Calcium antagonists
Calcium antagonists are a class of drugs that selectively block the entry of calcium ions through the cell membrane at the cellular level, thereby reducing intracellular calcium ion concentrations. It acts mainly on the heart and blood vessels. Currently, calcium antagonists can be subdivided into three generations according to their characteristics and duration of action.
The first generation of calcium antagonists are short-acting agents: the representative drugs are nifedipine, verapamil, diltiazem, etc., which are still the most commonly used antihypertensive drugs in China at this stage. These preparations need to be taken several times a day and can cause great fluctuations in blood pressure, which can cause reflex sympathetic excitation, leading to increased myocardial oxygen consumption, easily inducing arrhythmias, and cannot effectively reduce the morbidity and mortality of cardiovascular diseases.
The second generation of calcium antagonists are medium-acting preparations: divided into two subclasses, Class A is basically the first generation of calcium antagonists of the slow-release, controlled-release preparations, which are new dosage forms developed in the past 10 years or so, whose representative drugs are nifedipine controlled-release tablets, felodipine extended-release tablets, nifedipine extended-release tablets, etc.. These drugs are taken 1-2 times a day, and the 24-hour antihypertensive effect is smooth, which can avoid morning hypertension and help reduce the incidence of cerebrovascular disease, and the side effects such as headache, redness and palpitations are also significantly reduced after taking the drugs. class B is a new compound, and its representative drugs are nifedipine, nimodipine and nisoldipine.
The third generation of calcium antagonists are long-acting agents: they include amlodipine (Loxodipine), lacidipine and others. Studies have found that long-acting calcium antagonists can be used as basic antihypertensive drugs in patients with hypertensive disease with ischemic heart disease. Nowadays, more and more patients are using long-acting calcium antagonists for antihypertensive treatment.
Treatment of hypertension
Mild and moderate hypertension are the most common indications for calcium antagonists. In China, the main complication of hypertension is stroke, not myocardial infarction, so calcium antagonists are recommended as the first-line drug for the treatment of hypertension in the elderly. The biggest advantage of calcium antagonists is that they have mild side effects and are not resistant to long-term use. Long-acting calcium antagonists have stable and long-lasting antihypertensive effects, with significant efficacy, and are beneficial to the protection of the heart, kidney, brain and other organs, which can significantly reduce the incidence of cardiovascular disease. In patients with diabetic nephropathy, the combination of long-acting calcium antagonists and angiotensin-converting enzyme inhibitors has a better renal protective effect.
However, short-acting calcium antagonists, such as nifedipine, also have value. Sublingual or oral nifedipine tablets remain an easy and effective means of lowering blood pressure in patients who need to lower their blood pressure rapidly in a short period of time. It should be noted that a small number of patients with rapid heartbeat and flushing after nifedipine, and a rise in blood pressure instead of a drop, should go to the hospital quickly to prevent accidents.
Treatment of coronary heart disease
Calcium antagonists are commonly used in the treatment of coronary heart disease. However, they are not suitable for all kinds of coronary heart disease. Currently, calcium antagonists are mainly used for patients with variant angina, coronary artery disease combined with hypertension and most exertional angina; it is not suitable for the treatment of unstable angina and myocardial infarction. Variable angina is characterized by long episodes of angina, heavy chest pain during episodes, generally longer duration than exertional angina, and episodes mostly in quiet time, especially in the early morning. The occurrence of angina is mainly related to coronary artery spasm. Therefore, pharmacological treatment is mainly used in these patients, and interventional treatment is not advocated. Calcium antagonists can dilate and decongest the coronary arteries and increase coronary blood flow, so they are the drugs of choice for variant angina pectoris. The short-acting preparation nifedipine is more effective in relieving the spasm of the arteries, and is listed as the drug of choice for the treatment of variant angina pectoris. If the effect is not good, a second calcium antagonist, or other drugs can be added.
Exertional angina is angina that occurs when the patient is exerted or emotionally excited. Acute myocardial infarction and unstable angina are collectively referred to as acute coronary syndrome, the onset of which is mainly related to unstable coronary plaque and rupture complicated by thrombosis.
Treatment of hypertrophic cardiomyopathy
Hypertrophic cardiomyopathy is an asymmetric myocardial hypertrophy that occurs in the absence of a cause of myocardial hypertrophy (e.g., hypertension, prolonged heavy exercise). This disease is hereditary in general patients. Therefore, a thorough family examination should be performed as soon as it is detected.
Verapamil is the most used drug in the treatment of hypertrophic cardiomyopathy. Verapamil improves several indicators in patients with hypertrophic cardiomyopathy without contraindications to its use. The use of short-acting nifedipine in the treatment of hypertrophic cardiomyopathy remains controversial, and currently, it is advocated for use in combination with beta-blockers or in patients with hypertrophic cardiomyopathy in whom verapamil is contraindicated.
Treatment of cardiac insufficiency
Due to the lack of evidence for the effectiveness of calcium antagonists in the treatment of heart failure, this class of drugs is not recommended for the treatment of heart failure. Considering the safety of dosing, most calcium antagonists should be avoided even for the treatment of hypertension or angina pectoris in such patients. Only the long-acting agents amlodipine and felodipine have clinical trials showing safety for long-term use, but they also do not improve patient survival.
Treatment of cardiac arrhythmias
Calcium antagonists are most effective in the treatment of paroxysmal tachycardia, including sinus tachycardia, supraventricular tachycardia, and idiopathic ventricular tachycardia. It is also effective in atrial fibrillation and atrial flutter. For tachyarrhythmias in combination with hypertension, calcium antagonists are more suitable. Verapamil is the most effective of the commonly used drugs, followed by thiazepam, and nifedipine is basically ineffective.
Calcium antagonists are mainly used to lower blood pressure, treat and prevent stroke, and directly dilate cerebral blood vessels to improve cerebral ischemia in cerebrovascular disease. Recent studies have found that the benefits of antihypertensive therapy in reducing stroke are significantly greater than those in reducing myocardial infarction. However, the clinical effectiveness of calcium antagonists as neuroprotective agents during the acute phase of a stroke attack has not been demonstrated.
Treatment of atherosclerosis
Ca2+ is involved in all processes of atherosclerosis formation, so theoretically, calcium antagonists may have an impeding effect on atherosclerosis formation and progression. A recent international clinical study also demonstrated that calcium antagonists have an anti-atherosclerotic effect. However, some studies have also shown that calcium antagonists have no significant effect on the atherosclerotic process. More evidence is needed to support the use of calcium antagonists for the treatment of atherosclerosis. Therefore, calcium antagonists cannot be used clinically against atherosclerosis at this time.