Adverse reactions to insulin drugs that are not related to the biological effect of the insulin hormone. Insulin: indications and forms, instructions for use in medicine What is insulin

Pharmacological group: hormones; peptide hormones;
Pharmacological action: regulation of blood glucose levels, increased absorption of glucose by body tissues, increased lipogenesis and glycogenogenesis, protein synthesis, decreased rate of glucose production by the liver;
Effect on receptors: insulin receptor.

Insulin is a hormone that rises when blood glucose levels rise and works to lower glucose levels by introducing it into cells and increasing its use. It temporarily switches energy metabolism from fats to carbohydrates, while clearly not leading to an increase in fat mass. Its potency is defined as insulin sensitivity.

Insulin: basic information

Insulin is a peptide hormone produced in the islets of Langerhans of the pancreas. The release of the hormone in the human body is closely related to blood glucose levels, although these levels are also influenced by a number of other factors, including the activity of pancreatic and gastrointestinal hormones, amino acids, fatty acids and ketone bodies. The primary biological role of insulin is to promote the intracellular utilization and storage of amino acids, glucose, and fatty acids, while inhibiting the breakdown of glycogen, proteins, and fats. Insulin helps control blood sugar levels, so insulin medications are usually prescribed to patients with diabetes, a metabolic disorder characterized by hyperglycemia (high blood sugar). In skeletal muscle tissue, this hormone acts as an anabolic and anti-catabolic, which is why pharmaceutical insulin is used in athletics and bodybuilding. Insulin is a hormone that is secreted by the body from the pancreas and is known to regulate carbohydrate metabolism. It works with its sister hormone, glucagon, as well as a variety of other hormones to regulate the body's blood sugar levels and protect against too much sugar (hyperglycemia) or too little sugar (hypoglycemia). It is mostly an anabolic hormone, which means it acts on the formation of molecules and tissues. It has some catabolic properties (catabolism is a mechanism of action aimed at breaking down molecules and tissues to produce energy). When active, insulin and the active proteins it controls can be summarized by having two main effects:

Causes the removal of nutrients from the liver, adipose tissue and muscles; these nutrients come from the blood

Causes metabolism to switch to carbohydrates, using them as an energy source, and thus minimizing the use of fats and proteins for energy

Increases in response to food. The most notable are carbohydrates and, to a lesser extent, proteins. Unlike many hormones, insulin is most responsive to food and lifestyle; Manipulating insulin levels through food and lifestyle is common in dietary strategies. It is essential for survival, so subjects who produce little or no insulin need to take it (type I diabetes). Insulin has a phenomenon known as “insulin sensitivity,” which can generally be defined as “the amount of action a single insulin molecule can exert within a cell.” The more insulin sensitive you are, the less total amount of insulin is required to produce the same amount of effect. A larger scale and longer-lasting state of insulin insensitivity is observed in type II diabetes (among other comorbidities). Insulin is neither bad nor good for health and body composition. It has a specific role in the body and its activation may or may not be beneficial for certain subjects, and may also be unusual for others. Typically, obese and sedentary individuals exhibit limited insulin secretion, while strong athletes or relatively lean athletic subjects use carbohydrate regulation strategies to maximize insulin action.

Additional information about the hormone

Structure

The mRNA encodes for a polypeptide chain known as preproinsulin, which is then passively folded into insulin by amino acid affinity. Insulin is a peptide hormone (a hormone made up of amino acids) that consists of two chains, an alpha chain of 21 amino acids long and a beta chain of 30 amino acids long. It is linked by sulfide bridges between chains (A7-B7, A20-B19) and in the alpha chain (A6-A11), giving a hydrophobic core. This tertiary protein structure can exist on its own as a monomer, and also together with others as a dimer and hexamer. These forms of insulin are metabolically inert and become active when conformational (structural) changes occur upon binding to the insulin receptor.

Roles in the body

Natural synthesis, degradation and regulation

Insulin is synthesized in the pancreas, in a subspace known as the islets of Langerhans, which are located in beta cells and are the only producers of insulin. Insulin, after synthesis, is released into the blood. Once its action is complete, it is broken down by an insulin-degrading enzyme (insulisin), which is expressed ubiquitously and decreases with age.

Insulin receptor signaling cascade

For convenience, individual intermediaries that are of key importance in the signaling cascade are highlighted in bold. Stimulation of insulin occurs through the action of insulin on the outer surface of the insulin receptor (which is embedded in the cell membrane, located both on the outside and on the inside), which causes structural (conformational) changes that excite the tyrosine kinase on the inside of the receptor and cause multiple phosphorylation. Compounds that are directly phosphorylated on the interior of the insulin receptor include four designated substrates (insulin receptor substrate, IRS, 1-4), as well as a number of other proteins known as Gab1, Shc, Cbl, APD, and SIRP. Phosphorylation of these messengers causes structural changes in them, which gives rise to a post-receptor signaling cascade. PI3K (activated by IRS1-4 messengers) is in some cases considered a major second-tier messenger and acts through phosphoinositides to activate a messenger known as Akt, whose activity is highly correlated with GLUT4 trafficking. Inhibition of PI3k by wortmannin completely abolished insulin-mediated glucose uptake, indicating the criticality of this pathway. GLUT4 trafficking (the ability to transport sugars into the cell) is codependent with PI3K activation (as above) as well as the CAP/Cbl cascade. Activation of PI3K in vitro is not sufficient to explain all insulin-mediated glucose uptake. Activation of the prime messenger APS recruits CAP and c-Cbl to the insulin receptor, where they form a dimer complex (bound together) and then move via lipid rafts to GLUT4 vesicles, where they facilitate its movement to the cell surface via GTP-binding protein. For a visualization of the above, see the metabolic pathway of insulin in the Encyclopedia of Genes and Genomes of the Kyoto Institute of Chemical Research.

Effect on carbohydrate metabolism

Insulin is the primary metabolic regulator of blood glucose (also known as blood sugar). It works in concert with its sister hormone glucagon to maintain equilibrium in blood glucose levels. Insulin has the role of both increasing and decreasing blood glucose levels, namely by increasing glucose synthesis and glucose deposition in cells; both reactions are anabolic (tissue-forming), generally opposite to the catabolic effects of glucagon (tissue-destructive).

Regulation of glucose synthesis and breakdown

Glucose can be formed from non-glucose sources in the liver and kidneys. The kidneys reabsorb approximately as much glucose as they synthesize, suggesting that they can be self-sustaining. This is the reason why the liver is considered the main site of gluconeogenesis (gluco = glucose, neo = new, genesis = creation; creation of new glucose). Insulin is released from the pancreas in response to increases in blood glucose detected by beta cells. There are also neural sensors that can act directly from the pancreas. When blood sugar levels rise, insulin (and other factors) cause (throughout the body) the removal of glucose from the blood into the liver and other tissues (such as fat and muscle). Sugar can be taken into and out of the liver via GLUT2, which is fairly independent of hormonal regulation, despite the presence of some GLUT2 in the large intestine. In particular, the sensation of sweet taste may increase GLUT2 activity in the gut. Injection of glucose into the liver weakens the production of glucose and begins to promote the formation of glycogen through hepatic glycogenesis (glyco = glycogen, genesis = creation; creation of glycogen).

Glucose uptake by cells

Insulin works to transport glucose from the blood into muscle and fat cells through a transporter known as GLUT4. There are 6 GLUTs in the body (1-7, of which 6 is a pseudogene), but GLUT4 is the most widely expressed and is important for muscle and fat tissue, with GLUT5 responsible for fructose. GLUT4 is not a surface transporter but is contained in small vesicles inside the cell. These vesicles can move to the cell surface (cytoplasmic membrane) either by insulin stimulating its receptor or by the release of calcium from the sarcoplasmic reticulum (muscle contraction). As mentioned previously, the close interaction of PI3K activation (via insulin signaling) and CAP/Cbl signaling (partly via insulin) is required for efficient GLUT4 activation and glucose uptake into muscle and fat cells (where GLUT4 is most expressed).

Insulin sensitivity and insulin resistance

Insulin resistance occurs with high fat meals (usually 60% of total calorie intake or higher), which may be due to an unfavorable interaction with the CAP/Cbl signaling cascade required for GLUT4 translocation, since phosphorylation of the insulin receptor is effectively unaffected. and phosphorylation of IRS mediators is not significantly affected.

Insulin in bodybuilding

The use of insulin to improve body performance and appearance is quite controversial, since this hormone tends to promote the accumulation of nutrients in fat cells. However, this accumulation can be controlled by the user to some extent. A strict regimen of intense weight training plus a diet without excess fat ensures that protein and glucose are stored in muscle cells (instead of fatty acids stored in fat cells). This is especially important in the immediate post-exercise period, when the body's absorptive capacity is increased and insulin sensitivity in skeletal muscle is significantly increased compared to rest.
When taken immediately after training, the hormone promotes rapid and noticeable muscle growth. Soon after starting insulin therapy, you can observe a change in the appearance of the muscles (the muscles begin to look fuller and sometimes more prominent).
The fact that insulin is undetectable in urine tests makes it popular among many professional athletes and bodybuilders. Please note that, despite some progress in drug detection tests, especially when it comes to analogues, today the original insulin is still considered a “safe” drug. Insulin is often used in combination with other drugs that are "safe" to drug control, such as thyroid medications, and low-dose testosterone injections, which together can have a significant impact on the appearance and performance of the user, who may not have to fear a positive result. when analyzing urine. Users who are not drug tested often find that insulin in combination with anabolic/androgenic steroids acts synergistically. This is because AAS actively support an anabolic state through various mechanisms. Insulin markedly improves the transport of nutrients into muscle cells and inhibits protein breakdown, and anabolic steroids (among other things) markedly increase the rate of protein synthesis.
As already mentioned, in medicine, insulin is usually used to treat various forms of diabetes mellitus (if the human body is not able to produce insulin at sufficient levels (type I diabetes mellitus), or is not able to identify insulin in cellular areas when there is a certain level of it in the blood (mellitus mellitus). diabetes type II)). Type I diabetics therefore need to take insulin regularly because their bodies do not have sufficient levels of this hormone. In addition to the need for ongoing treatment, patients also need to constantly monitor their blood glucose levels and monitor their sugar intake. By making lifestyle changes, engaging in regular exercise, and developing a balanced diet, insulin-dependent individuals can live full, healthy lives. However, if left untreated, diabetes can be a deadly disease.

Story

Insulin first became available as a drug in the 1920s. The discovery of insulin is associated with the names of Canadian physician Fred Banting and Canadian physiologist Charles Best, who jointly developed the first insulin drugs as the world's first effective treatment for diabetes. Their work stems from an idea originally proposed by Banting, who, as a young doctor, had the audacity to suggest that an active extract could be extracted from animal pancreas that would regulate human blood sugar levels. In order to realize his idea, he turned to the world famous physiologist J.J.R. McLeod from the University of Toronto. McLeod, initially not very impressed with the unusual concept (but must have been impressed by Banting's conviction and tenacity), appointed a couple of graduate students to assist him in his work. To determine who would work with Banting, the students cast lots, and the choice fell on graduate Best.
Together, Banting and Brest changed the history of medicine.
The first insulin preparations produced by scientists were extracted from crude extracts of dog pancreas. However, at some point the supply of laboratory animals ran out, and in a desperate attempt to continue research, a couple of scientists began to look for stray dogs for their purposes. Loan scientists have discovered that they can work with the pancreas of slaughtered cows and pigs, which makes their work much easier (and more ethically acceptable). The first successful treatment of diabetes with insulin was carried out in January 1922. In August of that year, scientists successfully tested a group of clinical patients, including 15-year-old Elizabeth Hughes, daughter of presidential candidate Charles Evans Hughes. In 1918, Elizabeth was diagnosed with diabetes and her dramatic fight for life received national publicity.
Insulin saved Elizabeth from starvation, since at that time the only known way to slow the progression of this disease was severe calorie restriction. A year later, in 1923, Banging and MacLeod received the Nobel Prize for their discovery. Shortly afterwards, controversy ensues as to who is really responsible for this discovery, and Bunting ends up sharing his prize with Best and McLeod with J.B. Collip, a chemist assisting in the extraction and purification of insulin.
After hopes for their own insulin production collapsed, Banting and his team began collaborating with Eli Lilly & Co. The joint work led to the development of the first mass-produced insulin preparations. The drugs were an immediate and stunning success, and insulin became widely available commercially in 1923, the same year that Banting and MacLeod received the Nobel Prize. That same year, Danish scientist August Krogh founded the Nordisk Insulinlaboratorium, desperate to bring insulin technology back to Denmark to help his diabetic wife. This company, which later changed its name to Novo Nordisk, eventually became the world's second leading insulin manufacturer, along with Eli Lilly & Co.
By today's standards, the first insulin preparations were not pure enough. They typically contained 40 units of animal insulin per milliliter, as opposed to the standard concentration of 100 units accepted today. The large doses required for these initially low-concentration drugs were not very convenient for patients, and adverse reactions at injection sites were common. The drugs also contained significant protein impurities that could cause allergic reactions in users. Despite this, the drug has saved the lives of countless people who were literally facing a death sentence after receiving a diagnosis of diabetes. Eli Lilly and Novo Nordisk improved the purity of their products in subsequent years, but significant improvements in insulin technology did not occur until the mid-1930s, when the first long-acting insulin preparations were developed.
The first such drug used protamine and zinc to delay the action of insulin in the body, broadening the activity curve and reducing the number of injections required daily. The drug was named Protamine Zinc Insulin (PZI). Its effect lasted 24-36 hours. Following this, by 1950, Neutral Protamine Hagedorn (NPH) Insulin, also known as Isophane Insulin, was released. This drug was very similar to PCI insulin, except that it could be mixed with regular insulin without disrupting the release curve of the corresponding insulins. In other words, regular insulin could be mixed in the same syringe with NPH insulin, providing a biphasic release characterized by the early peak effect of regular insulin and the prolonged action caused by long-acting NPH.
In 1951, insulin Lente appeared, including the drugs Semilente, Lente and Ultra-Lente.
The amounts of zinc used in the preparations are different in each case, which provides great variability in terms of duration of action and pharmacokinetics. Like previous insulins, this drug was also produced without the use of protamine. Shortly thereafter, many physicians began successfully switching their patients from NPH Insulin to Lente, which required only one morning dose (although some patients still used evening doses of Lente insulin to maintain complete blood glucose control for 24 hours). Over the next 23 years, there were no significant changes in the development of new technologies for the use of insulin.
In 1974, chromatographic purification technologies made it possible to produce animal-derived insulin with extremely low levels of impurities (less than 1 pmol/L protein impurities).
Novo was the first company to produce monocomponent insulin using this technology.
Eli Lilly also makes its own version of the drug called "Single Peak" Insulin, which is associated with a single peak in protein levels observed in a chemical analysis. This improvement, although significant, did not last long. In 1975, Ciba-Geigy released the first synthetic insulin preparation (CGP 12831). It was only three years later that Genentech scientists developed insulin using a modified E. coli bacterium, the first synthetic insulin with an amino acid sequence identical to human insulin (however, animal insulins work fine in the human body, despite the fact that their structures are slightly different) . The US FDA approved the first such drugs, Humulin R (Regular) and Humulin NPH from Eli Lilly & Co, in 1982. The name Humulin is an abbreviation of the words "human" and "insulin".
Soon Novo releases semi-synthetic insulin Actrapid HM and Monotard HM.
The FDA has approved a number of other insulin drugs over the years, including various biphasic drugs that combine different amounts of fast-acting and slow-acting insulin. Most recently, the FDA approved Eli Lilly's rapid-acting insulin analog Humalog. Additional insulin analogues are currently being studied, including Lantus and Apidra from Aventis, and Levemir and NovoRapid from Novo Nordisk. There is a very wide range of different insulin drugs approved and marketed in the United States and other countries, and it is very important to understand that “insulin” represents a very broad class of drugs. This class is likely to continue to expand as new drugs have already been developed and successfully tested. Today, approximately 55 million people regularly use some form of injectable insulin to control diabetes, making this an extremely important and lucrative area of ​​medicine.

Types of insulin

There are two types of pharmaceutical insulin - animal and synthetic. Animal insulin is secreted from the pancreas of pigs or cows (or both). Animal-derived insulin products are divided into two categories: “standard” and “purified” insulin, depending on the level of purity and the content of other substances. When using such products, there is always a small chance of developing pancreatic cancer due to the possible presence of contaminants in the drug.
Biosynthetic, or synthetic, insulin is produced using recombinant DNA technology, the same procedure used in the manufacturing process. The result is a polypeptide hormone with one “A chain” containing 21 amino acids linked by two disulfide bonds to a “B chain” containing 30 amino acids. As a result of the biosynthetic process, a drug is created that is free of the protein that contaminates the pancreas, which is often observed with animal-derived insulin, and is structurally and biologically identical to human pancreatic insulin. Due to the possible presence of contaminants in animal insulin, and the fact that its structure differs (very slightly) from that of human insulin, synthetic insulin dominates the pharmaceutical market today. Biosynthetic human insulin/its analogues are also more popular among athletes.
There are a variety of synthetic insulins available, each with unique characteristics regarding speed of onset of action, peak and duration of activity, and dose concentration. This therapeutic diversity gives physicians the opportunity to tailor treatment programs for insulin-dependent diabetic patients and reduce the number of daily injections, providing patients with maximum comfort. Patients should be aware of all the features of the drug before using it. Because of the differences between the drugs, switching from one form of insulin drug to another should be done with extreme caution.

Short-acting insulins

Humalog ® (Insulin Lispro) Humalog ® is a short-acting human insulin analogue, specifically an insulin analogue Lys (B28) Pro (B29), which was created by substituting amino acids at positions 28 and 29. It is considered equivalent to regular soluble insulin when compared unit per unit, but has faster activity. The drug begins to act approximately 15 minutes after subcutaneous administration, and its maximum effect is achieved after 30-90 minutes. The total duration of action of the drug is 3-5 hours. Insulin Lispro is typically used as an adjunct to longer-acting insulins and can be taken before or immediately after a meal to mimic the natural response of insulin. Many athletes believe that the short-term action of this insulin makes it ideal for sports purposes, since its highest activity is concentrated in the post-exercise phase, characterized by increased responsiveness to nutrient absorption.
Novolog ® (Insulin Aspartate) is a short-acting analogue of human insulin created by replacing the amino acid at position B28 with aspartic acid. The onset of action of the drug is observed approximately 15 minutes after subcutaneous administration, and the maximum effect is achieved after 1-3 hours. The total duration of action is 3-5 hours. Insulin Lispro is typically used as an adjunct to longer-acting insulins and can be taken before or immediately after a meal to mimic the natural response of insulin. Many athletes believe that its short duration of action makes it ideal for sports purposes, as much of its activity can be concentrated in the post-exercise phase, characterized by increased susceptibility to nutrient absorption.
Humulin ® R “Regular” (Insulin Inj). Identical to human insulin. Also sold as Humulin-S® (soluble). The product contains zinc insulin crystals dissolved in a clear liquid. There are no additives present in the product to slow the release of this product, which is why it is commonly referred to as “soluble human insulin.” After subcutaneous administration, the drug begins to act within 20-30 minutes, and the maximum effect is achieved after 1-3 hours. The total duration of action is 5-8 hours. Humulin-S and Humalog are the two most popular forms of insulin among bodybuilders and athletes.

Intermediate and long-acting insulins

Humulin ® N, NPH (Insulin Isophane). Crystalline insulin suspension with protamine and zinc to delay release and spread action. Isophane insulin is considered an intermediate-acting insulin. The onset of action of the drug is observed approximately 1-2 hours after subcutaneous administration, and reaches its peak after 4-10 hours. The total duration of action is more than 14 hours. This type of insulin is not typically used for athletic purposes.
Humulin ® L Lente (medium action zinc suspension). A crystalline suspension of insulin with zinc to delay its release and extend its action. Humulin-L is considered an intermediate-acting insulin. The onset of action of the drug is observed after approximately 1-3 hours, and reaches its peak after 6-14 hours.
The total duration of action of the drug is more than 20 hours.
This type of insulin is not typically used in sports.

Humulin ® U Ultralente (long-acting zinc suspension)

A crystalline suspension of insulin with zinc to delay its release and extend its action. Humulin-L is considered a long-acting insulin. The onset of action of the drug is observed approximately 6 hours after administration, and reaches its peak after 14-18 hours. The total duration of action of the drug is 18-24 hours. This type of insulin is not typically used for athletic purposes.
Lantus (insulin glargine). Long-acting analogue of human insulin. In this type of insulin, the asparagine at position A21 is replaced and two are added to the C-terminus of insulin. The onset of action of the drug is observed approximately 1-2 hours after administration, and the drug is considered to have no significant peak (it has a very consistent release pattern throughout the duration of its activity). The total duration of action of the drug is 20-24 hours after subcutaneous injection. This type of insulin is not typically used for athletic purposes.

Biphasic Insulins

Humulin ® mixtures. These are mixtures of fast-acting regular soluble insulin with long- or intermediate-acting insulin to provide a longer-lasting effect. They are noted by the percentage of mixture, usually 10/90, 20/80, 30/70, 40/60 and 50/50. Mixtures using Humalog rapid-acting insulin are also available.

Warning: Concentrated Insulin

The most common forms of insulin come in a concentration of 100 IU of the hormone per milliliter. They are identified in the US and many other regions as "U-100" drugs. In addition to this, however, there are also concentrated forms of insulin available for patients requiring higher doses and more economical or convenient options than U-100 medications. In the USA you can also find products contained in a concentration 5 times higher than the norm, that is, 500 IU per milliliter. Such drugs are identified as "U-500", and are available only by prescription. Such products can be extremely dangerous when replacing U-100 insulin products without compensatory dosage adjustments. Given the overall difficulty in accurately measuring doses (2-15 IU) with such a high concentration drug, U-100 drugs are almost exclusively used for sports purposes.

Side effects of insulin

Hypoglycemia

Hypoglycemia is a major side effect when using insulin. This is a very dangerous disease that occurs when blood glucose levels drop too low. This is a fairly common and potentially fatal reaction with medical and non-medical use of insulin and should be taken seriously. Thus, it is very important to know all the signs of hypoglycemia.
The following is a list of symptoms that may indicate mild to moderate hypoglycemia: hunger, drowsiness, blurred vision, depression, dizziness, sweating, palpitations, tremors, restlessness, tingling in the arms, legs, lips or tongue, dizziness, inability to concentrate, headache , sleep disturbances, restlessness, slurred speech, irritability, abnormal behavior, erratic movements and personality changes. If any of these signals occur, you should immediately consume foods or drinks that contain simple sugars, such as candy or carbohydrate drinks. This will cause blood glucose levels to rise, which will protect the body from mild to moderate hypoglycemia. There is always a risk of developing severe hypoglycemia, a very serious illness that requires immediate emergency medical attention. Symptoms include confusion, seizures, loss of consciousness and death. Please note that in some cases, symptoms of hypoglycemia are mistaken for alcoholism.
It is also very important to pay attention to drowsiness after insulin injections. This is an early symptom of hypoglycemia, and a clear sign that the user should consume more carbohydrates.
It is not recommended to sleep at such times, as insulin may peak during rest and blood glucose levels may drop significantly. Without knowing this, some athletes face the risk of developing severe hypoglycemia. The danger of such a condition has already been discussed. Unfortunately, consuming more carbohydrates before bed does not provide any benefit. Users experimenting with insulin should stay awake for the duration of the drug and also avoid using insulin in the early evening to prevent possible drug activity at night. It is important to tell your loved ones about the use of the drug so that they can notify an ambulance in case of loss of consciousness. This information can help save valuable (possibly life-saving) time by helping healthcare providers provide the diagnosis and necessary treatment.

Lipodystrophy

Subcutaneous injection of insulin can cause an increase in adipose tissue at the injection site.
This may be exacerbated by repeated injections of insulin into the same area.

Allergy to insulin

In a small percentage of users, insulin use may cause localized allergies, including irritation, swelling, itching and/or redness at the injection sites. With long-term treatment, allergic phenomena may decrease. In some cases, this may be due to an allergy to an ingredient, or, in the case of animal-derived insulin, to contamination of the protein. Less common, but potentially more serious, is a systemic allergic reaction to insulin, which includes a rash all over the body, difficulty breathing, shortness of breath, increased heart rate, increased sweating, and/or decreased blood pressure. In rare cases, this phenomenon can be life-threatening. If any adverse reactions occur, the user should report to a medical facility.

Insulin administration

Given that there are different forms of insulin for medical use with different pharmacokinetic patterns, as well as products with different drug concentrations, it is critical for the user to be aware of insulin dosing and action on a case-by-case basis to monitor peak efficacy, overall duration of action, dosage and carbohydrate intake . In sports, the most popular are fast-acting insulin preparations (Novolog, Humalog and Humulin-R). It is important to emphasize that before using insulin, you must become familiar with the operation of the glucometer. This is a medical device that can quickly and accurately determine blood glucose levels. This device will help you monitor and optimize your insulin/carbohydrate intake.

Insulin doses

Short acting insulin

Short-acting insulin forms (Novolog, Humalog, Humulin-R) are intended for subcutaneous injection. After a subcutaneous injection, the injection site should be left alone and should not be rubbed under any circumstances, to prevent too rapid release of the drug into the blood. It is also necessary to change the sites of subcutaneous injections to avoid localized accumulation of subcutaneous fat due to the lipogenic properties of this hormone. Medical dosage will vary depending on the individual patient. In addition, changes in diet, activity level, or work/sleep schedule may affect the required insulin dose. Although not recommended by doctors, it is advisable to administer some doses of short-acting insulin intramuscularly. This, however, may increase the potential risk due to drug dissipation and its hypoglycemic effect.
Insulin dosing may vary slightly among athletes and is often dependent on factors such as body weight, insulin sensitivity, activity level, diet, and use of other medications.
Most users prefer to take insulin immediately after exercise, which is the most effective time to use the drug. Among bodybuilders, regular doses of insulin (Humulin-R) are used at 1 IU per 15-20 pounds of body weight, and the most common dose is 10 IU. This dose may be slightly reduced in users using the faster-acting drugs Humalog and Novolog, which provide a more powerful and faster peak effect. Beginner users usually start using the drug in low doses and gradually increase to the normal dosage. For example, on the first day of insulin therapy, a user may start with a dose of 2 IU. After each workout, the dose can be increased by 1IU, and this increase can continue to the level set by the user. Many believe that this use is safer and helps to take into account the individual characteristics of the body, since users have different tolerance to insulin.
Athletes using growth hormone often use slightly higher doses of insulin because growth hormone reduces insulin secretion and promotes cellular resistance to insulin.
We must remember that within a few hours after using insulin, you need to eat carbohydrates. You should consume at least 10-15 grams of simple carbohydrates per 1IU of insulin (with a minimum immediate intake of 100 grams regardless of dose). This should be done 10-30 minutes after subcutaneous administration of Humulin-R, or immediately after using Novolog or Humalog. Carbohydrate drinks are often used as a quick source of carbohydrates. To be safe, users should always have a sugar cube on hand in case of an unexpected drop in blood glucose levels. Many athletes take creatine monohydrate with a carbohydrate drink because insulin can help increase creatine production in the muscles. 30-60 minutes after the insulin injection, the user should eat well and consume a protein shake. A carbohydrate drink and protein shake are absolutely essential, as without it, blood sugar levels can drop dangerously low and the athlete may enter a state of hypoglycemia. Sufficient amounts of carbohydrates and proteins are a constant condition when using insulin.

The use of intermediate-acting, long-acting, biphasic insulins

Intermediate-acting, long-acting and biphasic insulins are intended for subcutaneous injection. Intramuscular injections will release the drug too quickly, potentially leading to the risk of hypoglycemia. After a subcutaneous injection, the injection site should be left alone and should not be rubbed to prevent the drug from being released into the blood too quickly. It is also recommended to regularly change subcutaneous injection sites to avoid localized accumulation of subcutaneous fat due to the lipogenic properties of this hormone. The dosage will vary depending on the individual characteristics of each individual patient.
In addition, changes in diet, activity level, or work/sleep schedule may affect your insulin dosage. Intermediate-acting, long-acting, and biphasic insulins are not widely used in sports due to their long-acting nature, making them poorly suited for use in the short post-exercise time period when nutrient absorption is high.

Jessen N, Goodyear LJ Contraction signaling to glucose transport in skeletal muscle. J Appl Physiol. (2005)

Bernard JR, et al High-fat feeding effects on components of the CAP/Cbl signaling cascade in Sprague-Dawley rat skeletal muscle. Metabolism. (2006)

Most people with diabetes tolerate insulin treatment well if they use the right dose. But in some cases, allergic reactions to insulin or additional components of the drug, as well as some other features, may occur.

Local manifestations and hypersensitivity, intolerance

Local manifestations at the site of insulin administration. These reactions include pain, redness, swelling, itching, hives, and inflammation.

Most of these symptoms are mild and usually subside within a few days or weeks of starting therapy. In some cases, it may be necessary to replace insulin with a drug containing other preservatives or stabilizers.

Immediate hypersensitivity - such allergic reactions develop quite rarely. They can develop both on insulin itself and on auxiliary compounds, and manifest themselves in the form of generalized skin reactions:

1. bronchospasm,
2. angioedema,
3. drop in blood pressure, shock.

That is, all of them can pose a threat to the patient’s life. In case of generalized allergies, it is necessary to replace the drug with short-acting insulin, and it is also necessary to carry out antiallergic measures.

Poor insulin tolerance due to a drop in the normal level of long-term habitual high glycemia. If such symptoms occur, then you need to maintain the glucose level at a higher level for about 10 days so that the body can adapt to the normal value.

Deterioration of vision and sodium excretion

Side effects from vision. Strong changes in the concentration of glucose in the blood due to regulation can lead to temporary visual impairment, as tissue turgor and the refractive value of the lens change with a decrease in eye refraction (lens hydration increases).

This reaction can occur at the very beginning of insulin use. This condition does not require treatment, you just need:

• reduce eye strain,
• use the computer less,
• read less
• watch less TV.

Pain Those who need to know that this is not dangerous and that their vision will be restored in a couple of weeks.

Formation of antibodies to insulin administration. Sometimes, with such a reaction, it is necessary to adjust the dose to eliminate the likelihood of developing hyper- or hypoglycemia.

In rare cases, insulin delays sodium excretion, causing swelling. This is especially true in cases where intensive insulin therapy causes a sharp improvement in metabolism. Insulin swelling occurs at the beginning of the treatment process, they are not dangerous and usually disappear after 3 to 4 days, although in some cases they can persist for up to two weeks. That's why it's so important to know.

Lipodystrophy and drug reactions

Lipodystrophy. May manifest as lipoatrophy (loss of subcutaneous tissue) and lipohypertrophy (increased tissue formation).

If an insulin injection enters an area of ​​lipodystrophy, insulin absorption may slow down, leading to changes in pharmacokinetics.

To reduce the manifestations of this reaction or prevent the onset of lipodystrophy, it is recommended to constantly change the injection site within the boundaries of one area of ​​the body intended for administering insulin subcutaneously.

Some medications weaken the glucose-lowering effect of insulin. Such drugs include:

• glucocorticosteroids;
• diuretics;
• danazol;
• diazoxide;
• isoniazid;
• glucagon;
• estrogens and gestagens;
• somatotropin;
• phenothiazine derivatives;
• thyroid hormones;
• sympathomimetics (salbutamol, adrenaline).

Alcohol and clonidine can lead to both increased and decreased hypoglycemic effects of insulin. Pentamidine can lead to hypoglycemia, which then gives way to hyperglycemia as follows.

Other side effects and actions

Somogyi syndrome is a post-hypoglycemic hyperglycemia that occurs as a result of the compensatory action of counter-insulin hormones (glucagon, cortisol, growth hormone, catecholamines) as a reaction to glucose deficiency in brain cells. Studies show that 30% of diabetic patients have undiagnosed nocturnal hypoglycemia; this is not yet a problem, but it should not be ignored.

The above hormones increase glycogenolysis, another side effect. Thus maintaining the required concentration of insulin in the blood. But these hormones, as a rule, are released in much greater quantities than necessary, which means that the glycemic response is also much greater than the costs. This condition can last from several hours to several days and is especially severe in the morning.

A high value of morning hyperglycemia always raises the question: is there an excess amount or a deficiency of night-time extended-release insulin? The correct answer will guarantee that carbohydrate metabolism will be well compensated, since in one situation the dose of night insulin should be reduced, and in another it should be increased or distributed differently.

The “dawn phenomenon” is a state of hyperglycemia in the morning (from 4 to 9 o’clock) due to increased glycogenolysis, in which glycogen in the liver breaks down due to excessive secretion of counter-insulin hormones without previous hypoglycemia.

As a result, insulin resistance occurs and the need for insulin increases, it can be noted that:

• the basal requirement is at the same level from 10 pm to midnight.
• Its decrease by 50% occurs from 12 o'clock at night to 4 o'clock in the morning.
• Increase by the same amount from 4 to 9 am.

Stable glycemia at night is quite difficult to achieve, since even modern long-acting insulin preparations cannot fully imitate such physiological changes in insulin secretion.

During the period of physiologically caused reduced nighttime insulin requirements, a side effect is the risk of nocturnal hypoglycemia when administered before bedtime with an extended-release drug will increase due to an increase in the activity of extended-release insulin. New long-acting drugs (peak-free), for example, glargine, may help solve this problem.

To date, there is no etiotropic therapy for type 1 diabetes mellitus, although attempts are constantly being made to develop it.

Any medicine, unfortunately, can have side effects. In some drugs they are less pronounced, in others they are more pronounced. This is especially true for potent and prescription medications. Insulin is a hormone by nature. Hormones are capable of exhibiting a pronounced biologically active effect even in microscopic doses.

The risk of side effects from a drug increases if it is administered incorrectly, the dosage is incorrectly selected, or if storage conditions are violated. It should only be prescribed by a doctor, taking into account the individual characteristics of the patient’s body.

When using injection therapy, you must always follow the instructions for the medicine and the recommendations of the endocrinologist. If any unusual symptoms appear, the patient should not hesitate to visit a doctor, since some side effects of insulin can significantly worsen his well-being and negatively affect vital systems and organs.

Hypoglycemia is one of the most common side effects that occurs with insulin treatment (a condition in which blood sugar drops below normal levels). Sometimes glucose levels may drop to 2.2 mmol/L or less. Such changes are dangerous, as they can lead to loss of consciousness, convulsions, stroke and even coma. But with timely assistance provided at the initial stages of the development of hypoglycemia, the patient’s condition, as a rule, quickly normalizes, and this pathology passes almost without a trace.

There are reasons that increase the risk of developing a pathological decrease in blood sugar when treated with insulin:

• spontaneous improvement in the ability of cells to absorb glucose during periods of remission (symptoms subsiding) of diabetes mellitus;
• violation of diet or skipping meals;
• grueling physical activity;
• incorrect dose of insulin;
• drinking alcohol;
• reducing the calorie intake below the norm recommended by the doctor;
• conditions that are associated with dehydration (diarrhea, vomiting);
• taking medications that are incompatible with insulin.

Hypoglycemia that is not diagnosed in time is especially dangerous. This phenomenon usually occurs in those people who have had diabetes for a long time, but cannot compensate for it normally. If their sugar levels are either low or high over a long period of time, they may not notice alarming symptoms because they think that this is the norm.

Patients need to regularly monitor their blood sugar and record these values, as well as how they feel in a diabetic diary.

Lipodystrophy is a thinning of subcutaneous fat, which occurs in diabetics due to frequent insulin injections in the same anatomical area. The fact is that in the injection area, insulin may be absorbed with a delay and not completely penetrate into the desired tissues. This can lead to a change in the strength of its influence and to thinning of the skin in this place. As a rule, modern drugs rarely have such a negative effect, but for prevention it is still advisable to periodically change injection sites. This will protect against lipodystrophy and keep the subcutaneous layer of fat unchanged.

Sometimes lipodystrophy can be so severe that subcutaneous fat tissue disappears almost completely. Even very high-calorie foods and reduced physical activity do not help restore it.

Lipodystrophy itself, of course, does not pose a threat to the patient’s life, but it can become a serious problem for him. Firstly, lipodystrophy increases the level of cholesterol in the blood, and because of this there is a risk of developing cardiovascular diseases. Secondly, because of it, the physiological pH level of the blood can shift towards increased acidity. A diabetic may experience problems with body weight due to a local metabolic disorder. Another unpleasant nuance with lipodystrophy is the occurrence of nagging pain in those places where the affected subcutaneous fat is located.

In the initial stages, lipodystrophy manifests itself as small depressions in the skin, which can subsequently increase in size and become the cause of a serious cosmetic defect (in addition to associated health problems)

Effect on vision and metabolism

Side effects from the eyes are uncommon and usually resolve within the first week of starting regular insulin therapy. The patient may experience a temporary decrease in visual acuity, since changes in blood glucose concentration affect tissue turgor (internal pressure).

When the sugar level in the bloodstream normalizes, the lens becomes more saturated with moisture, and this affects refraction (refraction of light rays). The eyes need time to adapt to the changes that occur in metabolism under the influence of insulin.

Visual acuity, as a rule, completely returns to its previous level within 7–10 days from the start of treatment. During this period, the body's response to insulin becomes physiological (natural) and all unpleasant eye symptoms disappear. To facilitate the transition stage, you need to protect the organ of vision from overstrain. To do this, it is important to exclude prolonged reading, working with a computer and watching TV. If a patient has chronic eye diseases (for example, myopia), then at the beginning of insulin therapy it is better for him to use glasses rather than contact lenses, even if he is used to wearing them all the time.

Since insulin speeds up the metabolic process, sometimes at the beginning of treatment the patient may develop severe swelling. Due to fluid retention, a person can gain 3-5 kg ​​within a week. This excess weight should go away in about 10-14 days from the start of therapy. If swelling does not go away and persists for a longer period of time, the patient should consult a doctor and conduct additional diagnostics of the body.

Allergy

Modern insulin preparations, obtained using biotechnology and genetic engineering methods, are of high quality and rarely cause allergic reactions. But despite this, these drugs still contain proteins, and by their nature they can be antigens. Antigens are substances that are foreign to the body, and when they enter it, they can provoke protective reactions of the immune system. According to statistics, insulin allergies occur in 5–30% of patients. There is also an individual tolerance to the drug, because the same medicine may not be suitable for different patients with the same manifestations of diabetes.

The risk of allergies increases if the patient has angiopathy, neuropathy and other complications of the disease

Allergies can be local or general. Most often, a local allergic response occurs, which is manifested by inflammation, redness, swelling and swelling at the injection site. Sometimes these symptoms may be accompanied by a small hives-like rash and itching.

The most terrible forms of general allergies are angioedema and anaphylactic shock. Fortunately, they are very rare, but you need to be aware of these pathological conditions, as they require emergency care.

If local reactions to insulin occur in the area close to the injection site, then in general forms of allergies the rash spreads throughout the body. It is often accompanied by severe swelling, breathing problems, heart failure and pressure surges.

How can I help? It is necessary to stop administering insulin, call an ambulance and free the patient from tight clothing so that nothing is squeezing the chest. A diabetic needs to be provided with rest and access to fresh, cool air. When calling a team, the ambulance dispatcher can tell you how to provide assistance in accordance with the symptoms that arise, so as not to harm the patient.

How to reduce the risk of side effects?

By using the right medication and following the recommendations of your doctor, you can significantly reduce the risk of unwanted effects of insulin. Before administering the hormone, you should always pay attention to the appearance of the solution (if the patient takes it from a bottle or ampoule). If there is cloudiness, color change or sediment appears, the hormone should not be injected.

To protect yourself from the side effects of insulin, it is advisable to adhere to the following recommendations:

• do not switch to a new type of insulin on your own (even if different brands have the same active ingredient with a similar dosage);
• adjust the dose of medication before and after physical activity;
• When using insulin pens, always monitor their serviceability and the expiration date of the cartridges;
• do not stop insulin therapy, trying to replace it with folk remedies, homeopathy, etc.;
• follow a diet and adhere to the rules of a healthy lifestyle.

Modern high-quality medicines for diabetics can minimize the negative effects on the body. But, unfortunately, no one is immune from side effects. Sometimes they can appear even after a long time of using the same medicine. To protect yourself from serious health consequences, if any questionable signs appear, you should not delay a visit to the doctor. The treating endocrinologist will help you choose the optimal drug, adjust the dosage if necessary, and give recommendations for further diagnosis and treatment.

Last updated: June 1, 2019

Protein-peptide hormonal drug; Insulin is used as a specific treatment for diabetes mellitus.

Insulin actively affects carbohydrate metabolism - it helps to reduce the content in the blood and its absorption by tissues, facilitates the penetration of glucose into cells, promotes the synthesis of glycogen, and prevents the conversion of fats and amino acids into carbohydrates.

Indications for use

Diabetes.

In small doses (5–10 units) insulin is used for liver diseases (hepatitis, initial stages of cirrhosis), acidosis, exhaustion, loss of nutrition, furunculosis, and thyrotoxicosis.

In neuropsychiatric practice, insulin is used for alcoholism and depletion of the nervous system (in doses that cause a hypoglycemic state).

In psychiatry - for insulin comatose therapy (in the treatment of some forms of schizophrenia, insulin solution is administered in significant quantities, which, with a gradual increase in doses, cause hypoglycemic shock).

In dermatology, insulin is used for diabetic toxiderma, as a nonspecific remedy for eczema, acne, urticaria, psoriasis, chronic pyoderma and yeast skin lesions.

Rules of application

Typically, insulin is administered subcutaneously or intramuscularly, intravenously - only in particularly severe cases of diabetic coma; suspended drugs are administered only subcutaneously.

Injections of the daily dose are made in 2-3 doses, half an hour to an hour before meals, the effect of a single dose of the drug begins after 30-60 minutes and lasts 4-8 hours.

With intravenous administration of insulin, the maximum hypoglycemic effect is achieved after 20–30 minutes, and the sugar level returns to its original level after 1–2 hours.

Before drawing suspensions of long-acting insulin preparations into a syringe, the contents should be shaken until a uniform suspension is formed in the bottle.

At diabetes mellitus treatment is carried out subject to simultaneous adherence to a diet; the dosage is set depending on the severity of the disease, the patient’s condition and the sugar content in the urine (at the rate of 1 unit for every 5 g of sugar excreted in the urine). Typically, insulin doses range from 10 to 40 units per day.

At diabetic coma the daily dose of the drug administered subcutaneously can be increased to 100 units or more, and when administered intravenously - up to 50 units per day.

At diabetic toxicoderma Insulin is prescribed in large doses, the amount of which depends on the severity of the underlying disease.

For other indications, small doses of insulin are usually prescribed (6–10 units per day), often (for general exhaustion, liver disease) in combination with a glucose load.

Side effects

With an overdose of insulin and untimely intake of carbohydrates, hypoglycemic shock can develop - a toxic symptom complex that is accompanied by general weakness, profuse sweating and salivation, dizziness, palpitations, shortness of breath; in severe cases - loss of consciousness, delirium, convulsions, coma.

Contraindications

Acute hepatitis, pancreatitis, nephritis, kidney stones, gastric and duodenal ulcers, decompensated heart disease.

special instructions

Caution in the use of insulin is necessary when prescribing it to patients suffering from coronary insufficiency and cerebrovascular accidents.

When using long-acting drugs, due to the possibility of individual fluctuations in the reaction to the administration of these drugs, it is recommended to examine 3-4 portions of urine for sugar, 24-hour urine for sugar, as well as blood glucose levels. This allows you to clarify the hours of insulin administration, taking into account the time of onset of the maximum glucose-lowering effect.

Long-acting insulin preparations are unsuitable (due to the slow development of the effect) for the treatment of precomatose and comatose states in diabetics.

The effect of insulin is enhanced by simultaneous administration.

Composition and release form

Insulin prescription

Insulin for injection is produced in sterile bottles with a capacity of 5 ml and 10 ml, with an activity of 20 IU, 40 IU or 80 IU in 1 ml of solution.

Insulin for medical use is a white hygroscopic powder, soluble in water, obtained by extraction of the pancreas glands of slaughter cattle (animal insulin) or synthetically. Contains 3.1% sulfur.

Insulin solutions are a clear, colorless or slightly yellowish liquid of an acidic reaction (pH 2.0–3.5), which are prepared by diluting crystalline insulin in water for injection, acidified with hydrochloric acid with the addition of 0.25–0.3% solution or for canning.

Suspensions of prolonged action are produced in sterile bottles of 5 ml and 10 ml, hermetically sealed with rubber stoppers with rolled aluminum caps.

Shelf life and storage conditions

Store with caution (list B) at a temperature of 1–10° C; freezing of insulin preparations is unacceptable.

The shelf life of insulin for injection is 2 years.

Insulin preparations

Suinsulin- an aqueous solution of crystalline insulin obtained from the pancreas of pigs. The drug is used when patients are resistant to the drug obtained from the pancreas of cattle.

Monosulin- a short-acting drug containing crystalline pork insulin, which has a rapid and relatively short-term sugar-lowering effect. It is used for insulin resistance, lipodystrophy, local and general allergic reactions resulting from injections of other insulin preparations. Monosulin is administered subcutaneously or intramuscularly 15–20 minutes before meals one to several times a day. The effect occurs within 15–20 minutes, the maximum effect is achieved after 2 hours, the duration of action of the drug is no more than 6 hours. In case of allergic reactions, an intradermal test (0.02–0.04 IU) is performed before using monosulin. For lipodystrophy, the solution is administered subcutaneously at the border of a healthy and affected area of ​​subcutaneous fat: in children 2–4 units, in adults 4–8 units for 30–40 days. If necessary, the course of treatment is repeated. In case of an overdose, feelings of hunger, weakness, sweating, palpitations, dizziness (hypoglycemia) are possible. Caution is required in case of coronary insufficiency and cerebrovascular accident.

A suspension consisting of suspensions of amorphous and crystalline zinc insulin.

A suspension in the form of an amorphous powder in an acetate buffer with a duration of action of 10–12 hours and maximum effect during the first 7 hours.

A sterile suspension of crystalline insulin in acetate buffer, a drug with a duration of action of up to 36 hours, the maximum occurs 16–20 hours after administration.

A sterile suspension of insulin crystals complexed with protamine in phosphate buffer.

10 ml bottles, composition: insulin - 40 units, zinc chloride - 0.08 mg, tryprotamine - 0.8 ml, glucose - 40 mg, sodium phosphate - about 4 mg, tricresol - 3 mg.

The long-acting drug, in terms of duration of action, occupies a middle place between the regular drug and Triprotamine-zinc-insulin.

Thin suspension of white color. The peculiarity of the suspension, compared to the usual drug, is the slower onset of the effect and its longer duration.

Sterile suspension of crystalline insulin, protamine, zinc chloride and sodium phosphate, long-acting preparation.

Long-acting insulin with the addition of aminoquinurea hydrochloride.

Insulin-long suspension- amorphous pork insulin mixed with zinc and crystalline bovine insulin combined with zinc (in a ratio of 3:7). A long-acting drug, administered subcutaneously and intramuscularly for moderate and severe forms of diabetes mellitus. The hypoglycemic effect occurs after 2–4 hours, reaches maximum activity after 8–10 hours and lasts 20–24 hours. Doses and the number of injections per day are set individually, taking into account the amount of sugar excreted in the urine at different times of the day and the blood sugar level. The drug is not used for diabetic coma and precomatose state. In case of overdose, a hypoglycemic state and allergic reactions (urticaria, rash, skin itching, Quincke's edema) may develop.

Insulin-semilong suspension- contains amorphous pork insulin in combination with zinc. Long-acting drug. Used for moderate and severe diabetes mellitus, for daytime hyperglycemia and glucosuria, administered subcutaneously or intramuscularly. The effect is observed after 1–1.5 hours, maximum activity after 5–8 hours. The duration of action of the drug is 10–12 hours.

Insulin ultralong suspension- contains crystalline bovine insulin in combination with zinc. Used subcutaneously and intramuscularly for moderate and severe diabetes mellitus, in the second half of the night and in the early morning hours. The hypoglycemic effect is observed after 6–8 hours. Duration of action is 30–36 hours.

Properties

(Insulinum) is a high-molecular protein, a hormone produced by the pancreas of mammals, secreted by basophilic insulinocytes (β-cells of the pancreatic islets of Langerhans).

Pharmacological properties

Frederick Banting, Charles Best and James Collip first obtained insulin from the pancreas of animals in 1921.

Insulin is a specific regulator of carbohydrate metabolism, which, by activating hexokinases, promotes the utilization of glucose - its penetration into tissues (mainly into muscles) and combustion, and also stimulates the synthesis of glycogen from glucose in muscle tissue and in the liver, and suppresses gluconeogenesis.

The specific sugar-lowering activity of 0.045 mg of crystalline insulin is taken as a unit of action (U) (1 ml of insulin solution contains 40 IU).

The therapeutic effect and the need for insulin in diabetes mellitus is associated with the elimination of disturbances that occur with this disease in the interstitial metabolism of carbohydrates and fats. This is manifested in an improvement in the general condition of patients, a decrease in blood sugar levels, a reduction or complete elimination of glucosuria and acetonuria, as well as a weakening of a number of body disorders that accompany diabetes mellitus (furunculosis, polyneuritis, polyarthritis, etc.).

Chemical and physical properties

Insulin is easily adsorbed by kaolin, activated carbon and other adsorbents, easily soluble in water, alkalis, acids and weak alcohol solutions; insoluble in 96% alcohol, acetone and ether.

The hormone is inactivated by sunlight (UV radiation), reducing and oxidizing agents, and is easily destroyed by proteolytic enzymes (especially trypsin). The thermal stability of insulin depends on the pH of the medium - in acidic solutions, insulin can withstand boiling for an hour, its stability in alkaline solutions is much lower.

Getting insulin

The most widely accepted method for obtaining animal insulin from the pancreas of pigs and cattle is the following (many modifications of the basic processes vary from manufacturer to manufacturer):

1. Primary extraction of finely ground pancreatic glands with acidic alcohol.
2. Evaporation of the alcohol extract under vacuum, degreasing and re-dissolving in 80% alcohol, from which crude insulin is precipitated with absolute alcohol or ether.
3. Dissolving raw insulin in distilled water and its subsequent purification using one of the following methods: precipitation from an aqueous solution with salts; precipitation of insulin picrate with picric acid; precipitation of insulin at the isoelectric point from a solution with pH=5.0; adsorption on kaolin or activated carbon.

Both insulin salts (usually chloride) and insulin base can be prepared.

Trade name of the drug:

International nonproprietary name:

Dosage form:

Compound:

Description:

Pharmacotherapeutic group:

ATX code:

Pharmacological properties

Pharmacodynamics

Rinsulin R is a human insulin produced using recombinant DNA technology. Short-acting insulin. It interacts with a specific receptor on the outer cytoplasmic membrane of cells and forms an insulin-receptor complex that stimulates intracellular processes, including the synthesis of a number of key enzymes (hexokinase, pyruvate kinase, glycogen synthase, etc.). The decrease in blood glucose levels is due to an increase in its intracellular transport, increased absorption and assimilation by tissues, stimulation of lipogenesis, glycogenogenesis, a decrease in the rate of glucose production by the liver, etc.
The duration of action of insulin drugs is mainly determined by the rate of absorption, which depends on several factors (for example, dose, route and site of administration), and therefore the insulin action profile is subject to significant fluctuations, both between different people and within the same person. person. On average, after subcutaneous administration, Rinsulin R begins to act within 30 minutes, the maximum effect develops between 1 and 3 hours, the duration of action is 8 hours.

Pharmacokinetics
The completeness of absorption and the onset of the effect of insulin depends on the method of administration (subcutaneous, intramuscular, intravenous), injection site (abdomen, thigh, buttocks), dose (volume of insulin administered), insulin concentration in the drug, etc. It is distributed unevenly throughout the tissues; does not penetrate the placental barrier and into breast milk. It is destroyed by insulinase mainly in the liver and kidneys. The half-life is several minutes. Excreted by the kidneys (30-80%).

Indications for use

• Diabetes mellitus type 1
• Type 2 diabetes mellitus: stage of resistance to oral hypoglycemic agents, partial resistance to these drugs (with combination therapy), intercurrent diseases
• Type 2 diabetes mellitus in pregnant women
• Emergency conditions in patients with diabetes mellitus, accompanied by decompensation of carbohydrate metabolism

Contraindications

• Increased individual sensitivity to insulin or any of the components of the drug
• Hypoglycemia

Use during pregnancy and breastfeeding

Directions for use and doses

Dosage regimen and route of administration

The drug is intended for subcutaneous, intramuscular and intravenous administration.
The dose and route of administration of the drug is determined by the doctor individually in each case based on the concentration of glucose in the blood.
On average, the daily dose of the drug ranges from 0.5 to 1 IU/kg body weight (depending on the individual characteristics of the patient and blood glucose concentration).
The drug is administered 30 minutes before a meal or light snack containing carbohydrates.
The temperature of the administered insulin should be at room temperature. When monotherapy with the drug, the frequency of administration is 3 times a day (if necessary, up to 5 - 6 times a day). With a daily dose exceeding 0.6 IU/kg, the drug must be administered in the form of 2 or more injections into different areas of the body. The drug is usually injected subcutaneously into the anterior abdominal wall. Injections can also be made into the thigh, buttock or shoulder in the projection of the deltoid muscle.
It is necessary to change injection sites within the anatomical area to prevent the development of lipodystrophies. When injecting insulin subcutaneously, care must be taken not to enter a blood vessel when injecting. After the injection, do not massage the injection site. Patients should be trained in the correct use of the insulin delivery device.
The drug can be administered intramuscularly and intravenously only under the supervision of a physician.
Vials can only be used if their contents are a clear, colorless liquid without visible particles. Do not use the drug if a precipitate appears in the solution. Rinsulin ® R is a short-acting insulin and is usually used in combination with intermediate-acting insulin (Rinsulin ® NPH).
It is possible to store the drug in use at room temperature (from 15 to 25°C) for no more than 28 days.

Side effect

Due to the effect on carbohydrate metabolism: hypoglycemic conditions (pallor of the skin, increased sweating, palpitations, tremor, chills, hunger, agitation, paresthesia of the oral mucosa, weakness, headache, dizziness, decreased visual acuity). Severe hypoglycemia can lead to the development of hypoglycemic coma.
Allergic reactions: skin rash, Quincke's edema, anaphylactic shock.
Local reactions: hyperemia, swelling and itching at the injection site, with long-term use - lipodystrophy at the injection site.
Others: swelling, transient decrease in visual acuity (usually at the beginning of therapy).
If the patient has noted the development of hypoglycemia or has had an episode of loss of consciousness, he needs to inform the doctor immediately.
If any other side effects not described above are detected, the patient You should also consult a doctor.

Overdose

Interaction with other drugs

special instructions

Precautions for use

During insulin therapy, constant monitoring of blood glucose concentration is necessary.
In addition to insulin overdose, the causes of hypoglycemia can be: drug replacement, skipping meals, vomiting, diarrhea, increased physical activity, diseases that reduce the need for insulin (impaired liver and kidney function, hypofunction of the adrenal cortex, pituitary gland or thyroid gland), change of injection site, as well as interactions with other drugs.
Incorrect dosing or interruptions in insulin administration, especially in patients with type 1 diabetes, can lead to hyperglycemia. Typically, the first symptoms of hyperglycemia develop gradually over several hours or days. They include the appearance of thirst, increased urination, nausea, vomiting, dizziness, redness and dryness of the skin, dry mouth, loss of appetite, and the smell of acetone in the exhaled air. If left untreated, hyperglycemia in type 1 diabetes can lead to life-threatening diabetic ketoacidosis.
The dose of insulin must be adjusted in case of dysfunction of the thyroid gland, Addison's disease, hypopituitarism, impaired liver and kidney function, and diabetes mellitus in people over 65 years of age.
Insulin dosage adjustments may also be necessary if the patient increases the intensity of physical activity or changes their usual diet.
Concomitant diseases, especially infections and conditions accompanied by fever, increase the need for insulin.
Transferring a patient to a new type of insulin or an insulin preparation from another manufacturer must be carried out under the supervision of a physician.
Due to the possibility of precipitation in some catheters, the use of the drug in insulin pumps is not recommended.

Impact on the ability to drive vehicles and machinery

In connection with the primary prescription of insulin, a change in its type, or in the presence of significant physical or mental stress, the ability to drive vehicles or various moving mechanisms may be impaired, as well as engage in other potentially hazardous activities that require increased attention and speed of reactions.

Release form

Storage conditions

Best before date

Vacation conditions

Manufacturer

Addresses of production sites:

1. 142279, Moscow region, Serpukhov district, r.p. Obolensk, bldg. 82, p. 4.
2. 142279, Moscow region, Serpukhov district, pos. Obolensk, bldg. 83, lit. AAN.

OJSC GEROPHARM-Bio
142279, Moscow region, Serpukhov district, r.p. Obolensk, bldg. 82, p. 4

Instructions to be given to the patient

Do not use the drug if a precipitate appears in the solution.
Injection technique when using insulin in vials

If the patient is using only one type of insulin

1. Disinfect the rubber membrane of the bottle
2. Fill the syringe with air in a volume corresponding to the required dose of insulin. Inject air into the insulin vial.
3. Turn the bottle with the syringe upside down and draw the required dose of insulin into the syringe. Remove the needle from the vial and remove air from the syringe. Check that your insulin dose is correct.
4. Give the injection right away.

1. Disinfect the rubber membranes of the bottles.
2. Immediately before drawing, roll the vial of long-acting insulin (“cloudy”) between your palms until the insulin becomes uniformly white and cloudy.
3. Fill the syringe with air in a volume corresponding to the dose of “cloudy” insulin. Inject air into the vial of cloudy insulin and remove the needle from the vial.
4. Fill the syringe with air in an amount corresponding to the dose of short-acting (“transparent”) insulin. Inject air into the vial of clear insulin. Turn the bottle with the syringe upside down and draw the required dose of “transparent” insulin. Remove the needle and remove air from the syringe. Check the correct dose.
5. Insert the needle into the vial with “cloudy” insulin, turn the vial with the syringe upside down and draw the required dose of insulin. Remove air from the syringe and check that the dose is correct. Immediately inject the collected insulin mixture.
6. Always draw insulins in the same sequence described above.

• It is necessary to disinfect the area of ​​skin where insulin will be injected.
• Use two fingers to gather a fold of skin, insert the needle into the base of the fold at an angle of about 45 degrees and inject insulin under the skin.
• After injection, the needle must remain under the skin for at least 6 seconds to ensure that the insulin is completely injected.
• If blood appears at the injection site after removing the needle, lightly press the injection site with a swab moistened with a disinfectant solution (for example, alcohol).
• It is necessary to change injection sites.