifestations are irritability, AV block, hypothermia and drowsiness, as well as a decrease in blood pressure values, hyperglycemia, bradycardia, nausea and cardiac arrest.

Has no antidote. In case of intoxication, it is necessary to carry out gastric lavage and take enterosorbents, as well as perform symptomatic and supportive actions. It is required to regularly monitor respiratory function, acid-base and electrolyte indicators, as well as hemodynamic values.

In the case of a decrease in blood pressure, dopamine or CaCl is used intravenously. If there is bradycardia or, in some situations, AV block due to drug overdose, intravenous injection of atropine or the use of an electrostimulator is used (if drug therapy does not work).

Interactions with other drugs

The drug potentiates the properties of other antihypertensive substances.

The use together with digoxin, amiodarone or β-blockers leads to potentiation of AV conduction and an increase in the risk of developing bradycardia.

Potentiation of the suppressive effect of isoflurane and halothane on the myocardium is observed when they are used together with diltiazem.

In the case of intravenous use of parenteral drugs Ca, the therapeutic effect of Cardil is weakened.

Primary metabolic processes of drugs are implemented using CYP3 A4. Substances that slow down the action of this enzyme (among them cimetidine), when combined with a medication, can lead to an increase in diltiazem indices inside the plasma. The activity of the substance can also be enhanced when combined with macrolides, nifedipine, antimycotics, as well as with azole derivatives, tamoxifen, fluoxetine and agents that slow down the HIV protease.

Medications that induce the effects of CYP3 A4 attenuate the effects of the drug. For example, a decrease in effectiveness is noted when combined with rifampicin, carbamazepine, or phenobarbital.

Cardil weakens metabolic processes caused by the activity of CYP3 A4 and P-glycoprotein. It is necessary to very carefully combine the drug with substances whose metabolism is realized using the specified isoenzyme - for example, with cyclosporine, methylprednisolone, phenytoin, theophylline and sirolimus, as well as with digitoxin and digoxin.

A combination of a drug and substances that slow down the activity of HMG-CoA reductase, whose metabolic processes are carried out using CYP3 A4 (this includes simvastatin and atorvastatin with lovastatin), is used with extreme caution. The joint use of these drugs may require a reduction in the portion of anticholesterol-lowering drugs (due to an increased likelihood of developing hepatotoxicity and rhabdomyolysis). The drug does not alter the pharmacokinetics of pravastatin with fluvastatin.

Cardil is able to increase serum values of drugs such as buspirone, propranolol, alfentanil with nifedipine, alprazolam and sildenafil with imipramine, diazepam and metoprolol with cisapride, as well as midazolam and portriptyline.

In the case of a combination of drugs with lithium substances, the risk of developing neurotoxic activity increases. Serum lithium values should be closely monitored when using such a drug combination.

Storage conditions

Cardil must be kept in a place closed from the penetration of small children. Temperature values are in the range of 15-25 ° С.

Shelf life

Cardil is allowed to be used within a 36-month term from the date of sale of the pharmaceutical substance.

Analogs

Analogues of drugs are the medicines Blokaltsin, Dilts with Diltiazem, Tiakem and Cortiazem, and in addition Silden with Altiazem RR, Dilren with Diakordin and Dilcardia.