Nicotinic acid injection solution 10 mg/ml

Nicotinic acid is a vital vitamin, the supply of which is absolutely necessary for all people, including healthy ones. The drug is available in the form of injections and tablets. It is used for the prevention and treatment of atherosclerosis, cerebrovascular accidents, colitis, gastritis with low acidity and other dangerous pathologies.

Historical information

The history of the antipellagric vitamin is perhaps one of the most fascinating and complex.
Back in 1867, Huber first obtained nicotinic acid by oxidizing nicotine with chromic acid, but only in 1937 was it proven that it is vitamin PP. In 1873 Weidel. obtained nicotinic acid by oxidation of nicotine with nitric acid, and in 1879 by oxidation of beta-picoline. He also suggested its name. At the same time, in 1879, the Russian organic chemist A. N. Vyshnegradsky synthesized nicotinic acid from 3-ethylpyridine. In 1877 Laiblin obtained nicotinic acid by oxidizing nicotine with permanganate. In 1912 Suzuki, Shimamura and Odake isolated nicotinic acid from rice bran, and in 1913, independently of them, Funk isolated it from rice bran and yeast. However, the isolated crystalline substance did not prevent or cure beriberi. In 1926, Vickery again isolated nicotinic acid from yeast. But none of the listed researchers suspected that this substance was a true antipellagric factor. This is even more surprising because around the same time, the American doctor Goldberger identified as the main cause of pellagra a deficiency in human nutrition of a new, hitherto unknown factor PP (pellagra preventing). He tried to make rats deficient in this substance. However, the cause of the disturbances he obtained in the experiment was subsequently found to be vitamin B6 deficiency.

In 1935, V.V. Efremov showed that vitamin B6 does not cure experimental pellagra in dogs.

In 1936, Koehn and Elvehjem found that liver extract did not prevent or cure canine pellagra or pellagra in humans.

In 1936, they obtained an active fraction from liver extract, 64 mg of which cured canine pellagra. From this fraction in 1937, Strong and Woolley obtained a crystalline substance, which turned out to be nicotinic acid.

In 1937, Elvehjem and co-authors established in experiments on dogs in which experimental pellagra was reproduced that nicotinic acid cures this disease. In 1937, nicotinic acid was successfully used for human pellagra.

In 1938, V.V. Efremov, for the first time in the USSR, cured severe pellagra with psychosis with nicotinic acid.

In the course of their search to uncover the etiology of pellagra, Goldberger and Tanner in 1922 hypothesized that the cause of this disease could be a lack of certain amino acids, namely tryptophan, which was later confirmed.

Warburg and Christian in 1934 first showed the importance of nicotinic acid in biochemical reactions. They isolated nicotinic acid amide from codehydrase II (NADP) and established its function as a constituent of the hydrogen transfer coenzyme. Almost simultaneously, in 1935, Euler et al. isolated a substance from codehydrase I (NAD), which was also identified with nicotinic acid amide. The great biological significance of nicotinic acid was then established by a number of studies showing that this substance is an important factor for some microorganisms.

Use of niacin in medicine

Due to the peculiarities of its chemical structure, niacin (chemical formula C6H5NO2) is actively used in traditional medicine. Vitamin PP penetrates deeply into the cells of the body, so the range of its use is extremely wide.

Indications for the use of nicotinic acid:

• spinal hernia;
• brain dysfunction (memory impairment, inattention, absent-mindedness);
• depression;
• angina;
• acquired diabetes mellitus;
• alopecia;
• osteoarthritis;
• cardiovascular diseases;
• period;
• multiple sclerosis;
• vitamin deficiency (lack of vitamin B3/PP leads to decreased immunity);
• osteochondrosis, including cervical;
• pellagra – a disease that occurs due to a deficiency of vitamin PP in the human body due to poor nutrition; manifests itself in people suffering from alcoholism and chronic gastrointestinal diseases, but it is also often found in pregnant women;
• dysfunction of the small intestine;
• pathological abnormalities in the functioning of the liver, gall bladder, thyroid gland;
• gastritis;
• dysbacteriosis;
• anorexia;
• malignant tumors;
• headache.

Nicotinic acid will not be superfluous for people who drink alcohol or oral contraceptives; for smokers it is completely irreplaceable. For children, vitamin B3/PP is prescribed exclusively by a pediatrician if there is an urgent need.

Niacin helps fight secondary symptoms of diseases. The drug is used for numbness of the fingers caused by dorsopathies. Used in conjunction with B vitamins.

For prevention, vitamin PP should be taken in tablets; in the treatment of diseases, it is better to use the liquid form of the drug. Treatment regimens and dosages are prescribed after examination and collection of the patient’s medical history.

Chemical and physical properties of vitamin PP

Nicotinic acid is quite easily isolated from most natural products. It is a white, needle-shaped, odorless, crystalline substance with a sour taste and a melting point of 234-237°. Its molecular weight is 123.11. One gram of nicotinic acid is soluble in 60 ml of water and 80 ml of ethyl alcohol at 25°. It is insoluble in ether, but soluble in aqueous solutions of alkali hydroxides and carbonates. Nicotinic acid is not hygroscopic, very stable in dry form. Its solutions can withstand autoclaving at 120° for 20 minutes without destruction. It tolerates boiling well in 1 N. and 2 n. solutions of mineral acids and alkalis. Nicotinic acid has an absorption spectrum in ultraviolet rays with a maximum at 260-260.5 nm. There is a linear relationship between the absorption coefficients of nicotinic acid and its concentration.

According to its chemical structure, nicotinic acid is beta-pyridinecarboxylic or pyridine-3-carboxylic acid. Nicotinamide is a white, odorless, crystalline powder with a bitter-salty taste. It melts at 129-131° and has a molecular weight of 122.12. One gram is dissolved in 1 ml of water and 1.5 ml of 95% ethyl alcohol. It is soluble in acetone, amyl alcohol, ethylene glycol, chloroform, butanol, and slightly soluble in ether and gasoline. Nicotinamide sharply increases the solubility of riboflavin. When dry, it is very stable at temperatures below 50°. In aqueous solution it can be autoclaved at 120° for 20 minutes without visible loss of activity. Under the influence of acids and alkalis, it turns into nicotinic acid.

Nicotinamide has an absorption maximum at 260-261.5 nm. According to its chemical structure, it is an amide of beta-pyridinecarboxylic or pyridine-3-carboxylic acid.

Nicotinic acid can be obtained from nicotine, from beta-picoline, quinoline, pyridine, etc. Nicotinamide can be obtained from nicotinic acid, its esters and from 3-cyano-pyridine. One of the most important analogues of nicotinic acid is 3-acetylpyridine, which is used in animal experiments to reproduce nicotinic acid deficiency, as is another analogue, 6-aminonicotinamide. 3-Acetylpyridine has almost no effect on healthy dogs, since only a small part of it is converted in the body into nicotinic acid, and the majority is excreted in the urine in the form of nicotinate and other compounds. When it was used in experiments on mice at a dose of 3 mg per day, symptoms of nicotinic acid deficiency appeared after 3-4 days.

The toxicity of 3-acetylpyridine LD50 for mice is 300-350 mg/kg, and for rats - 80 mg/kg. The toxicity of 6-aminonicotinamide (LD50 for mice 35 mg/kg) is significantly higher than that of 3-acetylpyridine. At a dose of 2 mg/kg, 50% of the animals died after 11 days.

Isonicotinic acid hydrazide (isonicotinylhydrazide, isoniazid) inhibits the growth of Mycobacterium tuberculosis, which lose about 50% of NAD at a concentration of isoniazid in the medium of 0.1 μg/ml. Based on this, it is successfully used as a treatment for tuberculosis.

Composition and other characteristics

Nicotinic acid (also vitamin PP or vitamin B3) is available in the form of tablets (50 mg of active ingredient each) and injections for injections (aqueous solution of 0.1% concentration). Tablets are produced in packs of 10 or 50 pieces, injections - in glass ampoules.

Vitamin B3 promotes vasodilation, lowering cholesterol and lipid levels. It is an essential, vital substance that is involved in many metabolic processes and is involved in maintaining homeostasis (constancy of the internal environment).

The drug is sold in pharmacies and is dispensed only with a prescription. Can be stored under normal conditions (room temperature, moderate humidity, away from sunlight). The shelf life is 5 years for solution and 4 years for tablets.

Distribution of vitamin PP in nature

Nicotinic acid is quite widespread in plant and especially animal products, which are much richer in nicotinic acid. Of the plant products, the richest are dry brewer's yeast (40 mg%) and baker's press yeast (28 mg%). A significant amount of nicotinic acid is found in grain products. For example, wheat contains over 5 mg%.

The distribution of nicotinic acid in wheat grain is approximately the same as that of thiamine. It is found predominantly in the outer layer of the endosperm, the germ and the bran, with the difference that the bran contains more nicotinic acid and less thiamine than the germ. Wallpaper flour contains all the nicotinic acid, and bread made from it contains 3.5 mg%, in 1st grade flour – 1 mg%, and in bread made from it – 0.7 mg%. Rye is significantly poorer than wheat in terms of vitamin PP - 1.1 mg%. Rye flour contains 1 mg%, and rye bread contains 0.45 mg% nicotinic acid. Corn contains about 2 mg%.

Of the cereals, the richest in nicotinic acid is buckwheat (over 4 mg%), then millet (over 2 mg%), barley (2 mg%), oatmeal (1.6 mg%), pearl barley (1.5 mg%), polished rice (1.6 mg%), semolina - 0.9 mg%.

In corn, as in most other grain crops, 95-98% of nicotinic acid is in a bound form that is not digestible by the body - an ester of a complex structure (niacitin). It is released completely only after alkaline hydrolysis. Nicotinic acid released by alkaline hydrolysis is easily absorbed by the body of animals and humans. Along with this, grain crops such as corn are very poor in tryptophan. This should be taken into account when assessing the content of niacin in diets.

Among other plant products, good sources are legumes, in which nicotinic acid is in digestible form: green peas, lentils, beans, soybeans (2 - 2.5 mg%). A good source of nicotinic acid is coffee beans, which contain from 2 to 10 mg%, depending on the variety and roasting. Peanuts are very rich in nicotinic acid (10 - 16 mg%), then spinach, tomatoes, cabbage, rutabaga, eggplant (0.5 - 0.7 mg%). Potatoes contain 0.9 mg% (boiled 0.5 mg%), carrots - 1 mg%, sweet peppers - 0.9 mg°/0, turnips - 0.8 mg%, red beets - 1.6 mg%, in fresh mushrooms - 6 mg%, in dried mushrooms - up to 60 mg%.

Animal products are very rich in nicotinic acid, with the exception of eggs (0.2 mg%) and milk (about 0.1 mg%). So poultry meat contains 6-8 mg%, lamb -5.8 mg%, beef -4 mg%, veal - over 6 mg%, pork - about 3 mg%, liver - 15-16 mg%, kidney -12 -15 mg%, heart -6 - 8 mg%. Fish is poorer in nicotinic acid than livestock meat. Fresh fish contains on average about 3 mg% nicotinic acid, frozen cod - about 2 mg%, pike - 3.5 mg%, pike perch - 1.8 mg%.

In animal tissues, almost all nicotinic acid is in the form of amide bound to the nucleotides NAD and NADP. In foods of plant origin, the nicotinamide content ranges from 7% (yellow corn) to 70% (potatoes) relative to total niacin. In most products of plant origin, nicotinic acid is distributed mainly in the outer shells. For example, wheat bran contains 330 mcg per 1 g, premium wheat flour - 12 mcg, whole wheat - 70 mcg, polished rice - 0.9 mcg, unpolished rice - 6.9 mcg, rice bran - 96.6 mcg, etc. d.

Nicotinic acid is one of the most stable vitamins in terms of storage and cooking. It is also very resistant to canning processes. In canned food stored for 2 years, its loss does not exceed 15%. There is virtually no loss during freezing or drying. Conventional cooking methods result in losses of 15 to 20% of activity. With some cooking methods, losses reach up to 50%. The composition of the soil can affect the content of niacin in plants. A decrease in the content of major ions in nutrient solutions reduced the content of niacin in oats. Fertilizing the soil with lime or adding nitrates to it increased the content of nicotinic acid in wheat.

special instructions

What is vitamin PP?

Wikipedia answers the question “what is nicotinic acid” that it is a white powdery substance, odorless and slightly sour in taste. The powder dissolves poorly in cold water, ethanol, ether and slightly better in hot water.

The gross formula of the substance is C₆H₅NO₂. It was first obtained in 1867 by the oxidation of nicotine with H2CrO4 (chromic acid).

The benefits and harms of vitamin B3

Pure vitamin B3 can strengthen the immune system so much that the human body acquires natural protection against Staphylococcus aureus and a number of other, no less serious, viruses.

Scientists are confident that very high doses can even stop HIV infection and bacterial infections, against which most existing drugs are powerless.

In addition, vitamin B3 has detoxifying .

The body of an adult man requires from 16 to 28 mg of vitamin B3 , the body of a woman - from 14 to 20 mg.

The need for the vitamin will increase during intense nervous and mental activity, increased physical activity, in people working in a hot shop, in a hot climate and in the Far North, during pregnancy and during breastfeeding, in people whose diets include vegetable proteins over animals (including people fasting and people on a low-protein diet).

Nicotinic acid is necessary for the release of energy from fats and carbohydrates, as well as for the normal course of protein metabolism. It normalizes the functioning of the pancreas and stomach, and is also part of the enzymes that ensure cellular respiration.

The vitamin has a beneficial effect on the heart, blood vessels, nervous system, maintains healthy mucous membranes of the oral cavity and intestines, and skin; takes part in ensuring normal vision, reduces high blood pressure and improves blood circulation.

Some scientists are inclined to believe that vitamin B3 prevents the cancerous degeneration of cells.

A lack of this substance in the body is accompanied by apathy, lethargy, fatigue, headaches, dizziness, dry and pale skin, insomnia, irritability, decreased appetite and body weight, constipation, palpitations, and decreased resistance to infections.

If a person does not receive enough nicotinic acid, he develops the disease pellagra . The first signs of the disease are:

• frequent, watery stools (3 or more times a day, without blood or mucus);
• poor appetite, heaviness in the stomach;
• belching and heartburn;
• redness of the oral mucosa;
• salivation , burning in the mouth;
• swelling and cracking of lips;
• protrusion of the papillae of the tongue with red dots;
• the appearance of deep cracks in the tongue and red spots on the face, hands, elbows and neck;
• swelling of the skin (which may hurt, itch, or form blisters);
• noise in ears;
• severe weakness;
• headache;
• crawling sensation and numbness;
• pressure fluctuations;
• unsteady gait.

Excess vitamin in turn can cause skin rashes, itching and fainting.

Products containing vitamin B3

To prevent hypovitaminosis PP , it is preferable to adjust the diet so that vitamin B3- containing foods are present in the diet.

Where is niacin found? In foods, the greatest amount of vitamin B3 can be found in liver, egg yolk, yeast, nuts, fish, milk, chicken, green vegetables, meat, legumes, ground nuts, buckwheat and any other food containing the α-amino acid tryptophan .

Heat treatment does not affect the amount of vitamin.

Why is Nicotinic acid needed in cosmetology?

Despite the fact that the instructions do not contain recommendations regarding the use of Nicotinic acid for hair growth or facial skin, this product is quite often used in beauty salons.

The rejuvenating effect of the drug is based on the ability of nicotinic acid to dilate blood vessels in the peripheral part of the circulatory system, increase the supply of oxygen to tissues, enhance the outflow and removal of aggressive waste and free radicals from skin cells.

As a result, the skin smoothes out, becomes more hydrated and acquires a beautiful and even color.

Nicotinic acid is also used for hair growth. One course usually requires at least 30 ampoules of solution.

After opening the ampoule, the solution is transferred with a syringe into a small container, after which it is distributed with your fingers (or a syringe without a needle) over the entire scalp: first at the temples and along the hairline, then along the partings. Typically, 1 ml of solution is sufficient for one procedure (this corresponds to the contents of 1 ampoule).

It is very important that your hair is clean, since a build-up of dust and grease will prevent the product from being absorbed into the scalp. Before using the drug, you should not use shampoos with silicones to wash your hair, as they will create a barrier for the drug to penetrate into the tissue.

Nicotinic acid is destroyed quite quickly in air, so the procedure should be performed as quickly as possible. An open ampoule cannot be stored.

Normal reactions to the drug are a slight burning sensation, a crawling sensation, redness and burning of the skin.

The appearance of hives, rashes, itching, and headaches indicate intolerance to nicotinic acid. If these symptoms occur, you should wash your hair and stop using the product further.

If, after using Nicotinic acid for hair, the scalp becomes dry or appears, it is recommended to dilute the solution with water in a 1:1 ratio. Such reactions are a consequence of skin sensitivity. Aloe juice can also be used as an alternative to water .

Once the solution is completely applied, the procedure is considered complete. Repeat it daily for a month. There is no need to wash off the drug.

After completing the course, almost all girls note hair growth of 3 cm.

An injection solution of Nicotinic acid has also found use as a remedy for cellulite. Before the procedure, the contents of one ampoule are diluted in 3 ml of water. Then a wide bandage is moistened in the resulting solution and tightly - but not tightly! - wrap it around problem areas.

This method is most effective in getting rid of cellulite on the thighs and abdomen, since these are the areas of the body that are most convenient to bandage. But to eliminate cellulite on the buttocks, it is recommended to use other means.

The bandages are wrapped in cling film and a towel (for insulation). Instead of a towel, you can use a blanket or blanket.

The duration of the first procedure should not exceed 15 minutes. If the skin responds well to the drug and there are no side effects, the time may be increased in the future.

Precautionary measures

It should be borne in mind that nicotinic acid injections are painful.

During treatment, it is necessary to constantly monitor liver function, especially if the patient is prescribed high doses of vitamin B3 .

To prevent hepatotoxicity, it is recommended to introduce a sufficient amount of methionine- foods into the patient’s diet (milk, dairy products, buckwheat, legumes, fish) or prescribe him to take lipotropic drugs (including methionine ).

Nicotinic acid, given its ability to irritate the mucous membrane, is used with caution for peptic ulcer disease (in remission) and hyperacid gastritis . If it is necessary to prescribe the drug in these cases, taking large doses is contraindicated.

To reduce the irritating effect on the mucous membrane of the digestive tract, it is recommended to take the tablets with milk.

Due to the likelihood of hepatotoxicity, taking high doses of vitamin B3 is also contraindicated for liver diseases (including hepatitis and cirrhosis ) and diabetes mellitus .

The use of the drug for the correction of dyslipidemia in diabetes mellitus is inappropriate.

Methods for determining vitamin PP

The chemical method of determination is based on the use of a reaction with bromine cyanide and then with an aromatic amine. The resulting colored compound is measured photometrically. The reaction proceeds in two stages: obtaining a pyridine derivative by reacting nicotinic acid with bromine cyanide and obtaining a colored dialdehyde compound by reacting with an aromatic amine.

Nicotinic acid is also determined by microbiological methods, most often using the culture of Lactobacillus arabinosus and subsequent turbidimetric determination, as well as with the protozoan Tetrahymena pyroformis. Neither niacin nor nicotinamide fluoresce by themselves, but they can be converted into fluorescent compounds. Such methods are widely used to determine the coenzyme forms of nicotinamide - NAD and NADP. The main metabolic product of nicotinic acid, Nl-methylnicotinamide, is also determined by the fluorimetric method. In various exchange reactions associated with the transfer of hydrogen, pyridine nucleotides, being coenzymes of specific dehydrogenases, act in both oxidized and reduced forms.

In the reduced form, the maximum of the absorption spectrum is in the ultraviolet region at 340 nm. Reduced pyridine nucleotides fluoresce when irradiated with ultraviolet rays. Thus, NADP-H has two absorption spectrum maxima at 260 and 340 nm and one fluorescence spectrum maximum at 457 nm. A parallelism was noted between the presence of fluorescence and the biological activity of the reduced coenzyme.

The most common, rapid, sensitive and simple method for determining nicotinic acid metabolites is the determination of Nl-methylnicotinamide in urine. This method is based on the condensation reaction of Nl-methylnicotinamide with acetone in the presence of alkali with the transition to a fluorescent derivative. In this way, 0.3 μg can be determined in 1 ml of diluted urine. Another metabolite excreted in the urine, 6-pyridone Nl-methylnicotinamide, is also determined fluorometrically.

The content of NAD and NADP in erythrocytes is also determined fluorimetrically, based on the method proposed for their determination in urine. For this purpose, blood proteins are precipitated with trichloroacetic acid. Condensation then occurs with acetone in the presence of an alkali, giving a fluorescent compound that is quantified. The content of NAD and NADP in tissues is also determined.

Why are nicotinic acid injections prescribed?

Nicotinic acid is indicated for the prevention of vitamin deficiency associated with insufficient intake of vitamin B3. The product is recommended for the prevention and treatment of the following diseases:

• atherosclerosis;
• cerebral vascular ischemia;
• diabetic type polyneuropathy;
• colitis, enterocolitis;
• trophic ulcers;
• long-term non-healing wounds;
• Raynaud's disease;
• facial nerve neuropathy;
• spasms of the ureters and bile ducts.

Metabolism of vitamin PP in the body

The fate of nicotinic acid entering the body depends on the type of food and the products it contains. As mentioned above, nicotinic acid, found in a number of grain products in the form of an ester - niacitin, is 95-96% not absorbed by the body of humans, dogs and rats, while niacin, found in animal and legume products, is absorbed by them entirely.

The human, dog and pig body is not able to synthesize nicotinic acid in the quantities necessary to cover the body's need for it, and therefore constantly needs to obtain it from food. Some mammals, such as rats, horses, cows and sheep, can synthesize niacin.

The source of nicotinic acid is tryptophan. Since 1945, a number of works have described the individual stages of the synthesis of nicotinic acid from tryptophan in mammals. There are two ways of endogenous synthesis of niacin in the body of animals: microbial synthesis in the intestines and biosynthesis in tissues. The main transformation of L-tryptophan follows the path of cleavage of its pyrrole ring by tryptophan pyrrolase with the formation of formyl-kynurenine, from which kynurenine and 3-hydroxykynurenine are formed, which are one of the main products of tryptophan dissimilation in the body. 3-hydroxykynurenine is further converted to 3-hydroxyanthranilic acid. After the inclusion of two oxygen atoms, 2-acroleyl-3-aminofumaric acid and quinolinic acid, which is a precursor of nicotinic acid, are formed. As a result of a series of intermediate reactions, nicotinic acid and Nl-methylnicotinamide are formed in omnivores and humans.

With a balanced diet, only a small part of tryptophan is excreted from the body of animals and humans in the urine in the form of specific products of its breakdown. When tryptophan is loaded in the urine, significant quantities of its metabolic products, such as kynurenine, 3-hydroxykynurenine, kynurenic and xanthurenic acids, are released in the urine. The participation of vitamin B6 in tryptophan metabolism in mammals was assumed due to the discovery of xanthurenic acid, one of the products of tryptophan metabolism, in the urine of vitamin B6 deficiency. In addition, a number of authors observed that in case of vitamin B6 deficiency in animals, a decrease in the concentration of NAD and NADP in red blood cells and a decrease in the excretion of Nl-methylnicotinamide in the urine.

It turned out that a derivative of vitamin B6, pyridoxal phosphate, is a coenzyme of kynureninase, involved in the hydrolytic breakdown of kynurenine and 3-hydroxykynurenine. Violation of the kynureninase reaction due to vitamin B6 deficiency leads to disruption of the synthesis of 3-hydroxyanthranilic acid and a decrease in the formation of nicotinic acid.

Nicotinic acid entering the body of humans and omnivores and carnivores is converted to nicotinamide and then methylated to Nl-methylnicotinamide, which is partially oxidized to Nl-methyl-2-pyridone-5-carboxamide. From 40 to 50% of the ingested nicotinic acid is released in this form. In herbivorous animals, nicotinic acid does not transform into amide and is excreted in the urine in free or bound form, and nicotinamide found in the food of these animals is excreted in the form of nicotinic or nicotinuric acids. Methylation of nicotinamide occurs by adding a methyl group to the nitrogen of the pyridine ring. Nl-methylnicotinamide has an adsorption maximum in ultraviolet rays of 264.5 nm. Nl-methylnicotinamide 6-pyridone - 260 and 290 nm.

Calculation of urinary excretion of nicotinic acid metabolites in people receiving various amounts of vitamin PP and tryptophan showed that on average from 55 to 60 mg of tryptophan contained in food is equivalent to 1 mg of nicotinic acid.

Horwitt suggested calling 1 mg of niacin, or 60 mg of tryptophan, "niacin equivalent." Thus, from 1.9 to 5% (on average 3.3%) of tryptophan is converted into nicotinic acid.

Food sources[edit | edit code]

Sources of niacin include liver, meat, fish, poultry, nuts and beans, as well as bread and cereals, primarily enriched or coarsely ground. Animal protein is especially rich in tryptophan. Absorption, exchange and excretion. Both nicotinic acid and nicotinamide are easily absorbed in all parts of the intestine and enter all tissues. When therapeutic doses of nicotinic acid or nicotinamide are administered, only small amounts of these substances appear unchanged in the urine, whereas when very large doses are administered, both compounds are excreted in the urine largely unchanged. Nicotinic acid and nicotinamide are converted in the body mainly into N-methylnicotinamide, which undergoes further metabolic transformations. Application. Nicotinic acid, nicotinamide and their derivatives are used for the prevention and treatment of pellagra. Exacerbation of pellagra requires intensive treatment. It is recommended to take these drugs 50 mg orally up to ten times a day. If oral administration is not possible, the drug is administered 25 mg IV 2 times a day or more often. Symptoms of pellagra can appear with two types of metabolic disorders. In Hartnup's disease, tryptophan transport in the intestines and kidneys is impaired. In some cases of carcinoids, large amounts of tryptophan are consumed by tumor cells for the synthesis of 5-hydroxytryptophan and serotonin.

The effect of the introduction of nicotinic acid and its derivatives is observed very quickly. Within 24 hours, severe redness and swelling of the tongue disappear, and steatorrhea decreases. Lesions in the mouth and other mucous membranes heal quickly. Within 24 hours, nausea, vomiting and diarrhea may stop, and discomfort in the epigastrium disappears. abdominal pain and bloating. Appetite improves. Sometimes mental symptoms subside overnight. Confused consciousness clears up, patients calm down, begin to perceive their surroundings and become aware of their condition. Nicotinic acid and its derivatives have such a specific effect in this regard that they can be used as diagnostic agents for overt psychoses in the absence of other signs of pellagra. It is recommended to use large doses of nicotinic acid, especially when psychosis is combined with encephalopathy. Skin lesions, especially those that are weeping, hyperpigmented, and ulcerated, respond more slowly to treatment. The porphyrinuria characteristic of pellagra disappears.

Pellagra can be combined with vitamin B1 deficiency manifested by neuropathy. Vitamin B1 deficiency cannot be treated with nicotinic acid and its derivatives; in such cases, thiamine should be used. The condition of many patients with pellagra is also improved by additional administration of riboflavin and pyridoxine.

Nicotinic acid in gram doses reduces the concentrations of cholesterol and LDL triglycerides, fibrinogen and lipoprotein(a) in plasma. Therefore, it is used for hyperlipoproteinemia (Chapter 36).

Promising results have been obtained with the use of nicotinamide for the prevention of insulin-dependent diabetes mellitus in at-risk groups (Elliott et al., 1996; Lampeter et al., 1998). Extensive research into this problem is currently underway.

Participation of vitamin PP in metabolism

Nicotinic acid and nicotinamide are substances necessary for the life of all animal and plant cells. They are part of the coenzymes NAD and NADP and, together with apoenzymes, catalyze the redox reactions of cellular metabolism. This role of nicotinic acid was established even before its value as vitamin PP was discovered. NAD was discovered back in 1905, in 1933 its adenine nucleotide structure was established, and in 1936 NAD in its pure form was isolated from brewer's yeast. It is a white amorphous powder, slightly soluble in phenol and methanol with hydrochloric acid. In ultraviolet rays it has an absorption spectrum of 260 and 340 nm.

NAD is a dinucleotide consisting of nicotinamide, two molecules of ribose, two molecules of phosphoric acid and adenine. NADP has a similar property to NAD to interact with hydrogen and the same absorption spectrum. It contains one molecule of nicotinamide, two molecules of ribose, one molecule of adenine and three molecules of phosphoric acid, differing from NAD by the presence of one phosphoric acid residue at the second position of adenosine.

NAD and NADP are found in all cells of the body of animals and plants. As an example, a table of their content in the tissues of rats is presented.

Interaction with other drugs

Vitamin PP enhances the effect of drugs with vasoactive effects, which can lead to a decrease in blood pressure. Concomitant use with bile acid skewestrants is not recommended - they should be used at least 1 hour apart.

Niacin may cause hyperglycemia, so patients should monitor their blood sugar levels. In case of simultaneous use with Amlodipine and Atorvastatino, the risk of developing myopathy may increase. Also, vitamin PP is not recommended to be used together with vitamin C.

It is worth considering that simultaneous use with nicotinic acid reduces the effectiveness of such drugs:

• "Gliquidone";
• "Repaglinide";
• "Insulin Lizpro";
• "Phenobarbital";
• "Metformin";
• "Glipizide".

Requirement of humans and animals for vitamin PP

We see that NAD is found in tissues in much larger quantities than NADP. Based on their content in tissues, one can judge the intensity of participation of these coenzymes in metabolism. In cells, the NAD/NAD-H2 ratio is higher than the NADP/NADP-H2 ratio. NAD and NADP in cells, based on the calculation of the enzymatic activity of the entire homogenate, are contained in greater quantities in the nucleus, where their synthesis occurs, and in smaller quantities in mitochondria and microsomes. The enzyme NAD-pyrophosphorylase is part of the enzymes of the cell nucleus, NAD-H -cytochrome C-reductase and NADP-H-cytochrome C-reductase - part of the enzymes of the nuclear membrane itself, NAD-H-dehydrogenase, NAD-H-cytochrome C-reductase, NAD-H-cytochrome B5-reductase, NAD-H- oxidase and NAD- and NADP-isocitrate dehydrogenase - in the composition of mitochondrial enzymes, NAD-H-cytochrome C-reductase, NAD-H2-oxidase, NADP-H2-cytochrome C-reductase - in the composition of enzymes of the endoplasmic reticulum. Thus, NAD and NADP participate as coenzymes in a number of very important enzyme metabolic systems in humans and animals. However, due to the structural features of the protein components of dehydrogenases, the connection of the coenzymes NAD and NADP with these enzymes is less strong than other vitamin-containing enzymes. As a result, NAD and NADP can take part in many oxidation and reduction reactions, migrating from one apoenzyme to another.

The nucleotides NAD and NADP, containing nicotinic acid amide as a catalytically active group, are among the most universal coenzymes in terms of distribution and biological role.

One of the most characteristic physical properties of nicotinamide coenzymes is the presence of reduced forms (NAD-H2 and NADP-H2) of an absorption band in ultraviolet light with a maximum at 340 nm. Excitation of NADP-H2 by radiation with this wavelength leads to the appearance of fluorescence with a maximum at 480 nm.

Spectrophotometric and spectrofluorimetric methods based on these properties are used for the analytical determination of nicotinamide coenzymes, as well as for measuring the activity of associated dehydrogenases.

With the participation of nicotinamide coenzymes, specific dehydrogenases catalyze the reversible reactions of dehydrogenation of alcohols, hydroxy acids and some amino acids into the corresponding aldehydes, ketones and keto acids. Currently, the properties of a large number of enzymes containing nicotinamide as a coenzyme have been isolated and studied.

The most important of these enzymes are:

1. Alcohol dehydrogenases (EC 1.1.1 -2).

R-CH2—OH+NAD (or NADP)—R-CHO + NAD-H (or NADP-H) + H+

2. Aldehyde dehydrogenases (EC 1.2.1.3-5)

R-CHO+H2O+NAD (or NADP)—-R-COOH+NAD-H (or NADP-H) + H+

3. Glucose dehydrogenase (EC 1.1.1.47).

D-glucose + NAD (or NADP) - delta-lactone-D-gluconic acid + NAD-H (or NADP-H) + H+

4. D-glucose-b-phosphate dehydrogenase (EC 1.1.1.49)

D-glucose-b-phosphate + NADP—-delta-lactone-6-phosphate of D-gluconic acid + NADP-H + H+

5. L-glutamic acid dehydrogenase (EC 1.4.1.2-4)

L-glutamic acid + NAD (or NADP) + H2O—— alpha-ketoglutaric acid + NH+ + NAD-H (or NADP-H)

6. L-glycero-3-phosphate dehydrogenase (EC 1.1.1.8)

L-glycero-3-phosphate + NAD - dioxyacetone phosphate + NAD-H + ​​H+

7. Lactic and malic acid dehydrogenase (EC 1.1.1.27-28; 1.1.1.37-40)

R-CHOH—COOH + NADP—— R—CO—COOH + NADP-H + H+

The most important biological function of nicotinamide coenzymes is their participation in the transfer of electrons and hydrogen from oxidizing substrates to oxygen during cellular respiration. NAD and NADP molecules in oxidized form have pronounced acceptor properties, regardless of whether they are obtained by biosynthesis or chemically. It can be concluded that the mechanism of chemical action of these coenzymes is based on the high electron affinity of nicotinamide. Based on quantum mechanics, this is determined by its lowest free molecular orbit. In oxidized forms, NAD and NADP are strong electron acceptors. Since their highest filled orbit is low, they are weak electron donors. For the reduced forms of NAD and NADP, the orbital energies have an inverse relationship, so coenzymes in the oxidized form tend to capture electrons, and in the reduced form, to give them away. We see this in the example of a number of compounds in the formation of which NAD is involved.

Thus, the coenzyme functions of NAD and NADP manifest themselves mainly in redox reactions, in the reversible addition of a hydrogen atom. The main function of coenzymes is expressed in the reversible transformation of the pyridine ring into a 1,4-dihydropyridine ring.

When the pyridine ring is hydrogenated, its light absorption changes. The dihydropyridine system has an absorption maximum at 340 nm, while the pyridine system has almost no absorption in this region. In dehydrogenation processes that are catalyzed by nicotinamide coenzymes, the substrate donates two hydrogen atoms (2H or 2H+ + 2e), but only one H atom joins the coenzyme molecule (in the fourth position of the pyridine ring), and the second H atom gives an electron to the coenzyme and turns into H+ (proton). It has been established that the transfer of the H atom from the substrate to NADP occurs directly and stereospecifically for a given enzyme, always in one direction of the plane of the pyridine core of NADP. Depending on the direction of addition of the hydrogen atom, all dehydrogenases containing NAD are divided into two types - A and B.

Type A includes dehydrogenases of alcohols, L-lactate, L-malate, D-glycerate, acetaldehyde, etc., while type B includes dehydrogenases of L-glutamate, D-glucose, D-glycero-3-phosphate, D-glyceraldehyde -3-phosphate, beta-hydroxysteroids, etc. An example of the step-by-step inclusion of NAD, NAD-H2, NADP and NADP-H2 in the course of enzymatic reactions is the Krebs citric acid cycle. This cycle serves as the crossing point for all important metabolic reactions in which nicotinamide adenine dinucleotides take part.

In some enzymatic reactions, for example in the reaction of anaerobic breakdown of glucose, there are 2 enzymes - lactate dehydrogenase and phosphoglycerin aldehyde dehydrogenase, which are connected by the NAD-NAD-H2 system. This reaction is reversible and its direction is determined by the coefficient NAD/NAD -H2 and the concentration of substances in the reaction.

A special group of enzymes are transhydrogenases, which catalyze reactions between NAD and NADP-H2 towards the dehydrogenation of NADP-H2 at the expense of NAD.

With the help of a specific dehydrogenase, the coenzyme of which is NADP, folic acid is converted into tetrahydrofolic acid (see section “Folic acid”).

A special issue is the structure of the molecule NAD-H, which is a dihydropyridine, having two main types containing an alkyl group at position 1: 1-alkyl-1,2-dihydropyridines and 1-alkyl-1,4-dihydropyridines.

Dihydropyridines containing a urea group in the 3rd position are of greatest biological importance. These compounds have three isomers: 1,2, 1,4 and 1,6.

Nicotinic acid in ampoules: side effects

Vitamin B3 leads to increased histamine secretion. This can lead to allergic reactions and other side effects:

• low pressure;
• redness of the skin (usually on the face and upper half of the body);
• burning, tingling;
• increased secretion of gastric juice;
• hives;
• itching;
• rush of blood to the head area.

If the course of treatment lasts several months, other negative consequences may occur:

• liver dysfunction;
• diarrhea;
• vomit;
• paresthesia;
• anorexia;
• heart rhythm disturbance;
• hyperglycemia;
• decreased glucose tolerance;
• formation of ulcers on the gastric mucosa;
• increased activity of individual enzymes.