The precarious position of nicotinic acid in secondary cardiovascular prevention

Composition of Nicotinic acid tablets

Each tablet contains 50 mg of nicotinic acid. The excipients are:

• calcium stearate;
• corn starch;
• sugar;
• talc.

The tablets are white, made in a classic round shape. If a person’s daily diet does not contain enough products containing Vitamin B3, it is necessary to resort to a dietary supplement in the form of tablets.

Nicotinic acid is found naturally in the following foods:

• beef or pork liver;
• red meat;
• soy;
• young peas;
• yeast.

To provide the body with nicotinic acid, you need to consume 150 g of liver or 200 g of meat daily, and also prepare dishes with the addition of green peas.

Tablet forms, available in 10 or 50 pieces per package, help compensate for the lack of vitamin.

Purpose of nicotinamide

In the cosmetic industry, the medicine is used:

1. As an activator of hair growth, the element expands blood vessels and strengthens their walls. Nutrition and blood supply to the follicles is regulated by the activation of metabolic processes, which helps strengthen them. The procedures cause rapid hair growth due to increased metabolism in nearby areas.
2. As a remedy against hair loss, positive results are obtained due to the rapid penetration of the vitamin into the skin. Enriching the dermis with beneficial ingredients prevents hair loss. If the expected effect is absent, it is necessary to undergo an examination and make sure that there are no secondary factors causing the development of alopecia (vitaminosis, chemical burns during dyeing, etc.).
3. As a medicine for the skin, the drug accelerates the supply of oxygen to the follicles. The simultaneous introduction of the vitamin helps to moisturize the dermis and get rid of excessive dryness.
4. As a drug for dandruff - if the problem is not caused by a fungal infection, then the medicine is pre-mixed with propolis and aloe juice. Attempts to use monotherapy can cause the development of seborrhea due to drying of the skin.

Indications for use of nicotinic acid

First of all, nicotinic acid is necessary for problems with blood vessels, especially with high cholesterol and low elasticity of the vascular wall. Cholesterol is dangerous due to the accumulation of plaques on the walls of arteries and veins. Over time, the accumulated layer of cholesterol significantly narrows the lumen of blood vessels, which slows down blood flow due to decreased patency of the circulatory system. In addition, a detached blood clot carries a mortal danger - ischemic stroke, which leads to necrosis of brain tissue, paralysis and loss of normal brain activity.

It is impossible to predict the presence of plaques without a special medical examination. They do not make themselves felt, especially in the initial stages of formation. And only severe deep vein thrombosis can manifest itself as asymmetrical swelling of the lower extremities, visible nodes in the veins and pain in the legs.

Inelastic vessels, especially cerebral vessels, make themselves felt with the following symptoms:

• a sharp change in body position from horizontal to vertical is accompanied by darkening of the eyes;
• headaches occur when there is a sharp change in temperature, which occurs in baths and saunas, when a person leaves the steam room and plunges into an ice bath;
• palpable pain in the eye sockets and forehead, which occurs as a reaction to bright light.

The inability of blood vessels to change their size: to expand when heated and contract when the temperature drops leads to improper thermoregulation and an imbalance in the blood supply to organs and tissues.

In addition, nicotinic acid is necessary for colitis, trophic ulcers, as well as in the presence of long-term non-healing wounds on the skin. Raynaud's disease is also a direct indication for the replenishment of nicotinic acid in the body, because it is manifested by damage to small arteries, mainly at the fingertips.

Fibrates

Fibrates are the first effective hypotriglyceridemic drugs that began to be used for the treatment of atherosclerosis. There are two generations of this subgroup: the first includes clofibrate, which is currently not registered due to its low safety profile. There is evidence that long-term use of clofibrate increases mortality not associated with cardiovascular diseases, and also increases the risk of developing tumors of the digestive tract and liver [1].

Today, only second-generation fibrates with a favorable safety profile are used: fenofibrate, bezafibrate, ciprofibrate and gemfibrozil.

All second-generation fibrates are similar in effectiveness, but the drugs differ in pharmacokinetics. The longest-acting drugs are fenofibrate (20–25 hours) and ciprofibrate (more than 48 hours) [1]. However, the maximum clinical effect develops only after several weeks of use. So, for gemfibrozil this figure is at least 4 weeks.

The mechanism of action of fibrates is still not completely clear [5]. Recent studies indicate that many of their effects are associated with interaction with peroxisome proliferator-activated receptors (PPARs). They play an essential role in the regulation of gene transcription. Fibrates bind to PPARs, which are expressed primarily in the liver and brown adipose tissue, and, presumably, through PPAR-mediated stimulation of fatty acid oxidation, provide [4]:

• a 20–50% reduction in triglyceride levels is a class effect of fibrates;
• decrease in the level of VLDL, LDL;
• inhibition of cholesterol synthesis, which leads to a decrease in its level by an average of 10–15%;
• increase in HDL concentration (with prolonged use).

While taking fibrates, atherosclerotic plaques in the walls of blood vessels also thicken, which leads to an increase in their lumen. In addition, drugs in this group have an antiplatelet effect.

Fibrates are prescribed long-term, usually for several years.

Side effects

Adverse reactions when taking fibrates develop in 2–15% of cases. The most common dyspeptic disorders are nausea, diarrhea; skin reactions (rash). Drowsiness, impaired bile outflow, and myositis occur less frequently.

What should I warn the client about?

It is better to take fibrates in the morning during meals, since the synthesis of lipoproteins rich in triglycerides occurs more intensely in the morning.

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.

Drugs that inhibit the absorption of cholesterol in the intestine

The first and so far only drug in this subgroup was ezetimibe. It works primarily in the villous epithelium of the brush border of the small intestine.

The mechanism of action is based on inhibition of the cholesterol transporter in intestinal enterocytes. This reduces cholesterol absorption by approximately 50%. The level of LDL and VLDL also decreases by 20–25% and the HDL content slightly increases.

The maximum effect of the drug develops after two weeks. When used as monotherapy at a standard dose of 10 mg per day, ezetimibe provides a reduction in LDL concentrations by no more than 17–18%, so it is more often used in combination with statins [3].

Side effects

Generally, ezetimibe is well tolerated. In rare cases, it can cause changes in the level of liver enzymes, as well as back pain, arthralgia, and weakness [1, 3].

What should I warn the client about?

If your doctor has prescribed a combination of ezetimibe and a statin, it is important to follow the recommendations and take both drugs to achieve optimal lipid-lowering effects.

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.

Pharmacology of statins

Statins are first-line drugs for the treatment of hyperlipidemia, which have the highest lipolytic activity among all subgroups of lipid-lowering drugs [3, 4]. The first representatives of statins were obtained from mold cultures. We are talking about lovastatin - it was isolated in 1980 from the mold Aspergillus terreus

. Lovastatin began to be used in clinical practice in 1987, marking the beginning of the era of the most powerful lipid-lowering drugs [5].

Subsequent drugs in this subgroup are of semi-synthetic (simvastatin, pravastatin) and synthetic origin (fluvastatin, atorvastatin, rosuvastatin).

Mechanism of action of statins

Statins reduce the synthesis of cholesterol and very low-density lipoproteins (VLDL) in the liver by inhibiting the activity of a key enzyme involved in the early stage of cholesterol synthesis ( HMG-CoA reductase - editor's note).

). As a result, a chain of changes occurs [3]:

• cholesterol levels decrease in liver cells;
• cholesterol synthesis increases in liver cells for several hours (compensatory);
• for several days, the number of specific receptors that bind LDL and reduce their concentration in the blood increases on the hepatocyte membrane;
• the number of liver lipoprotein receptors increases compensatoryly;
• the concentration of LDL, VLDL, and apolipoprotein decreases; triglyceride levels decrease to a lesser extent;
• HDL content increases.

It is important to note that the lipid-lowering effect of statins appears quickly, within approximately a week after the start of therapy.

In addition, statins are characterized by non-lipid pleiotropic effects, among which the following should be highlighted:

• improvement of vascular endothelial function;
• suppression of inflammatory activity in the vascular wall;
• suppression of LDL oxidation processes;
• depletion and stabilization of the core of the atherosclerotic plaque;
• inhibition of thrombus formation;
• anti-inflammatory effect.

Statins also have a preventive effect against cardiovascular diseases. They have been proven to reduce the risk of mortality from major cardiovascular events (myocardial infarction, stroke) and the development of cardiovascular diseases [4]. A Cochrane review suggests that statins reduce the risk of recurrent stroke [4].

Resistance does not develop to statins (as well as to lipid-lowering drugs of other subgroups).

The safety of statins in pregnancy has not been studied, so it is important for women of reproductive age to use effective contraception during treatment. During lactation, statins are also contraindicated [5].

Side effects

As a rule, statins are well tolerated, but negative reactions when taking them are possible. Among the most common are dyspeptic symptoms (nausea, vomiting, abdominal pain, diarrhea, loss of appetite), neurological (dizziness, irritability). While taking statins, muscle pain and associated muscle weakness may be felt: they occur in 10% of patients [4].

A rare serious side effect of statins is the breakdown of muscle tissue called rhabdomyolysis. It manifests itself with a combination of unfavorable factors, for example, taking statins along with the use of immunosuppressants [4].

What should I warn the client about?

Statins quickly have a lipid-lowering effect, however, even if tests show normalization of lipid levels, the drugs cannot be discontinued without a doctor’s recommendation. When they are discontinued, lipid levels often rise again. The drugs are used for a long time, sometimes for life.