2 English reference nicotinamide
3 overview nicotinic acid, also known as nicotinic acid, is one of the B vitamins. Coenzymes that constitute nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+) in vivo play the role of electron carriers or hydrogen donors in biological redox reactions [1].
Nicotinic acid is a water-soluble vitamin; It is a kind of vitamin B family, alias vitamin B3. The commonly used unit of measurement is milligram (mg). Nicotinic acid is a white needle-like crystal, slightly soluble in water, stable in nature, not easily destroyed by acid, alkali and heat, and is the most stable vitamin.
The human body can use tryptophan, one of the main amino acids, to synthesize nicotinic acid by itself;
People who lack vitamin B 1, vitamin B2 and vitamin B6 in the body cannot produce nicotinic acid from tryptophan;
The recommended daily intake for adults is 13 19mg, and that for lactating women is 20mg.
Nicotinic acid, like adrenocortical hormone, thyroxine and insulin, is an indispensable substance for the synthesis of sex hormones (estrogen, progesterone and testosterone).
Maintain a healthy nervous system and normal brain function;
Nicotinic acid in the form of nicotinic acid often causes redness and itching of the skin. In order to prevent this phenomenon, nicotinamide nicotinic acid is generally used (but this skin redness usually disappears in about 20 minutes).
4 another name for nicotinic acid; nicotinamide
5 Nicotinic acid Nicotinic acid is widely distributed in animal and plant foods, but most of them have little content, including yeast, peanuts, beans and meat (especially liver). There is a lot of nicotinic acid in corn, but it is combined and cannot be absorbed by human body. It needs to be hydrolyzed into free nicotinic acid after alkali treatment, which is easy to absorb. Tryptophan can be converted into nicotinic acid in human body. [2]
Nicotinic acid is one of the few relatively stable vitamins in food. Even after cooking and storage, it will not be lost in large quantities, which will affect the efficacy.
Nicotinic acid, also known as nicotinic acid or anti-pellagra factor, is rich in liver, lean meat, poultry, peanuts and yeast, and the contents of nicotinic acid and tryptophan in various grains are low. Nicotinic acid generates nicotinamide through amino transfer, nicotinamide reacts with phosphoribosyl pyrophosphate to generate nicotinamide mononucleotide, and nicotinamide mononucleotide combines with ATP to generate nicotinamide adenine dinucleotide (NAD), also known as coenzyme I (CO I). NAD combines with adenosine triphosphate (ATP) to form nicotinamide adenine dinucleotide phosphate (NADP), also known as coenzyme II (CO II). NAD and NADP act as dehydrocoenzymes in many anaerobic dehydrogenases. NAD and NADP are both main coenzymes in redox reaction system during cell metabolism.
Nicotinic acid is not only a food source, but also can be converted from tryptophan, which first becomes kynurenine. Tryptophan tyrosinase and formyl enzyme are needed to hydrolyze formyl kynurenine into kynurenine, and then kynurenine or xanthuric acid is decomposed into 3- hydroxy aminobenzoic acid by 1 kynurenine hydrolase, and then converted into nicotinic acid by the enzyme system of mammalian liver under the action of 5- phosphoribosyl pyrophosphate. People who lack vitamin B 1, vitamin B2 and vitamin B6 in the body cannot produce nicotinic acid from tryptophan;
6 metabolism of nicotinic acid The products of nicotinic acid metabolism are N' methylnicotinamide and N' methyl 2 pyridone 5 formamide, the former accounting for 20% ~ 30% of urine excretion, and the latter accounting for 40% ~ 60% of urine excretion.
The effect of nicotinic acid promotes the health of digestive system and relieves gastrointestinal dysfunction;
Make the skin healthier;
Prevent and relieve severe migraine;
Promote blood circulation and lower blood pressure;
Relieve diarrhea;
Relieve the uncomfortable symptoms of Meniere's syndrome; So that the human body can make full use of food to increase energy;
Treat inflammation of mouth and lips and prevent halitosis;
Reduce cholesterol and triglycerides.
8 Diseases caused by lack of nicotinic acid Nicotinic acid plays a role in hydrogen transfer in human metabolism. Large doses of nicotinic acid can dilate small blood vessels and reduce cholesterol content [2]. Nicotinic acid, like adrenocortical hormone, thyroxine and insulin, is an indispensable substance for the synthesis of sex hormones (estrogen, progesterone and testosterone). Nicotinic acid deficiency can cause oral dermatosis, and the main symptoms are dermatitis, diarrhea and dementia. Long-term use of remifentanil is prone to nicotinic acid deficiency [2].
Foods rich in nicotinic acid include animal liver and kidney, lean meat, whole wheat products, beer yeast, malt, fish, eggs, fried peanuts, white poultry, avocados, valleys, figs and prunes.
10 The daily demand of nicotinic acid in normal people is generally 20 ~ 30 mg. Eating 100g liver or 300g meat is enough.
Adverse reaction of nicotinic acid 1 1 nicotinic acid can dilate blood vessels and reduce TC. The latter can reduce triglyceride and LDLC；; By increasing lipoprotein esterase activity and promoting TC excretion through intestine, and by inhibiting VLDLC synthesis in liver. Inhibit HDLC decomposition and increase HDLC. It is mainly used to treat type Ⅲ, Ⅳ and Ⅴ hyperlipidemia, and can treat type Ⅱ hyperlipoproteinemia in large dose. The oral LD50 of mice is 4.0 ~ 7.Og/kg,, and that of rats is 7.Og/kg., and the subcutaneous injection is about 5g/kg. The usual dosage is 0. 1g, 3 times /d at the beginning, and gradually increases to 1 ~ 2g, 3 times /d at the beginning. It mainly damages cardiovascular system, nervous system, liver and skin. [3]
Dose 100mg or more will cause side effects, such as numbness, prickly carbuncle, skin redness and so on. People with sensitive skin may feel burning, tingling or itching. Never give it to animals, especially dogs, because niacin can cause dermatitis, sweating and extreme discomfort.
The clinical manifestations of 1 1. 1 are as follows [3]:
1. Cardiovascular system
Skin flushing, fever, headache, sometimes blood pressure drop, palpitation, atrial arrhythmia, etc.
2. Nervous system
Headache, dizziness, fatigue, syncope, tingling around the mouth, tingling in the limbs, depression, etc.
3. Digestive system
Nausea, vomiting, flatulence, hunger, diarrhea, jaundice, transaminase, alkaline phosphatase, unconjugated bilirubin, blood sugar, abnormal glucose tolerance and transient increase of serum uric acid.
4. Skin
Temporary itching, flushing and urticaria. Long-term medication can cause dry skin, mild exfoliation, acanthosis nigricans symptoms and hair loss. About 1/4 patients have hyperpigmentation of skin and increased secretion of sebaceous glands.
1 1.2 The treatment points of nicotine acidosis are [3]:
1. Stop taking the medicine immediately and give gastric lavage and catharsis to those who take it by mistake.
2. Intravenous injection of 5% glucose saline and vitamin C 2.5g during fluid replacement to promote excretion.
3. To maintain blood pressure, antihypertensive drugs and antiarrhythmic drugs can be used in time.
4. To protect the liver, inosine, biphenyl diester and diammonium glycyrrhizinate can be given.
5. Anti-allergic treatments such as astemizole and diphenhydramine. Add glucocorticoids if necessary.
6. Other symptomatic treatment.
12 enemy nicotinic acid, sulfanilamide, alcohol, food processing, sleeping pills, estrogen.
Nicotinic acid nutritional supplement 13 can buy nicotinic acid and nicotinamide. The difference between the two is that nicotinic acid may cause skin redness, while nicotinamide does not. If you want to take the former, take it after meals or take the same amount of inositol, which can reduce the occurrence of skin redness.
Generally sell 50 1000mg tablets or powders. High-quality multivitamin B or multivitamin preparation usually contains 50 1000mg nicotinic acid.
14 suggested that when taking antibiotics, it doesn't matter even if the skin redness caused by nicotinic acid is very serious. This is a common situation. If you switch to nicotinamide, you can relieve the symptoms;
For people who are worried about cholesterol, it is helpful to increase the intake of nicotinic acid;
When the skin is particularly sensitive to sunlight, it is often an early symptom of niacin deficiency.
15 medical examination of nicotinic acid 15. 1 examination name nicotinic acid
15.2 classified blood biochemical examination > serum vitamin determination
15.3 Determination principle of nicotinic acid (1) Determination of N' methylnicotinamide excretion in urine: Because N' methylnicotinamide in urine is a metabolite of nicotinic acid, measuring the metabolite in urine can indirectly reflect the level of nicotinic acid in the body. N' methylnicotinamide does not fluoresce, but condenses with acetone in alkaline environment to generate derivatives with yellow fluorescence; Then heated in an acidic solution to form a naphthyridine compound with strong blue fluorescence under 365nm light wave, and its fluorescence intensity is directly proportional to the content of N' methylnicotinamide.
(2) Load test: After emptying urine in the morning, take a standard diet containing nicotinic acid 10mg and tryptophan 100mg, and then collect urine for 24 hours to determine the contents of N' methylnicotinamide and N' methyl 2- pyridone in urine.
15.4 reagent (1)6mol/L sodium hydroxide.
(2)6 mol/L hydrochloric acid.
(3) acetone has no fluorescence, or a small amount of potassium permanganate is added and redistilled.
(4) Potassium dihydrogen phosphate solution, weigh 20g of potassium dihydrogen phosphate, dissolve it in water, and dilute it to 100ml.
(5) The recovery test of N' methylpyramide standard solution should be carried out on activated carbon to test its adsorption performance. So as to prevent the measured object from being adsorbed.
(6) N' methylnicotinamide storage standard solution (500mg/L), accurately weigh 62.7mg of dry N' chloromethylnicotinamide, dissolve it into 100ml with 0. 1mol/L hydrochloric acid, put it in a brown bottle and stabilize it at 4℃ for half a year.
(7) daub N' methylnicotinamide with standard solution (1000μg/L), absorb 2.0ml of the above storage standard solution, and dilute it to 1000ml with 0.0 1mol/L hydrochloric acid, which can be stable at 4℃ for several days.
(8) Quinine sulfate storage solution (100mg/L): Weigh quinine sulfate 100mg, dissolve it in 0.05mol/L sulfuric acid, dilute it to 1000ml, and store it in the dark at 4℃ for a long time.
(9) quinine sulfate application solution (300μg/L): Take 3.0ml quinine sulfate storage solution, dilute it to 1000ml with 0.05mol/L sulfuric acid, and store it in the dark at 4℃ for 3 months.
15.5 Operation method (1) Purification Take 2 calibrated 10ml test tubes and label them with measuring tube (U) and standard tube (S). Add 2ml of urine and 0.2ml of glacial acetic acid into the measuring tube and dilute it to 10ml with water. Add10ml N' methylnicotinamide application standard solution to the standard tube. Add 100mg activated carbon to the two tubes, mix them evenly for several times, immediately filter them with filter paper, and take the filtrate for determination.
(2) Take four test tubes with 10ml stoppers for reaction, mark the measuring tube (U), measuring blank tube (UB), standard tube (S) and standard blank tube (SB), and operate according to the following table (Table 1).
(3) firstly, use quinine sulfate application solution to adjust the reading to 50-80, and carry out fluorescence determination. The excitation wavelength is 330 ~ 360 nm and the emission wavelength is 430 ~ 450 nm, and then the fluorescence intensity of each tube is read.
15.6 See Table 2 for normal urine N' methylnicotinamide excretion.
Load test: the reference values of two metabolites in normal people are 7.0 ~ 37.0 mg, and when it is less than < 3.0mg, it is nicotinic acid deficiency in the body.
Clinical significance of 15.7 test results Nicotinic acid deficiency is also called pellegra. The main clinical manifestations are bilateral symmetrical dermatitis, organic psychosis, encephalopathy syndrome and digestive system syndrome (such as scarlet fever glossitis, tongue coating shedding and stomatitis). One of the main symptoms of nicotinic acid deficiency is digestive tract symptoms, such as stomatitis, glossitis, diarrhea and indigestion. With the passage of time, iron and folic acid deficiency may occur, so there are various types of anemia (small cell hypopigmentation, normal cells or large cells) in clinic. In addition, when nicotinic acid is deficient, skin keratin is insufficient, because dehydrocoenzyme catalyzes the oxidation of cysteine to form glutathione, which is a sulfur-hydrogen matrix enzyme with the activity of inhibiting epidermal tyrosinase. Tyrosinase can catalyze tyrosine to form melanin in skin. Therefore, when nicotinic acid is deficient, skin pigment is produced too much. Once rubbed or exposed to the sun, * * *, the rash and dermatitis symptoms peculiar to this disease will appear.
15.8 note that laboratory tests can only be used under conditions, and it is not reliable to determine the acid value of nicotine in blood. Up to now, measuring the excretion of N' methylnicotinamide (calculated by creatinine per gram), a metabolite of nicotinic acid in 24 hours urine, is considered to be the most effective test to judge the nutritional status of nicotinic acid in the body, and its measured value has decreased before clinical symptoms appear, which has clinical value.
15.9 nicotinic acid deficiency and diarrhea-related diseases
16 nicotinic acid pharmacopoeia standard 16. 1 product name 16. 1 Chinese name nicotinic acid
16. 1.2 hanyu pinyin eye calculation
16. 1.3 English name nicotinic acid
16.2 structural formula 16.3 molecular formula and molecular weight c6h5no2123.11.
16.4 source (name) and content (potency) this product is pyridine 3 carboxylic acid. Calculated by dry product, the content of C6H5NO2 should not be less than 99.0%.
16.5 characteristics this product is white crystal or crystalline powder, odorless or slightly smelly, with a slightly sour taste; Acidic reaction of aqueous solution.
This product is soluble in boiling water or boiling ethanol, slightly soluble in water, slightly soluble in ethanol and almost insoluble in ether; Soluble in sodium carbonate solution or sodium hydroxide solution.
16.5. 1 absorption coefficient Take this product, weigh it accurately, add 0. 1mol/L sodium hydroxide solution to dissolve it, dilute it quantitatively, make a solution containing about 20μg per 1ml, and use ultraviolet-visible spectrophotometry (Pharmacopoeia II 20 10
16.6 Identification (1) Take about 4mg of this product, add 8mg of 2,4-dinitrochlorobenzene, grind it evenly, put it in a test tube, slowly heat it until it melts, heat it for a few seconds, let it cool, and add 3ml of ethanol to make the potassium hydroxide test solution, which is purplish red.
(2) Take about 50mg of this product, add 20ml of water to dissolve it, then add 0.4% sodium hydroxide solution dropwise until litmus paper is neutral, and add 3ml of copper sulfate test solution, that is, slowly precipitate a light blue precipitate.
(3) Take this product, dissolve it in water and dilute it into a solution containing about 20μg per 1ml, and determine it by UV-Vis spectrophotometry (Appendix Ⅳ a of Pharmacopoeia Part II, 20 10 edition), with the maximum absorption at the wavelength of 262nm and the minimum absorption at the wavelength of 237nm; The ratio of absorbance at 237 nm to absorbance at 262 nm should be 0.35 ~ 0.39.
(4) The infrared absorption spectrum of this product should be consistent with that of the reference substance (Figure 422: Collection of infrared spectrum of drugs).
16.7 check 16.7. 1 the color of the solution is1.0g. Add 10ml sodium hydroxide test solution to dissolve it. If it is colored, mix it with the control solution with the same volume (use 1.5ml for colorimetry).
16.7.2 chloride: take 0.25g of this product and check it according to law (appendix VIII A of Pharmacopoeia II, 20 10 edition). Compared with the control solution made of standard sodium chloride solution (5.0ml), it should not be thicker (0.02%).
16.7.3 Take 0.50 g of this product as sulfate. Check according to law (Appendix VIII B of Pharmacopoeia II, 20 10 Edition). Compared with the control solution made of standard potassium sulfate solution 1.0ml, it should not be more concentrated (0.02%).
16.7.4 loss on drying takes this product, puts it in a phosphorus pentoxide dryer, and dries it under reduced pressure to a constant weight [4], and the weight loss shall not exceed 0.5% (Appendix VIII L of Pharmacopoeia II, 20 10).
16.7.5 residue on ignition shall not exceed 0. 1% (Appendix VIII N of Pharmacopoeia II, 20 10).
16.7.6 Take 1.0g of this product for heavy metals, add 1.5ml of dilute hydrochloric acid and water to make 25ml, slowly heat it until it is completely dissolved, let it cool, and check it according to law (the first method in Appendix VIII H of Pharmacopoeia II, 20 10 edition), and the content of heavy metals shall not exceed 20 parts per million.
16.8 content determination Take about 0.3g of this product, weigh it accurately, add 50ml of newly boiled cold water to dissolve it, add 3 drops of phenolphthalein indicator, and titrate with sodium hydroxide titrant (0. 1mol/L). Every 1ml sodium hydroxide titration solution (0. 1mol/L) is equivalent to 12.3 1mg of C6H5NO2.
16.9 vitamins.
16. 10 storage and sealed preservation.
16. 1 1 preparation (1) nicotinic acid tablets? (2) Nicotinic acid injection
16. 12 Edition People's Republic of China (PRC) Pharmacopoeia 20 10 Edition
17 instructions for nicotinic acid 17. 1 drug name nicotinic acid
17.2 English Names nicotinic acid, na, Bionic, Etacin, nicotinic acid, Peviton, Vastherm.
17.3 nicotinic acid alias nicotinic acid; Nick butyric acid; Nicotinic acid; Niasheng; Nicotinic acid; Vitamin PP; Pyridine 3 formic acid; Acidic nicotinic acid; Nicotinic acid; Nicotinic acid; Nicamin; Nicosode
17.4 classification of nervous system drugs >: cerebral vasodilators > others
17.5 dosage form 1. Tablets: 50mg each,100 mg; ;
2. Injection: 50mg (1 ml), 1 00mg (1ml), 20mg (2ml),100mg (2ml), 50mg (5ml).
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Pharmacological action of nicotinic acid 17.6 nicotinic acid belongs to B vitamins. High-dose nicotinic acid can obviously regulate blood lipid, and can rapidly reduce blood triglyceride, very low density lipoprotein cholesterol and LDLC. Nicotinic acid can inhibit the formation of cAMP in adipose tissue, reduce the activity of triglyceride, reduce the esterification of triglyceride in liver, reduce the formation of VLDLC, and finally reduce LDL. It can also enhance the activity of lipoprotein esterase. Nicotinic acid can synthesize nicotinic acid with glycine under the action of coenzyme A, which prevents liver cells from synthesizing cholesterol through coenzyme A. Nicotinic acid can also promote the activity of lipoprotein esterase and accelerate the hydrolysis of triglyceride in lipoprotein, so its effect of lowering TG is obviously stronger than that of lowering cholesterol. The mechanism of increasing HDLC is unknown. It is converted into nicotinamide in vivo, which is a component of coenzyme ⅰ and coenzyme ⅱ, and participates in lipid metabolism, tissue respiration oxidation and glycogen decomposition. Nicotinic acid can inhibit the synthesis of very low density lipoprotein, reduce the utilization of coenzyme A and affect the synthesis of cholesterol. High dose nicotinic acid can reduce the concentration of serum cholesterol and triacylglycerol. In addition, nicotinic acid can dilate peripheral blood vessels, which can take effect in a few minutes after oral administration and last for several minutes to 1 hour. When nicotinic acid is deficient, pellagra can be produced.
The pharmacokinetics 17.7 of nicotinic acid was absorbed from gastrointestinal tract, and reached the peak of plasma concentration 30 ~ 60 min after oral administration, and it was widely distributed in body tissues, with a short half-life of about 45min. When taken orally in large doses, the main metabolites are nicotinic acid, N- methylnicotinamide and 2- pyridone derivatives. 2/3 is excreted from urine in its original form.
Indications 17.8 Nicotinic acid is often used as vasodilator to treat vascular migraine and headache and prevent cerebral artery thrombosis. It can also be used to treat pulmonary embolism, inner ear vertigo, frostbite, central choroiditis, etc. High dose can reduce triacylglycerol. It can also be used for patients who strictly control or choose their diet or receive parenteral nutrition, and patients who suddenly lose weight due to malnutrition, pregnancy, breastfeeding and taking isoniazid. It can also be used for preventing and treating nicotinic acid deficiency such as pellagra. Raynaud's disease, reticular cyanosis, acrocyanosis, segmental hyaline vasculitis, arteriosclerosis obliterans, thromboangiitis obliterans, chilblain, erythema multiforme, etc. At present, nicotinamide is widely used in niacin deficiency. Type Ⅲ, Ⅳ and Ⅴ hyperlipidemia can also be used for type Ⅱ hyperlipidemia.
Contraindications to nicotinic acid 17.9 1. Gout, arterial bleeding, hypotension, hyperuricemia, liver function damage, diabetes, malignant arrhythmia and allergic history are prohibited.
2. Patients with peptic ulcer are prohibited.
17. 10 note: patients with arterial bleeding, diabetes, glaucoma, gout, hyperuricemia, ulcer hypotension and liver disease should use this product with caution. Nicotinic acid is seldom used in lipid-lowering therapy because of its many and serious adverse reactions. Liver function, blood sugar and uric acid should be checked regularly during taking the medicine, and the dosage should be reduced or stopped when it is obviously abnormal.
Adverse reaction of nicotinic acid 17. 1 1 nicotinic acid can cause severe skin flushing or itching reaction within 2 weeks after starting taking the drug. After a few weeks, this reaction can be alleviated in most patients, and some patients can stop taking drugs because of intolerance. If you take 0.3g aspirin 30 minutes in advance, you can obviously reduce flushing. This reaction can also be alleviated by gradually increasing from a small dose. It can also cause gastrointestinal dysfunction such as loss of appetite and diarrhea, and some patients can induce or aggravate ulcer disease. It can reduce the glucose tolerance of patients, increase the blood sugar of non-diabetic patients, or aggravate the condition of diabetic patients. Can make blood uric acid rise, even gouty arthritis, if there are the above changes, you should stop taking the medicine. Some patients also have pigmentation and dry skin. Individual patients may have liver function damage, increased SGPT and even jaundice. Sometimes cardiovascular reactions occur, and serious vascular reactions such as fever, dizziness, headache, dizziness, fatigue, syncope, and sometimes blood pressure will drop significantly. Arrhythmia may occur, mainly atrial arrhythmia. Facial tingling may occur in the nervous system, which may be the neuropathological effect or vascular reaction of nicotinic acid. It is reported that nicotinic acid can improve the mental state of users. The digestive system includes heartburn, vomiting, flatulence, hunger and diarrhea, some of which reflect the increase of intestinal peristalsis. Taking it after meals can reduce gastrointestinal adverse reactions. Ordinary transaminase and alkaline phosphatase temporarily increased. Patients who use sustained-release preparations may have chronic liver injury, reversible cholestasis and lymphocyte infiltration around biliary tract. Portal vein fibrosis and cholangitis may occur after long-term application.
17. 12 usage and dosage of nicotinic acid 1. Oral administration: 50 ~ 200mg each time, 3 ~ 4 times a day, after meals. Pellagra: 50 ~ 150~200mg each time and 150~200mg every day. Anti-hyperlipidemia: oral 100mg, three times a day, and after 4 ~ 7 days, it can be increased to 1 ~ 2g each time, three times a day. Hatknoop's disease: 50 ~ 200mg per day.
2. Intravenous or intramuscular injection: 10 ~ 50mg each time, 1 ~ 3 times a day. Cerebrovascular diseases: 50 ~ 200mg, added to 5% ~ 10% glucose solution, 100 ~ 200ml, intravenous drip, once a day.
17. 13 drug interaction nicotinic acid can aggravate the effect of antihypertensive drugs and phenothiazine drugs, and can strengthen the antihypertensive effect of ganglion blockers in some patients. The combination of nicotinic acid and adrenergic receptor blocking antihypertensive drugs such as guanethidine can synergistically enhance its vasodilating effect and produce orthostatic hypotension. The combination of aspirin and nicotinic acid can enhance the effect of nicotinic acid on reducing triacylglycerol, and the effect of treating hyperlipidemia is better than that of nicotinic acid alone. Isoniazid can block the combination of nicotinic acid and coenzyme ⅰ. The simultaneous application of tiopirone and nicotinic acid can inhibit the uric acid excretion of the former. A similar interaction will occur between nicotinic acid and probenecid. Nicotinic acid can inactivate fibrin
17. 14 expert comments