Analysis of Commonly Used Antihypertensive Drugs: Focusing on the Advantages of Calcium Channel Blockers

What are the commonly used antihypertensive drugs?

Currently, there are many antihypertensive drugs on the market, which can be mainly categorized into five classes: calcium channel blockers, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), diuretics, and beta-blockers. In addition, there are low-dose combination drugs, alpha-blockers, and other antihypertensive drugs. These drugs all have definite antihypertensive effects and can be used as initial and maintenance therapy.

Most of these five classes of drugs have been validated by evidence-based medicine (long-term, large-sample, randomized, double-blind studies), proving that they not only have definite antihypertensive efficacy but also have different advantages for different complications of hypertension. For example, beta-blockers, ACEIs, and ARBs are more effective for patients with coronary heart disease or myocardial infarction; calcium channel blockers and diuretics are more advantageous for stroke patients; and diuretics, ACEIs, and ARBs are more suitable for patients with heart failure. The advantages and disadvantages of each type of drug are detailed below.

What are the advantages and adverse reactions of calcium channel blockers?

The main mechanism of calcium channel blockers in lowering blood pressure is to relax vascular smooth muscle and directly dilate blood vessels, thus these drugs have a definite antihypertensive effect. Many of these drugs have been validated through evidence-based medicine. In addition, they have the following advantages:

(1) Advantages of calcium channel blockers:

① Most effectively reduces the incidence of stroke in the elderly and delays carotid atherosclerosis;

② Has no adverse effects on blood lipids or blood sugar;

③ Long-acting, controlled-release, and sustained-release dihydropyridine calcium channel blockers, due to their slow release, have a certain inhibitory effect on the heart while also having a vasodilatory effect. The vasodilatory effect is relatively mild and can also be used to treat angina pectoris;

④ Non-dihydropyridine calcium channel blockers have a good renal protective effect on severe kidney disease accompanied by proteinuria.

(2) Characteristics of certain calcium channel blockers:
① Long-acting, sustained-release formulations have a long plasma half-life or receptor-binding half-life, resulting in a high trough-to-peak ratio of antihypertensive effect, avoiding adverse reactions such as increased heart rate and excessive blood pressure fluctuations caused by rapid vasodilation in short-acting formulations.

② Nifedipine controlled-release tablets, due to their unique laser-perforated permeation controlled release system, achieve near-constant release over 24 hours, resulting in the most stable antihypertensive effect.

③ Amlodipine has a long plasma half-life of 33–50 hours, slow metabolism, and relatively stable antihypertensive effect. Amlodipine besylate is a mixture of levorotatory and dextrorotatory isomers; the levorotatory isomer has antihypertensive effects, while the dextrorotatory isomer has endothelial protective functions. The antihypertensive effect of 2.5 mg of levamlodipine besylate is comparable to that of 5 mg. Both morning and nighttime administration can lower nocturnal blood pressure in non-dipper elderly individuals. Nighttime administration is more effective in lowering systolic blood pressure throughout the day. ④ Lercanidipine has the highest lipophilicity, fewest adverse reactions, and best tolerability.

(3) Major adverse reactions of calcium channel blockers: Because calcium channel blockers lower blood pressure by directly dilating blood vessels, the body will reflexively excite the sympathetic nervous system and increase heart rate to counteract the decrease in blood pressure in order to maintain the original blood pressure level. Therefore, short-acting, strong-acting drugs of this class are most likely to cause adverse reactions such as palpitations, headaches, etc. To reduce or avoid these adverse reactions, it is best to use long-acting, controlled-release, or sustained-release formulations. The main adverse reactions are as follows:

① Tachycardia: Mainly seen in dihydropyridine drugs. Because the drugs dilate blood vessels, they cause an increase in sympathetic nervous system excitability; this is more common in short-acting dihydropyridine drugs. β-blockers can counteract this and enhance the blood pressure-lowering effect.

② Dilation of cerebral blood vessels, leading to headaches and facial flushing.

③ Gingival hyperplasia. ④ Constipation: The medication also dilates intestinal smooth muscle, weakening peristalsis and leading to constipation.

⑤ Pretibial and ankle edema: These are caused by vasodilation and impaired blood return from the lower limbs.

⑥ Bradycardia or conduction block: Mainly seen in non-dihydropyridine drugs (such as verapamil and diltiazem).

(4) Contraindications for calcium channel blockers: Because calcium channel blockers can cause tachycardia, increase myocardial oxygen consumption, and cause excessive blood pressure drop, their use should be avoided in the following situations:

① Unstable angina, acute phase of myocardial infarction, cardiogenic shock;

② Intracranial hemorrhage, increased intracranial pressure in the acute phase of stroke;

③ Tachyarrhythmias (not suitable for dihydropyridine drugs);

④ Severe congestive heart failure (use with caution).