Drug elimination: not limited by liver drug enzyme activity, few drug interactions
The elimination mode of amlodipine is similar to other dihydropyridine CCBs and also requires metabolism by CYP3A4. However, due to the large apparent distribution volume of amlodipine, the concentration in the blood and liver is very low (far lower than the concentration that saturates liver enzymes), and even direct hemodialysis cannot accelerate its elimination. The primary rate-limiting factor in its elimination is the rate of return from the tissues to the blood and then to the liver, rather than the catalytic capacity of the metabolic enzymes being saturated with substrate. Therefore, liver dysfunction generally does not affect the elimination of amlodipine, and there is no need to adjust the dose. Likewise, drugs that inhibit or induce hepatic enzyme activity do not significantly affect the elimination of amlodipine. This is the reason why clinical drug interactions rarely occur. For example: it does not affect the binding of digoxin, phenytoin, warfarin or indomethacin to plasma proteins; it does not change the binding of amlodipine with cimetidine, grapefruit juice, aluminum/magnesium, sildenafil, etc. pharmacokinetics.
Target: multi-target effect, may bring additional clinical benefits
Acting on L-type calcium channels. As a representative drug of dihydropyridine CCB, the mechanism of action of amlodipine besylate is mainly through specific binding to the α1 subunit of L-type calcium channels on the vascular smooth muscle cell membrane, blocking extracellular Calcium ions enter vascular smooth muscle cells through voltage-dependent L-type calcium channels, weakening the excitation-contraction coupling, thereby reducing the contractile responsiveness of resistance vessels. A large number of studies have proven that L-type Ca△2+△ channels are the main site of action of dihydropyridine CCBs and are the main source of their antihypertensive effects2.
New research evidence on N-type calcium channels shows that blocking N-type Ca△2+△ channels brings more benefits and makes up for the shortcomings of simple L-type channel blockade. N-type calcium channels are widely distributed in sympathetic nerve endings. After blocking, they regulate sympathetic nerve activity and block norepinephrine, effectively lowering blood pressure without increasing heart rate 2.
This double blocking of L-type and N-type calcium channels allows amlodipine besylate to effectively lower blood pressure while not excitating sympathetic nerves and thus not increasing heart rate. Rapid resting heart rate is an independent risk factor and predictor of cardiovascular death. Amlodipine has been proven by multiple large-scale clinical studies to lower blood pressure without increasing heart rate. It is the only CCB approved by the U.S. Food and Drug Administration (FDA) for the treatment of severe heart failure.
The antihypertensive treatment regimen based on amlodipine besylate has demonstrated sufficient advantages in preventing stroke and coronary heart disease in all comparative clinical studies. Amlodipine besylate is effective, stable, Long-lasting high-quality blood pressure reduction, effective inhibition of atherosclerosis, and good safety and compliance are the fundamental reasons for its strong evidence-based advantages.
What are the side effects of amlodipine besylate? What should I do if side effects occur?
1. First of all, most of the adverse reactions of this drug are mild to moderate. Only 1.5% discontinued the drug due to adverse reactions, which was not significantly different from the placebo. After side effects occur, be sure to follow up with your hypertension and other doctors to confirm the diagnosis. Whether to discontinue or reduce the dose, or change the antihypertensive drug regimen, etc. It is recommended that the decision be made by your doctor and not on your own.
2. The most common adverse reactions are headache and edema. Dose-related incidence rates >1% include: edema, dizziness, flushing, and palpitations. Reduce the dose under the guidance of a doctor, or start taking it at a low dose, and combine it with other antihypertensive drugs (such as pricis, sartans, diuretics, β-blockers, etc.), and the side effects can disappear. If these discomforts persist for a long time, stop taking this medicine under the guidance of a doctor.
The relationship with dose is not clear, but the incidence rate exceeds 1%: headache, fatigue, nausea, abdominal pain and drowsiness. Your doctor may also recommend stopping this medicine at this time. Flushing, edema, palpitations, and drowsiness occur more frequently in women than men.
3. There are also some side effects, such as hypotension, gum hyperplasia (relatively common), oral ulcers, tooth bleeding, ankle edema, itchy throat, and rarely, elevated prolactin, etc. If you take this medicine and find that you feel unwell, some of which may not necessarily be the side effects mentioned above, and sometimes there is no clear reason. The doctor will recommend that you stop taking this medicine and switch to other medicines for observation. If the discomfort reappears when you take this medicine again, the diagnosis can be confirmed. It’s a side effect. It is true that those who have the above-mentioned clear side effects do not need to take this antihypertensive drug again.
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