Calcium channel blockers are effective drugs with a wide range of pharmacological actions. The list of calcium antagonists contains more than twenty substances, each of which affects the body of an individual in a different way. 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 conduction system of the heart, myometrium and vascular smooth muscles. Medicines of this group make it difficult for calcium to penetrate into cells through calcium channels, which are proteins located in the cell membrane and pass the trace element through special openings.
The role of calcium in the body
This trace element in percentage terms is in fifth place among all mineral substances present in the body of an individual. It is necessary for the strength of bone tissue and the regulation of cardiac activity. Ions of the microelement, entering the muscle cells of the heart, exit them into the intercellular space with the help of ionicpumps. Due to their penetration into the cardiomyocyte, the myocardium contracts, and as a result of the exit, it relaxes. Thus, calcium takes an active part in the work of the heart muscle and is involved in the regulation of the heartbeat. The heart is an organ responsible for the blood supply to all organs and systems, and accordingly, if it fails, the entire 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 specialists in 1961. In practical medicine, it has proven itself not only as a good vasodilator, but also as an agent with a cardiotropic effect. "Verapamil" for several years after its creation was attributed to the group of beta-blockers, 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 became known as first-generation drugs.
Medicines of this group have found their use as coronary lytics in coronary heart disease, and are also used as antiarrhythmics and medicines for the treatment of hypertension. This widespread use is due to the action of calcium antagonists to relax the muscles of the vascular wall andexpand the arteries of the coronary, cerebral bed, without affecting the tone of the veins. "Diltiazem" and "Verapamil" reduce the consumption of oxygen by the myocardium and reduce its contractility, in addition, they suppress 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, to a lesser extent, has an effect on myocardial contractility and the cardiac conduction system. It is indicated for peripheral vasospasm and arterial hypertension. The only pharmacological group of calcium antagonist drugs that combines medicines:
- different in chemical structure;
- with various mechanisms of action;
- different in therapeutic activity, clinical action;
- different in contraindications and side effects.
Classification
Calcium antagonists are distinguished by chemical structure:
- Dihydropyridine. Preparations of this series increase the pulse. They are prescribed in the treatment of atherosclerosis of peripheral vessels, hypertension, left ventricular hypertrophy, angina pectoris. They are not indicated in the therapy of arrhythmia.
- Nonhydropyridines are benzodiazepine and phenylalkylamine derivatives. These medicines have shown high efficiency in the treatment of atherosclerosis of the carotid arteries, angina pectoris. They are endowed with a pronounced anti-ischemic, hypotensive, antiarrhythmic effect. Can reduce heart rate.
- Non-selective. These include derivatives of diphenylpiperazine. They improve cerebral circulation, do not have a special effect on the level of pressure, but are capable of a vasodilating effect.
Several generations of calcium antagonists have been successfully used in medicine:
- The first is Nifedipine, Verapamil, Diltiazem. The disadvantages of these drugs include rapid elimination from the body and low bioavailability.
- The second one is represented by modified release dosage forms - "Nifedipine XL", "Verapamil SR". Medicines have a longer therapeutic effect. However, the maximum level in the blood is reached at different times, and therefore it is quite difficult to predict their effectiveness.
- Third - these are long-acting drugs 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 divided into separate subgroups, and, depending on the indications for use, dihydropyridine drugs are distinguished, which are prescribed for angina pectoris, left ventricular hypertrophy, high blood pressure in the elderly, and non-dihydropyridine drugs - for atherosclerosis of the carotid arteries, supraventricular tachycardia.
In recent years, calcium channel blockers, depending on the effect on heart ratesubdivided into the following groups:
- reducing the rhythm, for example, "Verapamil", "Diltiazem";
- increasing or not changing the rhythm, for example, Nifedipine and all dihydropyridine derivatives
Duration of antihypertensive action
The basis of the hypotensive effect of all calcium channel blockers is their ability to dilate blood vessels, while contributing to a decrease in total peripheral resistance. The most vasodilating effect is expressed in "Nitrendipine", "Amlodipine", "Isradipine". The drugs have a high degree of absorption, but have variable (unsustainable) bioavailability. The speed 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 duration of the hypotensive effect (in hours):
- "Amlodipine" - extra long (24-36).
- Prolonged forms of drugs: Felodipine, Diltiazem, Nifedipine, Verapamil, Isradipine - long-term (18–24).
- Isradipine, Felodipine - medium (8-18).
- Nifedipine, Diltiazem, Verapamil - short (6-8).
Mechanism of action
The mechanism of action of calcium antagonists is different in terms of pharmacological properties. Consider their impact on the vascular system and heart, depending on the therapeutic goal:
- "Nifedipine" and other representatives of dihydropyridine derivatives are vasoselective agents. Cause relaxation of vascular smooth muscleblood stream, and do not affect cardiac function. Due to the expansion of blood vessels, blood pressure and myocardial oxygen demand decrease, spasm of the coronary vessels is prevented. Slowly released forms of the drug "Nifedipine" are indicated for hypertension and angina pectoris. Quick release - best used in times of crisis.
- "Verapamil" has an inhibitory effect on the heart muscle and smooth muscle of the arteries. The vasodilating property of this drug is slightly manifested than that of dihydropyridine derivatives. Apply "Verapamil" with ventricular or atrial flutter, to slow down the rhythm and prevent angina attacks, and as a drug with antiarrhythmic properties.
- Diltiazem is similar in its pharmacological effects to Verapamil. However, the vasodilatory effect is more pronounced, and the negative chrono- and inotropic effect is less pronounced than that of Verapamil.
In addition to improving the patency of arteries, veins, as well as small capillaries, the effect of calcium antagonists is manifested:
- reducing platelet aggregation;
- normalize heart rate;
- decrease in pulmonary artery pressure and bronchial dilatation;
- lowering blood pressure;
- antianginal, antiischemic and antiatherogenic action.
Contraindications
Same for all calcium channel blockers:
- individual intolerance, individual componentsdrug;
- breastfeeding;
- under 18;
- liver and kidney disorders;
- low blood pressure;
- heart failure with low left ventricular systolic function, excluding 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 in hypertensive crisis.
Side effects. Interactions with other drugs and food
Adverse reactions after taking this group of drugs have some differences.
For non-dihydropyridine calcium antagonists:
- undesirable simultaneous reception with beta-blockers;
- bradycardia;
- tachycardia;
- atrial flutter syndrome with episodes of antidromic tachycardia;
- atrioventricular conduction failure;
- sick sinus syndrome.
For dihydropyridine - reflex tachycardia.
For all calcium ion antagonists:
- low pressure;
- allergic reactions;
- drowsy;
- diarrhea;
- vomit;
- pain in the abdomen;
- tides;
- headache, dizziness;
- peripheral edema;
- decrease in systolic function of the left ventricle with the exception of "Felodipine" and "Amlodipine".
Combinations of antiarrhythmic drugs with antagonists are dangerouscalcium. A significant increase in the concentration of the latter is observed when they are co-administered with cardiac glycosides, non-steroidal anti-inflammatory drugs, sulfonamides, indirect anticoagulants, as well as with Lidocaine and Diazepam. In addition, calcium channel blockers increase the effect of diuretics and ACE inhibitors. During the period of treatment with this group of drugs, it is recommended to refrain from drinking grapefruit and juice from it. Drinking alcoholic beverages increases the severity of side effects.
Indications for use
Pathological conditions in which calcium antagonists are used:
- angina;
- atherosclerosis;
- pulmonary hypertension;
- hypertension;
- impaired cerebral and peripheral circulation;
- ischemic heart disease;
- subarachnoid bleeding;
- Raynaud's syndrome;
- dysmenorrhea;
- hypertrophic cardiomyopathy;
- dizziness;
- motion sickness;
- prevention of migraine attacks;
- myocardial infarction;
- urinary incontinence;
- glaucoma;
- obstructive pulmonary disease;
- preterm birth;
- esophageal spasm.
Calcium antagonist treatment
- Arterial hypertension. This group of drugs is recognized as one of the best among antihypertensive drugs. By reducing systemic vascular resistance, calcium channel blockers lower blood pressure. Under their influence, arteries fall mainly, and onveins they have an insignificant effect.
- Supraventricular arrhythmias. "Diltiazem" and "Verapamil" are able to resume the normal rhythm of the heart by acting on the atrioventricular and sinus nodes.
- Angina. Thanks to the intake of dihydropyridines, blood pressure drops, respectively, the load on the heart also 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, the blood supply to the myocardium improves.
- Hypertrophic cardiomyopathy. With this pathology, thickening of the heart walls occurs. "Verapamil" helps to weaken the contractions of the heart. It is prescribed for contraindications in an individual to taking beta-blockers.
- Pulmonary hypertension. For the treatment of this pathology, Amlodipine, Nifedipine or Diltiazem are recommended.
- Raynaud's disease is manifested by spastic vasoconstriction, the feet and hands are most susceptible to this. "Nifedipine" eliminates spasm of the arteries and thereby the frequency of attacks is reduced. It is possible to use other calcium ion antagonists - drugs "Amlodipine", "Diltiazem".
- Tocolysis. To prevent premature delivery while relaxing the muscles of the uterus, Nifedipine is prescribed.
- Subarachnoid hemorrhage. In this case, Nimodipine has a good effect on the cerebral arteries. It prevents vasospasm.
- Cluster headache. Taking Verapamil will help reduce the severity of seizures.
Calcium Antagonists Drug List
The most prescribed drugs are dihydropyridine derivatives:
- "Nifedipine". It has a wide range of indications for use. Long-acting formulations are used to treat angina 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". Influencing the vessels, they do not have a negative effect on the contractility of the heart. Due to the long action, it is convenient to use in the treatment of vasospastic angina and hypertension.
- Nicardipine. Used to treat high 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. Primarily used in subarachnoid hemorrhage to relieve and prevent subsequent spasm of the cerebral arteries.
The list of calcium antagonists of other groups includes:
- Phenylalkylamines - Isoptin, Finoptin, Gallopamil, Anipamil. In practical medicine, Verapamil is mainly used, which affects the conduction in the atrioventricular node and worsens the contractility of the heart. Used to treat angina pectoris.
- Benzodiazepines - Altiazem, Dilzem. A well-known representative is Diltiazem, which dilates blood vessels and negatively affects the conduction system.hearts. It is prescribed for angina pectoris.
Pharmacokinetics and pharmacodynamics of calcium channel blockers
Pharmacokinetic properties of a drug affect its clinical use:
- "Nifedipine" is not able to accumulate in the body of the individual. Thus, the constant use of this drug in one dosage does not increase its effect.
- Verapamil, when taken regularly, has the ability to accumulate, which further provokes an increase in the therapeutic effect and leads to unwanted reactions.
- Diltiazem, like the previous drug, accumulates in the body, but to a much lesser extent.
Depending on the age of the patient for many drugs, a change in pharmacokinetics is inherent. Calcium antagonists are no exception. In older adults, the half-life of Nifedipine, Diltiazem and Verapamil is lengthened, and their clearance also decreases. As a result, the incidence of adverse effects increases. Therefore, this category of patients needs to select a therapeutic dose individually, starting with the smallest.
The presence of renal insufficiency 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 leads to the manifestation of side effects.
Pharmacodynamic interaction is also important in clinical practice. Taking a beta-blocker with Diltiazem or Verapamil leads to a failure inleft ventricular function as a result of the summation of the negative inotropic effect of these drugs. The appointment of beta-blockers and "Nifedipine" will smooth out the side effects of these drugs.
The combination of nitrates with "Nifedipine" is not recommended, as it leads to a significant decrease in blood pressure, excessive vasodilation and the formation of unwanted reactions.
Thus, calcium channel blockers are highly effective drugs, which has been proven 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 particular drug from this group.
