Analysis of the Selection and Use of Calcium Channel Blockers for Hypertension Medications

What are some commonly used short-acting calcium channel blockers? What are their characteristics?

① Nifedipine (Adalat, Nifedipine): Its main function is to dilate blood vessels, especially peripheral vessels and coronary arteries. It has no significant effect on the heart, but tachycardia may occur due to the reflex activation of the sympathetic nervous system caused by peripheral vasodilation. The most common adverse reactions are headache, facial flushing, and palpitations. Because it has an anti-natriuretic effect, there is no fluid retention. Ankle edema is an effect of local microcirculation. It is well absorbed orally, takes effect in 10 minutes, reaches its maximum effect in 1-2 hours, and lasts for 6-7 hours. Sublingual administration is faster than oral administration. The oral dose is 5-10 mg three times a day. Sublingual administration can be used for emergency situations.

② Verapamil (Isoptin): Although it is also a vasodilator, it has an inhibitory effect on atrioventricular conduction, heart rate, and cardiac contractility. The main adverse reactions are headache and facial flushing, but these are less common than those of dihydropyridine drugs. In addition, it often causes constipation due to the obstruction of sodium influx and the resulting high relaxation of intestinal smooth muscle. Oral administration: 30-60 mg each time, 3-4 times daily.

③ Dilthium nitrate (Thioclase, Hexinshuang): Its pharmacological effects are between dihydropyridine drugs and verapamil, and it can be used for hypertension in the elderly. 30-60 mg each time, 3-4 times daily. ④ Nifedipine: It selectively acts on vascular smooth muscle, with a greater affinity for blood vessels than for the myocardium. It has the best selective effect on the coronary arteries. It can reduce total peripheral resistance and lower blood pressure. After oral administration of 30 mg, peak blood concentration is reached after 30 minutes. Oral administration: 10 mg each time, 2-3 times daily.

What are some commonly used long-acting calcium channel blockers? What are their characteristics?

① Amlodipine (Norvasc): A vascular selective calcium channel blocker. Therapeutic doses have minimal or no effect on cardiac contractility and atrioventricular conduction. It is slowly absorbed, has a slow onset of action, and a long duration of action, with a plasma half-life of 35–50 hours. Steady-state plasma concentrations are reached after 7–8 days of oral administration. Its characteristics include:

a. Long duration of action, requiring only once-daily dosing;

b. Rarely causes reflex tachycardia with rapid vasodilation;

c. Good tolerability;
d. High bioavailability, with minimal fluctuations in peak plasma concentration and blood pressure between doses. It can be used in combination with β-blockers or diuretics. The initial dose is 5 mg orally once daily, gradually increasing to 10 mg daily depending on the patient's condition.

② Nifedipine controlled-release tablets (Baixintong): Oral bioavailability 55%–65%, reaching maximum plasma concentration in 6 hours. Its characteristics are:

a. Oral administration maintains blood pressure for 24 hours, once daily;

b. Rapid onset of action, stable blood pressure reduction, and minimal blood pressure fluctuations;

c. Less likely to cause reflex tachycardia, and long-term use does not increase plasma norepinephrine levels;

d. Significantly improves patients' quality of life;

e. Long-term use can significantly inhibit the progression of atherosclerosis and reduce the occurrence of new atherosclerotic lesions. The adult dose is 30 mg once daily.

③ Felodipine (Plendil, Felodipine): Highly selective for blood vessels. It has a vasodilatory effect on coronary arteries, cerebral blood vessels, and peripheral blood vessels. Its average plasma half-life is 25 hours, maintaining stable blood pressure reduction for 24 hours. The initial dose is 2.5 mg once daily. The maintenance dose is 5 mg or 10 mg.

④ Levoamlodipine (Shuida): At the same dose, this drug is twice as effective as the racemic form (amlodipine suspension), while significantly reducing adverse reactions. This is especially important for elderly patients with hypertension or angina. The oral dose is 2.5 mg once daily.

⑤ Lacidipine (Sileping, Lexipine): A third-generation long-acting dihydropyridine drug with high vascular selectivity, high lipid solubility, and gentle antihypertensive effect. The initial adult dose is 4 mg once daily, preferably taken in the morning. After 3-4 weeks, it can be increased to 6 mg once daily. The dose should be halved for elderly patients and those with hepatic impairment.

Why should long-acting formulations of calcium channel blockers be chosen whenever possible? Some studies have suggested that short-acting calcium channel blockers are unsuitable as first-line antihypertensive drugs. The possible mechanism by which they cause cardiovascular events is that during repeated short-acting dosing, excessive fluctuations in drug concentration repeatedly induce sympathetic nerve activation, leading to repeated episodes of increased heart rate and blood pressure, or directly triggering myocardial ischemia and arrhythmias, thus inducing cardiovascular events. By 1998, a consensus had been largely reached: the use of short-acting calcium channel blockers alone is harmful to patients with coronary heart disease and is not recommended for use in these patients. Long-acting formulations can overcome this drawback. Therefore, most cardiovascular experts currently recommend that hypertensive patients with coronary heart disease or myocardial infarction who wish to use such drugs should choose long-acting formulations whenever possible, such as amlodipine (Norvasc), nifedipine controlled-release tablets (Adalat), and phenadipine extended-release tablets (Plendil). Sustained-release formulations release the active ingredient slowly and at a non-constant rate after oral administration, while controlled-release formulations release the active ingredient slowly, at a constant rate, or near a constant rate. This overcomes the adverse effects of ordinary tablets, allowing the drug concentration in the blood to gradually reach the effective concentration, reducing the occurrence of adverse reactions, and maintaining treatment for more than 24 hours. Therefore, the frequency of dosing can be extended to 1-2 times per day. Many clinical trials have confirmed the safety and efficacy of long-acting formulations for cardiovascular patients, especially elderly patients with isolated systolic hypertension.