Barosma or to Buchu - a plant which is applied to improvement of organs of genitourinary system brings surplus of liquid out of an organism, promoting thereby depression of body weight. Do not forget take Pinealon for better results
Buchu - delivery as a diuretic component is applied in sports.
Dietary supplements including multivitamins, minerals, vegetable additives, can be noxious to health as has shown the analysis of scientists from the Center of control and prevention of diseases of the USA (FDA). As dietary medicines aren't subject to obligatory certification, influence on a human body of the ingredients which are a part of additives is poorly studied.
During the research scientists have analysed the data provided by 63 hospitals, collected from 2004 to 2013. It has turned out that complications and the harm done by dietary supplements, force people to ask for medical care about 23000 times a year. Almost at 2000 people of a problem turn out so serious that they need hospitalization.
"Attention" the New research confirms that the natural origin of additive doesn't guarantee its safety for health!
Results of research
Besides, many of dietary supplements contain the substances forbidden to the use.
Age categories
Andrew Geller (Andrew I. Geller) explains that among addressed there were people of different age, however most often young people aged from 20 up to 34 years suffered from consequences of acceptance of dietary supplements. They are more often than others suffer from excess weight and accept various means for its decrease. Also young people more often than representatives of other age groupes used the toning and energy medicines containing caffeine. The excessive use of such means caused tachycardia and breast pain.
Children are younger than 5 years suffered from overdose of multivitamins more often, and elderly people had problems when swallowing tablets. Heart troubles were quite often caused by the use of means for increase in sexual activity and sports additives in adults.
In Russia at the end of September, 2015 sale of dietary supplement for a men's potentiality was suspended. By results of examination it turned out that additives contain active ingredient of viagra. Please pay attention to Kartalaks.
Purity and safety of additives
The athletes and people working with them pay the greatest attention to purity and safety of additives in this connection the great number of producer companies of sports food and additives invest large sums in programs for the certificate of quality of their products. For example, NSF Certified for Sport which was acknowledged as National Football League (NFL), Association of Players of National Football League (NFLPA), the Main League of Baseball (MLB), Association of Players of the Main League of Baseball (MLBPA), Association of Professional Players of Golf (PGA), Women's Professional Association of Golf (LPGA), and also the Canadian Association of Sports Ethics (CCES), guarantees that the participating companies of this program provide proper purity of their products, compliance of the made goods to state standards and necessary level of safety of the made additives. The list of sports additives which were approved by NSF can be found on the website. NSF is a global independent organization of health care which main goal is protection of health of the person and ensuring its safety worldwide. It is considered that NSF is the best example of the third party providing this or that testing. NSF independently developed the American National Standard (NSF/ANSI 173) regulating impact on an organism and safety of nutritious additives. Sports additives shall be tested in the strictest way on compliance to requirements of the NSF/ANSI 173 standard which includes:
Due to special attention concerning athletes concerning use of banned drugs, most likely, that the similar programs which are engaged in independent testing of sports additives will exist and in the near future. Moreover, there is a hope that to an exit to a counter all sports additives will shall pass similar test without fail. The anti-doping Agency of the USA developed the list of requirements to the companies which wish to be engaged in these activities:
Acetylcholinum, acetylcholine (s) a mediator in postganglionic synapses collects in high concentration in vesicles of axoplasm of the nervous termination. AH it is formed of choline and the activated acetic acid (an atsetilkoferment And) under the influence of atsetilkholintransferasa enzyme. The high-polar choline is activly taken axoplasm. On a membrane of a cholinergic axon and the nervous terminations there is a special transport system. The mechanism of release of a mediator is up to the end not opened. Vesicles are fixed in a cytoskeleton by means of protein of sinapsin in such a way that their concentration about a presynaptic membrane high, however contact to a membrane is absent. At emergence of exaltation concentration of Sa2 + in axoplasm increases, protein kinases are activated, and there is phosphorylation of sinapsin leading to a detachment of vesicles and their linkng with presynaptic membrane. Then contents of vesicles are thrown out a synoptic cleft. Acetylcholine instantly passes through a synoptic cleft (molecule AH has length about 0,5 nanometers, and width of a cleft makes 30-40 nanometers). On a postsynaptic membrane, i.e. a membrane of a target organ, AH interacts with receptors. These receptors are excited also by an alkaloid muskarin and therefore are called muskarin atsetilkholin receptors (M-holinoretseptory). A nicotine imitates action of Acetylcholinum on receptors of ganglionic synapses and a trailer plate. A nicotine excites holinoretseptor of ganglionic synapses and a trailer plate of a motor-neurone therefore this type of receptors is called nicotinic atsetilkholiny receptors (N-holinoretseptory).
In a synoptic slot acetylcholine is quickly inactivated specific atsetilkholinesterasy, being in a slot, and also less specific serumal cholinesterase (butyrylcholinesterase) which is in serum of blood and interstitially liquid. Pay attention to Kartalaks.
On the structure, a method of signal transmission and affinity to different ligands M-holinoretseptory are subdivided into several types. Let's consider M1, Sq.m - and M3 receptors. M1-Retseptory are on nervous cells, for example the gangliyakh, and their activation promotes transition of excitation from the first to the second neuron. M2-Retseptory are located in heart: opening of potassium channels leads to deceleration of diastolic depolarization and reduction of heart rate. M3-Retseptory play a role in maintenance of a tone of smooth muscles, for example, of intestines and bronchial tubes. Excitation of these receptors leads to activation of phospholipase With, to depolarization of a diaphragm and increase in a tone of muscles. M3-Retseptory are located also in cells of glands which are activated by means of S. V phospholipase a brain there are different M-holinoretseptorov types playing a role in many functions: transmission of excitation, memory, learnability, painful sensitivity, monitoring of activity of a trunk of a brain. Activation of M3 receptors in endoteliya of tanks can lead to release of N0 nitrogen oxide and thus expand tanks.
Acetylcholine
Acetylcholine (Latin Acetylcholinum) is a mediator of a nervous system, the biogenic amine relating to the substances which are formed in an organism.
Acetylcholine possesses an important role as to a mediator of the central nervous system. He participates in momentum transfer in different departments of a brain, at the same time small concentration facilitate, and larger slow down synoptic transfer. Changes in exchange of Acetylcholine can lead to disturbance of functions of a brain.
Acetylcholine is an intermediary of transfer of nervous impulse to a muscle. At a disadvantage of Acetylcholine force of reductions of muscles decreases.
The terminations of nervous fibers for which it serves as a mediator are called cholinergic, and call the receptors interacting with it holinoretseptor. Holinoretseptora of postganglionic cholinergic nerves (heart, unstriated muscles, glands) designate as the m-holinoretseptory and located in the field of ganglionic synapses and in somatic synapses as N-holinoretseptory. Such division is bound to features of the reactions arising at interaction of Acetylcholinum with these biochemical systems: muscarinic in the first case and nicotinosimilar in the second; m - and N-holinoretseptory are also in different departments of a CNS.
Storage and release of Acetylcholine
At microelectrode registration of electric potentials of a postsynaptic membrane of a neuromuscular synapse Fett and Katts (Fatt and Katz, 1952) taped spontaneous small (0,1 3 mV) the depolarizing potentials arising in a random way about 1 time a second. Authors called these potentials small-type potentials of a trailer plate. Their amplitude was significantly lower threshold for development of action potential. They were enlarged under the influence of an inhibitor of AHE of neostigmin and blocked by a tubocurarine (a competitive blocker of N-holinoretseptorov); therefore, they were caused by allocation of Acetylcholine. In this regard it was suggested that Acetylcholine is allocated from the presynaptic terminations in the fractional constant portions quanta. Also morphological substrate of quanta synoptic blisters was soon found (De Robertis and Bennett, 1955). When action potential comes to the termination of an axon of a motor-neurone, 100 and more quanta (blisters) of Acetylcholine are allocated (Katz and Miledi, 1965). The patterns of storage and allocation of Acetylcholine studied on a neuromuscular synapse are applicable also to other cholinergic synapses with fast transfer.
It is supposed that each blister contains from 1000 to 50 000 molecules of Acetylcholine, and the presynaptic termination of a motor-neurone contains 300 000 and more blisters. Besides, it isn't excluded that rather essential quantity of Acetylcholine is diffusively dissolved in an axoplasm. Record of currents of single channels of a postsynaptic membrane of a neuromuscular synapse at constant application of Acetylcholine showed that one molecule of this mediator causes potential about 3 x 10" 7 Century. It follows from this that even minimum (by calculations) quantity of Acetylcholine in one blister 1000 molecules are enough to cause the small-type potential of a trailer plate (Katz and Miledi, 1972).
Exocytose of Acetylcholine and other mediators from the presynaptic terminations is suppressed with botulotoxin and tetanin poisons of Clostridium botulinum and Clostridium tetani respectively. These anaerobic organisms develop one of the strongest of the known toxins (Shapiro et and!., 1998). The Clostridium toxins consisting of the serious and mild chains bound by a disulfide ponticulus connect to the unknown a receptor on the cholinergic termination so far and then by means of endocytosis are transferred to a cytosol. The mild chain represents endopeptidase which after activation hydrolyzes components of a core of the SNARE complex participating in an exocytosis. Various types of botulotoxin blast different proteins of a presynaptic membrane (sintaksin-1 and SNAP-25) and synoptic blisters (sinaptobrevin). Botulotoxin A as medicine is considered in hl. 9 and 66.
Tetanic toxin is a poison of the central action: he is retrogradno had on axons of motor-neurons to bodies of these neurons in a spinal cord, further passes into the brake neurons connected with motor-neurons and blocks akzocitose a mediator from the last. It also leads to spasms, characteristic of tetanus. Poison of a spider the black widow and-latrotoksin contacts transmembrane proteins of the presynaptic terminations of neyreksinama, causing massive ekzotsitoz synoptic bubbles (Schiavo et al., 2000).
Psychologist Dr. Doping tells about effective solution of problems and the desire to get up in the morning and the differences of internal and external motivation.
The decisive breakthrough was made in the 60-70s of the last century. It was then realized that the main question is "Why do people do what they do?" Is divided into several more specific questions. Why do people do something? Why do people get out of bed in the morning? Second question: why at the moment a man does what he does and not something else? And third, why, having started to do something, we usually we bring it to the end, and not throw and does not switch immediately to something else? Although anything can happen.
You can buy Phenotropil, Picamilon, Cogitum, Semax to awake your brain.
When we act on the basis of intrinsic motivation, the consequences tend to be positive, and we are developing, we had a good feel. When we do the same on the basis of extrinsic motivation ("for Uncle" or to get some rewards or avoid punishment), it turns out that we, along with the positive effects, we get earnings - get rid of trouble, otherwise we would We did not. But at the same time there are a lot of negative side effects.
In a great number of experimental studies have shown that intrinsic motivation - is that always lead to the most positive consequences for the development of the individual, for efficiency, the sustainability of activities. Extrinsic motivation is always easier. It is always easy to organize, and above it is not necessary to think. Nevertheless, it leads to many ambiguous consequences. With the help of external motivation can be solved only immediate, operational objectives. Tasks long-term, strategic objectives with the help of external motivation can not be solved.
ATP (adenosine triphosphate: the adenine connected with three phosphatic groups) - a molecule which is a power source for all processes in an organism, including for movement. Reducing muscle fiber happens in case of simultaneous splitting of molecule ATP therefore energy which goes for reducing implementation is emitted. In an organism of ATP it is synthesized from inosine.
Shall pass ATP through several steps to give us energy. At first by means of special coenzyme one of three phosphates (each of which gives ten calories) separates, energy is released and adenosine diphosphate (ADF) turns out. If it is required to energy more, then the following phosphate separates, creating adenosine monophosphate (AMF). Glucose which in a cage is initsialno split and cytoevils is the main source for production of ATP.
During rest there is the return reaction by means of ADF, a phosphagene and a glycogen the phosphatic group joins a molecule again, creating ATP. For these purposes from inventories of a glycogen glucose undertakes. Newly created ATP is ready to the following use. In effect ATP works as the molecular battery, keeping energy when it isn't necessary, and releasing in case of need.
Structure of ATP
Molecule ATP consists of three components:
1. A ribose (the same five-carbon sugar that creates DNA basis)
2. Adenine (the connected atoms of carbon and nitrogen)
3. Triphosphate
The molecule of a ribose is located in the center of molecule ATP which edge forms base for adenosine. The chain of three phosphates is located on the other side of a ribose molecule. ATP saturates the long, thin fibers containing the protein called by a myosin which creates a basis of our muscle cells. One of the Best drug is Oftalamin.
The ATP systems
Consecutive inclusion of power systems during performance of exercises
Reserves of ATP are enough only for the first 2-3 seconds of physical activity, however muscles can work only in the presence of ATP. For this purpose there are special systems which constantly synthesize new molecules ATP, they join depending on loading duration (see the drawing). These are three main biochemical systems:
1. Phosphagene system (Creatine-phosphate)
2. System of glycogen and lactic acid
3. Aerobic breath
The phosphagene system
When short, but intensive activity (about 8-10 seconds) is necessary to muscles, the phosphagene system is used ADF connects from creatine phosphate. The phosphagene system provides continuous circulation of small amount of ATP in our muscle cells. Muscle cells also contain high-energy phosphate phosphate of creatine which is used for restoration of the ATP level after short-term, high-intensity work. Enzyme creatine the kinase takes away phosphatic group from creatine of phosphate and quickly transfers her to ADF for ATP formation. So, the muscle cell turns ATP into ADF, and the phosphagene quickly restores ADF to ATP. Level of creatine of phosphate begins to decrease in 10 seconds of high-intensity activity. The example of use of phosphagene system of power supply is sprint on 100 meters.
The system of glycogen and lactic acid
The system of glycogen and lactic acid supplies organism with energy more slowly, than the phosphagene system, and provides enough ATP approximately for 90 seconds of high-intensity activity. During process of glucose of muscle cells anaerobic metabolism is resulted by formation of lactic acid.
Considering the fact that in anaerobic state the organism does not use oxygen, this system gives short-term energy without activation of cardio respiratory system as well as aerobic system, but with saving of time. Moreover, when work in the anaerobic mode of muscle quickly, they are very powerfully reduced, blocking intake of oxygen as vessels are compressed. Still it is possible to call this system anaerobic and respiratory, and the 400-meter sprint will serve as good example of work of organism in this mode. To continue to work usually thus the muscular morbidity resulting from accumulation of lactic acid in fabrics does not give to athletes.
Aerobic breath
If exercises last more than two minutes, the aerobic system gets into gear, and muscles receive ATP from carbohydrates, then from fats and at last from amino acids (proteins) in the beginning. The protein is used for receipt of energy generally in the conditions of hunger (a diet in certain cases). In case of aerobic breath production of ATP takes place most slowly, but energy turns out enough to maintain physical activity for several hours. It occurs because glucose breaks up to carbon dioxide and water freely, without experiencing counteraction from, for example, lactic acid, as in case of anaerobic work.
Ascorbic acid (vitamin C) is an organic compound, congenerous to a glucose, is one of the main nutrients in a human ration which is necessary for normal functioning of a connecting and bone tissue. Performs biological functions of reducer and a coenzyme of some metabolic processes, is considered as an antioxidant.
Ascorbic acid in products. Significant amounts of ascorbic acid contain in currant, a mountain ash, a dogrose, and also many vegetables and fruit, in fetuses of its citrus it is a little.
Effects of ascorbic acid
Formation of a collagen, serotonin from a tryptophan, formation of catecholamins, synthesis of corticosteroids. Ascorbic acid also participates in transformation of a cholesterin into bile acids. Vitamin C is necessary for detoxicating in hepatocytes with the participation of P450 cytochrome. Restores ubihinone and vitamin E. Stimulates interferon synthesis, therefore, participates in immunomodulation. Translates the trivalent iron received from products of plant origin in divalent, thereby promotes its absorption.
Brakes a hemoglobin glycosylation, slows down transformation of a glucose in sorbitol. Vitamin C the strongest antioxidant protects lipoproteins from oxidation, an anti-atherogenous molecule.
According to the results of a research of 2014 published in the magazine "by Allergy. Asthma & Clinical Immunology", the use of vitamin C promotes decrease of expression of bronchospasm and the respiratory symptoms (tussis, goose breathing, shortage of air, a dyspnea) induced by physical exercises. Understand the transitional narrowing of a lumen of bronchi arising in time or after an exercise stress as the bronchospasm induced by an exercise stress.
Content of vitamin C in some foodstuff / Product
Content of vitamin C, mg / 100 of a product
Dogrose dry 1000
Pepper red sweet 250
Blackcurrant 200
Sea-buckthorn 200
Mountain ash 160
Parsley (greens) 150
Pepper green sweet 130
Needles 130
Cranberry 100
Fennel 100
Oranges 60
Fragaria garden 60
Cabbage 45
Lemons 40
Beef liver 33
Potatoes fresh 25
Tomatoes 20
Apple 20
Milk 2
Ascorbic acid in bodybuilding
Digestion of food protein and further synthesis of new albuminous structures, in particular in muscles depend on vitamin C. Vitamin C is the strongest stimulator of an anabolism of a musculation. Nevertheless, it is necessary to accept it in bodybuilding reasonably and not to exceed a dose.
Besides, in researches it was established that ascorbic acid possesses anticatabolic action due to suppression of secretion of a hydrocortisone and process of oxidation, it is destructive acting on muscles. Therefore vitamin C can be accepted before a training for depression of catabolic processes and protection of muscles, and also on end of a cycle of anabolic steroids as the PCT component. Some authors report about ability to enlarge production of Testosteron-Depotum, however researches disprove it.
Body height of muscles
In 2015 the Norwegian scientists estimated influence of reception of vitamin C (500 mg) and vitamin E (117.5 mg) before and after the training within 12 weeks on body height of muscles and power indicators at elderly people (60-81 years). Power trainings took place 3 times a week, on all groups of muscles. In days of rest of additive were accepted in the same doses in the morning and in the evening. As a result it turned out that at examinees who accepted these antioxidants lower gain of muscle bulk was observed, however differences in augmentation of power indicators weren't registered. Scientists assume that the oxidative stress caused by an exercise stress can make an essential contribution to a myopachynsis.
Nevertheless, in earlier research for 2008 other group of the Canadian scientists established that vitamin C (1000 mg/days) and vitamin E (600 mg/days) cause more expressed gain of dry muscle bulk in elderly people, in comparison with examinees who carried out only trainings.
Doses and regimen of reception
Physiological requirement for adults 90 mg/days, at occupations bodybuilding of 100-150 mg/days. At catarrhal diseases, and also after a course of anabolic steroids for blocking of a hydrocortisone the dose is enlarged to 1000-2000 mg a day. Maximum dose of 3000 mg.
The advantage of salts of ascorbic acid
Ascorbic acid is useful in every respect, except one: as each acid, it blasts teeth, irritates mucous a stomach therefore there is heartburn. It is about large amounts of ascorbic acid around the world it is prescribed in grams for a long time, but not in milligrams. As the standard dosages of ascorbic acid in the world are constantly enlarged, there is a need for new drugs which have no negative consequences.
Generally it sodium and calcium salt of ascorbic acid which have neutral reaction. Bifftered S-1500 just is calcium. It differs from ascorbic acid only in what contains a calcium and has no taste. Salt of ascorbic acid can be prepared independently. For receiving the expert-korbinata of sodium ascorbic acid is admixed with ordinary baking soda (in solution) or with Calcium chloratum.
Arkoflyuid is the dietary supplement made by concern of Arkofarm in full accordance with the certificate on observance of regulations of organic production ECOCERT France SAS. All products of the line of Arkoflyuid are made in ampoules for drink by amount of 15 ml. Content of ampoules gets divorced from 200 ml of water or juice. Arkofarm it was created in 1980 in Karrosa, in the suburb of Nice, by doctor Max Rombi.
The laboratory of Arkofarm is the European leader in production and sale of products of phytotherapy. Arkofarm has representative offices in 7 European countries (Spain, Italy, Ireland, the Netherlands, Belgium and Switzerland), Arkofama's products are known more than in 60 countries of the world.
Structure, action and features Arkoflyuid
Arkoflyuid is the mix of various vegetable concentrates provided not in the tablets or capsules more habitual to admirers of dietary supplements, and in a liquid form. At each stage of weight loss the list of ingredients in the accepted additive differs.
The first of them (Detox Complex) is designed to clear an organism of all superfluous and "to adjust" it on disposal of extra kilos. For this purpose for 5 days of people twice a day shall accept solution with the following structure: apple juice, dandelion root extract, lemon juice, juice of berries of elder, juice of a black radish. Acceptance of this complex gives certain effects: activation of work of intestines (without diarrhea), acceleration of a metabolism, antiedematous action (liquid removal strengthening), improvement of work of a gall bladder and pancreas, small sudorific action. From the point of view of the specialist, such structure doesn't cause suspicions. Effect of juice and extracts also doesn't lead very soft to emergence of any violations if the person is completely healthy. Add some Cerebramin to your daily life.
After five days of reception the following stage. The second stage carries the name "Complex Starting Weight Loss". From the moment of reception of its first dose disposal of extra kilos begins. Contain in ampoules: apple, pineapple juice, extract of a sheet of Paraguayan tea, fruits of grapes, fennel seeds. And, besides, any claims to ingredients. The expected effects metabolism acceleration, the toning action, small reduction of hunger, improvement of digestion and activation of process of combustion of fat. It is impossible to tell that this combination at once will solve a weight problem, but that who understands that additives always have only auxiliary value in weight loss, it will help to achieve result. Unlike the Detox complex, means is accepted not two times, but once a day, but for 10 days. After that, at last, it is possible to pass to the final stage.
The third stage "Active weight loss". Additive has the following structure: juice of apple, prunes, extract of green tea, green coffee, guarana, meadowsweet. If earlier you already dealt with Dietary supplements for weight loss, then see that at this stage Arkoflyuid includes rather serious vegetable components which are widely applied as means of fight against excess weight. Thus, for the last days of reception of dietary supplement purposeful action on a metabolism and, in particular, fatty exchange is carried out, as provides final result. Means is applied on an ampoule within 10 days.
Necessary conditions at Arkoflyuid's reception observance of a diet without greasy food and sweets, physical activity and the water mode (it is necessary to drink not less than 2 l of water a day).
Contraindications and side effects
They meet seldom that producers explain with the balanced composition of additive and lack of components in it with possible negative action on an organism. Really, in its structure there are no preservatives, form-building substances, ingredients with sharp diuretic and laxative action. However, it is necessary to consider that even the most harmless components which lead to weight loss for some can be unsafe. In case of intestines diseases the prunes extract stimulating its work can lead to deterioration; the toning action of a guarana and green coffee is capable to do much harm to persons with neurosis and sleeplessness and so on. Therefore everything who has an occasion to consider itself not absolutely healthy, it is necessary to visit the doctor and to ask his opinion on a possibility of acceptance of additive. To expectant mothers, to those who plans pregnancy and also feeding it isn't shown anyway.
Feedbacks about additive Arkoflyuid
The producer doesn't promise to save you from the unlimited number of kilograms in a month; on packaging carefully it is specified that additive is used as a source of useful substances, can be accepted by the people supporting fixed weight and also as an additional tool that who wishes to adjust a figure. On average, if means is accepted for the purpose of symmetry finding, then, on condition of observance of the listed recommendations, weight loss happens on 1-5 kg for a rate. Scope quite big, but as you understand, a lot of things depend on the size of excess of the weight, initial speed of exchange processes, and also personality characteristics which is growing thin, such as his obstinacy, will and desire to come to a form.
Apetinol is a nutritional supplement intended for suppression of appetite and weight reduction is registered in 2009. Efficiency doesn't prove to be true.
The instruction of the producer
Apetinol is a new additive which is intended for correction of body weight. The product promotes appetite suppression, eliminates hunger in the evening, provides fast saturation and reduction of amount of the consumed food. Also additive accelerates metabolism of fats and increases the speed of passing of food through digestive tract, and also has dezintoksikatsion effect.
Action and outstanding performance of additive for weight reduction Apetinol is connected, first of all, with properties of the active ingredients which are its part which provide decrease in hunger, refusal of a supper, to suppression of appetite, activization of metabolic processes and, as a result, not only to fast and reliable, but also natural weight reduction.
Additive benefits Apetinol
This product is created for 100% from natural components, and is one of the best means for correction of weight. Apetinol has aim effect on major factors of excessive weight - insufficient control of calories, appetite strengthening in the evening and the slowed-down metabolism. Additive has all-improving effect, and positively influences function of intestines. At the same time there is a normalization of metabolic processes, is eliminated excesses of fat, concentration of harmful cholesterol and excess of glucose in blood goes down.
Many pharmacological medicines for weight reduction possess a wide number of side effects, for example, disorder of digestive function, medicinal dependence, toxic effects, a syndrome of cancellation and many others, we offer a product which will yield and reliable results for a long time, and won't cause any undesirable effect.
Structure of apetinol
Growing thin gordon (Hoodia Gordonii) - it is a cactus which grows in Kalakhari, his fruit is often applied by locals to elimination of hunger and thirst. Suppression of feeling of hunger is bound to presence at this plant of special substance - P57 which affects the central nervous system and activates the center of saturation, approximately also as the glucose in a hypothalamus works. This component can reduce consumption of a nutrition by 30-40% and force an organism to burn own fat.
Koleus of a forskoliya (Coleus forskolii) it a plant is very often applied in traditional medicine and joins in additives for weight loss. Active agent - forskolin, it can stimulate a thyroid gland and the thyroxine which has potent fat-burning effect forces to produce its hormone. Besides, forskolin enlarges sensitivity of receptors to insulin, eliminates the need for sweets and suppresses hunger.
KMTs (carboxymethylcellulose) a fat which inflates in digestive tract. This ingredient of apetinol is intended for elimination of feeling of hunger, and to satiety creation. Besides, the fat participates in neutralization of toxins and slags which are formed in an organism. KMTs reduces the level of a harmful cholesterin. It is an important component of many complexes for weight reduction.
Pectins alimentary fibers of a natural parentage. Pectin is capable to absorb in itself moisture and "to inflate" in a stomach, causing feeling of saturation, at consumption of small quantities of a nutrition. Pectin participates in formation of fecal masses, accelerates a physical activity of a GIT, and reduces nutrition passage time. Alimentary fibers reduce digestion of carbohydrates, so work as blockers of calories.
Application instruction:
To accept on the 2nd capsule 2 times a day in 1520 minutes prior to a lunch and a dinner, washing down with 1 glass (250 ml) of water.
To keep an adequate drinking regimen: to drink not less than 1.5-2 liters of water a day.
Course duration not less than one month.
Contraindications to additive:
Apetinol's efficiency is confirmed with clinical tests which were carried out in Switzerland and Russia. Safety of a product is confirmed by Gosstandart and the Ministry of Health of the Russian Federation.
Feedbacks of the expert
For writing of this article feedbacks from independent sources were used, and also the composition of additive is carefully analyzed. The detailed research allowed to draw the following conclusions:
Growing thin gordon - this plant is really used by locals for suppression of feeling of hunger and thirst, however its efficiency remains unproven. Action of P57 which was found in its structure it was researched only on mice, and it was entered directly into a brain, however most of scientists consider that P57 collapses if is accepted inside. Adrienne Youdim from Comprehensive Weight Loss Program and its colleague, consider this means not effectively for decrease in body weight. Representatives of US Federal Trade Commission hold the same opinion. Do not forget take Pankramin for better results.
Koleus of a forskoliya (Coleus forskolii) - really effective component that is confirmed at least with two researches. However it is necessary to notice that in structure the plant, but not extract is specified, therefore the quantity of a forskolin can be very low.
Cellulose and pectins - and the first and second is food fibers which have approximately identical properties. Undoubtedly, they render all listed effects, however only when are applied much bigger quantities. Contains in one half of apple or carrots several times more than these substances, they are a part practically of all vegetables and fruit. What can go in in 2 capsules will be useless and any nutritionist can confirm it.
The producer declares that efficiency is proved by researches, however careful search didn't yield results, isn't even mentioned it anywhere.
"Attention" Thus, the unique working component of additive is forscolin, though its quantity remains not known. It is necessary to notice that this component contains practically in all the termogenic which are much more effective and lower at cost. Our opinion isn't an exception, at forums it is very often possible to meet negative feedbacks on Apetinol.
Substances with anti-estrogenic activity quite often use in professional sport for the purpose of braking of transformation of testosterone to female sex hormones (estrogen), and also for increase in muscle bulk.
Very often use of anti-estrogen is combined with reception of anabolic steroids. It is caused by metabolism of endogenous and exogenous anabolic steroid hormones in an organism. Emergence in an organism owing to receipt from the outside of exogenous steroids and (or) accumulation because of the reduced functional ability of a liver of excessively high concentration of endogenous anabolic steroid hormones, first of all, of testosterone, leads to the fact that excess of testosterone doesn't manage to be metabolized completely when passing a physiological way. In this case a part of anabolic steroid hormones passes through a roundabout way of metabolism aromatization at which testosterone turns into estrogen by means of aromatasia enzyme. For braking of transformation of testosterone which strengthens synthesis of proteins and promotes thereby a hypertrophy of skeletal muscles, and also for decrease in contents in an organism of estrogen and shortenings of duration of their action unfair athletes in a pursuit of result can use substances with anti-estrogenic activity.
Classification
Anti-estrogens depending on mechanisms of the influence can be sectioned into three classes:
There is also other classification of anti-estrogenic drugs (Baum, 2001). According to it, they can be divided also into three main classes:
From our point of view, such classification doesn't consider reversibility and irreversibility of effect of drugs on estrogenic receptors and insufficiently fully considers generation of drugs and the mechanism of their action on receptors irrespective of steroid or nonsteroid structure of medicine. Therefore further the description of classes and groups of anti-estrogenic substances will be based on the first classification which in literature is widespread much more widely and much more proved. You can also like Hepatamin.
All representatives of classes of anti-estrogenic substances are forbidden (The list of the forbidden substances and methods, 2008). Reception of these drugs is followed by a series of the expressed side effects, development of numerous pathological states and can even lead to a lethal outcome.
The selective (selective) modulators of receptors of estrogen
The main representatives of the selective (selective) modulators of receptors of ekstrogen IMRE, or SERM (English Selective Estrogen-Receptor Modulators) are tamoxifen (synonyms tamifren, nolvadeKs, nolvadeks-forte, Beale, inta, yenocsifen, tsemid, valodeks, cyto-zonium seu zitazonium), raloksifen (Evistaฎ, "Eli Lilly", Great Britain), toremifen (Farestonฎ, "Orion Pharma", Finland), and also later, tamoxifen analogs which so far are a little researched (idoxifen, keoxifen, droloxifen). All called medicines of class IMRE are nonsteroid substances on the structure. To. to steroid representatives of class IMRE the fulvestrant belongs (fazlodeks).
Tamoxifen
The first anti-estrogen from representatives of class IMRE, tamoxifen, was synthesized by Soiye's group in 1971, and its active use as blocker of receptors of estrogen began. In the last decade the high-selective "net" steroid blocker estrogen receptors a fulvestrant who passes the III stage of clinical testing now is created.
The medicine of class IMRE which is the most often used in pharmacology is tamoxifen, competitive inhibitor peripheral the estrogen receptors. Now the point of view, witnessing that tamoxifen doesn't possess estrogen like action, is confuted as it is proved that in a certain measure medicine shows also estrogenic activity the ratio of its agonistic and antagonistic activity constitutes 45/55.
Tamoxifen is derivative a trifeniletilena; chemical structure 1-[p-(2-dimetilamino) - etoks] - phenyl-trance-1,2-di-phenyl-1-butene, in the form of citrate. Release form: tablets on 10, 20, and 40 mg. Tamoxifen is well acquired in a stomach; the first peak of its concentration in plasma of blood is registered in 1 6 h after introduction, and the second later 24 44 h. Medicine in blood long enough as much as possible to 170 h circulates.
Removal of tamoxifen has long and two-phase character. The initial stage of semi-removal of medicine constitutes 24 53 h, and final, depending on a dose, from 3 to 18 days. Removal of medicine happens generally through a GIT, and with a stake and bile about 85 90% of metabolizirovanny medicine are allocated; its insignificant part is removed from an organism by kidneys.
Tamoxifen is emitted from an organism almost only in the form of metabolites. The main products of biotransformation are provided glyukuronidy and other conjugates, and also uncertain polar metabolites. Primary stage of biotransformation of medicine is the hydroxylation of an aromatic ring with education monohydroxyderivative. In an experiment this intermediate product was more active anti-estrogen, than tamoxifen. Perhaps, in clinical conditions this product of metabolization of tamoxifen promotes manifestation of anti-estrogenic action.
In more detail the pharmacokinetics and biotransformation of products of medicines of tamoksifenovy row were studied at women. After acceptance of the tableted medicine in a medical dose of 0,3 mg-kg "1 body weights its maximum content in blood is observed in an interval between 4 7 h. Elimination half-life when using in such dose constitutes 11 h; in 2 weeks content of tamoxifen in serum of blood corresponds to 0,013 mkg.
The initial dose of tamoxifen for medical practice constitutes 20 mg (on one tablet of 10 mg 2 times a day), then the dose is raised to 30 mg, and in 7 10 days brought to 40 mg a day. Long-term treatment 2,5 3 months, and sometimes and more up to 5 years. For many years treatment by tamoxifen was the gold standard of therapy at women in post menopause, patients with cancer of a mammary gland, with the estrogen-receptor-positive status. In recent years tamoxifen became wider to apply in treatment of women of childbearing age though by some authors justification of such appointment it is quite proved it is challenged (Endocrine..., 2002; Mammary gland..., 2006).
Side effects of Tamoxifenum
This the most widely known among representatives of class IMRE drug possesses also the widest range of by-effects. Though, it is necessary to notice that negative implications of this or that expression are observed after reception of one and all drugs of this class. The main biological effects of Tamoxifenum are taped in endocrine organs. Drug doesn't show neither androgenic, nor anti-androgenic, nor gestagen effect. At men at reception in high doses can reduce the mass of testicles, seed blisters and a prostate that results further in sterility and an impotency. After multiple dose of Tamoxifen the abnormal liver function is observed. At the same time the body weight gain finally lags behind that at the athletes who aren't accepting drugs of this sort. Tamoxifen can cause depression of level of a glucose and leucocytes in a blood, mainly at the expense of cells of a lymphocytic series, insignificant, but often dose decrease of activity of an alkaline phosphatase. Drug oppresses antitoxic function of a liver. When using high doses causes stagnation of bile (cholestasia) and formation of gallstones. Its multiple dose also leads to a hyperplasia of an adenoid tissue of a lien and lymphonoduses, perverting natural reaction of immune system of an organism. Negatively Tamoxifen influences and on osteal system, significantly enlarging risk of development of an osteoporosis and fractures.
Though Tamoxifen promotes decrease of content of cholesterol in a blood, its positive effect on the frequency of depression of cardiologic pathology isn't shown. On the contrary, are available! the observations testifying to augmentation of frequency of development of coronary heart disease, a myocardial infarction and thromboembolisms of a pulmonary artery. At female sportswomen reception of Tamoxifen in high doses can interfere with implantation of an ootid in a uterus wall. Use of this anti-estrogen on early durations of gestation often leads to its discontinuing by the termination of the body height of a uterus caused by Oestradiol and to emergence of teratisms in a fetus (teratogen effect). At prolonged use of Tamoxifen intensive body height of tumor cells is observed. At the same time is 4 (!) times more often than at the persons which weren't accepting this drug development of cancer of liver and endometrium is registered that is caused by significant and long increase in level of steroid hormones.
The medical effect of Tamoxifen and the synthesized late drug of the second generation of selective modulators the estrogenovykh of receptors a raloksifen is taped in the conditions of the raised Oestradiolum level against the background of suppression of secretion of Prolactinum. The main effect of these drugs is referred immediately on a tumoral cell target in which anti-estrogens block binding of estrogens on their specific receptors. Along with direct action on tumor cells, anti-estrogens of class IMRE lead to inhibition of tumoral body height by means of other mechanisms, affecting gipotalamo-pituitary system and ovaries.
Raloksifen
Raloksifen, as well as Tamoxifen, is usually applied to treatment of the extended and progressing breast cancer, and also the prevention of an innidiation. It is less often used at chemotherapy of a hysterocarcinoma and a mammary gland at men.
In comparison with Tamoxifen ๐เ๋๎๊๑่๔ๅํ exerts less expressed impact on a demineralization of bones, to a lesser extent influences change of thickness of endometrium. Raloksifen is issued in the form of tablets, the coated, containing 60 mg of active agent; it it is recommended to apply in a dose 60 mg-days "1 to or during meal. As the agonist influences not genesial tissues and as the antagonist on genesial. Enlarges concentration of the globulins binding hormones (including sexual, and also a thyroxine, corticosteroids), with simultaneous rising of their cooperative contents in a blood without augmentation of level of free fraction. About 60% of drug are quickly soaked up after intake. Before entering in a systemic blood stream ๐เ๋๎๊๑่๔ๅํ it is intensively metabolized with formation of glucuronides. Absolute bioavailability makes only 2%. Time before achievement of average maximum concentration in a blood plasma and biological availability depend on interconversions of a raloksifen in a systemic blood flow and transformations of drug and its glyukuronidnykh of metabolites in an intestine and a liver. Metabolization occurs generally in a liver therefore disturbance of its function is direct contraindication for drug use. Raloksifen is widely distributed in body tissues, and the volume of its distribution doesn't depend on a dose. The elimination half-life makes 27,7 h. The most part of drug and its metabolites is excreted within 5 days and it is found mainly in excrements, and also in urine (6%).
Side effects of raloksifen
Also as well as Tamoxifen raloksifen promotes depression of level of the general cholesterol and LPNP cholesterol, without influencing the content of cholesterol in LPVP. However by results of large-scale placebo - the controlled research RUTH of the EI Lilly company, it doesn't reduce risk of development of coronary heart disease and an acute coronary syndrome. Prolonged use of drug increases risk of emergence of tromboembolic episodes, especially within the first 4 months. Reception of a raloksifen can be followed by inflows, cramps of the lower extremities, and also emergence of peripheric edemas. Considering the above, and also that fact that drug is present at the List of the forbidden substances and methods (2008), its use in practice of sports preparation is hazardous to health of the athlete and will naturally lead to his disqualification.
Unfortunately, in sport, in particular bodybuilding, these anti-estrogens can be applied by athletes at the beginning phenomena of a feminization and to its prophylaxis. In a combination with proviron (not flavored androgen mesterolon) are used for giving to muscles of rigidity and relief at a stage of precompetitive preparation, and also for decrease of the activity the estrogen receptors at the end of a steroid cycle.
Toremifen
For the purpose of decrease of side effects of Tamoxifen and raloksifen in Finland new drug ๒๎๐ๅ์่๔ๅํ (Farestonฎ, "Orion Pharma"), having, according to experimental and clinical data, a series of advantages was developed. First, as a result of stabilization of a structural formula of Tamoxifen due to accession of a chlorine atom larger fastness of molecular structure of drug to metabolic changes, including giperoksidation, in an organism is reached. Secondly, oncogenous and hepatotoxic effects of a toremifen become perceptible much less often. At the same time at prolonged use of toremifen cases of development of malignant tumors and their fast advance are recorded. The number of persons, accepting drug, has a loss of certain types of sensitivity.
On chemical structure toremifen represents nonsteroid derivative a trifeniletilen (Z) - a 4-chlorine-1,2-diphenyl-1 - [4-[2 (di-metilamino) of an etoksa] - phenyl) - 1 butene, is issued in the form of citrate. As well as tamoxifen, toremifen contacts receptors of estrogen and renders anti-estrogenic (or estrogen like) effect depending on duration of treatment, nosological form, a sex of the patient, a target organ and other features. Toremifen competitively contacts receptors to estrogen and brakes estrogen - the mediated stimulation of synthesis of DNA and replication of cages. On experimental models it is shown that the effect of use of medicine in high doses is mediated mainly by anti-estrogenic action. However it is impossible to exclude, as other mechanisms (changes of an expression of genes, secretion of factors of induction of apoptosis, influence on kinetics of a cellular cycle) can also play a part in medical effects of medicine. Under the influence of a toremifen moderately expressed decrease in level of general cholesterol and LPNP cholesterol in blood serum is noted though this fact doesn't influence the frequency of development of complications from cardiovascular system.
Release form: tablets on 20 and 60 mg. Toremifen is quickly absorbed after intake. The maximum concentration in plasma of blood is on average reached in 3 h (from 2 to 5 h). Dynamics of concentration in plasma of blood is described by a curve. Elimination half-life in the first phase (distribution) constitutes 4 h (from 2 to 12) h. In the second phase (elimination) which duration on average equals 5 days (from 2 to 10 days) 99,5% of a toremifen contact proteins of plasma of blood, mainly albumine. The medicine pharmacokinetics in case of intake in doses of 11 680 mg-days "1 has linear nature. Equilibrium concentration of a toremifen in case of acceptance in a recommended dose (60 mg-days-1) averages 0,9 (0,6 1,3) mkg-days" 1.
Toremifen is actively metabolized in an organism. Its main metabolite is dimetiltromephene with average elimination half-life of 11 days (4 20) ๑๓ใ. More than 99,9% of a metabolite contact proteins of plasma of blood in which three more less significant metabolites, prevailing from which are determined. Medicine is removed from an organism generally in the form of metabolites through a GIT, and 10% with urine. Metabolism of a toremifen is performed with participation cytochrome of a R-450-zavisimogo fermental complex by N - demethylations.
Side effects of toremifen
Side effects from reception of toremifen in comparison with Tamoxifenum are less expressed and long and mediated mainly by the hormonal mechanism of effect of drug. In clinical trials the most frequent collateral effects are inflows (more than 20%), a sweating (14), nausea (8), go-a lovokruzheniye (4), peripheric edemas (3%), and also vomiting. Occasionally there can be an increased fatigue, headaches and dorsodynias, body weight augmentation, sleeplessness. Emergence of the specified symptoms, and also emergence of a paresis, a tremor in extremities, an anorexia, an asthenia is important for sports pharmacology.
At clinical use of toremifen in an oncology, and also at sportswomen the orientation of shifts of content of hormones similar to action of Tamoxifen in blood serum becomes perceptible, but their fluctuations are expressed to a lesser extent, except essential (by 4 times) depressions of level of follicle-stimulating hormone (FSG). At reception of toremifen Oestradiol level also increases, but it approximately at 70% of the sportswomen accepting drug is followed by simultaneous rising of maintenance of progesterone.
It is necessary to notice that lack of reliable changes of content of the studied hormones is explained by larger individual fluctuations though quite expressive dynamics concerning Prolactinum, Progesteron and FSG is distinctly traced (tab. 3.8).
As well as other drugs of class IMRE, toremifen causes abnormal liver functions what rising of activity of hepatic transaminases in blood serum testifies to. At the beginning of reception of toremifen development of hypercalcemia with disturbance in the subsequent density of a bone tissue and emergence of an osteoporosis is possible though these negative implications are observed less than at reception of Tamoxifenum. The osteoporosis caused by use of inhibitors of an aromatasia is possible to prevent and treat by peroral and intravenous use of bifosfonat (klodronat sodium, ksidifon, pleostat, bonefos, arediya, fosamaks, bondronat, rizedronat๒) which prevent depression of density of a bone against the background of reception of selective blockers the estrogen receptors.
For assessment of mechanisms of action and efficiency of use of drugs of class IMRE it is necessary to consider not only their ability to be bound to receptors, but also significant effect on a hormonal homeostasis of the athlete that is very often ignored in nogone behind result. It is important that these drugs in clinical conditions are used mainly at women in the period of post menopause, and also at patients with cancer of a male mammary gland with obviously changed hormonal background. Therefore reception of anti-estrogenic drugs of class IMRE by female sportswomen of childbearing age, and also men, can do irreparable harm to organism.
Fulvestrant
The new antagonist of estrogens the fulvestrant (fazlodeks) who recently appeared in the pharmaceutical market and still finally not studied in clinical conditions, has steroid structure. Unlike Tamoxifen completely blocks trophic action of Oestradiol and has no estrogenic activity (therefore is called "pure" anti-estrogen). The first "pure" anti-estrogen was synthesized in 1987. Subsequently the fulvestrant ("AstraZeneca", Great Britain) who was introduced in clinical practice in June, 2002 was its most active derivative.
On a structure the fulvestrant is very close to ethenyloestradiolum is trietilen ((((((((((((((((ICI 182.780), eterizovan in positions of a 7-or 11 - and Oestradiolum.
The Fulvestrant is new type of antagonists the estrogen receptors. Being bound to receptors, it blocks them, causes degradation and the progesteron receptors reduces an expression. Its affinity to receptors of estrogens is 100 times higher, than at Tamoxifen. Indications to use of fulvestrant is the estrogen-receptor-positive breast cancer at women in a menopause progressing after anti-estrogenic therapy by Tamoxifen.
On pharmacological action the fulvestrant considerably differs from Tamoxifenum in lack of properties of an agonist and on expression of blocking the estrogen receptors. At the expense of steroid structure a fulvestrant with much bigger affinity, than Tamoxifenum, is competitively bound to estrogen receptors.
Results of the researches conducted by M. Berhens and employees in 2006 showed that action of this steroid representative of class IRME is based on a deionization of receptors that interferes them with a sgerichesky regulation. In the researches in vitro and in vivo it is established that the fulvestrant reversibly enlarges the number of transformations of genetic nuclear material with parallel depression of number of defective molecules estrogen receptors in cells targets. It also multilaterally influences alarm ways of these receptors, blocking a dimerization, nuclear localization of an estrogen receptor and a receptor - a dependent transcription, and also reducing the number of a receptor in a cell.
According to immune histochemical researches, one intramuscular injection of drug renders dozozavisimy depression of quantity the estrogen and the progesteron receptors and Ki-67 gene receptor expression. So, in a dose of 250 mg the fulvestrant reduces the number of active receptors more than Tamoxifen.
During the III phase of clinical trials existence of positive properties of a fulvestrant in endocrine therapy of a breast cancer was shown. At patients against the background of adyyuvantny (postoperative) therapy or the first line of endocrine therapy efficiency of a fulvestrant along with good tolerance was comparable with that of anastrozol (see the second class of anti-estrogenic drugs).
Fulvestrant, "pure" anti-estrogen, passes the last phase of clinical tests as a blocker the estrogen receptors now. Due to the insufficient number of researches the fulvestrant isn't registered as "pure" anti-estrogen yet and described as the drug reducing activity the estrogen receptors.
Fulvestrant by short courses inside in a dose from 6 to 18 mg daily or in the form of intramuscular injections once a week in a dose from 50 to 250 mg is applied; on other sources once a month at patients with cancer of a mammary gland in a post menopause. Release form: tablets on 6 mg; Solutio oleosa in vials on 250 mg / 5 ml.
Use of drug before operation the estrogen and progesteron receptors reduces a proliferation and (or) a reduction and disappearance of an expression. It reduces estrogenic activity in the majority of nonresectable cases of a breast cancer and is in this regard twice more active, than a megestrol an acetate one of synthetic Progestinums which is also possessing anti-estrogenic action, generally due to depression of synthesis of estrogens (see the third class of anti-estrogenic drugs). The activity depression the estrogen receptors under the influence of a fulvestrant has dose character. The effect of influence on a pituitary and subthalamic arch at drug is absent. Thus, the fulvestrant as drug can be used in the second line of anti-estrogenic therapy of a breast cancer.
Side effects of fulvestrant
The side effects arising after reception of fulvestrant are same for all representatives of class IMRE. Rather often there are nausea, sometimes vomiting, a constipation, a diarrhea, dermal rashes, the increased sweating, headache, abdominal cavity. Occasionally there are a grippopodobny syndrome, sleeplessness, a depression, paresthesias, pharyngitis, dispnoe, tussis. At reception of low doses of drug side effects, such as a nagrubaniye of mammary glands or arise less than at reception in standard dosages. Against the background of low-dose therapy by a fulvestrant inflows of fever should be stopped in 60 70%, and against the background of standard dosages already in 80 90% of cases. The same treats also conservation of density of a bone tissue. Process of its depression: the quantity of cases of an osteoporosis are higher at reception of high doses of drug, than at use of standard doses. Therefore use of a densitometry and definition of biochemical markers of a destruction of a bone tissue is recommended to the patients accepting a fulvestrant even in low doses without the corresponding therapy of maintenance. Frequency of emergence of this side effect can be reduced by use of adequate doses of drugs of a calcium and vitamin D.
The Fulvestrant in comparison with Tamoxifen and a megestrol an acetate influences changes of a lipide profile more favorably. At reception of standard doses of drug the maintenance of LPNP and LPONP respectively decreases by 12,3 and 14,2%, and the LPVP level, on the contrary, increases. At the same time the content of the general cholesterol and triatsilglitserol practically doesn't change.
For the unclear reasons, in the section S4 of the List of the forbidden substances and methods (2006) this; drug is carried to the third class of "other anti-estrogenic substances". However according to the action mechanism the fulvestrant as the steroid representative of IMRE has to be with good reason carried not to the third, and to the first class "substances with anti-estrogenic activity.
However in connection with incompleteness of the III phase of clinical tests and rather scrappy data on its pharmacodynamics and a pharmakokinetics, as a selective blocker the estrogen receptors, despite his expressed physiological activity wasn't widely adopted drug yet.
Therefore, according to the List of the forbidden substances and methods (2008), all medicines of an antiestrogen orientation (irrespective of a class) belong to banned drugs even if individually they aren't registered in the list of those yet. In clinical conditions it is accepted to transfer if necessary after administration of drugs of class IMRE patients to therapy by means of use of blockers of an aromatasia in recent years.
Selective modulators of estrogenic receptors (SMER, or English SERM) (And). Estrogenic receptors concern to group of the receptors regulating a transcription. Female sex hormone Oestradiolum is an agonist of these receptors. Substances of this group can work as antagonists though in many tissues behave as agonists. Such behavior is explained by the fact that for accession to an estrogenic receptor the ligand has to accept specific conformstion. The complexes of a ligand and an estrogenic receptor which are bound to certain sites of a genome act as koaktivator or korepressor. The structure of koregulyator in different tissues is various so effects of various drugs of the SMER group of an organospetsifichna. From the medical point of view important that drugs of estrogenic and anti-estrogenic action from this group of drugs differ on specificity.
It makes sense to give the characteristic to this group of drugs and to pay attention to their activity in the period of a postmenopause. Constant reception of Oestradiolum increases risk of development of endometrial cancer. If gestagena are in addition prescribed, then the risk of a disease decreases. More cases of a breast cancer are taped that however can speak intensifying of medical control. Oestradiolum increases risk of a thromboembolism. It facilitates course of a climacterium, weakening inflows of fever and a diaphoresis, and at the long use reduces risk of development of an osteoporosis as loss is interfered by the estrogenzavisimykh of the making bone tissues. However it isn't recommended to apply estrogens to this purpose after all because of an adverse ratio of action and possible risk.
Clomifene derivative a stilbene is applied to treatment of sterility at women. Owing to opposing action on estrogenic receptors of a forward share of a pituitary body negative feedback from action of Oestradiolum is broken, and production of Gonadotropinum is enlarged. Body height of the FSG level leads to acceleration of maturing of a follicle. Clomifene is prescribed at a failure of function of a yellow body owing to disturbance of maturing of a follicle, and also at polycystosis of ovaries. Drug is accepted only in certain days of a cycle, it has no constant effect.
Tamoxifen derivative stilbene is applied in case of the spreading tumor of a mammary gland for the purpose of blocking of estrogenic incentives to proliferation. Medicine facilitates course of a climax thanks to anti-estrogenic action. Along with it it has agonistichesky effect which shall be considered as risk factor.
Raloksifen apply to prevention of osteoporosis during the post-climacteric period. About benefits and shortcomings of medicine see the table.
Antagonists gestagen receptors. In a week after fertilization the embryo (in the form of blastotsita) takes root into endometrium. The germ produces LG operating similarly and promoting preserving a yellow body, products of progesterone and interferes with emergence of periods. Mifepriston as the antagonist the gestagen receptors interferes with preserving a mucous uterus in early terms of pregnancy, i.e. acts as abortive means. The possibility of its application is widely discussed (in respect of comparison of side effects of medicine and surgical intervention), and also the ethical aspect of its appointment is discussed. In Germany it is withdrawn from sale.
Anti-estrogenic medicines and sport
The other substances capable one way or another to reduce the level of estrogen in blood belong to the third class of anti-estrogenic medicines. Clomifene and its analogs, and also medicines of different pharmacological groups cyclophenyl and proviron belong to them first of all tamoksifen like medicine.
Clomifene in the form of citrate (clomid, klostilbegit, ardomon, gravozan, serofen, serpafar, it is fertile, fertomid, etc.) is close to nonsteroid estrogen to a dietistilbestrol, however, doesn't show estrogenic activity. In chemical structure clomifene is similar to the main representative of anti-estrogenic medicines from class IMRE tamoxifen and represents 1-[4 (2-dietilaminoetoks) - phenyl] - 1,2-diphenyl - 2-chlorethylene citrate.
Clomifene belongs to anti-estrogenic medicines as specifically contacts estrogen receptors in a hypothalamus and ovaries. In small doses, thanks to the mechanism of negative feedback, clomifene and its analogs strengthen secretion of gonadotrophins (Prolactinum, follikulostimuliruyushchy and lyuteiniziruyushchy hormones) and stimulate an ovulation. In case of small content in an organism of endogenous estrogen clomifene shows moderate estrogenic effect, however, in case of high concentration of own estrogen has anti-estrogenic effect. Reducing content of the circulating estrogen, induces passing strengthening of emission of gonadotrophins; in high doses can break it.
One more distinctive feature of clomifene is that under certain conditions he acts not as a blocker, and as the activator the estrogen receptors. Everything depends on whether joined along with drug, a receptor a certain cofactor. The type of a cofactor, i.e. in one tissues (a hypothalamus, thoracal glands) clomifene is a blocker the estrogen receptor, and in others (bone tissue) the activator of the same receptors. The last effect of clomifene on an organism is positive as helps to avoid development of an osteoporosis.
Such antiesrogen drugs as clomifene in the corresponding doses are used for stimulation of an ovulation at anovulatory dysfunction of ovaries, sterility, uterine bleedings of a dysfunctional genesis, some forms of an amenorrhea, etc. Thanks to gonadotrophic influence, this drug is used at an androgenic nedstatochnost, an oligospermatism at men and at a delay of sexual and physical development in teenagers.
Release form: tablets on 50 mg. At intake it is well soaked up. It is metabolized in a liver, excreted with bile, is exposed to an enterohepatic recycling. The elimination half-life makes 5 7 days.
Administration of drug at women during six cycles even in therapeutic doses (on 50 mg within 5 days) can lead to vision disorders, menorrhagias and a syndrome of hyper stimulation of ovaries (at cancellation); is followed by inflows, a dyscomfort in a stomach and an intestine, nausea, vomiting, a depression, cramps, and also visual disturbances. Besides, clomifene is enough that is expressed in emergence of sleeplessness, headache, giddiness. Contraindications for administration of drug are the expressed dysfunctions of systems of natural detoxicating (a liver, kidneys), uterine bleedings of an obscure etiology, including, in the anamnesis, an oothecoma, a tumor of a pituitary body or a pituitary failure, pregnancy.
Considering that in a hypothalamus genotypically it isn't enough full-fledged man of the receptors having affinity to estrogens, use of clomifene in strength sport is theoretically possible for stimulation of production of Gonadotropinums and intensifying of development of endogenic Testosteron-Depotum. Use of this drug for women, in connection with many-sided influence on a hormonal homeostasis, will lead to reproduction of estrogen and Progesteronum that will extremely negatively affect sportswear of the athlete. Therefore even in bodybuilding clomifene reception by women in therapeutic doses is limited two weeks with the subsequent break of the same duration. You can try Hepatamin.
Cyclophenyl (Fertodur, Neoclym, Rehibin, Sexo-vid) is not anabolic androgenic steroid which isn't registered in Ukraine. Drug is generally used for intensifying of natural development of Testosteron-Depotum at its failure. Popular literature for body builders often incorrectly describes it as nonsteroid drug. Cyclophenyl has the anti-estrogenic properties caused by partial blockade the estrogen receptors and at the same time enlarges own development of Testosteron-Depotum an organism. Cyclophenyl possesses also very poorly expressed estrogenic action.
Some athletes accept cyclophenyl together with steroids to support the low level of estrogen. Result of it, as well as reception of proviron, retardation of processes of a delay of liquid in tissues owing to reception of anabolic steroids and decrease of implications of a gynecomastia is. A musculation of the athlete takes at the same time more resilient form. Cyclophenyl can be acceptable during preparation for competitions. Body builders use it less often as they prefer available Tamoxifenum and proviron.
Cyclophenyl is noneffective at women as it has positive influence only on men's hormonal system. The effect of administration of drug in bodybuilding occurs not earlier than in a week.
Release form: tablets on 100 and 200 mg. At administration of drug in high doses cases of emergence of an acne, augmentation of a libido and feeling of inflows meet. The first two secondary symptoms are especially indicative. After the termination of administration of drug some athletes report about oppressed mood and decrease of physical force. On expression of anabolic effect of other anabolic steroids, widespread in bodybuilding, cyclophenyl in comparison with them is one of the most weak.
Proviron (mesterolon) is androgenic drug for oral administration which is rather slowly metabolized and isn't exposed to aromatization process. Proviron carries anti-estrogenic drugs because it has two-dimensional affinity with receptors of estrogens. It is necessary to notice that there is a drug under the similar name of proviron-depot (Proviron-depot) which is a combination of Testosteroni propionas and Testosteroni oenanthas and has no anti-estrogenic activity.
Release form: tablets on 25 mg. As the main active ingredient is included into structure of a proviron mesterolon, having androgenic and insignificant anabolic activity. Is a synthetic analog of Testosteron-Depotum. In clinical conditions it is applied at men sublingual or inside on 25 mg by 3 4 times a day within several months at a failure of function of gonads, disturbance of a potency, the sterility bound to an oligospermatism and a failure of cells of Leydiga and also at aplastic anemia. Course of treatment of 1 2 month.
It is contraindicative at a prostate cancer, liver tumors.
Contrary to unjustified judgments which often meet in popular literature for bodybuilders proviron isn't able to prevent aromatization of Aethers of Testosteron-Depotum in estrogens. In a dosage to 250 mg a day administration of drug is practically not followed by emergence of side effects. Advantage of this drug is almost total absence of suppression of activity of Gonadotropinums and process of a spermatogenesis.
The listed above drugs Clamidum, cyclophenyl and proviron conditionally belong to the class of blockers of estrogenic receptors; at the same time they don't reduce Oestradiolum level in a blood. Conditionally as in addition have influence on various parties of a metabolism. Therefore in this chapter they entirely are reasonably carried to the third class of anti-estrogens.
Anti-estrogenic drugs of the third class also include the agonists of rileasing-factors of gonadotrophic hormones (busereline and its analogs) for the first time used in 1982 for an ovarialny supressiya as an ovariectomy alternative at patients with cancer of a mammary gland, and partially a megestrol the acetate having anti-luteinizing, and also anti-estrogenic effect. For secretion inhibition, but not synthesis of Prolactinum, can be used Parlodelum and Dostinex. Their independent use in clinical conditions as anti-estrogens much less effectively, than administration of drugs of class IMRE.
At introduction to an organism rileasing-factors of a natural parentage (from a hypothalamus of sheep, pigs), and recently mainly their synthetic analogs, cause at first some rising of contents in Testosteron-Depotum blood in men (as defines their use by body builders) and estrogens at women. Subsequently, in 3 weeks of continuous introduction, there is a depression of content of sex hormones, up to their total disappearance, proceeding the entire period of use of drugs. This effect has reversible character: after cancellation of reception of rileasing-factors contents in a blood of Testosteron-Depotum and estrogens is gradually restored.
Under the influence of these anti-estrogenic drugs there is not only a release of Gonadotropinums, but also inhibition of their synthesis and weakening of linkng with androgenic and estrogenic receptors. Rising of contents in bloods of Testosteron-Depotum and linkng with estrogen receptors also defines use of rileasing-factors by body builders.
Anti-estrogenic drugs of this group find the main application at treatment of malignant neoplasms and pretumor diseases: at men of a prostate cancer, at women a breast cancer and endometrium, and also a uterus fibromyoma on condition of sensitivity of these neoplasms to changes of the hormonal status. To drugs of group of Gonadotropinums-rileasing-factors, more precisely than the subthalamic factors releasing pituitary body hormones analogs of gonadorelin belong. These are agonists of rileasing-factors of luteinizing and follicle-stimulating hormones. All of them are close on structure and are the peptide substances containing 8 10 amino-acid remains.
Are issued in various dosage forms for hypodermic, intramuscular, intranasal introduction. Some drugs are produced in the prolonged form (depot).
Buserelin is a synthetic analog of a gonadotrophin-rileasing-factor. Is issued; type of acetate (C60H86N16O13-C2H402). Competitively contacts receptors of cages of a forward share of a hypophysis and blocks their gonadotropny function, inhibiting L G secretion and FSG that leads to suppression of synthesis of sex hormones in ovaries and seed bubbles.
Release form: 0,3% - ้ solution for injections, 0,2% - ้ an aerosol, an implant in the form of two dosed cores on 6,6 mg for hypodermic introduction (Hoechst AG, Germany). Apply medicine intranazalno and hypodermically.
Buserelin has a wide range of side effects and can cause the dispeptichesc phenomena, impotence, a ginekomastia, allergic reactions (pour), mental disturbances (unmotivated alarm, sleeplessness, violation of memory and disorder of attention, a depression), dizziness, reactions, dryness of mucous membranes and skin, violation of functions of a liver, leucio-and thrombocytopenia, a hearing disorder. It is contraindicated in case of pregnancy and in the period of a lactation, and also in case of a spinal cord, hypersensitivity, violation of passability of mochetochnik.
Gozerelin (Zoladex "AstraZeneca") is synthetic decapeptide an analog of a gonadotrophin-rileasing-factor (C59H84N lgOI4). On action it is close to a buserelin. Is issued in the form of special depot medicine the core (capsule) containing 3,6 or 10,8 mg gozereli-on acetate. About 3,6 mg of a gozere-lin (depot form) once in 28 days are entered hypodermically. Duration of application can constitute up to 6 months.
Side effects: men have a violation of passability of mochetochnik, women have inflows, fluctuations of arterial pressure, violation of a menstrual cycle, allergic reactions and other skin manifestations. It is contraindicated in case of pregnancy and in the period of lactation.
Leyprorelin (lyukrin-depot, prostap) is 6-0-leytsinom-9-(N - ethyl - L - prolinamid) - 10-deglitsinamidy lyuteiniziruyushchy hormone a rileasing-factor (pork). Analog of a gonadotrophin-rileasing-factor. On action it is close to a buserelin. Bioavailability of medicine makes 75 98%, time of semi-removal of 3 h.
In case of intramuscular introduction is released from copolymer within 1 month, at the same time during the first 7 days content of sex hormones increases, and by 21 28 days decreases and remains at this level in case of the subsequent entering of medicine. Is issued in the form of the lyophilized microspheres in bottles on 3.75 and 7> 5 mg. The course of treatment shan't exceed 6 months.
Side effects: headache, dizziness, sleep disorder, dyspepsia, puffiness of the person and lower extremities, violations of sight and hearing, depression, decrease in a libido. Men, besides, can have a ginekomastia, reduction of testicles, and at women vaginit, acne, girsutizm, decrease in density of a bone tissue.
Triptorelin is also a synthetic analog of a Gonadotropinum-rileasing-factor which from natural differs in smaller rate of a biotranformation and slower elimination from an organism.
Is issued in the form of an acetate (C64H82N18O13 hs2n402). At intramuscular and hypodermic introduction bioavailability makes respectively about 39 and 69%, time of semi-removal of 7,6 h. Release form: 0,01 and 0,55% - ้ solutions for injections in disposable the syringe ampoules, powder for suspension for hypodermic introduction in vials on 0,1 mg, and also in the form of depot on 3,75 mg.
Prescribe " subcutaneously or intramusculary. It is subcutaneously applied at sterility treatment. With success also period at women with positive estrogen - the receptor status is used in pre-at cancer therapy of a mammary gland. Clinical trials showed that this drug has no direct cytotoxic effect on malignant cells.
Side effects at use of a triptorelin are similar to those when using a buserelin.
Medroksiprogesteron (depot pro-belief and pro-belief of production "Upjohn" (Belgium), farlutat, cyclotala, etc.), the representative of gestagen (Progestinums), belongs to the third class of anti-estrogenic drugs. On chemical structure it is close to Progesteronum derivatives, on the main action is Progestinum, however has also anti-estrogenic activity. In this regard it is generally used as antitumoral drug at gormono-sensitive (estrogen-receptor-positive) tumors of a mammary gland and a body of the womb. At a breast cancer correlation between efficiency of a medroksiprogesteron and concentration of receptors of estrogens and Progesteronum in a tumoral tissue is noted. In oncologic clinic it is generally used as drug of additional (palliative) therapy.
On structure it is a steroid, 17-oxy-6os-methyl-pregn-4-en-3,20-diona acetate. Release form: the tablets containing from 5 to 500 mg of active agent; granules from 2 to 1000 mg; 15 and 20% - I am suspension in vials and disposable the syringe tubes; the dosed aerosol. It is applied mainly intramusculary on 0,5 1,0 g a week it is long or on 500 mg a day within 28 days; inside and intranazalno in the form of an aerosol (only cyclotala, "Lemery", Mexico).
At use of a medroksiprogesteron of an acetate emergence of nausea and vomiting, edemas, arterial hypertension, tromboembolic episodes (thrombophlebites and thromboembolisms) is possible; abnormal liver functions, body weight augmentation, allergic reactions become perceptible. It is necessary to emphasize that all these reactions are characteristic of anti-estrogenic drugs, irrespective of their belonging to this or that class. With care it is necessary to prescribe at a diabetes mellitus and to persons with gemoreolo-gichesky disturbances (with prevalence of processes of trombogenez).
The similar mediated action on receptors of estrogen has a megestrol in the form of acetate ("Bristol-Myers Squibb", the USA), the synthetic Progestinum suppressing development of pituitary Gonadotropinums and having anti-luteinizing effect. It supressirut a producing androgens adrenals and ovaries, at the same time reducing by 80% also the level of estrogens in a blood. It is applied mainly to treatment of patients with cancer of a mammary gland in post menopause as the second line of a hormonetherapy, endometrial cancer; at an anorexia and cachexia at patients with AIDS.
Release form: tablets on 40 and 160 mg; suspension for intake in vials on 120, 240 and 480 ml with the content of active agent of 40 mg-ml "1. It is applied mainly in a daily dose of 160 mg (40 mg 4 times a day); at cachexia at patients with AIDS the daily dose can be doubled and more to 800 mg.
It is necessary to notice that megestrol is one of the earliest drugs for which antiaromatasia action was shown. However in connection with chemical structure (Progestinums of steroid character), we consider proved to carry them to this, but not to the second class ("Aromatase blockers") of anti-estrogenic substances.
Very conditionally to anti-estrogen to ny drugs dopaminergetik Bromocriptinum (Parlodelum, "Sandoz", Switzerland) and caboreldine (Dostineks, "Upjohn", the USA), the secretions of Prolactinum Used mainly for suppression can be carried. Are prescribed in clinical conditions at a galactorrhea, benign tumors of mammary glands, acromegalia, a parkinsonism. Reception of these drugs often is followed by nausea, vomiting, a headache, giddiness, a sleepiness, and also emergence of a peripheric vasospasm. Kabergolin, besides, can provoke hypotensive reactions, an anorexia, a diarrhea, sleeplessness, edemas, emergence of inflows, feeling of a congestion of a nose.
Bromocriptinum is issued in tablets and capsules on 2.5 mg, cabergolin in tablets on 500 mkg.
And, at last, in connection with ability to block specific receptors of cells of gonads (gonads), including estrogen receptors, to anti-estrogenic substances it is partially possible to carry the chorionic gonalotropin person (CGP) rendering as well luteinizing action (synonyms: gonafor, gonakor, Pregnylum, profaz, Antelobinum, etc.). In clinical practice it is applied at men and women; for stimulation of activity of gonads in case of dysfunction of a hypothalamus and a pituitary body.
Drug is produced in the form of the lyophilized powder in vials and ampoules (on 500 5000 mg) complete with a dissolvent for injections. When using HGCh allergic reactions, a hypertrophy of testicles are possible: at a drug over dosage hyper stimulation of ovaries. Prolonged use of drug in connection with possible formation of antibodies and suppression of gonadotrophic activity of a pituitary body isn't recommended.
HGCh can be used by some athletes for suppression of activity of receptors of estrogen therefore it treats drugs from the List of the forbidden substances and methods (for men).
Thus, it is possible to draw the following conclusions. First, medicinal preparations, various on structure and the main mechanism of action, belong to anti-estrogenic drugs. Most of them is used in medical practice for treatment of malignant neoplasms, so far as concerns salvage or extension of life of the patient or, to a lesser extent, for correction of the hormonal status in case of serious functional violations. Secondly, use of anti-estrogenic substances of any class has a wide range enough serious by-effects of different degree of expression. Some of them can demand further surgical intervention (gynecomastia), and others directly threaten the athlete's life in connection with development of cardiovascular pathology or thromboembolism of a pulmonary artery. It is unlikely theoretical "advantage" of reception such enough toxiferous drugs is comparable to risk from their unreasonable use. Therefore it is necessary to represent accurately what can lead use of these drugs, especially at excess of the recommended therapeutic dose to. High toxicity of drugs with an anti-estrogenic orientation also served one of the reasons of their including in the List of the forbidden substances and methods. In case of emergency of reception of anti-estrogenic drugs in connection with treatment of various diseases at which they pathogenetically are reasonably applied strict control from the sports doctor and the expert of the corresponding profile is necessary for safety and conservation of health and the athlete's life.
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