The drug dexamethasone, whose successful clinical trials the head of WHO called a scientific breakthrough, can indeed be effective for patients in intensive care. It suppresses immune activity and stops the “cytokine storm” from which many people infected with COVID-19 are dying today. However, it should never be taken by people with mild to moderate symptoms of the disease, scientists warn. If a person starts using it ahead of time, he will simply destroy his immune system and it will be almost impossible to save him. Also, with long-term use, this anti-inflammatory drug can cause obesity, diabetes, osteoporosis, glaucoma and even mental disorders. Therefore, the drug should be used with great caution under strict medical supervision.
Breakthrough from the past
Effective: 35 regions will receive the first batches of Avifavir
Deliveries will be made in two weeks
Immunosuppressants, which include the anti-inflammatory drug dexamethasone, can help fight severe coronavirus infection. As Oleg Batishchev, deputy director for scientific work at the Institute of Physics and Chemistry of the Russian Academy of Sciences, told Izvestia, this remedy helps with complications caused by overactivity of the immune system (the so-called cytokine storm).
— As far as I know, quite a lot of drugs were tested that were supposed to help combat the development of this path of the disease. “All of them have existed for a long time, and they were used in the treatment of a number of other, mainly autoimmune, pathologies,” the scientist said. “The fact that dexamethasone showed its effectiveness is certainly an important finding. I hope this will help treat severe forms of COVID-19.
Researchers at the University of Oxford previously announced breakthrough results. A report on their website suggests that inexpensive and long-established dexamethasone reduces mortality in hospitalized patients with severe respiratory complications of COVID-19. British infectious disease specialists conducted a randomized trial in which 2,104 patients received 6 mg of this drug once a day (in tablet form or intravenously) for ten days.
Photo: tass/dpa/Marcel Kusch
The results were so impressive that WHO immediately reported them. This is despite the fact that the study itself has not yet been published. The WHO Director General called the data on the effectiveness of dexamethasone a “scientific breakthrough.” According to him, the anti-inflammatory drug reduces the risk of death of patients with COVID-19 connected to ventilators by 35%. And among patients receiving oxygen - by 20%.
Izvestia Help
Dexamethasone has been widely used since the 1980s. This is a medicine from the group of glucocorticosteroids, which has a pronounced anti-inflammatory, antiallergic, decongestant and immunosuppressive (suppressing immunity) effect on the body. The product is of synthetic origin; in fact, it is an analogue of a person’s own hormones secreted by the adrenal glands. It suppresses the functions of tissue macrophages and also limits the migration of leukocytes to the area of inflammation. As experts emphasize, the use of this drug is dangerous, since all steroids have a large number of serious side effects.
Dexamethasone
Dexamethasone is a synthetic hormone of the adrenal cortex with glucocorticosteroid action (GCS). It has anti-inflammatory and immunosuppressive effects, and also affects energy metabolism, glucose homeostasis and (via negative feedback) the secretion of hypothalamic activating factor and pituitary adrenocorticotropic hormone.
GCS are fat-soluble substances and therefore easily penetrate into target cells through cell membranes. The binding of a hormone to a receptor causes conformational changes in the receptor and increases its affinity for DNA. The hormone-receptor complex enters the cell nucleus and binds to the regulatory region of the DNA molecule, also known as the glucocorticoid response element (GRE).
The activated receptor binds to GREs or specific genes and regulates messenger RNA (mRNA) transcription. The newly formed mRNA is transported to ribosomes, which then participate in the formation of new proteins. Depending on the type of target cells and cellular processes, the formation of new proteins can be either enhanced (for example, the synthesis of tyrosine transaminase in liver cells) or suppressed (for example, the synthesis of IL-2 in lymphocytes). Since receptors for GCS are found in all tissues, their action is realized in most cells of the body.
Effect on energy metabolism and glucose homeostasis:
Dexamethasone, along with insulin, glucagon and catecholamines, regulates the accumulation and expenditure of energy. In the liver, it stimulates the formation of glucose from pyruvate and amino acids and the formation of glycogen. In peripheral tissues, particularly in muscles, it reduces glucose consumption and mobilizes amino acids (from proteins), which are a substrate for gluconeogenesis in the liver. Direct effects on fat metabolism include central redistribution of adipose tissue and increased lipolysis in response to catecholamines.
Through receptors in the proximal tubules of the kidneys, dexamethasone stimulates renal blood flow and glomerular filtration, inhibits the formation and secretion of vasopressin and improves the ability of the kidneys to excrete acids.
Increases the sensitivity of blood vessels to pressor agents.
In high doses, dexamethasone suppresses the formation of collagen types I and III by fibroblasts and the formation of glycosaminoglycans; by inhibiting the formation of extracellular collagen and matrix, they slow down wound healing. Long-term use of high doses causes progressive bone tissue resorption as an indirect effect, and directly reduces its formation (stimulates the secretion of parathyroid hormone and suppresses the secretion of calcitonin). In addition, it leads to a negative calcium balance, reduces calcium absorption in the intestines and increases its excretion by the kidneys. This usually results in secondary hyperparathyroidism and phosphaturia.
Action on the hypothalamus and pituitary gland:
Dexamethasone has a 30 times more pronounced effect than endogenous cortisol. Therefore, it is a more potent inhibitor of the secretion of corticotropin-releasing factor (CRF) and adrenocorticotropic hormone (ACTH). In pharmacological doses, it inhibits the hypothalamic-pituitary-adrenal system and promotes the development of secondary adrenal insufficiency.
Adrenal insufficiency can develop as early as 5-7 days of dexamethasone administration in daily doses equivalent to 20-30 mg of prednisone or after 30 days of low-dose therapy. After discontinuation of a short course of therapy (up to 5 days) with high doses, the function of the adrenal cortex can be restored within one week; after a long course, normalization occurs later; this process usually takes up to 1 year. Some patients may develop irreversible atrophy of the adrenal cortex.
Anti-inflammatory and immunosuppressive effects
glucocorticosteroids is associated with their molecular and biochemical effects. The molecular anti-inflammatory effect is the result of the interaction of glucocorticosteroids with glucocorticoid receptors and changes in the expression of a number of genes that regulate the formation of many information molecules, proteins and enzymes involved in the process of inflammation. This leads to a decrease or prevention of the tissue response to inflammation: inhibition of the accumulation of macrophages and leukocytes, suppression of phagocytosis and release of lysosomal enzymes, synthesis of inflammatory mediators, blocking of the macrophage inhibitory factor.
Dexamethasone reduces the expansion and permeability of capillaries, reduces the adhesion of leukocytes to the endothelium, and inhibits the synthesis of Pg, leukotrienes, and thromboxanes.
Dexamethasone reduces the formation of leukotrienes by reducing the release of arachidonic acid from cellular phospholipids, which results from inhibition of phospholipase A2 activity. The effect on phospholipase is mediated by an increase in the concentration of lipocortin (macrocortin), which is an inhibitor of phospholipase A2. The suppressive effect of dexamethasone on the synthesis of prostaglandins and thromboxane is the result of a decrease in the synthesis of specific mDNA encoding the formation of cyclooxygenase.
Dexamethasone prevents or inhibits cellular immune reactions (delayed hypersensitivity reactions), reduces the number of T-lymphocytes (T-helper type I), monocytes and eosinophils, the binding of immunoglobulins to their receptors, inhibits the synthesis of interleukins: reduces T-lymphocytic blastogenesis and reduces primary immune answer. Activates humoral immunity by stimulating T-helper type II - enhances the production of antibodies. A significant effect is a decrease in the formation of tumor necrosis factor (TNF) and IL-1.
Non-magic wand
Dual purpose: the “elixir of youth” was tested for the treatment of COVID-19
Antioxidant SkQ reduces the likelihood of damage to internal organs, blood clots and strokes
Despite WHO statements, the drug itself will not be a “magic wand” for coronavirus, a leading researcher at the Laboratory of Molecular Biology at Moscow State University told Izvestia. M.V. Lomonosov Roman Zinovkin.
“Its use cannot be considered a scientific breakthrough; it is simply a fairly logical move dictated by the characteristics of COVID-19,” the scientist emphasized. — First of all, the drug is an immunosuppressant. When a person has an infection, giving them immune suppressants is an unusual solution. But in severe cases of COVID-19, when the body's own immune system begins to destroy the body, this approach appears to work.
At the same time, in patients treated with dexamethasone, the risk of secondary bacterial pneumonia increases, which will develop more actively against the background of suppressed immunity. In addition, it is possible that antibodies to SARS-Cov-2 will be synthesized worse - in smaller quantities than without this drug. As a result, a person who has had an infection and taken dexamethasone has a higher chance of getting sick a second time. This medicine can only be used for patients in serious condition - on mechanical ventilation and with oxygen support, explained Roman Zinovkin.
Photo: IZVESTIA/Zurab Javakhadze
Doctors themselves say that there is nothing unexpected about the fact that this medicine turned out to be effective. It is used for various life-threatening conditions, including lung pathologies, emergency physician Andrei Ignatov told Izvestia.
— Dexamethasone is the drug of choice, the so-called therapy of despair. It is used for health reasons to stop acute inflammation,” the specialist noted. — At the same time, like any hormones, this medicine has serious side effects.
Non-Covid fate: patients with arthritis and lupus are running out of medications
Hydroxychloroquine disappeared in March - at the height of the coronavirus epidemic
In particular, with prolonged use, the normal functioning of the patient’s own adrenal glands may be disrupted. Also, taking the drug temporarily increases blood sugar, which will contribute to weight gain and, in extreme cases, the development of diabetes. Another serious limitation is that glucocorticosteroids can cause osteoporosis. Dexamethasone removes calcium from bones, which makes them more brittle. In this connection, it is possible to develop cataracts, glaucoma, and even mental problems may arise.
Why does osteochondrosis of the cervical spine develop and what are its main symptoms?
The development of pathology is influenced by a sedentary lifestyle, hard work with physical activity, age-related changes, injuries and hormonal imbalance.
The disease manifests itself:
- aching pain in the cervical region, radiating to the back of the head and shoulder girdle;
- numbness of the limbs;
- limited neck mobility;
- swelling of the face;
- a sharp increase in pressure, VSD.
In advanced cases, patients with osteochondrosis may develop impaired motor coordination, intervertebral hernia, deterioration of hearing or vision, and cerebral blood supply.