Nifedipine is the first generation calcium antagonist, an antihypertensive, angina prevention and treatment drug. It was one of the best-selling drugs in the world in the mid-1980s. The characteristics of this drug are: fast onset of action, high peak/trough ratio, which leads to activation of neurohumoral fluids. After years of clinical use, the efficacy of this drug has been affirmed. Nifedipine also has a strong price advantage. However, the drug has a short effect time, large blood pressure fluctuations, and has negative muscle strength and negative conduction effects. Increased mortality in patients with coronary heart disease. Nifedipine Sustained-release Tablets Nifedipine is one of the calcium antagonists. It has the strongest effect on dilating coronary arteries and peripheral arteries and has a significant effect on inhibiting vasospasm. It is the drug of choice for variant angina pectoris and is clinically suitable for Prevention and treatment of coronary heart disease angina pectoris, especially variant angina pectoris and angina pectoris caused by coronary artery spasm. It is suitable for various types of hypertension and has good curative effect on refractory and severe hypertension. Because it can reduce afterload, it also has a good effect on refractory congestive heart failure and is suitable for long-term use. In addition, it is also suitable for patients with angina pectoris suffering from respiratory obstructive diseases, and its efficacy is better than that of β-blockers.
Nifedipine has mild adverse reactions and is related to its vasodilatory effect. The main adverse reactions were transient lowering of blood pressure, hot flashes, nausea, dizziness, headache, etc., but no hypotension or shock occurred. Patients can tolerate these adverse reactions and usually get better in 2 to 4 days without stopping the medication.
Now, let’s learn more about nifedipine:
[Overview]
Nifedipine (NF), chemical name is 2,16-dimethyl-4(2-nitrophenyl)-1,4-dihydro-3,5-pyridinedicarboxylic acid dimethyl ester , also known as nifedipine and cardiotide, has the effect of inhibiting Ca2+ influx, can relax vascular smooth muscle, dilate coronary arteries, increase coronary blood flow, improve myocardial tolerance to ischemia, and at the same time dilate peripheral arteries, reducing Peripheral vascular resistance is commonly used clinically for the treatment of coronary heart disease, angina pectoris and hypertension.
[Physical and chemical properties]
Nifedipine is a light yellow crystalline powder, odorless and tasteless, and easily decomposes when exposed to light. When exposed to ultraviolet light, it will decompose into nitroso derivatives and nitro derivatives. Nifedipine has poor solubility in water, but is easily soluble in organic solvents such as acetone and chloroform, and slightly soluble in ethanol and acetic acid. Due to its poor water solubility, the bioavailability of nifedipine after oral administration is low and the individual differences are large.
[Pharmacological effects]
Nifedipine is a calcium channel blocker widely used to treat angina pectoris and hypertension. It mainly prevents the influx of calcium ions (Ca2+) across the membrane. Entering the muscle cells, it then causes the relaxation of vascular smooth muscles, dilation of coronary arteries, increases blood flow, reduces peripheral vascular resistance, and lowers blood pressure. At the same time, nifedipine can improve the ischemic tolerance of cardiomyocytes. When nifedipine is taken in small doses, it has little effect on blood pressure when dilating coronary arteries, so nifedipine is also used to fight angina. In addition, nifedipine can be used in combination with other drugs to treat diseases of the digestive, urinary, respiratory and other systems. For the digestive system, nifedipine can relax the smooth muscle of the esophagus, slow down gastrointestinal motility, and repair diseased mucosa. At the same time, because it can reduce portal vein pressure, it can promote the healing of gastrointestinal wounds and provide relief. The role of pain. For the urinary system, nifedipine can relax the smooth muscle of the bladder, expand its internal volume, and relieve symptoms such as urgency and frequency of urination. For the respiratory system, nifedipine can be used to treat pulmonary hypertension and high-altitude pulmonary edema.
[Pharmacokinetics]
1. Absorption and bioavailability Nifedipine is a fat-soluble drug. It is completely absorbed in the gastrointestinal tract after oral administration. The absorption site is mainly the jejunum, and then is massively metabolized by the liver. The first-pass effect is obvious and the bioavailability is very low. It is 50%-70%; the blood concentration is linearly related to the dose. It appears in the blood vegetables within 2-3 minutes after administration. The action time is fast. Intravenous injection is less than 1 minute. Sublingual administration within 5 minutes. Oral administration. The blood drug concentration reaches its peak in about 1 hour.
2. Distribution and protein binding Nifedipine mainly binds to plasma albumin, A2 lipoprotein and B globulin in the body, with a protein binding rate of more than 90%, and is widely distributed in tissues.
3. Metabolism Nifedipine is mainly metabolized in the small intestine and liver. The metabolites have no pharmacological activity. About 80% of the metabolites are excreted in the urine. , the remainder is excreted through feces, and renal function has no effect on the metabolism of corbendipine in the body. 4. T1/2 and elimination rate: The elimination half-life of nifedipine after oral administration is approximately 2-5 hours; the elimination rate depends on hepatic blood flow and the activity of liver metabolic enzymes.
[Preparation method]
Add 1.51g (10mmol) o-nitrobenzaldehyde, 3.02g (26mmol) methyl acetoacetate, 1.03g (13mmol) ammonium bicarbonate and 3mL methanol into a 25mL round bottom flask. Mix the raw materials evenly and start heating slowly. to 50°C, keep stirring for 1 hour, then heat to reflux for 1.5 hours, cool to room temperature, precipitate a yellow solid, filter with suction, wash with a small amount of methanol, and dry to obtain 1.96 g of yellow solid with a yield of 56.6%.
Figure 1 shows the reaction formula for synthesizing nifedipine
【Clinical Application】
1. Treatment of gastrointestinal reactions caused by intravenous infusion of erythromycin. NF can prevent calcium ions from entering the gastrointestinal smooth muscle, decouple the excitation-contraction coupling, relieve smooth muscle spasm, and therefore reduce the effects of erythromycin. Caused gastrointestinal reactions, curative effect usually takes 20 minutes.
2. Treatment of peptic ulcer NF can relieve smooth muscle spasm, relatively dilate blood vessels, increase gastric mucosal blood flow, enhance tissue resistance and repair, thereby promoting ulcer healing. At the same time, NF has a blood pressure-lowering effect, and its blood pressure-lowering amplitude is related to the basal blood pressure before treatment, but has little effect on the blood pressure of normal people. Therefore, NF can be used for patients with peptic ulcer combined with hypertension, coronary heart disease, and angina pectoris. Studies have shown that NF can inhibit the synthesis and secretion of endothelin by hepatic stellate cells, inhibit the contraction of hepatic stellate cells, and reduce intrahepatic resistance and portal vein pressure, so it can be used in patients with liver cirrhosis and peptic ulcer.
3. Prevention and treatment of premature birth F The mechanism of treating premature birth is to selectively inhibit the influx of calcium during the repolarization phase of the action potential of uterine smooth muscle cells, thereby effectively inhibiting uterine contraction. NF has few adverse reactions in the treatment of premature labor and has no adverse effects on pregnant women and newborns. It can be used as a commonly used drug in the treatment of premature labor.
4. Treat primary dysmenorrhea. NF can inhibit smooth muscle contraction, relax vascular smooth muscle, relieve uterine smooth muscle spasm, improve its blood supply, and relieve pain.
5. Treatment of anal fissure NF can inhibit the entry of extracellular calcium from the internal sphincter of patients with anal fissure into the sarcoplasm, reduce the mechanical contraction of muscle fibers, thereby reducing oxygen consumption. It also has anti-inflammatory activity and regulates microcirculation. , relax the internal anal sphincter, reduce the pressure in the anal canal, and increase the blood perfusion of the anal canal, thereby relieving pain and healing the anal fissure.
6. Treatment of infantile asthmatic pneumonia with NF can reduce the concentration of intracellular calcium ions, reduce airway hyperresponsiveness, reduce the release of biotransmitters from mast cells, reduce secretion, relax smooth muscles, and improve ventilation; furthermore, , Children with hypoxia have varying degrees of cardiac function damage. NF can improve the blood supply of coronary blood vessels, reduce the pre- and afterload of the heart, increase the cardiac index, improve cardiac function and blood circulation of lung tissue, and reduce inflammation. Repair and absorb exudates, thereby improving ventilation.
7. Treatment of chronic asthmatic bronchitis NF has a good effect in the adjuvant treatment of chronic asthmatic bronchitis. 8. Treat neurogenic frequent urination in children. NF reduces calcium influx by blocking cell membrane calcium ion channels. Thereby relaxing the detrusor muscle and increasing urine storage in the bladder. Oryzanol can regulate autonomic nerve function and promote the recovery of micturition reflex function. Combining the two drugs on the basis of psychological treatment has a better effect in treating this disease.
【Oral Characteristics】
Advantages: It is absorbed quickly and completely after oral administration. Its blood concentration can be measured in 10 minutes, and the peak blood concentration is reached in about 1.5 hours. The peak time can be reached earlier when chewed or sublingually, and can be used to quickly lower the blood concentration. Blood pressure, the effect is obvious and the effect is fast. Disadvantages: Nifedipine has poor water solubility, significant first-pass effect in the liver, short degradation cycle, high frequency of administration, low oral bioavailability, and obvious individual differences. At the same time, when the plasma drug concentration reaches its peak, it will be accompanied by varying degrees of side effects. Therefore, Users often feel dizzy the first few times they take it. Common side effects include headache, fatigue, cough, shortness of breath, drowsiness, bradycardia, etc. In severe cases, it can lead to a rapid drop in blood pressure, loss of consciousness, cerebral ischemia and infarction, myocardial infarction, complete heart obstruction, and even death.
[Main reference materials]
[1]Ding Chenghui. Progress in clinical application of nifedipine[J]. Modern Medicine and Health, 2007(14):2121-2122.
[2] Lu Bingcong. Preparation and in vitro and in vivo evaluation of nifedipine liposomes [D]. Jilin University, 2017.
[3]Li Defeng. Preparation and evaluation of nifedipine injection[D]. Southwest University, 2014.
[4]Li Gongchun, Tian Yuan, Li Cunxi, Wu Changzeng, Niu Liangfeng, Ju Zhiyu, Sun Ting. Synthesis of nifedipine [J]. Zhejiang Chemical Industry, 2015, 46(03): 26-29.
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