Nitroglycerine*
— Glycerol C3H5 (HO) 3, under the action of nitric acid or a mixture of nitric and sulfuric acids, can form nitric acid esters: C 3H5 (HO) 2(NO3), C 3H5 (HO)(NO 3)2 and C 3H5 ( NO 3)3.
Of these, only two are currently known - mononitrogen and trinitrogen. The first, obtained by mixing glycerin with moderately diluted nitric acid (1 part HNO 3 to 3 parts H 2 O), is a liquid that is easily soluble in water and alcohol, almost insoluble in ether and does not explode on impact. Trinitrogen ether is obtained by the action of a mixture of the strongest acids, nitric and sulfuric, on glycerin and differs from the previous one in its relation to solvents, and especially in its extremely strong explosiveness upon rapid heating and impact. This last ether is the powerful explosive substance that was first prepared by Sobrero in the Pelus laboratory in 1847 and has since been called N in explosive technology. Among the first persons who gave impetus to its use in practice, Professor Zinin should be named ( 1854) and artillery lieutenant (later lieutenant general) V.F. Petrushevsky, but the main merit in this regard undoubtedly belongs to the Swedish engineer. Alfred Nobel, who invented a way (by turning it into dynamite) to make it safe enough for transportation and handling. Currently, N. production represents one of the prominent branches of the manufacturing industry.
1) To prepare nitroglycerin, the general reaction for producing nitric acid esters of alcoholic substances is used, i.e. the action on glycerin (1 part) with strong nitric acid (3 parts) in the presence of concentrated sulfuric acid (6 parts):
C 3H5 (HO) 3 + 3HNO3 = C 3H5 (NO 3)3 + 3H2O.
The presence of sulfuric acid is necessary, on the one hand, to absorb the water released during the reaction, which, otherwise, diluting the nitric acid, thereby preventing the completeness of nitration (incomplete nitrogen esters of glycerol would begin to be obtained), on the other hand, to release the resulting N. from a solution in nitric acid, since it, being highly soluble in this acid, does not dissolve in a mixture of it with sulfuric acid. This reaction of N. formation is accompanied by significant self-heating, because both the esterification of glycerol with nitric acid and the combination of the resulting water with sulfuric acid separate heat. If, as a result of self-heating, the temperature of the mixture increased to 50°, then the action of the acids would easily be directed in the other direction: the oxidation of glycerin and nitrogen would begin, accompanied by the rapid release of nitrogen oxides (red-brown vapors) and even greater self-heating, which could finally lead to to the explosion of the resulting nitroglycerin. Therefore, the reaction should be carried out with constant cooling of the mixture of acids and add glycerin to the latter little by little, stirring each poured portion. Formed directly upon contact with N. acids, having a lower beat. weighing (1.6) compared to the acid mixture (not less than 1.7), floats to the surface, from where it can be collected after the reaction is completed. But self-heating during the preparation of N. can be counteracted in another way, namely by forcing part of the heat to be released before the formation of N. itself and, in particular, by slowing down the reaction of this formation by a preliminary change in the chemical state of the reacting substances. Boutmi and Faucher achieved this by first preparing two separate mixtures - sulfur-glycerin and sulfur-nitrogen. The latter is composed of equal parts of H 2 SO 4 n HNO 3, and the first of one part of C 3H5 (HO) 3 with a triple amount of H 2SO4, which produces sulfur-glycerol ether C 3H5 (HO) 2HSO4 with significant heat release. If both mixtures, after cooling, are mixed together in such a proportion that the ratio of the amounts of C 3H5 (HO) 3, H 2 SO 4 and HNO 3 is approximately the same as in the previous method, then: a) conversion of sulfur-glycerol ether in N. it proceeds gradually and slowly, so that it ends only after 12 or even 24 hours; b) the amount of heat released during this entire process is significantly reduced, since that part of the heat that occurs as a result of the combination of water with sulfuric acid has already been released earlier during the formation of the sulfur-glycerin mixture, and on the other hand, the glycerin itself, having turned into sulfur-glycerol ether, then lost part of its energy in the form of heat. Due to both of these reasons, the preparation of N. using this method cannot be accompanied by significant heating, since the reduced amount of heat during the slow course of the reaction has time to be transferred to the environment. The reason why the three-body system C 3H5 (HO) 3, H2SO4 and HNO 3, regardless of the initial state, is transformed so that glycerol preferentially combines with nitric acid, and sulfuric acid with the liberated water, according to Berthelot’s interpretation, is that that it is precisely such a final system of bodies that corresponds to the greatest separation of heat, i.e., the principle of maximum work accepted by this scientist as a general rule for the course of chemical reactions. In reality, the question is more complicated, because in the reaction of nitrogen formation, as in the vast majority of other reactions, the usual operation of the general law of chemical masses is observed. In fact, experiments show that from a given amount of glycerin, under ordinary preparation conditions, the theoretical yield of its trinitrogen ester is never obtained, namely: from 100 parts of C 3H5 (HO) 3 no more than 234, and usually about 210 parts. instead of 247. This is explained by the fact that, as a given amount of glycerol is added, less and less HNO 3 remains in the acid mixture, while the mass of H 2SO4 remains the same, until such a ratio finally occurs between the amounts of that and another acid, in which, in the presence of previously isolated water, glycerol is converted into incomplete nitrogen esters or even completely ceases to be nitrated, forming only sulfuric acid ester.
Factory preparation of N. can be done using both of these methods. But the Boutmi and Faucher method, used soon after its appearance at several factories (French - in Vonge; Belgian - in Namur; English - in Pamberey), is now completely abandoned, as less profitable (product yield is only 190 parts out of 100 including glycerin) and, moreover, (judging by the accidents at these factories) no safer compared to the usual method, especially since with such prolonged contact of N. with acids (12 - 24 hours), which occurs during nitration by This method still does not prevent the possibility of developing an oxidation reaction with the rapid release of nitrogen oxides. As for the usual method, being generally more economically advantageous, it is, at the same time, now considered safer if the starting materials are of proper purity. The form in which it is used in factories may vary greatly in its details. At first, N. was usually prepared in small portions, similar to how it is done in laboratories. So, according to Kopp, to 2 8 00 g of an acid mixture in a clay or cast iron pot placed in a vessel with water (5 - 6 liters), add 350 g of glycerin from a mug with constant stirring with a glass or iron rod; the resulting mixture is poured into a separating funnel and the settled acids are released, and N. is poured into the above-mentioned vessel with water for washing. Later, on the one hand, they began to increase the portions of glycerin processed at a time, and on the other, to use various mechanical devices for stirring during nitration. An important improvement in the latter respect was the use (for the first time at the Mowbray factories in Massachusetts) of blowing the mixture with compressed air, which produces not only agitation, but also cooling due to its expansion: clay pots placed in a common water bath around an exhaust pipe are poured 7 - 8 kg of an acid mixture of ordinary composition, see above), and 0.8 kg of glycerin is added to this mixture using siphons from bottles placed on the shelf; in this case, a stream of compressed air is passed into each pot through a special tube. Since 1880, they began to move to methods in which large quantities of glycerin were processed at a time, as is done at Nobel’s factories, which we will describe in more detail.
The starting materials, i.e. nitric, sulfuric and glycerin acids, must be as clean and anhydrous as possible, namely: sulfuric acid. V. 1.84 with a content of at least 95 - 96% H 2SO4, nitrogen - sp. weight 1.50 with a content of not less than 93% HNO 3 and glycerol. V. 1.26 with a content of no more than 3% water. Impurities such as significant amounts of nitrous oxide in nitric acid or the presence of fatty acids in glycerin are especially harmful, since they contribute to the initiation of dangerous oxidation reactions and interfere with the purity of washing the prepared N. The preparation of the acid mixture is carried out in large cylindrical cast iron vessels with or without stirrers inside stirrers In the latter case, the entire weighed amount of nitric acid is poured in first, and sulfuric acid in an appropriate amount is added afterwards, due to the difference in beats. weights of both acids by local heating, homogeneity of mixing is achieved by itself. The mixing proportion currently used is approx. per 1 part of nitric acid. 1.666 parts (mostly) or 2 parts (less often) sulfuric acid. From the mixing vessels, the mixture is transferred to nitration apparatus either by gravity, or using thick-walled cast iron pneumatic lifts (montejus). Relative amounts for nitration - for 1 part of glycerin from 8 to 8.5 parts of the acid mixture. This amount of the mixture is significantly greater than that required by theory, since 8 - 8.5 parts of it contain about 3 parts of HNO 3, while according to theory, only 2.05 parts of this acid are required to convert 1 part of glycerol into N. In large-scale production, nitric acid is usually prepared at the same plant from Chilean saltpeter using a spent acid mixture. The nitration of glycerol itself is carried out in a nitration apparatus (Fig. 1).
Fig. 1.
It consists of a lead vessel A
, placed in a wooden vat
B
and closed with a removable lead lid
I
, which is covered with cement during operation.
Passing through the lid are: the ends of two lead coils D
located inside the apparatus and intended to cool the mixture by means of cold water flowing through them;
tube C
, which brings compressed cold air into the apparatus for stirring during operation;
pipe F
, which removes nitric acid vapor from the apparatus;
thermometers E
, of which one reaches almost to the bottom, and the other is immersed only in the upper layer of liquid;
tube G
for pouring a measured amount of acid mixture;
tube H
for infusing glycerin, bent at the bottom of the apparatus into a ring, with small holes.
In addition, the lid has several glass windows L
for observing the phenomena occurring in the apparatus.
A similar window J
is also installed in the exhaust pipe to observe brown vapors of nitrogen oxides formed in cases of dangerous oxidation reactions or so-called development in the apparatus.
decomposition of N. Vessel M
is used to measure the amount of glycerin, determined by the indicator tube
N
, as well as to inject it into the acid mixture by means of compressed (up to 2 atmospheres) air admitted through tube
O.
Through tap
K
, the liquid is discharged from the apparatus. During operation, cold water is carried not only through the internal coil, but also through the annular space between the lead and wooden external machines. 150 kg of glycerin are processed at a time. Having let in the required amount of the acid mixture and cooled it (by passing cold compressed air and a stream of water) to 15 - 20 °, they begin spraying glycerin (at a temperature not lower than 20 °), regulating its influx so that the heating in the apparatus does not rise above 25 - 30°. If the temperature continues to rise, approaching the indicated limit even after the influx of glycerin has stopped, then the passage of cold air is increased, and if even after that the rise does not stop, then the contents of the apparatus are quickly released into a large vat of water; otherwise, decomposition of H. may easily begin, which may end in an explosion. The entire operation of processing glycerin with acids, including filling with the mixture and emptying, requires no more than 1 - 1 1/2 hours of time. Separation of N. from acids is carried out by settling their mixture in the so-called. separator (Fig. 2).
Fig. 2.
This is a lead quadrangular box with a conical bottom, inserted into the same wooden box A.
The cover contains: exhaust pipe
D
with window
E
;
tube K
for introducing the mixture from the nitration apparatus;
a hole for inserting a thermometer and several windows. The same window J
with tightly sealed glass is also located on the side wall to observe the levels of acid and floating H. From the conical bottom of the vessel there is a tube
G
with a window
F
and taps
H.
Floating of N to the surface of acids occurs more easily if it is lowered as it is released through tap
J
into the adjacent rinsing tank
L.
Presence of foreign matter, e.g.
fats in glycerin, lead sulphate, etc., makes isolation difficult. Under normal conditions, with clean materials, the operation lasts about 30 minutes. After draining almost the entire mass of N., the acidic mixture is released through one of the lower taps until
a layer of cloudy mixture consisting of impurities and various lower nitroproducts appears
F. At this moment, close the tap and release the remainder of the mixture into a suitable vessel for transfer to vat L.
Lower nitro products, formed from glycerol itself or foreign impurities, have a lower specification.
weighing compared to N., float on it in the form of foam and are especially prone to decomposition with significant heat release when exposed to air. This must be kept in mind when producing N. separation, since the presence of the said foam can cause decomposition inside the separator; then red-brown vapors appear in window E
and the temperature begins to rise by itself. In such cases, the contents are released through the third lower tap into a large vat of water, as in decompositions in a nitration apparatus.
Washing N., separated from excess acids, is done in two steps. First, it is subjected to pre-washing in the above-mentioned vat L.
This is a cylindrical lead vessel with an inclined bottom and two taps
M
, of which the lower one is intended for releasing N., and the upper one for pouring out water.
Chatting is carried out using compressed (up to 2 atmospheres) air admitted through pipe N
, which is bent at the bottom and equipped with a number of small holes. Settling, due to the large difference in beats. weights of water and N., occurs quickly. The initial water temperature should be approx. 15°, and during high tide N. should not rise above 30°. After the first wash, the second and third are performed in the same way; wash for the last time in another 2.5% soda solution, pouring this solution into a layer several centimeters thick. To completely remove the acid, N. is lowered into wooden vats lined with lead inside and similar in design to the previous vat. Using triple the volume of water, 10 to 18 washes of 15 minutes are performed here. each with stirring the mixture using compressed air (or mechanical mixers); during the 3rd and 5th washes, a 1% soda solution is taken instead of water. The most favorable water temperature is 25 - 33°; in some factories the first flush is carried out at 50°. A product is considered well washed if it passes the heat resistance test described below. The last operation during fabrication consists of filtering the N. to dehydrate and remove random solid impurities. For this purpose, it is passed through special filters (Fig. 3).
Fig. 3.
Into the lid of a wooden cylindrical vessel lined with lead A
a lead filtration cylinder
G
;
on the lower edge of its K
lies a bronze ring
L
with a mesh
M
and felt;
a layer of calcined table salt O
and another felt
P
with a lead ring
Q
;
R
is pressed onto the upper felt .
Using the J
, the filtration cylinder can be easily removed for cleaning or inspection of the inside of the vessel. Such a filter, moistened with anhydrous H., does not allow mechanically mixed (emulsified) water to pass through it, while the last traces of moisture (dissolved in N.) are absorbed by table salt; for the purpose of better drying, dried magnesium chloride is sometimes added to the latter. In the acidic liquid separated from the product, a small amount of N may form over time; therefore, this liquid, before it is put into processing to extract HNO 3 and H 2 SO 4, is subjected to preliminary settling (about a week) in large separators designed similar to those described above; pop-up N. is drained from time to time and undergoes regular washing. On the other hand, the discharged wash water also carries with it a certain amount of product mechanically; To separate and capture the finely crushed N. in these waters, they are passed through a long lead box with transverse partitions equipped with cutouts alternately, sometimes at the bottom, sometimes at the top (Fig. 4).
Fig. 4.
Regarding the N extracted during both of these operations, it should be noted that it requires especially thorough washing, since it is in it that the aforementioned harmful lower nitroproducts accumulate.
2) Pure N., prepared from completely colorless glycerin with the help of pure acids, is an oily, colorless liquid, like water, odorless at ordinary temperatures, with a sweetish, somewhat pungent taste; but complete colorlessness is rarely obtained, and its ordinary specimens are yellowish or brownish in color. Very poisonous; poisoning can occur not only by ingestion and inhalation of vapors, but also through the skin by simple touch, and is usually manifested by severe dizziness, headaches, vomiting, etc.; Deaths are possible when ingesting significant quantities (up to 10 g). In case of mild poisoning, suffering is alleviated by strong black coffee and acetic acid morphine (in very small doses), but workers in factories get used to such poisoning and, without any visible effect on health, soon cease to feel painful attacks. In the cold, N. freezes into a white crystalline mass. Its melting point increases with increasing purity: a product of ordinary purification melts at + 9° or + 10°, and recrystallized several times at + 13.3°. Ud. liquid weight 1.599, solid 1.735. Water dissolves N. in an extremely small amount (about 0.003%), but it is soluble in many organic solvents, for example. in methyl, ethyl and amyl alcohols, acetone, in ordinary and acetic ether, acetic acid, chloroform, benzene, etc. From very strong solutions in methyl alcohol, when cooled, it is possible to crystallize N. and thereby achieve its greatest purification; crystallization occurs especially easily if a ready-made crystal is dropped into a solution cooled to 0°. N. himself dissolves camphor, soluble pyroxylin (collodion) and other similar substances. In the form of solutions in methyl alcohol, Nobel, before the discovery of dynamites, proposed transporting and storing N., since in this state it is not sensitive to accidental impacts, but with the addition of water it immediately precipitates with all its properties. Vapor elasticity of N. in a void: at 15° - 5 mm, at 87° - 27 mm, at 100° - 30 mm. A two-hour wash in water heated to 50°, with compressed air passing through, produces a loss of 0.15% through evaporation. These losses can be significant if N. in heated preparations is in a finely crushed state, for example. dynamite heated at 40° - 50° C. over several days, sometimes loses up to 10%. Well washed and dried N. is a permanent substance, for an indefinitely long time - at temperatures up to 50°, and for shorter periods of time - at temperatures up to 100°. But if it is not pure enough (contains acids), it can slowly decompose even at ordinary temperatures: brown vapors of nitrogen oxides appear, the liquid turns greenish and receives a strongly acidic reaction, oxalic and other organic acids are formed, etc. In this state slow decomposition of N. easily explodes from the action of relatively weak impulses, and even by itself - due to local self-heating. With new washing, such a product that has begun to decompose cannot always be returned to its original normal state. Therefore, the completeness of N. purification during fabrication is of great importance and must be tested every time. For this purpose, two tests are usually performed - neutrality and resistance at 65°. The first is carried out in such a way that about 2 cubic meters. cm of product is shaken for some time with 10 cc. cm of water and, by separation, determine the reaction of the latter in the presence of phenolphthalein. The resistance test at 65° is carried out by placing about 3 g of the product in a glass tube with a strip of iodine-starch paper suspended on a stopper and half-moistened and determining the period of time from the beginning of inserting the equipped tube into a bath at a temperature of 65° until a brown color appears at the border of the wetted and unwetted part of the strip; such coloring, which appears due to the release of iodine from potassium iodide under the influence of the resulting nitrogen oxides, should not occur earlier than 10 or even 30 minutes. The purer the product, the longer its resistance to heat in this test [The resistance test at 65° was originally applied by Abel to pyroxylin and has since been known as the Abel test. The readings of this test depend on the conditions, namely: a) iodine-starch paper should be prepared from cleanly washed Swedish filter paper, saturating the latter with a mixture of solutions of 3 g of starch in 250 cc. cm of water and 1 g of potassium iodide per 250 cc. cm of water; after drying at ordinary temperatures, the sheets are cut into strips of 12 × 15 mm and stored in sealed dark glass jars, b) assay tubes, 14 cm long and 16 mm wide, must be tightly closed with stoppers equipped with hooks at the bottom for hanging iodine-starch papers; c) wetting the upper half of the paper strips is done with a 10% solution of pure glycerin; d) during testing, the equipped tubes are pushed into the bath so much that the iodine-starch papers are immediately above the lid of the bath]. But to fully judge the purity of N., it is also necessary to test it in relation to its composition. The latter in practice comes down to the determination of moisture and nitrogen in it. Determination of humidity is carried out by leaving a sample of N. for a long time at ordinary temp. in a void above calcium chloride, and nitrogen is usually determined using a nitrometer (see); a completely clean and dry product should contain about 18.5% nitrogen, i.e., the amount required by the formula N itself. By heating very small quantities carefully, it is possible to distill N. without decomposition, for example. placing a drop of it on a moderately heated metal plate. But if the plate is heated so much that N. immediately comes to a boil, then the drop explodes. According to Champion's experiments, very small amounts of nitrogen at high temperatures are generally contained as follows: at 185° - boiling with the release of brown vapors; at 194° - slow volatilization; at 200° - rapid volatilization; at 218° - rapid combustion; at 241° - explosion (difficult); 257° - strong explosion; at 267° - weak explosion; at 287° - an even weaker explosion with flame. At red heat, a drop of N. takes on a spheroidal state and evaporates without an explosion. According to Kopp, a faint flash occurs on a red-hot metal plate. But other phenomena occur when significant quantities of H are exposed to high temperatures. First, a slow decomposition occurs over a more or less short period of time with the release of brown vapors and the volatilization of part of the product itself, but as soon as the temperature due to self-heating or the absorption of heat from the bath rises to 180 ° (approximately), and the decomposing liquid boils, then immediately there is a strong explosion of the entire taken mass. Burning and heated bodies ignite N. very difficult: a lit match goes out in it, a hot platinum wire stops emitting light, etc. But once lit, it burns out gradually until the temperature of the rest of the mass rises to 160°, and then general explosion. Nitroglycerin explodes much more easily on impact. When an anvil is struck with a hammer, the part itself that was directly hit explodes, while adjacent parts are scattered without an explosion; the amount of work required for this is determined to be 0.75 kilograms. Frozen N. is less sensitive to shock; in this state, for an explosion, he needs to impart an impact work almost 3 times greater. The best means for exploding N. when using it is to ignite a capsule with mercury fulminate (0.1 - 0.3 g for liquid and 1 - 2 g for frozen) in direct contact with the charge. During an explosion, decomposition occurs according to the equation:
2C 3 H5(NO3)3 = 6CO2 + 5H2O + 3N2 + 0.5O2
i.e., the following are formed: water vapor, carbon dioxide, nitrogen and oxygen. They try to utilize this oxygen in dynamites (see) with an active absorber. The absence of carbon monoxide makes explosion products completely harmless, which is especially valuable for underground blasting. On the volume of gases formed, the amount of heat released, the speed of propagation of the explosion in large charges, force, etc., see respectively. article In relation to various chemical reagents, N. is contained similarly to other nitrogen esters: it is washed with alkalis, decomposed with acids to release nitric acid, and with reducing agents it is converted back into glycerol with the release of nitric oxide or ammonia. To discover the smallest quantities of N., aniline and concentrated sulfuric acid are added to the test liquid: a purple-red color is obtained, which, when diluted with water, turns green (Werber).
I. M. Cheltsov. Δ.
N. ( med.
)
.
When inhaling vapors, as well as after lubricating the tongue, N., in small doses, causes headache, nausea, dizziness, a feeling of heat and rapid heartbeat; after internal use of larger doses, headache, trembling, muscle weakness, reaching complete paralysis, shortness of breath, and, in some cases of fatal poisoning, severe respiratory distress, cyanosis, and deep depression of the nervous system were observed. Despite these dangerous properties, N., used in homeopathy for various nervous diseases (under the name “glonoina”), was recently proposed as a remedy against neuralgia, especially against attacks of angina pectoris; Further, this drug has been tested for bronchial asthma, in some cases of migraine, for epileptic seizures, and St. John's dance. Witt, and for acute and chronic inflammation of the kidneys. N. is prescribed 0.0002 - 0.001 g several times a day or in drops, from 1 to 5 drops in a 1% oil or alcohol solution; This product is also prepared in lozenges.
D.K.
Table of contents
Curiosities of science: a killer and a doctor in one bottle
Author Anton Evseev
17.10.2012 15:00
Science » Good to know
It happens that a scientist himself cannot evaluate all aspects of his discovery. The chemist Ascanio Sobrero, who obtained nitroglycerin, and the industrialist Alfred Nobel, who developed a method for its production, never realized that this substance could not only blow up rocks, but also treat angina. The paradox is that both of them suffered from this disease.
In 1847, the talented Italian chemist Ascanio Sobrero was able to synthesize a substance that he called “pyroglycerin.” It was a trinitrate of the polyhydric alcohol glycerol and therefore later became known as nitroglycerin. Sobrero himself believed that it could be useful in military affairs - the scientist himself once served in the army, fought in the artillery, and even after the end of hostilities continued to work at the Artillery Academy. Therefore, his main research was aimed at meeting the needs and demands of the rapidly growing military industry.
Sobrero immediately appreciated the “explosive” nature of the substance he discovered - during one of the experiments he even received burns to his hands and face. However, in his article he mentioned another interesting effect of nitroglycerin. The scientist wrote that “if you drop “pyroglycerin” on your tongue, your head immediately starts to hurt badly.” Thus, without meaning to, Sobrero described one of the pharmacological properties of nitroglycerin, namely its ability to contract the smooth muscles of blood vessels.
List of flammable and explosive substances
LIST OF FLAMMABLE AND EXPLOSIVE SUBSTANCES
1. Explosives 1.1. Nitroglycerin 2. Explosives 2.1. Potassium permanganate 2.2. Silver nitrate 3. Flammable substances 3.1. Alcohol and alcohol solutions 3.2. Alcohol and essential tinctures 3.3. Alcohol and ether extracts 3.4. Ether 3.5. Turpentine 3.6. Lactic acid 3.7. Chloroethyl 3.8. Collodion 3.9. Cleolus 3.10. Novikov liquid 3.11. Organic oils 4. Flammable substances 4.1. Dressing material (cotton wool, gauze, etc.) 4.2. Sulfur 4.3. Glycerin 4.4. Vegetable oils 4.5. Medicinal plant raw materials If it is necessary to store fire and explosive substances not listed in the appendix, the issue of their storage must be resolved after determining their fire and explosion hazard and in agreement with the Ministry of Emergency Situations. The procedure for handling and storing the above products and materials in pharmacies is regulated by the INSTRUCTIONS ON THE PROCEDURE FOR STORAGE AND HANDLING IN PHARMACY WAREHOUSES, PHARMACY INSTITUTIONS AND ENTERPRISES WITH MEDICINES AND MEDICAL DEVICES WITH FLAMMABLE AND EXPLOSIVE PROPERTIES from 05/19/1998 N 149. Compliance of pharmacy premises with fire safety regulations safety is checked by inspectors of the territorial departments of the Ministry of Emergency Situations of the Republic of Belarus.
1. GENERAL PROVISIONS
1.1. This Instruction applies to all pharmacies and enterprises, regardless of their departmental affiliation and form of ownership. 1.2. All employees of pharmacy institutions must know and comply with the requirements set out in these Instructions. Responsibility for compliance with the requirements of the Instruction by employees rests with the heads of institutions and enterprises. 1.3. Each new employee must undergo introductory and primary training at the workplace on the storage of flammable, explosive substances, compressed gases, safety and fire safety, and providing first aid to victims of an accident. 1.4. All pharmacies and enterprises must have and store in appropriate places primary fire extinguishing agents in quantities agreed upon with the local authorities of the Ministry of Emergency Situations. 1.5. In places where flammable and explosive substances are stored, as well as in workplaces where these substances are used during work, this Instruction must be posted. 1.6. In pharmacies and enterprises, fire safety rules for the institution must be developed, agreed upon with the Ministry of Emergency Situations and approved by the administration, drawn up and placed in places accessible for review, and floor-by-floor evacuation plans in the event of a fire or natural disaster.
2. REQUIREMENTS FOR FLAMMABLE AND EXPLOSIVE STORAGE PREMISES
2.1. Substances that are flammable, capable of forming explosive mixtures, and also prone to spontaneous combustion upon contact with air, water, flammable substances or exposure to sunlight, must be stored in isolation under conditions that completely exclude the possibility of such contact, as well as the influence of high temperatures and mechanical stress. 2.2. Warehouses for storing flammable and explosive substances must fully comply with the current Construction Norms and Design Rules (SNiP). They must be insulated, dry, protected from light, direct sunlight, precipitation and groundwater. These rooms, as well as adjacent corridors and utility rooms must be equipped with mechanical supply and exhaust ventilation. 2.3. Premises for storing flammable (flammable) substances must be made of fireproof and fire-resistant materials and located at a distance of at least 20 m from other storage buildings and 50 m from residential premises. 2.4. Flammable and explosive medicinal products should be stored according to the principle of uniformity in accordance with their physicochemical and fire hazard properties and the nature of the packaging. For this purpose, fire-resistant warehouses are divided into separate rooms (compartments), isolated from each other by blank fireproof walls (partitions). 2.5. In the absence of separate storage facilities for flammable substances, it is allowed to store them in common fireproof buildings, also divided into sections, with mandatory isolation of substances allocated for storage by fireproof walls from neighboring premises and fully meeting fire safety requirements agreed with the Ministry of Emergency Situations. These rooms must have ventilation. 2.6. The required amount of flammable substances for current consumption may be kept in the packaging rooms of warehouses or pharmacies, but subject to strict adherence to fire safety measures. The remaining amount of flammable substances at the end of work at the end of the shift is returned to the main storage site. 2.7. The floors of warehouses and unloading areas must have a hard, even surface, eliminating potholes and other uneven surfaces. It is prohibited to use boards and iron sheets to level floors. Floors must ensure convenient and safe movement of people, cargo and vehicles, have sufficient strength and withstand the loads of stored materials, and ensure simplicity and ease of cleaning the warehouse. 2.8. Warehouse premises for storing flammable and explosive medicines must be equipped with fireproof and stable racks and pallets designed for the appropriate load. The racks are installed at a distance of 25 cm from the floor and walls, the width of the racks should not exceed 1 m and have edgings of at least 25 cm. The longitudinal passages between the racks should be at least 1.35 m. 2.9. Electrical wiring, lighting fixtures and electrical equipment must be explosion-proof (electrical wiring hidden in pipes, electric lamps in hermetic fittings), with switches and push-button switches placed (removed) in the corridor. 2.10. In pharmacies and enterprises, isolated rooms are provided for the storage of flammable and explosive substances. 2.11. The storage room for flammable and explosive substances must be blocked by security and fire alarms. 2.12. Premises intended for storing flammable and combustible substances must be located on the ground floor, have a window opening in the outer wall of at least 1.1 sq.m with a width or height of at least 0.75 m, a reinforced concrete ceiling, walls made of fireproof materials with a limit fire resistance of at least 0.75 hours, cemented floor with a slope from the door and a door with a fire resistance limit of at least 0.6 hours, have an external exit from the building or into the building into a corridor isolated from all other rooms. 2.13. In rural pharmacies, it is allowed to store flammable and combustible liquids in built-in fireproof cabinets with doors with a width of at least 0.7 m and a height of at least 1.2 m. The location of the cabinet must be removed from heat-dissipating surfaces and passages, and access to it must be provided Free access. 2.14. In pharmacies and enterprises built into buildings for other purposes, the amount of stored flammable substances in bulk (flammable liquids) should not exceed 100 kg. 2.15. Flammable liquids in quantities over 100 kg must be stored in a separate building in glass or metal containers, isolated from storage areas for flammable substances of other groups. 2.16. The premises for the reception, dispensing and packaging of medicines and medical products with flammable and explosive properties must be under special attention and constant strict control. Upon receipt of goods, it is necessary to urgently distribute it to the main storage areas. To avoid accidents, even short-term storage of these medical products is strictly prohibited in the reception and release areas. When receiving them, special attention should be paid to the condition of the closure of individual storage containers. The simultaneous packaging of several medicines in one room is strictly prohibited. The amount of substances at the packer’s workplace should not exceed shift requirements. At the end of the working day, the remaining substances are returned to the main storage premises. After finishing the packaging of each name of medicinal substances, the premises are thoroughly ventilated. 2.17. In warehouses for the main storage of flammable and explosive substances, the following indelible, clearly visible inscriptions must be made on the outside, as well as on the doors of each room for storing and working with these substances and inside these premises: “Flammable”, “Explosive”, “Smoking is prohibited”. In case of fire, call “01”. 2.18. Signs with the inscription “Responsible for ensuring fire safety ______________________” must be posted near the entrance to each storage room for flammable and explosive substances and inside the room.
The responsible person must inspect the premises daily to remove remaining flammable and explosive substances and take other measures at the end of the working day.
3. SPECIAL REQUIREMENTS FOR THE STORAGE OF FLAMMABLE AND EXPLOSIVE SUBSTANCES
3.1. Storage of flammable substances:
3.1.1. The group of flammable substances stored in pharmacies and enterprises includes flammable substances, which are mainly liquids and flammable substances. 3.1.2. In warehouses, flammable and combustible liquids must be stored separately from other goods. 3.1.3. The main dangerous properties of flammable and combustible liquid substances are fluidity, easy evaporation and easy flammability from any external source: open flame, spark, electric discharge, etc. Therefore, storage and work with flammable substances should be carried out with great care and away from fire. If necessary, heating of these substances should be done in water baths or electric stoves with a closed spiral. 3.1.4. Vapors from most flammable liquids are harmful to the body, and prolonged inhalation of these vapors may cause loss of consciousness. Therefore, containers with these substances must be tightly sealed. It is prohibited to store flammable and combustible substances in open containers. 3.1.5. Flammable liquids (collodion, ethyl alcohol, turpentine, ether and others) are stored in tightly sealed durable glass or metal containers to prevent evaporation of liquids from the vessels. 3.1.6. Bottles, cylinders and other large containers with flammable and combustible liquids must be stored on rack shelves in one row in height; it is prohibited to store them in several rows in height using different cushioning materials. Storing these substances near heating appliances is not permitted. The distance from the rack or stack to the heating element must be at least 1 m. 3.1.7. Storage of flammable and combustible liquids in bottles should be carried out in containers that protect against impacts, or in bottle tippers in one row. 3.1.8. Industrial pharmacies at workplaces can store quantities of these substances that do not exceed shift requirements. In this case, the containers must be tightly closed. 3.1.9. It is not allowed to store flammable and combustible liquid substances in completely filled containers. The degree of filling should be no more than 90% of the volume. Alcohols in large quantities are stored in metal containers, which are filled to no more than 95% of the volume. 3.1.10. It is not allowed to store flammable substances together with mineral acids (especially sulfuric and nitric), compressed and liquefied gases, flammable substances (dressing material, vegetable oils, sulfur), as well as with inorganic salts that produce explosive mixtures with organic substances ( potassium chlorate, potassium permanganate, potassium chromate, etc.). 3.1.11. Medical ether and ether for anesthesia are stored in original packaging, in a dark, cool place (away from fire and heating devices). 3.1.12. Calcium hypochloride is not flammable, but upon contact with liquid oily organic products it can cause them to ignite, and with ammonia and ammonium salts it can cause an explosion, so it should be stored in isolation, taking into account the described properties. 3.1.13. When handling flammable liquids (packaging, carrying, loading, etc.), special care must be taken, as well as constantly monitoring the condition of the container, its tightness and serviceability. If container malfunctions are detected, immediately take measures to eliminate them, or the substances contained in it are transferred to another serviceable container. 3.1.14. Barrel plugs may only be unscrewed and screwed in with soft metal tools that do not produce sparks when struck or with wooden hammers. When rolling drums and loading them into storage, care must be taken to avoid hitting the drum and causing sparks. Any liquid spilled on the floor must be cleaned up immediately. 3.1.15. Certain flammable liquids (alcohol, medicinal ether, etc.) have the ability to generate static electricity during storage, the spark of which can cause the liquid to ignite. Therefore, packaging of such liquids in a warehouse should be done in separate rooms equipped with fire protection equipment. During the process of draining and packaging, metal vessels must be grounded. 3.1.16. Containers emptied of flammable liquids should be left open for some time. 3.2. Storage of explosive substances. 3.2.1. This group of substances includes explosives and explosive substances, that is, capable of forming explosive mixtures. 3.2.2. Substances of this group must be stored in an insulated fire-resistant warehouse in special rooms (compartments) isolated with fireproof walls. Storage of silver nitrate in pharmacies and warehouses in small quantities (in warehouses up to 5 kg, in pharmacies up to 50 g) must be carried out in isolation in accordance with the rules for storing toxic substances. 3.2.3. When storing explosive substances, measures should be taken to prevent contamination by dust, which can cause an explosion. 3.2.4. Containers with explosive substances (bars, tin drums, bottles, etc.) must be tightly closed to prevent vapors from entering the air. 3.2.5. Potassium permanganate is explosive when interacting with dust, sulfur, organic oils, ethers, alcohol, glycerin, organic acids and other organic substances. It should be stored in warehouses in a special compartment in tin drums, and in industrial pharmacies - in rods with ground stoppers separately from the above products. Shared storage with flammable and combustible substances is not allowed. Tin drums and rods with potassium permanganate are removed from dust in a timely manner, carefully, avoiding friction. 3.2.6. Nitroglycerin solution (explosive) should be stored in pharmacies or pharmaceutical warehouses in small, well-closed flasks or metal containers in a cool, dark place, taking precautions against fire. Move dishes with nitroglycerin and weigh out this drug with extreme caution, since the evaporation of spilled nitroglycerin threatens an explosion. Contact of even small amounts on the skin can cause poisoning (severe headaches). 3.2.7. Ether during storage (especially if in contact with air) forms peroxides, which can cause explosions when shaken, impacted, rubbed or raised in temperature, so working with it requires special care. 3.2.8. The storage of all explosive and flammable substances with acids and alkalis is strictly prohibited. 3.2.9. Carrying cylinders with flammable and flammable liquids must be carried out by two people in specially adapted cages or baskets with working grip handles. Baskets with large bottles, boxes or crates (over 20 kg), as well as substances placed in solid containers, must be carried (moved) only on special trolleys with soft running wheels. 3.2.10. When storing nitric and sulfuric acids, measures must be taken to prevent them from coming into contact with wood, straw and other substances of organic origin. For these purposes, use metal pallets with sand. When working, personal protective equipment is used (rubber boots, safety glasses, rubberized aprons). 3.2.11. In case of electrical lighting accidents, it is strictly forbidden to enter premises storing explosive and flammable substances with kerosene lamps and candles. In these cases, only flashlights should be used.
Download – Procedure for handling and storing in pharmacies medicines and medical products with flammable and explosive properties
NITROGLYCERINE, NOBEL AND NOBEL LAUREATES
Nitroglycerin is the basis of dynamite and has enormous destructive power.
But taken in small quantities, this substance serves as a medicine that, in emergency cases, helps the heart cope with excessive stress. NITROGLYCERIN MADE NOBEL
A. Blood circulation in a patient during an attack of angina. B. Blood circulation after taking nitroglycerin.
Chemical transformations of nitroglycerin in the vascular endothelium with the release of nitric oxide
The formation of nitric oxide from the amino acid arginine under the influence of the endothelial enzyme NO synthetase.
The mechanism of the vasodilator action of the parasympathetic nervous system.
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Italian chemist Ascanio Sobrero synthesized nitroglycerin back in 1846. He discovered, fortunately without disasters or casualties, the ability of this substance to explode from the weakest impacts, shocks and heating. Since then, nitroglycerin has been considered a very promising explosive for the mining industry. Promising, but inconvenient, since it could not even be transported.
Not long before this, the Nobel family arrived in Russia from Sweden “to catch happiness” and wealth. The geography of their activities extended from Finland to Azerbaijan, and the scope - from gunpowder to oil. And everywhere with success. But after the defeat in the Crimean War, Russia began to purchase weapons and explosives abroad, and government orders for the production of these products in the country ceased. Emmanuel Nobel returned to Sweden, where he again began building factories for the production of explosives. Alfred, one of Nobel's four sons, studied the process of producing nitroglycerin back in St. Petersburg, working with Professor N. N. Zinin. Interest in this substance was quite natural, since its explosive power was twice as high as the effectiveness of TNT, already known at that time. After the tragic death of his youngest son during an explosion at one of the factories, the head of the family fell ill and retired. The production of explosives passed into the hands of Alfred Nobel. At first there was a series of failures. Workers died not only from explosions, but also from nitroglycerin poisoning. The invited doctor D. Merrill quickly figured out that nitroglycerin is a vascular poison that causes a drop in blood pressure, which leads to death. Not only is it dangerous to get nitroglycerin in your mouth, but also to inhale its vapors. Nobel had to rebuild factories to ensure the safety of workers. He soon invented dynamite by mixing nitroglycerin with diatomite, a fine-fiber sedimentary rock. Such a mixture is not poisonous and does not explode on impact, but retains explosive properties when detonated by a fuse.
In 1879, Dr. Merrill discovered that nitroglycerin could be used as a medicine, in particular to relieve spasms of the blood vessels of the heart.
And on time. The use of nitroglycerin saved Alfred from death during one of his angina attacks. After retiring, Alfred Nobel became increasingly interested in science, worked on his own and generously encouraged promising research by young scientists, especially in the field of medicine. NOBEL LAUREATES
In 1896, Alfred Nobel died, bequeathing a special fund to turn his property into securities, the income from which should be given annually in the form of prizes named after him to scientists for major scientific discoveries and inventions in the field of physics, chemistry, physiology and medicine, as well as to individuals who achieved the greatest success in literature and the struggle for peace. The draft charter of the Nobel Committee was adopted by the Swedish Riksdag, and the will came into force, despite many objections. Opponents of the appointment of such bonuses pointed out, in particular, the possibility of all sorts of frauds arising around them. Indeed, from time to time there are certain mistakes of both a subjective and objective nature.
The first Nobel laureates in 1901 were Wilhelm Roentgen in physics, Jacob Van't Hoff in chemistry and Emil Behring in medicine. The name of Roentgen is known to everyone, Van't Hoff will probably be remembered by those who carefully read school textbooks, and no one knows Bering, but the anti-diphtheria serum he invented is used by the whole world. Further bonuses did not go so smoothly. One of the principles for selecting candidates is the frequency of citations, but not all scientists widely advertised their discoveries, and not all had the opportunity to publish works abroad. Now it is difficult for us to understand why the candidacies of such Russian scientists as V. I. Vernadsky, K. A. Timiryazev, K. E. Tsiolkovsky and many others did not receive sufficient support from the international scientific community. D.I. Mendeleev was not awarded the prize in chemistry in 1906 because of his advanced age. Ivan Petrovich Pavlov became a Nobel laureate in 1904 for his work in the field of digestive physiology, which was just an episode in his life. A proposal twenty years later to honor his brilliant work on conditioned reflexes with a prize did not receive support. When the Nobel Committee finally decided to take this step, Pavlov died, and the prize is not awarded posthumously. There were also “late” awards. An example of this is the prize awarded in 2000 to the largest Russian scientist Zhores Alferov for work carried out 20 years ago. Pyotr Kapitsa has been waiting for the award for 40 years. A kind of record is the award to Francis Peyton Rose, who was awarded 55 years after he discovered a virus that causes malignant tumors.
Despite difficulties and mistakes, the Nobel Prize remains one of the most authoritative and honorable. Its presentation always turns into a real celebration.
In 1998, a prize, based on money from the production of the explosive nitroglycerin, was given for research into the drug nitroglycerin.
It has long been known, but discovered the secret of its influence on blood vessels only a few years ago. NITROGLYCERIN AS A MEDICINE
Despite more than a century of use of nitroglycerin, the study of the mechanism of its therapeutic action has progressed with difficulty. Let's open a textbook on pharmacology from the 1896 edition, that is, almost 20 years after the start of using this medicine. In the “Physiological Action” section we read: “Taking a few drops of a 1% alcohol solution first causes a feeling of constriction in the cardiac region, and then a feeling of heat; at the same time, there is a rush to the face, and it turns purple. Heart contractions become stronger and faster; the pulse becomes arrhythmic, blood pressure decreases, peripheral vessels dilate.” What kind of physiology is there? Just a description of the symptoms of poisoning. To obtain a therapeutic effect when taken orally, doses of 10-20 mg were required, since, when absorbed from the intestines, nitroglycerin enters primarily the liver, where it is partially destroyed. But such doses cause toxic effects. Later, doctors realized that it was better to prescribe nitroglycerin “under the tongue”, then it enters the bloodstream, bypassing the intestinal tract. The currently recommended doses are 0.5-1 mg in the form of tablets, capsules or an alcohol solution with sugar.
Since the heart is forced to pump through itself from 4 to 25 liters of blood per minute, it is constantly in a state of some tension. This tension persists even during short periods of relaxation - diastole, which has a very adverse effect on the flow of blood through the internal small vessels of the heart, arterioles and capillaries. At the moment of contraction - systole - they are completely compressed.
The effects of nitroglycerin are highly dependent on the doses used. In an average therapeutic dose, this substance first causes dilation of large veins. The capacity of the venous vascular system increases, and part of the total blood volume is “deposited” in them. Therefore, less blood returns to the heart, which leads to a decrease in the so-called cardiac preload. Reducing the tone of the heart muscle and the pressure in its cavities ensures the expansion of all blood vessels of the heart, which naturally improves its blood supply, reduces the need for oxygen in the heart muscle and improves metabolism. At the same time, nitroglycerin relieves local spasms of heart vessels affected by sclerosis. When taking maximum therapeutic doses, not only the heart but also the cerebral arteries dilate, which leads to headaches. The effect is unpleasant, but not dangerous. An overdose leads to dilation of the arteries throughout the body and a drop in blood pressure.
If your doctor has recommended that you take nitroglycerin, you need to experimentally determine your individual sensitivity to the drug in a calm state. Usually, to obtain the desired effect, which is manifested by a feeling of flushing in the face and a mild headache, one tablet or capsule (0.5 mg) is enough. If there is no reaction, the dose should be doubled, and if there is an excessive reaction - severe headache, dizziness, weakness, pallor, increased heart rate - reduce (in this case, the doctor will prescribe nitroglycerin in solution). Nitroglycerin is also produced in the form of ointments and plates for gluing to the gums.
The following must be remembered:
- Headache when first taking nitroglycerin is caused by vasodilation and indicates that the drug is working. After several doses this phenomenon disappears, but the effect on the heart vessels remains, so the dose should not be increased.
- Nitroglycerin is quickly destroyed in heat. Keep a supply of it in the refrigerator and monitor the expiration date.
- If you have angina, carry the drug with you at all times and if pain occurs, take it immediately, preferably while sitting or lying down.
- If the pain does not go away, then after 1-3 minutes you can put a second tablet and even a third under your tongue. It is also necessary to call an ambulance. To avoid an overdose, take the next tablet no earlier than 15-30 minutes later, when the effect of the nitroglycerin already taken has ended.
- With prolonged use—about a month—addiction (tolerance) to nitroglycerin occurs and it stops working. After a month's break, sensitivity is restored.
To prevent attacks, long-acting nitroglycerin (or other nitrates) preparations are used. They are taken in advance before going out into the cold, before physical or mental stress.
To prolong the effect of the drug, nitroglycerin is placed in capsules of different sizes, which dissolve sequentially, releasing the active principle and providing an effect for 8-12 hours. Due to the heterogeneity of the carrier, tablets of long-acting drugs appear speckled. These are the drugs nitrogranulong, nitro-mac retard, sustak, nitrong. Transdermal patch-type systems with a duration of action of 24 hours have been created; they are glued to the skin.
Some nitrates have a delayed, but longer-lasting effect than nitroglycerin. Isosorbitol dinitrate acts for 4-6 hours; in the form of plates glued to the oral mucosa (dinitrosorbilong) - 6-8 hours, in the form of an ointment - 12 hours, in aerosol cans for application to the skin - 18 hours. A prolonged dinitrate has been created, the duration of the effect of which reaches 24 hours (cardiquet).
Isosorbitol mononitrate differs from dinitrate in the faster onset of effect. It can be used if addiction to dinitrate has occurred. Prolonged forms (olicard retard, efox long) retain the effect for 24 hours.
Nitrates also include the drug erinite, which has fewer side effects, but is also less effective. New nitrates include dilcoran (tetranitrate), which combines well with other drugs for the treatment of angina and lasts for 10 hours.
It should be noted that nitrates can, if not completely eliminate, then weaken any spasm of the smooth muscles of the internal organs, in particular in gallstone and renal colic.
Nitrates and their intermediate- and long-acting preparations are used to treat heart failure. By reducing the flow of venous blood to the heart and eliminating stagnation in the pulmonary circulation, these drugs, of course, do not restore the strength of the heart muscle, but they alleviate the course of the disease and weaken attacks of cardiac asthma. AN UNEXPECTED COINCIDENCE
It has long been known that nitroglycerin causes vasodilation, but what is the mechanism of this process? It is no less well known that, unlike the sympathetic nervous system, which causes vasoconstriction, the parasympathetic nervous system causes them to dilate, but how? If sympathetic fibers penetrate into the thickness of the vessel and directly approach their muscles, and the transmitter of nerve impulses released by these fibers, norepinephrine, causes contractions of isolated vascular muscles, then everything is clear. But the fibers of the parasympathetic nerves do not approach the muscle layer and end in the outer lining of the vessels. And acetylcholine, the transmitter of parasympathetic impulses, not only does not act on isolated vascular muscles, but even loses its vasodilating effect when the inner membrane, which has nothing to do with nerves or muscles at all, is removed. Mystery!
Since the 80s of the last century, many scientists in different laboratories have begun to study these incomprehensible phenomena (see “Science and Life” No. 7, 2001). Without going into history and subtleties, we note that thanks to “elegant” biochemical and physiological research, several important facts were established.
It turned out that nitrates, interacting in the vascular endothelium with a complex of enzymes, are partially converted into nitrites with the subsequent release of free NO - nitric oxide, due to which vasodilation occurs.
Under physiological conditions, nitric oxide is formed from the amino acid arginine with the participation of the enzyme NO synthetase. The amino acid arginine is not essential, since it is synthesized in all tissues of the body. Its deficiency is possible only with a hereditary disease - cystinuria, in which its excessive excretion occurs in the urine.
As a result of activation of the parasympathetic nerve, acetylcholine is released from its endings in the outer lining of the arteries, which diffuses through all layers of the vessel to the endothelium (inner lining), where it interacts with a special receptor protein sensitive to it, the cholinergic receptor. Activation of the cholinergic receptor leads to its interaction with the enzyme NO synthetase and the formation of nitric oxide. The latter penetrates the muscular lining of the vessel, activating the enzyme guanylate cyclase. This enzyme converts inactive guanosine monophosphate (GMP) found in the muscle into active cyclic guanosine monophosphate (cGMP), which is the factor that causes relaxation of vascular smooth muscle. Nitric oxide is then quickly inactivated, turning into nitrites, cGMP again turns into inactive GMP. The system returns to its original state and waits for the next arrival of the parasympathetic impulse.
The figure shows the fate of all participants in the regulation of vascular tone: nitric oxide, being oxidized and included in metabolism, forms numerous nitrites, cGMP is converted back into GMP, but where does acetylcholine go? This question seemed to hang in the air, since the removal of acetylcholine from the reaction turned out to be off the main road. This situation is shown in the figure with a question mark. The author of this article recently managed to prove that in the vascular endothelium there is an enzyme called cholinesterase, which destroys acetylcholine after it interacts with the cholinergic receptor.
The tone of parasympathetic nerves, the sensitivity of NO synthetase and the rate of inactivation of nitric oxide vary in different tissues and organs. They are maximum in the heart, brain and genitals. In men, parasympathetic impulses cause an erection, and in women - swelling of the clitoris and labia minora.
The coincidence promised in the subtitle was that, completely independently of the work described, the American company Pfizer began work on the synthesis and introduction of a new drug, sildenafil, intended for the treatment of sore throat. In a clinical trial of sildenafil, it was found that its side effect is the occurrence of a persistent erection. The company's managers thought about it and asked the researchers what was the matter.
Meanwhile, the Nobel Committee, from all the scientists working on the problem of nitric oxide, selected three who became laureates in 1998: Robert Furchgott, Luis Ignarro and Ferid Murad, whose contribution to elucidating the mechanism of action of nitroglycerin, the regulation of vascular tone by the parasympathetic nervous system and the role of nitric oxide is truly great
Very soon it was discovered that sildenafil has the ability to slow down the breakdown of cyclic guanosyl monophosphate and thereby prolong its vasodilatory effect, and therefore enhance erection. On March 17, 1998, the company launched a new drug called “Viagra” for the treatment of impotence. The new medicine quickly gained popularity. This is how the scientific discovery coincided with its immediate industrial use. And the names of Nobel laureates began to be associated not so much with science as with practice. There is no harm in this, but clarity is necessary in everything.
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all posts by the author The history of the creation of one of the most popular medicines is connected with St. Petersburg. Or rather, with the name of the famous scientist Alfred Nobel. And his teacher was the Russian scientist Professor Zinin. In Paris, Nobel met the Italian scientist who first obtained nitroglycerin, Ascanio Sobrero, and began practical experiments with the substance. However, Nobel was interested, first of all, in the explosive properties of the substance, and the result of his work was not a useful medicine at all, but dangerous dynamite... Not many people know that the scientist paid dearly for this discovery - his younger brother Emil died in one of the explosions. However, some of Nobel's developments benefited medicine and pharmacology: in 1863, he invented a special injector-mixer that made it possible to secure the industrial production of nitroglycerin.
Even with the discovery of nitroglycerin, Sobrero himself and other enthusiasts tried to try its effect on themselves. But when taking the substance, the testers experienced severe headaches, so the development of the substance in the pharmacological direction was delayed for a long time. Only 33 years later, the Englishman Murrell, an employee of Westminster and Royal Hospitals, was able to select the required concentration of the drug and a suitable solvent. At the end of the 19th century, the list of diseases in the treatment of which nitroglycerin was used was very wide: this included both traditional angina pectoris and asthma, migraine, even epilepsy.
Nitroglycerin is still the most popular drug for relieving angina attacks. But his merits in the development of pharmacology are not limited to this. Using nitroglycerin as an example, the so-called “prophylaxis syndrome” was first described by rubbing it into the temples.
Almost always, withdrawal syndrome goes hand in hand with another danger - the development of tolerance to the drug. The essence of the problem is that with long-term use, the patient has to greatly increase the dose - otherwise the therapeutic effect will no longer be achieved. In the fight against the problems that arose, scientists went by inventing new forms of the drug. Today there are many of them: sublingual capsules, tablets, solutions and patches. However, the most popular dosage form, a real “first aid”, remains the usual capsules. They began to be used back in 1925 and are still preferred in emergency situations to this form. Tablets are increasingly used to prevent attacks.
The last significant event involving nitroglycerin occurred in 1998. Three scientists - Furgott, Ignarro and Murad - received the Nobel Prize for their detailed description of the physiological effects of nitroglycerin. After all, until then the mechanism of action of the drug was unclear: when prescribing it, doctors relied only on empirical information. It turned out that when nitroglycerin enters the smooth muscle cell of blood vessels, it is converted into nitric oxide, which, in turn, activates an enzyme that can relax the smooth muscle cell and dilate the vessel. As a result, the myocardial oxygen demand decreases and oxygen saturation of the heart muscle increases.
Scientists have put a lot of effort into developing other forms of nitrates that would differ from nitroglycerin in terms of pharmacokinetics. However, for now, nitroglycerin remains the mainstay. It is still not possible to cope with the side effects that occur when taking it: in many patients the drug causes severe headaches and dizziness. Some patients consider these to be indicators that the medicine is not right for them. Doctors refute this opinion: changes in well-being after taking nitroglycerin, on the contrary, indicate that the medicine is effective. Doctors also remind that after taking the medicine, you should lie down for a while: a horizontal position will increase the effectiveness of the drug and minimize side effects.
