*For medical professionals only
These 3 commonly used "horizons", how to distinguish?
Calcium antagonists (CCBs) are first-line drugs for the treatment of hypertension, and there are many kinds, even in the same category, each drug from pharmacokinetics to clinical effects, is also "harmonious and different, each with its own strengths and weaknesses".
Recently, Jie XiaoYao received questions from readers and friends.
Today, let's take a look at the difference between the three commonly used "horizons" of felodipine, nifedipine and amlodipine.
One
"Sprint, middle run and long run", the pharmacokinetics difference is large
In terms of the half-life and duration of the drug itself, nifedipine has the fastest onset of action and the shortest half-life, followed by felodipine, and amlodipine has the longest duration and slowest onset.
Table 1 Pharmacokinetic properties of nifedipine, felodipine and amlodipine[1]
Note: This table is compiled from the "Drug Comparison and Clinical Reasonable Choice - Cardiovascular Disease Fascicle" published by the People's Medical Publishing House, and there may be pharmacokinetic differences in different manufacturers or dosage forms, for reference only.
Two
Commonly used dosage forms are "each in a faction", and the dosage should be paid attention to
In addition to the pharmacokinetic characteristics of the drug itself, the dosage form of the drug is also a key factor affecting the efficacy of the drug.
▎Nifedipine: ordinary tablets, extended-release tablets, controlled-release tablets
Nifedipine tablets are short-acting antihypertensive drugs and are not currently used as long-term antihypertensives. However, through pharmaceutical technology, after making nifedipine into sustained-release tablets and controlled-release tablets, it can effectively slow down and prolong the time of action of the drug.
Nifedipine extended-release tablets are taken twice a day; controlled-release tablets can be taken once a day.
Among them, nifedipine controlled-release tablets have an unabsorbable shell, when the tablets are slowly released and absorbed into the body, complete empty tablets can be found in the feces.
▎Felodipine: ordinary tablets, extended-release tablets (capsules)
Regular tablets of felodipine, taken 2 times a day. Felodipine extended-release tablets should not be crushed, crushed, or chewed.
The bioavailability of felodipine is greatly affected by food, and peak concentrations can increase by 60% when given a high-fat meal or carbohydrate diet. Felodipine extended-release tablets should be taken in the morning on an empty stomach.
▎ Amlodipine: ordinary tablets
Amlodipine is a long-acting drug, the drug metabolism half-life is more than 30h, and it can be taken once a day. Amlodipine can be taken before or after a meal, not in the early morning.
Three
"Connections" vary, keeping in mind the interactions
Hepatic drug enzyme CYP3A4 inducers and inhibitors have a greater impact on CCB drugs, and there are more drugs with interactions.
In addition, special attention should be paid to:
■ Amlodipine can increase the blood concentration of simvastatin, so when the two drugs are combined, the maximum dose of simvastatin is 20 mg / day.
■ Cimetidine can inhibit the metabolism of felodipine and nifedipine in vivo, can increase the peak concentration and bioavailability of felodipine by about 55%, and can increase the bioavailability of nifedipine by 77% to 99%.
■ Among the foods, the main thing to pay attention to is grapefruit. Grapefruit juice has the most obvious effect on felodipine and nifedipine.
Studies have found that taking felodipine and grapefruit / grapefruit juice at the same time can increase the blood concentration of felodipine by about 2 times;
Taking nifedipine and grapefruit / grapefruit juice at the same time, in addition to increasing the blood concentration, will also prolong the time of action of the drug;
Amlodipine and grapefruit/grapefruit juice are taken with no significant effects.
Four
"The right medicine" is very important, and the antihypertensive characteristics are compared[2]
Nifedipine
Advantages: Controlled-release tablets plasma drug concentration fluctuations are small, peak-to-valley ratio is close to 1, compared with amlodipine, nifedipine controlled-release tablets blood pressure control speed is faster, usually take 3-5 days to achieve the best antihypertensive effect.
Disadvantages: The antihypertensive effect of nifedipine ordinary tablets comes too quickly, easily stimulates the sympathetic nervous system, produces adverse reactions, and the action time is short, the antihypertensive effect is unstable, and the blood pressure fluctuation is large.
Recommendation: For patients with severe increases in blood pressure who require rapid antihypertensive, the choice of nifedipine controlled-release tablets is more appropriate than the selection of amlodipine long-acting drugs.
Felodipine
Advantages: Its onset of action is faster than amlodipine, which can make the blood pressure reach the steady-state level as soon as possible. Felodipine is much more selective to blood vessels than to the heart, so while the antihypertensive effect is good, the impact on the heart is not large.
Disadvantages: Because the half-life is shorter than amlodipine, it is slightly inferior to amlodipine in controlling nocturnal and early morning hypertension.
Recommendation: Suitable for patients with mild to moderate hypertension, in which felodipine has been relatively rarely studied.
Amlodipine
Advantages: the half-life is very long, you can take the drug once a day, it is very convenient, the effect is stable, the drug can be divided, the drug accumulates in the body, and occasionally missing once has little impact.
Disadvantages: the onset of action is relatively slow, the initial antihypertensive effect may not be obvious, generally 1-2 weeks to play a hypotensive effect, 6-8 weeks to achieve the strongest antihypertensive effect.
Recommendation: For patients with poor adherence and easy to miss one or more doses, amlodipine with a relatively long half-life should be used.
Five
CCB "common disease", the effect on heart failure[3]
CCBs all inhibit myocardial contractility, but studies have found that nifedipine has a stronger inhibitory effect on myocardial contractility, which may aggravate the symptoms of heart failure;
The selectivity of peripheral blood vessels of felodipine is significantly higher than that of the heart (118:1), and the risk of aggravating the symptoms of heart failure is lower;
The effect of amlodipine on patients with heart failure is neutral and unlikely to exacerbate the symptoms of heart failure.
Six
"Special personnel", pay attention to the difference in medication for special groups
Pregnant patients: nifedipine controlled-release tablets are available, while amlodipine and felodipine have not been evaluated for their safety and efficacy and are generally not selected;
Children: Amlodipine instructions mention that it can be used in children aged 6 to 17 years with hypertension, while nifedipine and felodipine do not have records and safety data on the use of drugs in children.
Patients with liver impairment: felodipine is not recommended in patients with hepatic insufficiency; amlodipine should be slowly increased when used in patients with severe hepatic insufficiency; medication in patients with nifedipine liver impairment should be strictly monitored, and the dose should be reduced in severe cases.
Renal insufficiency: amlodipine, felodipine, and nifedipine generally do not require adjustment of the recommended dose.
Patients with heart failure[4]: blood pressure remains > 130/80 mmHg after treatment with antihypertensives (diuretics, ACE/ARB, β blockers, aldosterone receptor antagonists), and amlodipine or felodipine is recommended. For patients with stable angina with heart failure, amlodipine or felodipine is recommended when long-acting CCB must be applied.