Calcium antagonists: list of drugs, mechanism of action

Calcium channel blockers are effective drugs with a wide range of pharmacological effects. The list of calcium antagonists contains more than twenty substances, each of which has a different effect on the individual’s body. For a long time they have been used in practical medicine - therapy, neurology, gynecology due to their effect on the cellular tissue of the heart muscle, the conducting system of the heart, myometrium and vascular smooth muscle. Medicines of this group impede the penetration of calcium into cells through calcium channels, which are proteins located in the cell membrane and passing the trace element through special holes.

The role of calcium in the body

This trace element in percentage terms ranks fifth among all minerals in the body of an individual. It is necessary for bone strength and regulation of cardiac activity. The trace element ions entering the muscle cells of the heart exit from them into the intercellular space using ion pumps. Due to their penetration into the cardiomyocyte, the myocardium is reduced, and as a result of exit, it relaxes. Thus, calcium takes an active part in the work of the heart muscle and is involved in the regulation of heartbeat. The heart is the organ responsible for the blood supply to all organs and systems, and accordingly, when it fails, the whole body will suffer.

general information

Calcium antagonists have been successfully used in cardiology for over fifty years. The ancestor of this group of antihypertensive drugs is the drug "Verapamil", created by German experts in 1961. In practical medicine, he has established himself not only as a good vasodilator, but also as a means with a cardiotropic effect. “Verapamil” was assigned to the group of beta-blockers for several years after its creation, however, further study of the mechanism of action of the drug showed that it is able to suppress transmembrane calcium current. In the future, it was proposed to combine drugs similar in mechanism of action with Verapamil into one group called calcium channel blockers. In the late 60s and early 70s, the drugs Nifedipine and Diltiazem were produced, which they began to call first-generation drugs.

Medicines of this group have found their application as coronaryolytics in coronary heart disease, and are also used as antiarrhythmics and medicines for the treatment of hypertension. Such widespread use is due to the action of calcium antagonists to relax the muscles of the vascular wall and expand the arteries of the coronary, cerebral bed, without affecting the tone of the veins. "Diltiazem" and "Verapamil" reduce myocardial oxygen consumption and reduce its contractility, in addition, inhibit the activity of the sinus node and supraventricular arrhythmias, in addition, they are endowed with an antihypertensive effect. "Diltiazem" in its properties is in an intermediate position between "Verapamil" and "Nifedipine." The latter has a lesser effect on myocardial contractility and the conduction heart system. It is indicated for peripheral vasospasm and arterial hypertension. The only pharmacological group of calcium antagonist drugs that combines medicines:

• various in chemical structure;
• with various mechanisms of action;
• differing in therapeutic activity, clinical effect;
• different in contraindications and side effects.

Classification

The chemical structure distinguishes calcium antagonists:

• Dihydropyridine. Drugs in this series increase the pulse. They are prescribed in the treatment of peripheral vascular atherosclerosis, hypertension, left ventricular hypertrophy, angina pectoris. In the treatment of arrhythmias, they are not indicated.
• Nonhydropyridines are derivatives of benzodiazepine and phenylalkylamine. These medicines have shown high efficacy in the treatment of atherosclerosis of the carotid arteries, angina pectoris. They are endowed with a pronounced anti-ischemic, hypotensive, antiarrhythmic effect. Able to reduce heart rate.
• Non-selective. These include diphenylpiperazine derivatives. They improve cerebral circulation, do not significantly affect the level of pressure, but are capable of vasodilating action.

Several generations of calcium antagonist preparations have been successfully used in medicine:

• The first is Nifedipine, Verapamil, Diltiazem. The disadvantages of these medications include rapid elimination from the body and low bioavailability.
• The second is represented by dosage forms of modified release - Nifedipine XL, Verapamil SR. Medications have a longer therapeutic effect. However, the maximum level of concentration in the blood is reached at different times, and therefore it is quite difficult to predict their effectiveness.
• The third is long-acting medications endowed with high bioavailability. Their representatives are Amlodipine, Lercanidipine, which are often prescribed for the treatment of hypertension.

There are other classifications of calcium antagonists in the literature. For example, benzodiazepine and phenylalkylamine derivatives are isolated into separate subgroups, and depending on the indications for use, dihydropyridine derivatives are prescribed, which are prescribed for angina pectoris, left ventricular hypertrophy, high blood pressure in elderly individuals and non-dihydropyridine drugs for carotid atherosclerosis, supraventrica.

In recent years, calcium channel blockers, depending on the effect on heart rate, are divided into the following groups:

• restraining rhythm, for example, Verapamil, Diltiazem;
• increasing or not changing the rhythm, for example, "Nifedipine" and all derivatives of dihydropyridine

Duration of antihypertensive action

The basis of the hypotensive effect of all calcium channel blockers is their ability to expand blood vessels, while contributing to a decrease in total peripheral resistance. The most vasodilating effect is expressed in "Nitrendipin", "Amlodipine", "Isradipine". The drugs have a high degree of absorption, but have a variable (unstable) bioavailability. The rate of onset of maximum plasma concentration varies from one to twelve hours, depending on the generation of drugs. List of calcium antagonist drugs differing in the extent of the hypotensive effect (in hours):

• Amlodipine is an extra long (24–36).
• The prolonged forms of drugs: “Felodipine”, “Diltiazem”, “Nifedipine”, “Verapamil”, “Isradipine” - long-term (18-24).
• “Isradipine”, “Felodipine” - average (8–18).
• “Nifedipine”, “Diltiazem”, “Verapamil” - short (6–8).

Mechanism of action

According to pharmacological properties, the mechanism of action of calcium antagonists is different. Consider their effect on the vascular system and heart, depending on the therapeutic goal:

1. "Nifedipine" and other representatives of dihydropyridine derivatives are vasoselective agents. They cause relaxation of the smooth muscles of the bloodstream vessels, and do not affect the cardiac function. Due to vasodilation, blood pressure and oxygen demand of the myocardium are reduced, coronary spasm is prevented. Slow-release forms of Nifedipine are indicated for hypertension and angina pectoris. Quick Release - Best used for crises.
2. Verapamil has an inhibitory effect on the heart muscle and smooth muscle of the arteries. The vasodilating property of this medication appears slightly less than that of dihydropyridine derivatives. “Verapamil” is used for fluttering of the ventricles or atria, to slow down the rhythm and prevent angina attacks, and as a drug with antiarrhythmic properties.
3. "Diltiazem" in its pharmacological effects is similar to "Verapamil." However, the vasodilating effect is more pronounced, and the negative chrono- and inotropic effects are less pronounced than Verapamil.

In addition to improving patency of arteries, veins, as well as small capillaries, the effect of calcium antagonists is manifested:

• decreased platelet aggregation;
• normalization of heart rate;
• a decrease in pressure in the pulmonary artery and dilatation of the bronchi;
• lowering blood pressure;
• antianginal, anti-ischemic and anti-atherogenic effect.

Contraindications

Identical for all calcium channel blockers:

• individual intolerance of the individual components of the drug;
• lactation;
• age up to 18 years;
• impaired liver and kidney function;
• low pressure;
• heart failure, accompanied by low systolic function of the left ventricle, with the exception of Felodipine and Amlodipine;
• pregnancy: Verapamil is allowed in the second and third trimester, and Nifedipine throughout the entire period, in addition, it is considered the most effective for hypertensive crisis.

Side effects. Interaction with other medicines and food

Adverse reactions after taking this group of drugs have some differences.

For non-dihydropyridine calcium antagonists:

• simultaneous reception with beta-blockers is undesirable;
• bradycardia;
• tachycardia;
• atrial flutter syndrome with episodes of antidromic tachycardia;
• failure of atrioventricular conduction;
• weak sinus syndrome .

For dihydropyridines, reflex tachycardia.

For all calcium ion antagonists:

• low pressure;
• allergic reactions;
• drowsiness;
• diarrhea;
• vomiting
• pain in the abdomen;
• tides;
• headache, dizziness;
• peripheral edema;
• decreased systolic function of the left ventricle with the exception of “Felodipine” and “Amlodipine”.

Combinations of antiarrhythmic drugs with calcium antagonists are dangerous. A significant increase in the concentration of the latter is observed when they are used together with cardiac glycosides, non-steroidal anti-inflammatory drugs, sulfonamides, indirect anticoagulants, as well as with Lidocaine and Diazepam. In addition, calcium channel blockers enhance the action of diuretics and ACE inhibitors. During treatment with this group of drugs, it is recommended to refrain from consuming grapefruit and juice from it. Reception of alcohol-containing drinks increases the severity of side effects.

Indications for use

Pathological conditions in which calcium antagonists are used:

• angina pectoris;
• atherosclerosis;
• pulmonary hypertension;
• hypertension;
• impaired cerebral and peripheral circulation;
• coronary heart disease;
• subarachnoid hemorrhage;
• Raynaud's syndrome;
• dysmenorrhea;
• hypertrophic cardiomyopathy;
• dizziness;
• motion sickness;
• prevention of migraine attacks;
• myocardial infarction;
• urinary incontinence;
• glaucoma;
• obstructive pulmonary disease;
• premature birth;
• esophageal spasm.

Calcium Antagonist Treatment

1. Arterial hypertension. This group of drugs is recognized as one of the best among antihypertensive drugs. By lowering systemic vascular resistance, calcium channel blockers lower blood pressure. Arteries fall mainly under their influence, and they have an insignificant effect on the veins.
2. Supraventricular arrhythmias. "Diltiazem" and "Verapamil" are able to resume normal heart rhythm by acting on the atrioventricular and sinus nodes.
3. Angina pectoris. Due to the intake of dihydropyridines, blood pressure decreases, respectively, and the load on the heart decreases, and as a result, the need for oxygen decreases. In addition, calcium antagonists prevent spasm of the coronary vessels, causing their expansion. Thanks to this, myocardial blood supply improves.
4. Hypertrophic cardiomyopathy. With this pathology, a thickening of the heart walls occurs. Verapamil helps to weaken heart contractions. It is prescribed for contraindications in the individual to receive beta-blockers.
5. Pulmonary hypertension. For the treatment of this pathology, Amlodipine, Nifedipine, or Diltiazem are recommended.
6. Raynaud's disease is manifested by spastic vasoconstriction, the feet and hands are most prone to this. "Nifedipine" eliminates arterial spasm and thereby reduces the frequency of seizures. You can use other antagonists of calcium ions - drugs "Amlodipine", "Diltiazem."
7. Tocolysis. To prevent premature delivery while relaxing the muscles of the uterus, Nifedipine is prescribed.
8. Subarachnoid hemorrhage. In this case, Nimodipine has a good effect on cerebral arteries. It prevents spasm of blood vessels.
9. Cluster headache. Reducing the severity of seizures will help taking Verapamil.

Calcium Antagonists: Drug List

The most prescribed medications are dihydropyridine derivatives:

• "Nifedipine." It has a wide range of indications for use. Dosage forms of the drug with prolonged action are used to treat angina pectoris and hypertension.
• "Ispradipine", "Lercanidipine" are similar to the first drug in terms of characteristics. They are recommended exclusively for the treatment of arterial hypertension.
• Amlodipine, Felodipine, Lomir, Norvask. By acting on the vessels, they do not adversely affect the contractility of the heart. Due to the long-term action, they are convenient for use in the treatment of vasospastic angina and hypertension.
• Nicardipine. Used to treat blood pressure, angina pectoris. The mechanism of action on the vessels is similar to "Nifedipine."
• Nimodipine has a selective effect on the arteries of the brain. It is mainly used for subarachnoid hemorrhage to relieve and prevent subsequent cerebral artery spasm.

The list of calcium antagonists of other groups include:

• Phenylalkylamines - Isoptin, Finoptin, Gallopamil, Anipamil. In practical medicine, “Verapamil” is mainly used, which affects the conductivity in the atrioventricular node and worsens the contractility of the heart. It is used to treat angina pectoris.
• Benzodiazepines - "Altiazem", "Dilzem". A well-known representative is "Diltiazem", which dilates blood vessels and negatively affects the conduction system of the heart. It is prescribed for angina pectoris.

Pharmacokinetics and pharmacodynamics of calcium channel blockers

Pharmacokinetic properties of the drug affect its clinical use:

• "Nifedipine" is not able to accumulate in the body of an individual. Thus, the continuous use of this drug in a single dosage does not enhance its effect.
• “Verapamil” with regular admission has the ability to accumulate, which further provokes an increase in the therapeutic effect and leads to undesirable reactions.
• Diltiazem, like the previous drug, accumulates in the body, but to a much lesser extent.

Depending on the patient's age, a change in pharmacokinetics is inherent in many drugs. Calcium antagonists are no exception. Half-life of “Nifedipine”, “Diltiazem” and “Verapamil” is lengthened in age category countries, and in addition, their clearance is reduced. As a result, the incidence of adverse effects is increasing. Therefore, it is necessary for this category of patients to select a therapeutic dose individually, starting with the lowest.

The presence of renal failure in an individual has almost no effect on the pharmacokinetics of Diltiazem and Verapamil. And when taking "Nifedipine" in such patients, its half-life increases, which entails the manifestation of side effects.

Pharmacodynamic interaction is also important in clinical practice. Reception of a beta-blocker with "Diltiazem" or "Verapamil" leads to a malfunction of the left ventricle as a result of the summation of the negative inotropic effect of these drugs. The use of beta-blockers and Nifedipine will alleviate the side effects of these drugs.

A combination of nitrates with Nifedipine is not recommended, as it leads to a significant decrease in blood pressure, excessive vasodilation and the formation of undesirable reactions.

Thus, calcium channel blockers are highly effective agents, which is proved by many years of experience in their use. The presence of a different mechanism of action, interaction and side effects requires a differentiated approach to prescribing a specific medication from this group.