What Is Nifedipine?

Nifedipine is used to prevent and treat coronary heart disease angina pectoris, especially angina pectoris caused by variant angina pectoris and coronary artery spasm. It has no adverse effects on respiratory function, so it is suitable for patients with angina pectoris with respiratory obstructive disease, and its efficacy is better than -receptor antagonists. It is also suitable for various types of hypertension, and has good effects on refractory and severe hypertension. Since it can reduce the afterload, it also has a good effect on refractory congestive heart failure, and it is suitable for long-term use.

Nifedipine is used to prevent and treat coronary heart disease angina pectoris, especially angina pectoris caused by variant angina pectoris and coronary artery spasm. It has no adverse effects on respiratory function, so it is suitable for patients with angina pectoris with respiratory obstructive disease, and its efficacy is better than -receptor antagonists. It is also suitable for various types of hypertension, and has good effects on refractory and severe hypertension. Since it can reduce the afterload, it also has a good effect on refractory congestive heart failure, and it is suitable for long-term use.

Drug type

Essential medicines

Drug name

Nifedipine

English name

Nifedipine

Chinese alias

Nifedipine; reserpine; nifedipine

English alias

Nifelat; Baya-1o4o; Procardia

Brief introduction of nifedipine compounds

Basic information about nifedipine

Chinese name: nifedipine

Chinese alias: Lixinping; 1,4-dihydro-2,6-dimethyl-4- (2-nitrophenyl) -3,5-pyridinedicarboxylic acid dimethyl ester; Axandine; Nifedipine

English name: nifedipine

English alias: dimethyl 2,6-dimethyl-4- (2-nitrophenyl) -1,4-dihydropyridine-3,5-dicarboxylate; Adalat CC; 1,4-Dihydro-2,6-dimethyl-4- (2- nitrophenyl) -3,5-pyridinedicarboxylic acid Dimethyl Ester; Cordipin; Procardia XL;

CAS number: 21829-25-4

Molecular formula: C ₁₇ H ₁₈ N ₂ O ₆

Structural formula:

Molecular weight: 346.33500

Exact mass: 346.11600

PSA: 110.45000

LogP: 3.02760

Physical and chemical properties of nifedipine

Appearance and properties: yellow crystalline solid, odorless, tasteless, unstable to light. Soluble in acetone or chloroform, slightly soluble in ethanol, and almost insoluble in water.

Density: 1.271g / cm ³

Melting point: 171-175 ° C

Boiling point: 475.3ºC at 760 mmHg

Flash point: 241.2ºC

Refractive index: 1.584

Qualitative: stable under normal temperature and pressure

Storage conditions: ventilated, dry at low temperature, stored separately from food materials in the warehouse

Vapor pressure: 2.68E-08mmHg at 25 ° C

Nifedipine safety information

Symbol: GHS07

Signal Word: Warning

Hazard statement: H302

Customs Code: 2933290090

WGK Germany: 1

Danger category code: R22

Safety instructions: S26-S36

RTECS number: US7975000

Dangerous goods sign: Xn

Production method of nifedipine

The o-nitrobenzaldehyde, methyl acetoacetate, methanol and ammonia were refluxed together, then frozen, crystallized and filtered to obtain crude nifedipine. The crude product was recrystallized from methanol to obtain the finished product, with a yield of 50%.

Uses of nifedipine

1. Selectively inhibit calcium influx of myocardial cell membrane, block myocardial cell excitation-contraction coupling, weaken myocardial contractility, reduce myocardial energy and oxygen consumption, and directly protect myocardial cells by preventing calcium overload.

2. Inhibit the excitation-contraction coupling of blood vessels, bronchial tubes and uterine smooth muscles, and dilate systemic blood vessels (including lung, liver, kidney, brain, femoral and mesenteric arteries) and coronary arteries. The mechanism of expanding vascular smooth muscle is more complicated

1) Prevent calcium inflow

2) hinder the release of calcium in the cell wall

3) Block -adrenergic receptors on the vascular membrane

4) Inhibition of phosphodiesterase activity

5) Interaction with Calmodulin

6) Activate Na +, K + -ATPase

7) Activate the calcium ion pump

3. Inhibition of platelet aggregation Nifedipine can inhibit ADP and collagen-induced human platelet aggregation at a concentration of 50 ugml ^[1] .

Nifedipine Pharmacopoeia Standard

[Identification] (1) Take about 25mg of this product, add 1mL of acetone to dissolve, add 3 ~ 5 drops of 20% sodium hydroxide solution, shake, the solution is orange-red. (2) Take an appropriate amount of this product, add 2ml of chloroform to dissolve, add anhydrous ethanol to make a solution containing about 15µg per ml, and measure according to ultraviolet-visible spectrophotometry (Appendix IV A). It has a wavelength of 237mn Large absorption, large absorption at a wavelength of 320 ~ 355nm. (3) The infrared light absorption spectrum of this product should be consistent with the control spectrum (spectrum set 469).

[Inspection] The related substances should be protected from light. Take this product, weigh it accurately, add methanol to dissolve and quantitatively dilute it to make a solution containing about 1mg per 1ml as the test solution; take another 2,6-dimethyl-4- (2-nitrophenyl) ) Dimethyl-3,5-pyridinedicarboxylate (impurity I) reference and dimethyl 2,6-dimethyl-4- (2-nitrosophenyl) -3,5pyridine dicarboxylate (impurity ) The reference substance is precisely weighed, dissolved in methanol and quantitatively diluted to make a mixed solution containing about 10 µg of each ml, which is used as the reference stock solution; the appropriate amounts of the test solution and the reference stock solution are precisely measured. A mixed solution containing 2 g of nifedipine, 1 g of impurity and 1 g of impurity in each ml was used as a control solution. According to the high performance liquid chromatography (Appendix VD) test, octadecylsilane bonded silica gel was used as the filler; methanol-water (60:40) was used as the mobile phase; the detection wavelength was 235mn. Take nifedipine reference substance, impurity I reference substance and impurity II reference substance, each of which is suitable for bismuth, dissolved in methyl chloride and diluted to make a mixed solution containing about 1mg, 10µg and 10µg per 1ml. Take 20µl and inject the liquid color In the instrument, the resolution between the impurity I peak, impurity II peak and nifedipine peak should all meet the requirements. Take 20µl of the control solution and inject it into the liquid chromatograph, adjust the detection sensitivity so that the peak height of the nifedipine chromatographic peak is about 50% of the full scale; take precise amounts of 20µ each of the test solution and the control solution, and inject the solution separately. For a phase chromatograph, record the chromatogram to twice the retention time of the main component peak. For the chromatogram of the test solution, if there are chromatographic peaks with the same retention time as the impurity 1 peak and impurity peak, the peak area calculated according to the external standard method shall not exceed 0.1%; the peak area of other single impurities shall not be larger than the control solution. Peak area of nifedipine (0.2%); total amount of impurities must not exceed 0.5%. Take this product after losing weight and dry it at 105 to constant weight, and the weight loss should not exceed 0.5% (Appendix L). Take 1.0g of this product and check it according to law (Appendix N). The remaining residue should not exceed 0.1%. The heavy metal is taken from the residue left by the burning residue and checked according to law (Appendix H second method). The content of heavy metal must not exceed 10 parts per million.

[Including the most determination] Take about 0.4g of this product, accurately weigh, add 50ml of absolute ethanol, dissolve at a slight temperature, add perchloric acid solution (take 8.5ml of 70% perchloric acid, add water to 100ml), 50ml of o-diazo 3 drops of phenanthrene indicator solution, titrate immediately with cerium sulfate titration solution (0.1 mol / L), and near the end point, heat to about 50 ° C in a water bath, continue to titrate until the orange-red color disappears, and use the titration result Blank test correction. Each 1ml of cerium sulfate titration solution (0.1mol / L) is equivalent to 17.32mg of C17H18N2O6 ^[2] .

[Category] Calcium channel blockers.

[Storage] shading and sealed.

Nifedipine drug description

Nifedipine pharmacology

It can inhibit Ca2 + influx, relax vascular smooth muscle, expand coronary arteries, increase coronary blood flow, increase myocardial tolerance to ischemia, and at the same time expand peripheral arteries, reduce peripheral vascular resistance, thereby reducing blood pressure. Low-dose expansion of the coronary arteries does not affect blood pressure and is a better antianginal medicine. Used as an antihypertensive drug, there are no adverse reactions such as water and sodium retention and edema that are common in vasodilators. Oral absorption is good, effective after 10 minutes, the maximum effect is achieved in 1 to 2 hours, and the effect is maintained for 6 to 7 hours. Sublingual administration is more rapid than oral administration. The antihypertensive effect occurs after 10 minutes of spray administration, and the effect is most significant after 1 hour, and the blood pressure rises after about 3 hours (individuals can last for 11 hours). Intravenous injection can lower blood pressure by 21% -26% within 10 minutes.

Nifedipine indications

It is used to prevent and treat coronary heart disease angina pectoris, especially angina pectoris caused by variant angina pectoris and coronary artery spasm. It has no adverse effects on respiratory function, so it is suitable for patients with angina pectoris with respiratory obstructive disease, and its efficacy is better than -receptor antagonists. It is also suitable for various types of hypertension, and has good effects on refractory and severe hypertension. Since it can reduce the afterload, it also has a good effect on refractory congestive heart failure, and it is suitable for long-term use.

Nifedipine usage and dosage

Due to different dosage forms and specifications, please read the drug instructions carefully or follow the doctor's advice.

Nifedipine adverse reactions

Adverse reactions are generally mild. Facial flushing is common in first-time users, followed by palpitations and sinus tachycardia. Individuals have numbness of the tongue, dry mouth, sweating, headache, nausea, and loss of appetite.

Nifedipine contraindications

Disabled during pregnancy.

Nifedipine precautions

Use with caution in patients with hypotension.

Nifedipine drug interactions

Use with other antihypertensive drugs can cause low blood pressure. Co-administration with -receptor antagonists can cause hypotension, heart function depression, and heart failure. Sudden discontinuation of p-receptor antagonist therapy and activation of this product may occasionally cause angina pectoris, and the former dosage must be gradually reduced. Drugs with high protein-binding rate such as dicoumarin, digitalis, phenytoin, quinidine, quinine, warfarin, etc., often change the free concentration of these drugs. Combined with nitrates, the treatment of angina pectoris can be enhanced. When used in combination with cimetidine and other drugs, the peak blood concentration of this product increases, and attention should be paid to adjusting the dose.

Nifedipine preparation

Tablet: 5mg, 10mg

Nifedipine tablets

Nifedipine tablets

Indications of nifedipine function

1. Angina pectoris: variant angina pectoris; unstable angina pectoris; chronic stable angina pectoris.

2. Hypertension (alone or in combination with other antihypertensive drugs).

Nifedipine usage and dosage

1. The dose of nifedipine should be adjusted gradually depending on the patient's tolerance and control of angina pectoris. Overdose of nifedipine can cause hypotension.

2. Start with a small dose, usually the starting dose is 10mg / time, orally 3 times a day; the commonly used maintenance dose is 10-20mg / time, 3 times a day. Some patients with significant coronary spasm can be used 20 to 30 mg / time, 3 to 4 times a day. The maximum dose should not exceed 120mg / day. If the condition is urgent, you can chew or take 10 mg / time under the tongue, and decide to re-administer it according to the patient's response to the drug.

3. It usually takes 7 to 14 days to adjust the dose. If the patient's symptoms are obvious and the condition is urgent, the dose adjustment period can be shortened. Depending on the patient's response to the drug, the frequency of attacks and the dose of nitroglycerin under the tongue, the amount of nifedipine can be adjusted from 10-20 mg to 30 mg / time within 3 days, 3 times a day.

4. In-patients under strict monitoring can increase 10mg every 4-6 hours according to the control of angina pectoris or ischemic arrhythmia.

Nifedipine adverse reactions

1. Peripheral edema is common after taking medication (peripheral edema is dose-related, the incidence rate is 4% when taking 60mg / day, and 12.5% when taking 120mg / day); dizziness; headache; nausea; fatigue and facial flushing (10% ). Transient hypotension (5%), no need to stop medication (transient hypotension is dose-related, the incidence rate is 2% at a dose <60mg / day, and the incidence rate is 120% / day) . Angina pectoris in some patients may be related to hypotension. Palpitations; stuffy nose; chest tightness; shortness of breath; constipation; diarrhea; gastrointestinal cramps; abdominal distension; skeletal muscle inflammation; joint stiffness; ). Syncope (0.5%), reduced doses or in combination with other antianginal medications no longer occur.

2. Rare anemia; leukopenia; thrombocytopenia; purpura; allergic hepatitis; gingival hyperplasia; depression; paranoia; instant blindness at peak blood concentration; erythematous limb pain; antinuclear antibody positive arthritis (<0.5%).

3. Possible serious adverse reactions: the incidence of myocardial infarction and congestive heart failure is 4%; the incidence of pulmonary edema is 2%; the incidence of arrhythmia and conduction block is less than 0.5% each.

4. People who are allergic to this product may develop allergic hepatitis, rash, and even exfoliative dermatitis.

Contraindications: Those who are allergic to nifedipine are prohibited.

Nifedipine precautions

1. Hypotension. Most patients have only mild hypotension after taking nifedipine, and some patients have severe hypotension symptoms. This response often occurs during dose adjustments or additions, especially when combined with beta-blockers. Monitor your blood pressure during this period, especially when combined with other antihypertensive drugs.

2. Fentanyl anesthesia patients undergoing coronary artery bypass grafting (or other surgery), taking nifedipine alone or in combination with -blockers can cause severe hypotension, and should be stopped at least if conditions permit Medicine for 36 hours.

3. Angina pectoris and / or myocardial infarction. In very few patients, especially those with severe coronary stenosis, taking nifedipine alone or in combination with -blockers can cause severe hypotension, and should be discontinued for at least 36 hours if conditions permit.

4. Peripheral edema. Mild to moderate peripheral edema occurred in 10% of patients and was associated with arterial dilatation. Edema mostly occurs in the lower extremities and can be treated with diuretics. For patients with congestive heart failure, it is necessary to distinguish whether edema is caused by further deterioration of left ventricular function.

5. Beta-blocker "bounce" symptoms. Sudden discontinuation of beta-blockers and use of nifedipine may even worsen angina pectoris. The former must be gradually reduced.

6. Congestive heart failure. A small number of patients receiving -blockers can develop heart failure after taking nifedipine, and patients with severe aortic stenosis are at greater risk.

7. Disturbance to diagnosis When using this product, there may be elevated alkaline phosphatase, creatine phosphokinase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase. Generally there are no clinical symptoms. However, cholestasis and jaundice have been reported; reduced platelet aggregation and prolonged bleeding time; direct Coomb test with / without hemolytic anemia.

8. Hepatic and renal insufficiency, those who are taking -blockers should be used with caution, it is advisable to start with small doses to prevent the induction or exacerbation of hypotension and increase the incidence of angina pectoris, heart failure and even myocardial infarction. Patients with chronic renal failure occasionally have reversible elevated blood urea nitrogen and creatinine, and the relationship with nifedipine is not clear.

9. Suspension should not be stopped for long-term administration to avoid rebound phenomenon due to withdrawal syndrome.

Nifedipine ingredients

The main ingredient of this product is nifedipine.

Nifedipine traits

This product is a sugar-coated tablet, which is yellow after removing the sugar coating.

Nifedipine medication for pregnant and lactating women

1. No detailed clinical research data. Clinically, nifedipine is used in pregnant women with hypertension.

2. Nifedipine can be secreted into breast milk. Women who are breastfeeding should stop taking medicine or breastfeeding.

Nifedipine medication for the elderly

The half-life of nifedipine is prolonged in the elderly. Pay attention to adjusting the dose when applying.

Nifedipine drug interactions

1. Nitrate esters. Combined with this product to control the onset of angina pectoris, has better tolerance.

2. Beta-blockers. The vast majority of patients have better tolerance and efficacy of this product, but individual patients may induce and exacerbate hypotension, heart failure and angina.

3. Digitalis. This product may increase blood digoxin concentration, suggesting that the blood concentration of digoxin should be monitored when first using, adjusting the dose or discontinuing this product.

4. Drugs with high protein binding rate, such as dicoumarins, phenytoin, quinidine, quinine, warfarin, etc. When used with this product, the free concentration of these drugs often changes.

5. The peak plasma concentration of cimetidine increases when used with this product. Pay attention to adjusting the dose.

Pharmacological effects of nifedipine

(1) This product can relax coronary arteries in normal blood supply area and ischemic area, antagonize spontaneous or ergometrine-induced coronary spasm, increase myocardial oxygen delivery in patients with coronary spasm, relieve and prevent coronary spasm.

(2) This product can inhibit myocardial contraction, reduce myocardial metabolism, and reduce myocardial oxygen consumption.

(3) This product can relax peripheral resistance blood vessels, reduce peripheral resistance, reduce systolic blood pressure and diastolic blood pressure, and reduce cardiac afterload.

(4) This product can delay sinoatrial node function and atrioventricular conduction in isolated hearts; overall animal and human electrophysiological studies have not found that this product can delay atrioventricular conduction, prolong sinus node recovery time, and slow sinoatrial node The role of rate.

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