Sibutramine: the more dangerous, the mechanism of action, how to take, the consequences

Rapid weight loss without any effort - sounds very tempting for many who are tired of extra pounds. Therefore, "magic" drugs for weight loss are used, and, apparently, will always be in demand in a part of the predominantly female population, dissatisfied with their weight.

Sibutramine hydrochloride monohydrate, discovered by the international corporation Abbott Laboratories on the eve of the last decade of the last century and did not justify its first purpose as an antidepressant, proved to be a pronounced anorectic. The effect of this substance in suppressing the feeling of hunger was surprisingly effective, and the loss of excess kilograms was so significant that it was used as a medicine for obesity since 1997, prescribing to overweight patients caused by uncontrolled absorption of food.

Why is sibutramine prohibited?

The glory of Sibutramine as an effective fat burner, besides eliminating the desire to eat, quickly spread across countries and continents, since the problem of excess weight is quite acute not only in the US, but in most of the economically developed countries of Europe. The World Health Organization regards this problem as an epidemic and, naturally, the emergence of a new drug that eliminates hunger and stimulates metabolic processes in the body has been perceived more than favorably. Sibutramine and medications containing it were prescribed to patients with excess weight to the right and to the left.

However, reports of mental disorders in patients taking this drug with a given active component began to appear quickly enough. Among them, cases of suicides, acute cardiovascular pathologies with a lethal outcome, especially among the elderly, have become more frequent. In addition, drugs with Sibutramine may, according to some reports, cause similar to drug dependence. All these facts and a long list of side effects that were discovered during more thorough research of the properties of this drug, explains why Sibutramine is prohibited. Since 2010, the sale of medicines with this active ingredient has been temporarily discontinued in the territory of the European Union, in Australia, the USA, Canada and Ukraine, in Russia they can only be bought on prescription.

Indications for the use of this tool are primary food obesity of II-III degree, when the body mass index rises for 30-35 kg / m² with ineffectiveness of other methods of treatment. Both immediately after the appearance, and now this medicine for extra pounds was recommended not to everyone in a row, but in especially severe cases of obesity. In the scheme of treatment with Sibutramin, a low-calorie diet and exercise are suggested. It is also prescribed for people suffering from insulin-dependent diabetes, hyper- or hypoproteinemia. In this case, the recommended body mass index of the patient is 27kg / m² and above.

Complex therapy, including medications with Sibutramine, is conducted under the supervision of a specialist with practical experience in treating obesity. An important part of it is the formation of the patient's psychological readiness to change his habits in terms of diet and diet, as well as to changes in lifestyle, and to preserve them after the abolition of drug treatment.

Pharmacodynamics

The mechanism of action of this substance is that it contributes to the rapid satisfaction of hunger, activating a feeling of satiety and, thereby, reducing the amount of food consumed without effort on the part of the patient.

The beginning of the transmission of chemical signals (for example, about saturation during food intake) between the neurons of the brain is the release of neurotransmitters, serotonin and norepinephrine, into the intercellular space (synapse), where the signal is obtained. Sibutramine molecules block the return of the neurotransmitters back to the presynaptic cell. Due to this, the synapse increases the concentration of serotonin and norepinephrine, potentiating the stimulation of the neuron receiving the impulse. The saturation signal enters the postsynaptic cells more intensively, the body does not require the intake of a large amount of food. In addition, the drug increases the production of heat by the body, boosting metabolic processes and forming monodemethyl- and didemetylsibutramine-active metabolites, capable in themselves to inhibit the re-acquisition of released neurotransmitters (serotonin and norepinephrine), and also the pleasure hormone of dopamine, but to a much lesser extent. Acting in this way, Sibutramine promotes the rapid development of a feeling of satiety, and, it becomes permanent. The desire to have a snack disappears by itself, food consumption is significantly reduced, which leads to rapid weight loss.

The active substance and its active metabolites are indifferent to the release of the enzyme monoamine oxidase and its activation, do not interact with neurotransmitters, including catecholamines, serotonin, histamine, acetylcholine, glutamic acid and benzodiazepines. They suppress the capture of membrane receptors of serotonin by platelets and can change their functions.

Reducing fat deposits with these medications is accompanied by an increase in the level of high-density lipoproteins ("good" cholesterol) in blood plasma against a background of a quantitative decrease in triacylglycerides, total cholesterol due to "bad" and uric acid.

During treatment with these medicines, there were mainly cases of a slight increase in blood pressure and heart rate, but there were also more serious changes in these parameters. Most drugs with sibutramine are mono preparations, however, Reduxin also contains microcrystalline cellulose, a natural and non-food-producing non-food product, besides the main active ingredient. He has the property of staying in the stomach, swelling under the influence of liquid, thus providing a feeling of satiety. In combination with sibutramine, it complements its action. Capable of absorbing not only water, but also putrefactive bacteria, it cleanses the intestines and prevents food poisoning.

[1], [2], [3], [4], [5], [6]

Pharmacokinetics

At oral reception there is a fast absorption of an active component from a gastrointestinal tract (about 80%). Getting into the liver, Sibutramine is metabolized to monodemethyl- and didbutylsibutramine. At the end of 72 minutes after using the drug, dosed at 0.015 g, the greatest concentration of the active ingredient is observed, and from three to four hours its metabolites are observed. Taking the capsule along with the food, the patient reduces the maximum concentration of metabolites by one third, and, the time of its achievement increases by three hours, without changing the total concentration and distribution. Sibutramine (almost completely) and its metabolites (> 90%) bind to serum albumins and spread with good speed in the tissues of the body. The concentration of active substances in the serum achieves a state of equilibrium four days after the start of therapy and twice exceeds their serum concentration, determined after the first intake.

Excretion of inactive demethylated metabolites from the body mainly occurs in the urine, less than 1% is excreted with caloric masses. The half-life of sibutramine is 66 minutes, its metabolites (monodesmethyl- and didesmethylsibutramine) - 14 and 16 hours respectively.

[7], [8], [9], [10], [11], [12], [13], [14], [15]

Dosing and administration

The drug is taken once in the morning regardless of food intake. Treatment begins with a single capsule of 0.01 g, which is swallowed whole and washed down with water in sufficient quantity. If you lose less than two kilograms of weight during the first four weeks of therapy and good tolerability, a higher daily dosage of 0.015 g is prescribed. If in the next four weeks the weight decreases by less than two kilograms, the drug is canceled as ineffective in this case, since higher dosages are not recommended.

Treatment stops in the following cases:

• when for three months the patient loses less than 5% of the initial weight;
• when weight loss stabilized at less than 5% of the initial weight;
• when after already achieved weight reduction, the patient again recruits three kilograms or more.

Treatment with this drug is probably no more than two years.

[36], [37], [38], [39], [40], [41]

Use of the sibutramine during pregnancy

The results of tests of Sibutramine in laboratory animals indicate that this active substance has no effect on fertility, however, the teratogenic effect of sibutramine on the fetus was observed in descendants of experimental rabbits. They have been found to have physical anomalies concerning the appearance, as well as the structure of the skeleton.

Medications containing Sibutramine are not allowed for pregnant and lactating women. Throughout the treatment course and one and a half months after the end of treatment with these drugs, female fertile age patients should use reliable contraceptives.

Contraindications

• age restrictions: is not assigned to minors or persons over 65;
• secondary obesity caused by diseases of the endocrine and central nervous system, other organic causes;
• eating disorders - bulimia, anorexia (in the presence or in the anamnesis);
• mental pathologies;
• generalized tick;
• circulatory disorders in the brain (in the presence or in the anamnesis);
• toxic goiter;
• ischemic heart disease (in the presence or in the anamnesis), disturbances of the rhythm and heart rate, chronic decompensated cardiac muscle dysfunction;
• circulatory disturbance in peripheral vessels;
• uncontrolled increase in blood pressure above 145 mm Hg;
• severe degree of impaired liver and / or kidney function;
• adenoma of the prostate with delayed urination;
• pheochromocytoma
• substance abuse and / or alcoholism;
• angle-closure glaucoma;
• hypolactasia, glucose-galactose malabsorption syndrome;
• known sensitization to sibutramine and / or other ingredients of the drug.

With special care is assigned to patients who have a history of: hypertension, circulatory disorders, muscle spasms, coronary insufficiency, epilepsy, hepatic and / or renal dysfunction, cholelithiasis, glaucoma, hemorrhages, tics, and - taking drugs that disrupt blood coagulability.

[16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26]

Side effects of the sibutramine

This substance - a very effective anorektik, and, of course, that those who want to lose weight and read rave reviews, which are many, the question arises: What is dangerous Sibutramine?

Of course, like any substance, it can cause allergies. In most cases - this is not an anaphylactic shock, but a more harmless reaction of the body, for example, a rash from Sibutramine. Unpleasant, but not dangerous. Stop taking - it will scratch and pass.

A more serious consequence is addiction. This drug is not recommended for more than one year, but people who started taking it, often can not stop, they develop a real drug addiction, which, in fact, is a subset of drug addiction. Not everyone. However, who can guarantee that his body will be resistant to this property of this drug?

There will not be a true narcotic buzz from Sibutramine, but when canceled, which is recommended to be carried out gradually, there may appear sensations similar to "breaking". This happens even with a short, three months, taking the drug. It is dizziness and migraines, sleep disturbances and anxiety, increased excitability or apathy and thoughts of suicide. Sibutramine has a direct effect on the brain and central unequal system. This is how he fights overeating and overweight. But it is not always possible to influence the psyche and the nervous system without undesirable consequences. The first appointment of Sibutramine was accompanied by severe neuropsychic disorders, suicides, deaths from acute cardiac and cerebral pathologies, patients became dependent on the drug and its long reception turned into sad consequences. Current dosages of Sibutramine are much lower than those recommended at the beginning, the drug is better purified, but the undesirable effects, albeit less pronounced, are still there. During the period of therapy with this medicine, it is impossible to perform work at altitude, drive vehicles, work with mechanisms requiring increased concentration of attention. This drug is contraindicated in people who have a history of alcoholic or toxic addiction or anamnesis, since the effects will overlap.

The instructions to the drug indicate that the side effects most often occurred in the first month of treatment, and if it continued, the frequency and intensity of these effects decreased with time. Negative actions, in the main, were reversible and passed with the withdrawal of the drug.

The most common were heart palpitations, hypertension, hyperemia of the skin with sensations of heat, constipation, a complete lack of appetite, exacerbation of hemorrhoids, nausea, a feeling of dryness in the oral cavity, insomnia, fainting, numbness in parts of the body, panic attacks, increased sweating, perversion of taste.

In the post-registration study SCOUT, initiated by the relevant body of the European Union after many cases of severe adverse events, in which many patients with obesity and a high likelihood of cardiovascular disease participated, the following data were obtained: risk of non-fatal (!) Heart attack, stroke, heart attack of patients taking sibutramine increased by 16% compared with those who took placebo. However, which is very comforting, with the help of resuscitation it was possible to save 1.4% more patients who took this drug. But the deaths, both from vascular pathologies, and from all causes, in both groups of patients were met with the same frequency.

There were undesirable effects in the form of allergies from minor rashes to anaphylactic shock. In the blood, the number of platelets decreased, that is, the blood was poorly folded, there were cases of autoimmune damage to the walls of blood vessels (hemorrhagic purpura), mental disorders, as already mentioned above. In these cases, treatment was recommended to be discontinued.

The nervous system reacted to the drug with convulsions, short-term failures in memory, amnesia.

Pain syndromes in the head, back, ears, visual and hearing disorders, digestion, ENT diseases, herpes. The list of side effects is endless. He concludes the report that occasionally withdrawal syndrome is accompanied by a headache and increased appetite (!).

Women who plan to give birth after the course of Sibutramine, it makes sense to seriously think about. The drug is teratogenic, its ability to cause mutations has not yet been confirmed, but use this tool for a short time and the main thing - it is often not official. Therefore, additions to the list are still possible.

[27], [28], [29], [30], [31], [32], [33], [34], [35]

Overdose

Taking doses of Sibutramine exceeding the recommended ones increases the likelihood of developing undesirable effects and increasing their severity. The consequences of an overdose have not been sufficiently studied and there is no specific antidote.

As part of the first aid in case of an overdose, gastric lavage and enterosorbents are prescribed for an hour from the moment of receiving a dose exceeding the recommended dose.

It is necessary to observe the condition of the patient within 24 hours after receiving an overestimated amount of the drug. When the symptoms of side effects develop, appropriate treatment is performed. The most frequent consequences of overdose, increased blood pressure and heart palpitations, is stopped with ß-blockers.
The use of the "artificial kidney" apparatus in case of an overdose of sibutramine is inexpedient, as studies show that the products of sibutramine metabolism by hemodialysis are practically not eliminated.

[42], [43], [44]

Interactions with other drugs

Not applicable in combination:

• with other medicines that stop mental pathologies or are addressed to patients with alimentary obesity, which have a central effect;
• with drugs that inhibit the enzymatic activity of monoamine oxidase (between the medications containing sibutramine and monoamine oxidase inhibitors, there should be a time interval of at least two weeks);
• with drugs that stimulate the production of serotonin, and suppressing its reverse capture;
• with drugs inactivating microsomal enzymes of the liver;
• with drugs that can cause heart palpitations and increase blood pressure, as well as to excite the sympathetic nervous system.

Preparations containing Sibutramine do not affect the pharmacodynamics of oral contraceptives.

It should also be noted that sibutramine and alcohol are not compatible.

Currently, medicinal products containing Sibutramine are temporarily banned in Ukraine and their leave from pharmacies working in the legal field is impossible even according to prescriptions. However, to buy drugs with Sibutramine is not difficult, the Internet is full of suggestions. True, the sale of illicit drugs, like their purchase - is punishable. This is also worth considering.

[45], [46], [47], [48], [49], [50]

Storage conditions

The storage conditions of preparations based on Sibutramine do not differ from those for most drugs. Storage temperature should not exceed 25 ° C, shelf life - up to three years. The preparation does not need to be removed from the original packaging and left in places accessible to young children.

[51], [52], [53], [54], [55], [56], [57], [58], [59]

Analogues 

The most studied drug used to treat alimentary obesity is Xenical (a synonym for Orlistat). This is also an expensive analogue of Sibutramine. The active substance inhibits the absorption of fats in the small intestine, where they must be absorbed, and removes them from the feces. It works only when a low-calorie diet is observed, increasing its effect by about 20%. The main side effects are expressed in the disorder of the intestine, flatulence, incontinence of the stool and directly depend on the fat content of the food taken. The higher its fat content, the more pronounced undesirable actions.

The difference between orlistat and sibutramine is in the mechanism of action, if the first drug mixes well with fats, removes them from the body and causes the body to use fat reserves to compensate for energy consumption, the second - reduces appetite, acting on its centers in the human brain. Sibutramine has a direct effect through the central nervous system on other body systems. Orlistat almost does not enter the general bloodstream, acting in the intestine, and practically does not affect the body's systems. This drug is an analogue of Sibutramine only on the pharmacological effect - weight loss, the mechanisms of their action are completely different.

Anorectic Fenfluramine is a serotonergic drug, an amphetamine derivative, closer to Sibutramine by the mechanism of action, and, accordingly, is a prohibited narcotic drug.

The antidepressant Fluoxetine, inhibits the reuptake of serotonin, accordingly has anorectic properties. The list can be continued, but all these drugs, affecting the central nervous system, have more or less side effects like Sibutramine, and are capable of causing irreparable harm to health.

There are no real analogues of Sibutramine, there are cheaper synonyms of Indian production, for example, Gold Line, Redus, Slimia. Chinese food supplements are definitely a "cat in a sack".

Reduxin Light, has nothing to do with Sibutramine, contains the active substance of oxytryptane, which has sedative and appetizing properties. It is a bioadditive.

Cheap analogues - Gold Line Light, Lystata, not containing Sibutramine, but with a package reminiscent of sibutramine-containing products. This is more of an advertising trick, respectively, and the effectiveness of these tools is quite low.

[60], [61], [62], [63], [64], [65], [66], [67]

Reviews of losing weight and doctors

Reviews of slimming and their relatives about Sibutramine are very often intimidating, side effects, encourage many to stop treatment, but not everyone can get rid of the undesirable consequences of taking it. Judging by the reviews, these effects are not always reversible. Quite a lot of reviews say that people are very sorry for their decision to resort to this drug. Although a lot of reviews are clearly positive, emphasizing the high effectiveness of this substance, and, in addition to dry mouth, no other side effects are called.

The doctors' reviews are rather restrained, they do not negate the high effectiveness of Sibutramine, emphasize the need to comply with the rules of prescribing and medical supervision of patients, self-medication is completely excluded, since the drug causes serious side effects - nobody denies this. It is emphasized that half of the patients face at least one of the side effects caused by Sibutramine. Yet it is not for nothing that this substance was banned, even temporarily, in most economically developed countries.