Nicotine and nicotinic acid: synonyms or different concepts

Remember when we were scared as children that a drop of nicotine would kill an adult healthy horse? It was an unsuccessful attempt to explain that smoking is bad. But for many this information did not leave a response in the soul. A horse in a city is an almost fabulously rare creature. And a drop of nicotine seemed bad.

At a doctor’s appointment, you may find “nicotinic acid” in a set of prescriptions. The question arises: are nicotine and nicotinic acid the same substance or different? Maybe the doctor wants to harm us, not cure us?

Nicotine - what is it?

Most nicotine is found in tobacco.

Nicotine is a natural alkaloid. Contained mainly in green plants of the nightshade family.

The maximum concentrations of this substance are found in tobacco and shag. In the latter, the proportion of this alkaloid varies from 7 to 14%.

This substance is present in lower concentrations in tomatoes, peppers, and eggplants. Nicotine alkaloids are also found in coca leaves.

Nicotine is a powerful insecticide. And in the recent past, it was widely used to treat plants against pests. Currently, derivatives of this substance are used as insecticides.

Initially, tobacco was prescribed as a medicine for pathological headaches - migraines. Later, a mixture of natural alkaloids was obtained by sublimation. The organic extract was used in the treatment of asthma, inflammatory processes in the spleen, and to relieve epileptic seizures.

In appearance, nicotine in its pure form is an oily liquid. It is very hygroscopic and mixes with water in any proportions.

Methods

The databases MEDLINE, Embase, Cochrane Controlled Clinical Trial Register (Central), ClinicalTrials.gov and TrialResults-center (up to October 2017) were searched for studies.

The systematic review included clinical studies evaluating the use of the drug for the treatment of cardiovascular diseases. The meta-analysis included randomized clinical trials that assessed at least 1 long-term cardiovascular effect of niacin.

As primary endpoints

included cardiovascular disease, mortality from ischemic heart disease, as well as acute coronary syndrome, non-fatal and fatal stroke, revascularization and major adverse events.

The harm of nicotine

Nicotine is a very harmful substance.

Nicotine is a dangerous neurotoxin. When poisoned, it causes cardiac arrest and paralysis of the nervous system.

The average lethal dose for humans is in the range of 0.5–1 mg per 1 kg of body weight. That is, for a man weighing 75 kg, 35 to 75 mg of this alkaloid is enough. So, indeed, a drop of pure nicotine will kill not only a horse, but also an elephant.

When smoking leaves of nicotine-containing plants, physical dependence develops. Constant contact with an alkaloid provokes pathologies of the heart and blood vessels, oncopathologies of the respiratory system and oral cavity, inflammatory processes in the gums, and stomatitis.

PRINCIPLES OF TREATING lipid metabolism disorders

I. A. Libov, Candidate of Medical Sciences D. A. Itkin S. V. Cherkesova

RMAPO, Moscow

The need to correct lipid metabolism disorders is currently beyond doubt. Numerous studies conducted before the beginning of the 90s have proven the possibility of reducing cholesterol (CH), triglycerides (TG) and normalizing lipid metabolism parameters against the background of cholesterol-lowering therapy.

But does a pronounced decrease in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) always improve life prognosis?

The CARE study showed that reducing LDL-C below 3.2 mmol/L did not lead to a further reduction in mortality. At the same time, according to the POST-CABGT study, which included patients after coronary artery bypass surgery (CABG), when LDL cholesterol was reduced to a level of less than 2.6 mmol/l (compared to patients with a level of 3.4-3.5 mmol /l) the need for repeat CABG operations is reduced by 29%. Similar results were obtained in the CARS study, which included patients with coronary artery disease, a relatively normal level of TC (from 4.1 to 5.6 mmol/l) and an average level of LDL-C (3.17 mmol/l). Currently, European cardiologists consider achieving an LDL cholesterol level of less than 3.0 mmol/l as the goal of cholesterol-lowering therapy for secondary prevention of coronary artery disease, and American cardiologists consider it to be less than 2.6 mmol/l.

The effectiveness of both drug and non-drug methods for correcting the level of dyslipidemia has been shown. Moreover, any correction should begin with the elimination of risk factors that contribute to the progression of atherosclerosis, such as smoking, physical inactivity, as well as with the normalization of body mass index.

In cases of dyslipidemia occurring against the background of diseases such as hypothyroidism, nephrotic syndrome, etc., it is necessary first of all to begin treatment of the underlying disease.

One of the main methods of non-drug treatment is following a diet with limited consumption of animal fats and easily digestible carbohydrates, and limiting caloric intake. In the Veterans Administrations study, patients were prescribed a diet higher in polyunsaturated fatty acids and lower in animal fat (compared to patients on a standard North American diet). Diet therapy for eight years led to a decrease in TC levels by 12.7% and a decrease in the incidence of myocardial infarction (MI) by 20%. However, there was no decrease in overall mortality in any of the groups of patients. In the Finnish Mental Hospital Study, over a six-year observation period in 450 patients of both sexes aged 34-64 years, a low cholesterol diet showed a 15% decrease in cholesterol levels in the blood. At the same time, achieving an average TC level of 5.8 mmol/l did not cause a significant reduction in overall mortality or mortality from cardiovascular diseases. In the DART study, which included more than 2,000 patients with a mean age of 56.5 years, adherence to the diet for two years resulted in a non-significant reduction in overall mortality and mortality from coronary artery disease. However, ischemic events (non-fatal MI) were even more common in the group of patients on the diet. The largest study, the Minnesota Coronary Survey, included approximately 5,000 patients of both sexes and all ages with an average baseline TC level of 5.3 mmol/L, and found that following a cholesterol-lowering diet alone resulted in a 14.5% reduction in TC levels over 4.5 years. compared to a control group following a standard diet. This study also did not show a reduction in cardiovascular disease or overall mortality.

In our opinion, treatment of patients with hypercholesterolemia and hypertriglyceridemia must in all cases begin with the elimination of risk factors and the appointment of a hypocholesterolemic diet. Moreover, if the diet is effective, then it can be considered as monotherapy only if the patient is truly able to follow the diet for the rest of his life. However, in patients with coronary artery disease during an exacerbation of the disease and in the presence of severe hypercholesterolemia, along with diet, simultaneous administration of cholesterol-lowering drugs in adequate doses is recommended. Normalizing the level of lipid metabolism indicators only on the background of diet in such patients is not possible, and untimely initiation of treatment can lead to the development of adverse complications.

In the absence of an “acute” situation, the failure of non-drug therapy for three months is an indication for drug therapy. It should be noted that the use of lipid-lowering drugs, no matter what class they belong to, in no case means a refusal to follow a diet. On the contrary, any cholesterol-lowering therapy will be effective if you follow a diet.

Currently, there are five main classes of drugs used, taking into account their mechanism of action, effectiveness and side effects, as well as contraindications for a particular type of dyslipidemia.

I Statins. II Nicotinic acid and its derivatives. III Fibrates. IV Bile acid sequestrants. V Antioxidants.

To date, the effect on overall mortality, mortality from cardiovascular diseases and the risk of developing cardiovascular complications has been proven only for drugs from the statin group. The action of these drugs is based on inhibition of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-co-A) reductase. By inhibiting cholesterol biosynthesis in the liver and intestines, statins reduce intracellular cholesterol reserves. This causes the formation of an increased number of receptors for LDL and accelerates their removal from the plasma.

Other mechanisms of action of statins on vascular endothelium and platelet aggregation have not been fully studied.

The effect of statins is primarily aimed at reducing LDL cholesterol and total cholesterol. Recent work has shown that the use of high doses of statins can significantly reduce triglyceride levels and compete with the effect of fibrates.

To date, the following drugs from the statin group are registered in Russia:

• lovastatin (Mevacor, Merck Sharp & Dohme)
• simvastatin (Zocor, same company)
• pravastatin (lipostat, Bristol Mayer Scweeb)
• fluvastatin (lescol, Novartis)
• Atorvastatin (Liprimar, Pfizer)
• cerivastatin (lipobay, Bayer)

According to WC Roberts (1997), a 10 mg dose of simvastatin is approximately equivalent to 20 mg of lovastatin or pravastatin and 40 mg of fluvastatin. According to his studies, doubling the statin dose relative to the initial dose leads to an additional reduction in TC by approximately 5% and LDL-C by 7%. However, the increase in high-density lipoprotein cholesterol (HDL-C) levels does not depend on increasing the dose of the drug.

Drugs from the statin group are used for primary and secondary prevention of coronary artery disease. Secondary prevention refers to the use of drugs in patients with proven coronary artery disease.

It seems to us that the greatest effectiveness when prescribing statins should be determined not only by the level of initial indicators of lipid metabolism, but also by a combination of the total risk of developing cardiovascular complications and the clinical course of the disease. Thus, in patients with acute coronary syndrome, the clinical effect of statins may be more pronounced than in patients with stable angina, and tactics should be more aggressive. However, these conclusions are based on our practical experience; they have not yet been confirmed in multicenter randomized studies.

Statins, like aspirin and β-blockers, are drugs that affect the prognosis of the disease in patients with coronary artery disease.

The effectiveness of statins has also been proven in studies on primary prevention.

Studies 4S, CARE, LIPID, WOSCOPS, AFCAPS/TEXCAPS and others demonstrate the effectiveness of statin therapy for secondary and primary prevention of coronary artery disease. At the same time, the effect of statins on “endpoints” in secondary prevention is more pronounced and more economically justified. Therefore, the use of statins in patients with diagnosed coronary artery disease in combination with dyslipidemia can be recommended to all patients. The effectiveness of statin therapy is higher in the group of patients with more severe lipid metabolism disorders. The development of “coronary events” in a number of patients with coronary artery disease against the background of normal values ​​of lipid metabolism indicates the multifactorial nature of the genesis of these complications and emphasizes the importance of not only the level of dyslipidemia, but also a combination of a number of factors, the most important of which are the clinical manifestations of exacerbation of the disease.

One of the possible reasons for the effectiveness of cholesterol-lowering drugs in the prevention of coronary artery disease is their ability to slow down the progression and even the possibility of regression of the atherosclerotic process, demonstrated in a number of studies. These effects were studied by measuring vessel diameter using arteriography or intravascular ultrasound.

In the MAAS study in patients with coronary artery disease, treatment with simvastatin at a dose of 20 mg for four years revealed a statistically significant reduction in the development of new coronary artery stenoses and regression of existing coronary stenoses; The lumen of the vessels increased from 0.06 to 0.17 mm in the presence of an initial stenosis of more than 50%.

Slowing the progression or regression of atherosclerosis is achieved through intensive and aggressive cholesterol-lowering therapy with a significant reduction in LDL-C levels. Simvastatin and atorvastatin have the greatest hypocholesterolemic activity in the same dosage. In the SMAC study, the use of atorvastatin and simvastatin at a dose of 10-20 mg per day allowed almost 50% of patients with coronary artery disease and an initial LDL-C level of 4.2 to 7.8 mmol/l to achieve the target level after 52 weeks of treatment. At the same time, the effect of atorvastatin occurred somewhat faster, and after 16 weeks of treatment it was achieved in 46% of patients compared to 27% during treatment with simvastatin. By the end of the year, this difference leveled out, amounting to 50% during treatment with atorvastatin and 48% during treatment with simvastatin, and was statistically insignificant. This study showed a pronounced hypocholesterolemic effectiveness of both statins and approximately the same effect after a year of treatment with both drugs. However, in most European countries the cost of simvastatin was slightly lower than that of atorvastatin. In this study, no serious side effects requiring drug discontinuation were observed.

Another important lipid-lowering agent used to normalize lipid metabolism is nicotinic acid and its derivatives (niacin). According to V. Parson, the advantage of this group of drugs is that “they do everything as it should.” Along with reducing the level of TC and LDL-C, drugs in this group reduce triglyceride levels and are more successful than any other lipid-lowering drugs in increasing the level of HDL-C. These drugs also have a number of other advantages. For example, they reduce the level of lipoprotein "a", which is given great importance as an important independent risk factor for the development of complications such as heart attack and stroke. Nicotinic acid preparations and its derivatives reduce LDL levels, acting primarily on their small, most atherogenic particles. These drugs increase HDL-C levels at the expense of the HDL2 fraction, which is the most active in removing lipids from plaques, and thereby prevent the progression of atherosclerosis.

A number of studies have shown the possibility of reducing cardiovascular complications and overall mortality with the use of niacin.

The US Cardiovascular Drug Program compared a number of cholesterol-modifying drugs. The study was conducted in men 30-65 years old who had a history of at least one heart attack. The effects of estrogens, thyroxine, clofibrate and niacin were studied. Each group consisted of approximately 1,100 patients, and the placebo group was twice as large. The expected duration of the study was 5 years, but for the first two drugs it was stopped early due to the development of a large number of heart attacks and other complications. Clofibrate did not have a beneficial effect on mortality or cardiovascular events. Thus, nicotinic acid was the only drug that was able to reduce the number of non-fatal heart attacks by approximately 27%, strokes by 24%, the number of hospitalizations for cardiovascular complications by 12%, and the need for surgical treatment of the heart and blood vessels. by 46%.

The trend towards a decrease in mortality, observed over 5 years of observation while taking niacin, turned out to be statistically insignificant.

An important advantage of this group of drugs is their relatively low cost compared to other lipid-lowering drugs. Currently, slow-release forms of niacin are most often used. They provide a longer and more gradual release of the active compound and cause a significant reduction in side effects. These drugs include:

• combination of nicotinic acid with polygel;
• nicotinic acid in capsules with an inert filler;
• nicotinic acid in a tropical wax matrix (the drug enduracin, which is most widely used in a dose of 500 mg three times a day.

The effectiveness of these drugs also varies somewhat. According to Figge et al. (1988), the bioavailability of extended-release niacin preparations having a wax matrix is ​​almost twice as high as that of dosed-release niacin. Therefore, the effectiveness of enduracin at a dose of 1500 mg per day in relation to LDL-C and HDL-C, according to D. Keenan, was even slightly greater than when taking 3000 mg of extended-release niacin.

Large-scale studies comparing the efficacy characteristics, dosage, and side effects of various long-acting forms of nicotinic acid are still lacking.

The maximum daily dose of nicotinic acid preparations should not exceed 6 g, and for enduracin - 3 g. Increasing the dose did not lead to improved results, and the number of side effects may increase. A common feature of all nicotinic acid preparations is the need to gradually increase the dose under the control of lipid metabolism levels, even if they are well tolerated. Most often, treatment begins with a dose of 500 mg per day for a week, then 500 mg twice a day for another 1-3 weeks, and then the dose is adjusted depending on lipid metabolism. To reduce adverse reactions, drugs are used with meals, limit the consumption of hot drinks, and when the first signs of hyperemia appear, small doses of aspirin (100-325 mg) are added, which helps reduce these manifestations in the first 3-4 days until they disappear completely.

The most common side effects when taking niacin are hot flashes and skin itching, as well as feelings of hyperesthesia and paresthesia; constipation, diarrhea, dizziness, palpitations, impaired accommodation, dry skin or impaired pigmentation. All these side effects range from 2 to 7%

(D. Keenan) and do not differ significantly from side effects in the placebo group. Typically, biochemical tests are performed every four weeks to monitor for unwanted liver complications. The appearance of nausea, vomiting or other ailments requires temporary discontinuation of the drug and additional study of liver tests. At the same time, a slight increase in the levels of AST, ALT, LDH, GGTP during treatment with niacin is allowed. In addition to liver tests, when treating with nicotinic acid preparations, the level of sugar and uric acid should be regularly monitored.

The use of other groups of drugs, such as fibrates, ion exchange resins (bile acid sequestrants) and antioxidants, also allows, in a number of cases, to improve impaired lipid metabolism. However, to date, no data have been obtained on their effect on overall mortality, mortality from cardiovascular diseases, the development of cardiovascular complications, the need for surgical treatments, the frequency of hospitalizations, etc. Recent large-scale studies on the use of fibrates and antioxidants may make it possible to more accurately determine their role and place in the treatment of dyslipidemia in a wide range of patients.

For literature inquiries, please contact the Department of Therapy and Adolescent Medicine of the Russian Medical Academy of Postgraduate Education at tel.

A nicotinic acid. A little biology and chemistry

Nicotinic acid or vitamin PP - this substance takes an active part in metabolic processes in the body, regulates fat metabolism, and promotes the production of enzymes.

In its natural state it is found in bread, meat products, buckwheat, mushrooms, vegetables and fruits.

A lack of this substance leads to hypovitaminosis. In this case, pellagra develops. Without proper treatment, this disease ends sadly. In addition to vitamin deficiency, the following organs and systems suffer from a lack of vitamin PP:

1. blood cell synthesis is disrupted;
2. the production of bile and gastric juice decreases;
3. hormonal imbalance occurs;
4. neuralgia of various parts of the nervous system develops;
5. impaired control of blood sugar and cholesterol;
6. Pregnant women experience disturbances in the development of the nervous system of the unborn baby.

Drug interactions

Nicotinic acid is used with caution simultaneously with other vasoactive drugs, since it enhances the effect of vascular relaxation, which causes a drop in blood pressure.

Concomitant use with bile acid sequestrants is also dangerous, since they also reduce cholesterol in the blood. If there is a need for both drugs, nicotinic acid should be taken no earlier than an hour after taking the sequestrants.

Vitamin B3 may help improve blood sugar levels. Therefore, patients with diabetes should undergo treatment under the supervision of a specialist. Additionally, you should keep in mind that taking dietary supplements containing nicotinic acid reduces the effectiveness of the following medications:

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

In addition, for any other prescriptions, you should inform your doctor about taking nicotinic acid in order to exclude dangerous combinations.

Nicotinic acid as a medical product

Nicotinic acid helps with liver inflammation.

Pharmacies offer nicotinic acid in ampoules for intramuscular injection and tablet forms in various dosages. Indications for use:

• pellagra;
• gastrointestinal pathologies - hypoacid gastritis;
• inflammatory processes in the liver;
• cirrhosis;
• spasm of blood vessels in various organs and systems;
• inflammatory processes in the peripheral nervous system;
• skin ulcers;
• trophic violations of the integrity of the skin;
• treatment of the consequences of toxic effects.

Vitamin PP is a vital compound, but there are a number of conditions for which it should not be used. Contraindications for use:

1. individual intolerance;
2. ulcer in the acute stage;
3. increased blood pressure;
4. liver diseases;
5. heart rhythm disturbances;
6. chronic inflammatory diseases;
7. pregnancy;
8. lactation;
9. disorders in the circulatory system;
10. neurotic conditions.

Effective dosages depend on the age and diagnosis of the patient. The drug is administered by drip, so intramuscular injections are painful. It is advisable to carry out the manipulation after eating. This will reduce the likelihood of developing unpleasant sensations of itching and heat. Effective dosages for various diseases:

• coronary disease, stroke - once a day at the rate of 1 ml of the drug per 10 ml of saline - a course of 10 to 15 droppers;
• pellagra - the dosage is the same, but 2 droppers are indicated per day, and the duration of treatment is from 15 to 20 days.

Other drugs containing vitamin PP are indicated for the treatment of children. But if there is no alternative, then nicotinic acid is prescribed in an amount of no more than 20 ml per day. An excess of vitamins is just as dangerous as their deficiency. In addition, medications can cause unpleasant side effects. Adverse reactions of nicotinic acid:

1. allergic reactions;
2. paresthesia;
3. dizziness;
4. numbness in the limbs;
5. Redout;
6. skin hyperemia;
7. if the speed of drug administration is not observed, blood pressure sharply decreases;
8. feeling of heat.

These phenomena do not require the intervention of medical personnel and go away on their own. There are tablet dosage forms of vitamin PP. Indications, contraindications and side effects are similar to the solution for infusion. Only effective dosages change:

• pellagra – 100 mg 4 times a day – course up to 20 days;
• other diseases – 50 mg 4 times a day.

This vitamin is included in many multivitamin complexes.

Nicotinic acid tablets: instructions for use

It is recommended to start taking Vitamin B3 tablets with a minimum course of 50 mg of the drug per day at a time. In the absence of negative reactions, you can gradually increase the daily dose if prescribed by your doctor. For better absorption of nicotinic acid, it is necessary to take it with food, and what is important is that the food must contain fat, because Vitamin B3 is a fat-soluble substance.

In the first week of use, redness of the facial skin, a feeling of heat, and itching may occur. Symptoms usually disappear over time if the course of treatment is continued without increasing the dosage, in a stable manner.

Vitamin B. Hypervitaminosis

Symptoms

Taking into account the above features of the metabolism of B vitamins, one could assume a statistical predominance of one-time, acute overdoses caused by more or less random intake of concentrated drugs in large volumes.
However, if we add psychological (self-prescribed treatment and prevention) and iatrogenic (inadequate dosages of vitamin therapy prescribed by a doctor) to the biochemical nuances, a significant proportion of chronic hypervitaminosis B also becomes clear. The vast majority of such cases are overdoses of B1, B3, B5, B6, B9 and B12. The most typical and common symptoms are increased excitability, emotional instability, tachycardia, headaches, nausea, redness of the skin, dyssomnia (certain sleep disorders).

Vitamin B1 (thiamine) in excess doses can cause anaphylactic shock, skin reactions such as urticaria and increased photosensitivity, kidney and liver dysfunction.

Vitamin B3 (niacin, vitamin PP, nicotinic acid) in overdose causes, in addition to the above-mentioned symptom complex, severe dyspepsia, dizziness, itching and paresthesia (false tactile sensations), muscle pain, cardiovascular disorders (high blood pressure in a standing position).

Acute hypervitaminosis B5 (pantothenic acid) can, among other things, cause dehydration.

Overdose of B6 (adermine, pyridoxine) – atactic phenomena in the form of impaired coordination of movements, confusion, convulsions, increased acidity of gastric secretions.

Hypervitaminosis B9 (folic acid) – cramps in the lower extremities, allergic reactions. In addition, in 2016 , the results of a study conducted by employees of the Johns Hopkins Institute (USA) on medical and statistical data for the period 1998-2013 were published. It has been shown that unreasonable and deliberately excessive consumption of folic acid and cobalt-containing vitamins B12 by pregnant women (and the importance of these vitamins during gestation is well known) increases the risk of autism in children by 2-3 times, especially if “hyperprophylaxis” occurred in the third trimester. In addition, B12 increases blood clotting and, accordingly, the risk of blood clots. In general, the results of the study make us think seriously and once again raise the question of the feasibility, the need for the most careful monitoring, taking into account all indications and contraindications for vitamin therapy and vitamin prophylaxis during pregnancy: in many cases, the optimal level of con in the blood was exceeded by 15-17 or more times . The most severe complications of hypervitaminosis B include renal and liver failure, steatohepatosis, pulmonary edema, anaphylactic shock, exacerbation of gastroenterological and cardiac diseases.

It is interesting to note that the clinical picture of hypervitaminosis B is largely reminiscent or even repeats the symptoms of hypovitaminosis.