At the present stage it is due to a number of factors. Thus, according to the World Health Organization (WHO), the number of acute respiratory viral infections per year reaches 1.5 billion cases (and this is every third inhabitant of the planet), which accounts for 75% of infectious pathologies in the world, and during epidemics - about 90% of all cases. The latter leads to the fact that this particular pathology ranks first in the structure of causes of high morbidity and temporary disability.

In addition, quite often there is a direct connection between the development of chronic pathology of the heart, lungs, kidneys, etc. and the fact that a person suffered ARVI in the past.

In Ukraine, about 10-14 million people suffer from influenza and ARVI every year, which accounts for 25-30% of the total incidence, and therefore awareness of rational treatment and existing systems for the prevention of these diseases is an important task for researchers, scientists and practitioners in the field of fundamental and clinical medicine .

At the global and international levels, this problem has always been and is under constant attention.

Thus, in June 2007 in Toronto (Canada), the VI world symposium “Option for the control of Influenza VI” examined the next problems of influenza control (prevention, control and treatment of seasonal influenza through the use of vaccines, antiviral drugs and infection control programs, and exchange of information on preventing influenza pandemics). This forum was held within the framework of traditional global anti-influenza events, which have been held for the last twenty years under the auspices of the UN, WHO, national health services, a number of international medical associations, etc. Ukraine is a full member of all these international organizations, whose activities are aimed at cooperation in the prevention and flu treatment.

The essence of the conclusions made by the symposium participants was as follows:

• The world is on the verge of another influenza pandemic.
• Every country should have an adequate influenza surveillance system and be included in the World Influenza Information Network.
• It is necessary to ensure the exchange of strains (new, probably pandemic) between countries where they are allocated by the world influenza center for the rapid production of a pandemic vaccine.
• The volume of seasonal use should be increased.
• In addition to the development of new antiviral drugs, it is necessary to constantly monitor the sensitivity and emergence of resistance of influenza viruses to antiviral drugs.

Accordingly, activities began to be carried out in these areas and information was accumulated, which necessitated the need to carry out the appropriate necessary organizational and preventive measures at the global and national levels. One of the leading directions in this matter is active educational work among various specialties of medical workers on pharmacotherapeutic and preventive measures. The latter would avoid unnecessary hype around this issue, especially regarding information about effectiveness and safety.

Properties of antiviral drugs

In this regard, there is a need to once again address the issues of basic clinical and pharmacological properties of antiviral drugs.

Today there is a limited number of antiviral drugs with proven clinical effectiveness, namely:

• Antiherpetic;
• Anticytomegalovirus;
• Anti-flu;
• Against HIV infection;
• Antiviral drugs with an extended spectrum of activity.

Another point that poses difficulty when carrying out treatment with antiviral drugs is the ability of viruses to mutate. Accordingly, the sensitivity of the modified virus to certain drugs decreases, as does the effectiveness of pharmacotherapy. Clarification of the characteristics of the process of reproduction of viruses, their structure and differences in the metabolic processes of the human body and the virus contributed to the synthesis of a number of antiviral drugs.

Today it is known that the influenza virus shell contains the proteins hemagglutinin (H) and neuraminidase (N), due to which the virus binds to the target cell and destroys sialic acids when leaving the cell. Reproduction (replication) of viruses is a process during which, using its own genetic material and the synthetic apparatus of the host cell, the virus reproduces offspring similar to itself. In general terms, virus replication at the level of an individual cell consists of several successive stages of the reproduction cycle. The virus first attaches to the surface of the cell, then penetrates its outer membranes. Already in the host cell, the virion is stripped and viral RNA is transported into the cell nucleus. Subsequently, the viral genome is reproduced, new virions are collected and released from the affected cell by budding.

At the level of tissues or organs, reproduction cycles are often asynchronous, and the virus enters healthy cells from affected cells. Reproduction of the virus in a cell lasts about 6-8 hours and is characterized by an increase in the number of virions in geometric progression, when up to 10,000 new ones are formed from one virus. This process spreads to a significant number of host cells, is accompanied by inhibition of their metabolism and biological functions, and is manifested by corresponding pathological symptoms.

A significant obstacle to the effective treatment of viral infections is that viral replication occurs to a large extent during the manifestation of disease symptoms; the course of this pathological process is complicated by immune deficiency; the effectiveness of treatment may decrease as a result of the ability of viruses to recombine and mutate.

Modern antiviral drugs are most effective during the period of viral replication. The earlier treatment begins, the more positive its consequences.

This is the basis for the fundamental division of modern antiviral drugs used to treat influenza according to their mechanism of action into the following groups:

• Antiviral drugs directly interfere with viral replication;
• Antiviral drugs that modulate the host immune system.

Antiviral drugs that affect the virus

The first group includes the drugs amantadine, rimantadine, zanamivir, oseltamivir, arbidol, amizon and inosine pranobex (all of these drugs are registered in Ukraine and approved for medical use).

And they are inhibitors of neuraminidase (sialidase), one of the key enzymes involved in the replication of influenza A and B viruses. As a result of inhibition of neuraminidase, the release of virions from infected cells is inhibited, their aggregation on the cell surface increases and the spread of the virus in the body is slowed down. Under the influence of neuraminidase inhibitors, the resistance of viruses to the harmful effects of mucous secretions of the respiratory tract decreases. Also, neurominidase inhibitors reduce the production of cytokines, thereby preventing the development of a local inflammatory reaction and weakening the systemic manifestations of a viral infection (fever and other symptoms).

The antiviral effect is associated with its ability to stabilize hemagglutinin and prevent its transition to an active state. Accordingly, fusion of the lipid viral envelope with the cell membrane and endosome membranes does not occur in the early stages of virus reproduction. Arbidol tends to penetrate unchanged into infected and uninfected cells of the human body and is localized in the cytoplasm and nucleus of the cell. In addition to its direct effect on the virus, arbidol also has antioxidant, immunomodulatory, and interferonogenic effects.

Drugs and (adamantane derivatives) are blockers of ion channels formed by the M2 proteins of the influenza A virus. As a result of exposure to these proteins, the ability of the virus to penetrate the host cell is disrupted and the release of ribonucleoprotein does not occur. These drugs also act at the stage of virion assembly, possibly due to changes in hemagglutinin processing.

A drug whose active ingredient is inosine pranobex, known in Ukraine under the name "", has a direct antiviral effect. The latter is due to the ability to bind to the ribosomes of virus-infected cells, slows down the synthesis of viral mRNA (impaired transcription and translation) and leads to inhibition of the replication of RNA and DNA genomic viruses. The drug is also characterized by induction of interferon formation. The immunomodulatory properties of the antiviral drug are due to the ability of the drug to enhance the differentiation of T-lymphocytes, stimulate myogen-induced proliferation of T- and B-lymphocytes, increase the functional activity of T-lymphocytes, as well as their ability to form lymphokines. The synthesis of interleukin-1, microbiocidity, the expression of membrane receptors and the ability to respond to lymphokines and chematactic factors are stimulated.

Thus, predominantly cellular immunity is stimulated, which is especially effective in conditions of cellular immunodeficiency. The above allows us to recommend it both for the treatment and prevention of acute and chronic viral infections. It has also been proven that the drug is capable of potentiating the antiviral effect of interferon, acyclovir and other antiviral drugs.

It has been established that the use of Groprinosin helps reduce the severity of symptoms of the disease and its duration.

The antiviral effect is associated with its direct effect on the hemagglutinin of the influenza virus, as a result of which the virion loses its ability to attach to target cells for further replication. Amizon also has an anti-inflammatory interferonogenic effect.

Antiviral drugs that affect the immune system

The second group includes drugs from the cytokine group - interferons, powerful cytokines that have antiviral, immunomodulatory and antiproliferative properties. They are synthesized by cells under the influence of various factors and initiate biochemical mechanisms of cell protection that have an antiviral effect: α (more than 20 representatives), β and γ. The synthesis of interferons α and β occurs in almost all cells, γ - are formed only in T and NK lymphocytes when they are stimulated by antigens, myogens and some cytokines.

Antiviral activity interferon is that it disrupts the penetration of the viral particle into the cell, suppresses the synthesis of m-RNA and the translation of viral proteins (adenylate synthetase, protein kinases), as well as by blocking the processes of “assembly” of the viral part and its exit from the infected cell. Inhibition of the synthesis of viral proteins is considered the main mechanism of action of interferon. Interferons, depending on the type of virus, act at different stages of its reproduction. For the prevention and treatment of influenza, human leukocyte interferon and interferon-alpha2-b are used.

Interferon-alpha2-b preparations approved for medical use in Ukraine:

• Alphatron,
• Laferbion,
• Lipoferon,

A number of drugs are inducers of interferon production. Thus, the antiviral drugs Kagocel, tyrolone (Amiksin), and amizon stimulate the formation of late interferon (a mixture of interferons α, β and γ) in the human body. Methylglucamine acridone acetate (known as Cycloferon) is an early α-interferon inducer.

All of the above medications are used for the treatment and prevention of influenza A and B, with the exception of the drugs amantadine and rimantadine, which are active only against the influenza A virus.

Pandemic (California, swine flu) is not sensitive to adamantane-type drugs due to the S31N mutation in the M gene. For the treatment of patients with this pandemic flu, WHO recommends the use of oseltamivir and zanamivir. It is effective to prescribe these medications no later than 48 hours from the moment of manifestation of the disease.

Side effects of antiviral drugs

It should be noted that, like all drugs, antiviral drugs that are used to treat influenza have inherent adverse reactions. Let us dwell on the adverse reactions of antiviral drugs that directly disrupt the replication of the influenza virus.

Separately, it should be noted that for interferon drugs, for example, interferon-alpha2-b, the ability to cause a flu-like clinical picture, which is accompanied by corresponding symptoms, is specific, which is also influenced by the duration of use of the drug.

In the structure of side effects of antiviral drugs that occurred during the medical use of drugs intended for the treatment of influenza in Ukraine, the greatest number of manifestations were allergic reactions and, especially, disorders of the skin and its appendages, as well as complications of the gastrointestinal tract.

According to the distribution of side effects by demographic indicators, in 22% of cases side effects of antiviral drugs occurred in children (aged 28 days-23 months - 3.0%, 2-11 years - 11.4%, 12-17 years - 7 .5%), in 78% of cases - occurred in adults: aged 18-30 years - 22.5%, 31-45 years - 24.6%, 46-60 years - 23.7%, 61-72 years - 6.0%, 73-80 years old - 1.2%, over 80 years old - 0.3%. By gender, adverse reactions predominantly occurred in women (72.8%), in men - in 27.2% of cases.

It should be emphasized that the development of possible expected side effects increases in the presence of certain risk factors on the part of patients, especially if they are not taken into account by doctors when prescribing antiviral drugs. Risk factors include:

• concomitant diseases that are contraindications to the use of the drug,
• pregnancy,
• breast-feeding,
• early childhood,
• neonatal period,
• elderly and senile age, etc.

The above allows us to conclude that when prescribing antiviral drugs, risk groups include:

• children aged 2 to 11 years,
• adults, especially women, aged 31 to 45 years,
• patients who have a burdened allergic history,
• patients who have concomitant diseases of the gastrointestinal tract, liver, kidneys and nervous system.

Therefore, prescribing antiviral drugs to such patients requires caution regarding the likelihood of side effects, both on the part of the doctor and the patient.

It is an axiom that there have not been, are not, and never will be absolutely safe medications. Any drug can cause adverse reactions. According to current legislation, the adverse effects of the use of drugs are indicated in the relevant sections of the instructions for medical use approved by the Ministry of Health.

The advisability of using an antiviral drug is determined by the risk/benefit ratio. Only if the benefit outweighs the risk should the drug be used according to the instructions for use. This is the current objective information on the safety and effectiveness of antiviral drugs in the treatment of influenza, which should be used by doctors of all specialties, especially during an influenza epidemic or pandemic.

Side effects of Oseltamivir (Tamiflu)

Even at the stage of clinical trials of this antiviral drug, it was found that most often when it was used by adults for therapeutic purposes, side effects such as nausea and vomiting occurred. Diarrhea, bronchitis, abdominal pain, dizziness, headache, cough, insomnia, weakness, nosebleeds, and conjunctivitis were observed much less frequently. Patients who took Oseltamivir to prevent influenza experienced pain of various localizations, rhinorrhea, dyspepsia and upper respiratory tract infections.

Children were more likely to vomit. Side effects that occurred in less than 1% of children receiving Oseltamivir included abdominal pain, nosebleeds, hearing loss, and conjunctivitis (occurring suddenly, stopping despite continued treatment, and in the vast majority of cases not causing discontinuation of treatment) , nausea, diarrhea, bronchial asthma (including exacerbations), acute otitis media, pneumonia, sinusitis, bronchitis, dermatitis, lymphadenopathy.

During the post-registration period, when the drug began to be widely used, new adverse effects of its use were discovered. So, in isolated cases, allergic reactions occurred on the part of the skin and its appendages (dermatitis, rash, eczema, urticaria, cases of erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis, anaphylactic / anaphylactoid reactions were recorded).

Isolated cases of hepatitis and increased levels of liver enzymes have been observed in influenza patients receiving Oseltamivir; Cases of gastrointestinal bleeding rarely occurred, but manifestations of hemorrhagic colitis disappeared when the flu weakened or after discontinuation of the drug.

It turned out that the drug Tamiflu can cause neuropsychiatric disorders.

Since 2004, regulatory agencies have received reports that influenza patients (primarily children and adolescents) who took Tamiflu experienced seizures, delirium, behavioral changes, confusion, hallucinations, anxiety, and nightmares that rarely resulted in accidental injury or death.

In October 2006, Japan's Ministry of Health and Welfare reported 54 deaths from Tamiflu, mostly from liver failure. The latter, according to scientists, most likely arose as a result of severe influenza. However, 16 cases occurred between the ages of 10 and 19 years. They developed mental disorders due to the flu and taking Tamiflu, while 15 patients died by suicide by jumping or falling out of their houses, one died under the wheels of a truck.

In March 2007, the Japanese Ministry of Health and Welfare ordered the manufacturer of Tamiflu to include in the instructions for medical use of this drug a prohibition of use in patients aged 10 to 19 years (however, the drug was still used in this age group to treat some cases of swine flu 2009 (H1N1)). The instructions for medical use of Tamiflu by that time already contained a clause about the possible development of mental adverse reactions, including behavioral disorders and hallucinations.

Based on an analysis of 10,000 cases of Tamiflu administered to children under 18 years of age who were diagnosed with influenza during the period 2006-2007, the Ministry of Health and Welfare of Japan concluded in April 2009 that the development of abnormal behavior, including sudden running and jumping were 1.54 times higher among teenagers who took Tamiflu compared to children with influenza who were not prescribed this drug.

In March 2008, the US FDA added information to physicians about neuropsychiatric disorders associated with the use of Tamiflu in patients with influenza in the “disclaimers” section.

In Ukraine, back in August 2007, the instructions for the medical use of the drug "Tamiflu" in patients with influenza noted that its use can lead to the development of psychoneurotic disorders (convulsions, delirium, including changes in the level of consciousness, confusion, inappropriate behavior, delirium, hallucinations , agitation, anxiety, nightmares). It is not known whether psychoneurotic disorders are associated with the use of Tamiflu, since psychoneurotic disorders have also been reported in flu patients who did not use this drug. Therefore, the manufacturer recommended monitoring the behavior of patients, especially children and adolescents, in whom adverse reactions from the central nervous system were most often recorded. In case of any manifestations of inappropriate behavior of the patient, you should immediately consult a doctor.

It should be emphasized that according to the WHO Center for International Monitoring of Adverse Effects (March 2010), only in 270 cases out of 3,566 a cause-and-effect relationship between registered cases of adverse reactions and the effect of Tamiflu was proven.

The classification of antiviral agents can be based on various reasons.

• 1. Distribution of antiviral drugs according to M.D. Mashkovsky:
  • - interferons;
  • - interferon inducers;
  • - immunomodulators;
  • - nucleosides;
  • - derivatives of adamantane and other groups;
  • - herbal preparations.

Today, interferons belong to cytokines, and they are represented by a family of proteins with antiviral, immunomodulatory, antitumor and other types of activity, which allows them to be classified as factors of innate (natural) immunity, multifunctional bioregulators with a wide spectrum of action and homeostatic agents. Interferons are natural protective proteins produced by the body's cells in response to infection by viruses. The production of interferon by a cell is a reaction to the penetration of a foreign nucleic acid into it. Interferon does not have a direct antiviral effect, but inhibits the reproduction of the virus in the body, activating the immune system and causing changes in cells that suppress the synthesis of viral nucleic acids. Interferon preparations include: interferon alpha, interlock, intron, reaferon, betaferon.

Interferon inducers are antiviral drugs, the mechanism of action of which is associated with stimulation of cells' production of their own interferon. Interferon inducers include: neovir, cycloferon. Interferon inducers are a family of high- and low-molecular natural and synthetic compounds; they can be considered as an independent class capable of “switching on” the interferon system, causing the body’s cells to synthesize their own (endogenous) interferons. Induction of interferon is possible by various cells, the participation of which in the synthesis of interferon is determined by their sensitivity to interferon inducers and the method of its introduction into the body. During induction, a mixture of interferons (alpha/beta/gamma) is formed, which have an antiviral effect and regulate the synthesis of cytokines.

The term “immunomodulators” refers to a group of drugs that, when taken in therapeutic doses, restore the function of the immune system. The main criterion for prescribing immunotropic drugs, the target of which are phagocytic cells, is the clinical picture of the disease, manifested by an infectious-inflammatory process that is difficult to adequately respond to anti-infectious treatment. The basis for prescribing an immunotropic drug is the clinical picture of the disease.

Nucleosides are glycosylamines containing a nitrogenous base linked to ribose or deoxyribose. Used as a remedy for viral diseases. Drugs in this group include: acyclovir, famciclovir, indoxuridine, ribamidil, etc.

Derivatives of adamantane and other groups - arbidol, rimantidine, oxoltn, adapromine, etc.

Preparations of plant origin - flakozid, helepin, megosin, alpizarin, etc.

• 2. Distribution of antiviral drugs depending on the mechanism of action. It concerns different stages of interaction between the virus and the cell. Thus, substances are known that act as follows:
  • - inhibit the adsorption of the virus on the cell and its penetration into the cell, as well as the process of release of the viral genome. These include drugs such as midantan and remantadine;
  • - inhibit the synthesis of early viral proteins. For example, guanidine;
  • - inhibit the synthesis of nucleic acids (zidovudine, acyclovir, vidarabine, idoxuridine);
  • - inhibit the “assembly” of virions (metisazone);
  • - increase cell resistance to the virus (interferons).
• 3. Classification of antiviral drugs by origin:
  • - nucleoside analogues - zidovudine, acyclovir, vidarabine, ganciclovir, trifluridine;
  • - lipid derivatives - saquinavir;
  • - adamantane derivatives - midantan, remantadine;
  • - derivatives of ladolcarbolic acid - foscarnet;
  • - thiosemicarbazone derivatives - metisazone;
  • - drugs produced by the cells of the macroorganism - interferons.
• 4. Distribution of antiviral drugs depending on the direction of their action:

• - herpes simplex virus - acyclovir, vilacyclovir, foscarnet, vidarabine, trifluridine;
• - cytomegalovirus - ganciclovir, foscarnet;
• - herpes zoster and chickenpox virus - acyclovir, foscarnet;
• - variola virus - metisazan;
• - hepatitis B and C virus - interferons.

• - human immunodeficiency virus - zidovudine, didanosine, zalcitabine, saquinavir, ritonavir;
• - influenza virus type A - midantan, remantadine;
• - influenza virus types B and A - arbidol;
• - respiratory syncytial virus - ribamidil.
• 5. Classification of antiviral drugs by type of virus:
  • - antiherpetic (herpes);
  • - anticytomegalovirus;
  • - anti-influenza (flu) (M2 channel blockers, neuroamindase inhibitors)
  • - antiretroviral drugs;
  • - with an extended spectrum of activity (inosine pranobex, interferons, lamivudine, ribavirin).
• 6. But in a more understandable way, antiviral drugs can be divided, depending on the type of disease, into groups:
  • - anti-influenza drugs (rimantadine, oxolin, etc.);
  • - antiherpetic and anticytomegalovirus (tebrofen, rhiodoxon, etc.);
  • - drugs that affect the human immunodeficiency virus (azidothymidine, phosphanoformate);
  • - Broad-spectrum drugs (interferons and interferonogens).

Content

Most viral diseases present with flu-like symptoms of varying severity. Depending on the specific pathology, different antiviral agents can be used. Their classifications are based on the mechanism and spectrum of action, origin and some other criteria.

Classification of antiviral agents by mechanism of action

Groups of antiviral drugs according to this classification are distinguished taking into account the stage at which the virus interacts with the cell the drug begins to act. There are 4 options for how antiviral agents affect the body:

Types of antiviral drugs by spectrum of action

The difference between antiviral drugs is the selectivity of their action. Taking this into account, drugs are divided into types depending on the virus on which they are most capable of influencing. The classification of antiviral agents taking into account their spectrum of action is presented in the table:

By origin

Different substances have antiviral properties, so drugs based on them are classified according to their origin. It distinguishes the following types of drugs:

Classification according to M.D. Mashkovsky

The founder of Soviet pharmacology proposed his classification. According to it, antiviral drugs for children and adults were divided into the following groups:

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136. Antiviral agents. Classification. Pharmacological characteristics of anti-influenza drugs and drugs for the treatment of viral hepatitis.

Antiviral drugs-medicines intended for the treatment of various viral diseases: influenza, herpes, HIV infection, etc. They can be used to prevent infection with certain viruses.

Classification of antiviral agents.

1. Anti-flu:remantadine, arbidol, oseltamivir, etc.

2. Antiherpetic:idoxuridine, acyclovir, etc.

3. Active against HIV:zidovudine, saquinavir, etc.

A) Reverse transcriptase inhibitors:

a) nucleoside: abacavir, didanosine, zalcitabine, zidovudine, lamivudine, stavudine

b) non-nucleoside: delaverdine, ifavirenz, nevirapine

B) Protease inhibitors: amprenavir, atazanavir, indinavir, lopinavir/ritonavir, ritonavir, nelfinavir, saquinavir, tipranavir, fosamprenavir

B) Integrase inhibitors: raltegravir

D) Virus binding receptor inhibitors: maravirox

D) Fusion inhibitors: enfuvirtide

4. Drugs of different groups:ribavirin.

5. Preparations of interferons and interferonogenesis stimulators:interferon recombinant human leukocyte interferon (reaferon), anaferon.

Anti-flu drugs.

This is a group of antiviral drugs used for the prevention and treatment of patients with influenza infection.

Remantadine (rimantadine, polyrem, flumadine) - available in tablets of 0.5.

The drug is prescribed orally, up to 3 times a day, depending on the goals of treatment: for the prevention of morbidity it is prescribed 1 time per day, for the treatment of a patient with a developed disease - 3 times a day. It is well absorbed from the gastrointestinal tract, and it should be remembered that to achieve minimum serum concentrations, elderly patients require half the dose of the drug. In the blood, it is 40% bound to plasma proteins. Remantadine is distributed relatively evenly in the patient’s body, penetrating into all organs, tissues and body fluids, incl. in the CSF. It is metabolized in the liver by hydroxylation and conjugation. Up to 90% of the dose taken is excreted through the kidneys in the urine. T ½ is about 30 hours.

The point of action of the drug is the M2 protein of the influenza A virus, which forms an ion channel in its shell. When the function of this protein is suppressed, protons from endosomes cannot enter the virus, which blocks the stage of dissociation of the ribonucleoprotein and the release of the virus into the cytoplasm of the patient’s cell. As a result, the processes of undressing and assembly of the virus are suppressed.

Resistance to the drug occurs when even one amino acid is replaced in the transmembrane region of the M2 protein. The sensitivity and resistance of influenza viruses to rimantadine and amantadine are cross-susceptible.

O.E. 1) Antiviral against influenza A viruses.

2) Antitoxic.

P.P. Prevention and early treatment of patients with influenza caused by type A virus.

P.E. Decreased appetite, nausea, irritability, insomnia, allergies.

Midantan (amantadine) is a drug in the same group as rimantadine, therefore it acts and is used similarly. Differences: 1) a more toxic agent; 2) is also used as an antiparkinsonian drug.

Arbidol

The drug is prescribed orally, on an empty stomach, up to 4 times a day, depending on the goals of treatment: for the prevention of morbidity it is prescribed 1-2 times a day, for the treatment of a patient with a developed disease - 4 times a day. Arbidol is quickly absorbed into the gastrointestinal tract and is distributed relatively evenly throughout the patient’s body, accumulating most in the liver. The drug is metabolized in the liver. It is excreted mainly with bile through the intestines (up to 40% of the dose taken unchanged), very slightly through the kidneys with urine (up to 0.12%). On the first day, up to 90% of the dose taken is excreted. T ½ is about 17 hours.

Directly inhibits the replication of influenza A and B viruses by interacting with viral hemagglutinin. This inhibits the fusion of the lipid envelope of the virus with the cell membrane of the host cell.

O.E. 1) Antiviral against influenza A and B viruses, coronavirus.

2) Immunostimulating: humoral and cellular reactions are stimulated, interferonogenesis and phagocytosis are induced.

3) Antioxidant.

P.P.

2) Prevention and treatment of patients with ARVI.

3) Complex therapy of patients with secondary immunodeficiencies.

P.E. Nausea, vomiting, allergies.

Oseltamivir - Available in tablets of 0.5.

The drug is prescribed orally, 2 times a day. It is produced in the form of phosphate, from which the active metabolite oseltamivir carboxylate is formed in the liver as a result of presystemic elimination.

Oseltamivir is well absorbed from the gastrointestinal tract, the bioavailability of this absorption route is about 75%, food intake does not have a significant effect on it. In the blood, approximately 42% binds to plasma proteins. It is well distributed in the patient's body. Metabolized in the liver by esterases. Excreted through the kidneys in urine. T ½ is approximately 6 -10 hours.

The drug inhibits neuraminidase of influenza viruses, thereby slowing down their replication processes. Ultimately, the ability of viruses to penetrate human cells is impaired, the release of virions from infected cells is reduced, which limits the spread of infection.

S.D. Influenza viruses A and B.

P.P. 1) Prevention and treatment of patients with influenza caused by type A and B viruses.

P.E. Nausea, vomiting, diarrhea, abdominal pain; headache, dizziness, nervousness, insomnia, central nervous system stimulation to the point of convulsions; phenomena of bronchitis; hepatoxicity; allergies.

Oksolin Available in ointments of various concentrations, in solutions for external use.

Apply topically, up to 6 times a day. The mechanism of action is associated with the protection of human cells from the penetration of the virus into them. This is achieved by blocking the binding site of viruses with the membranes of the host cells. It has no effect on viruses that have entered cells.

S.D. Influenza viruses, herpes, adenoviruses, rhinoviruses, molluscum contagiosum, etc.

P.P. 1) Intranasal 0.25% ointment for the prevention of influenza.

2) Subconjunctivally 0.2% aqueous solution and 0.25% ointment for adenoviral conjunctivitis.

3) Subconjunctival 0.25% ointment for herpetic eye lesions.

4) Intranasal 0.25% and 05% ointments for viral rhinitis.

5) 1 and 2% ointment for skin herpes, molluscum contagiosum.

6) 2 and 3% ointments for genital warts.

P.E. Local irritation: lacrimation, redness of the eyeballs; allergies.

Acyclovir (Zovirax, Acivir) - available in tablets of 0.2; 0.4; 0.8; in bottles containing a powdery substance in an amount of 0.25; in 3% eye ointment; in 5% skin ointment or cream.

The drug is prescribed orally, after dissolution, intravenously and locally, up to 5 times a day. When administered orally, about 30% of the dose taken is absorbed into the gastrointestinal tract; this figure decreases with increasing dose of the drug taken. In the blood, approximately 20% binds to plasma proteins. Acyclovir is distributed relatively evenly in the patient’s body, penetrating well into tissues and biological fluids, incl. into the contents of vesicles in chickenpox, aqueous humor of the eye and CSF. The drug penetrates into saliva somewhat less well, and in vaginal discharge this process varies widely. Acyclovir accumulates in breast milk, amniotic fluid, and placenta. The drug is slightly absorbed through the skin. Excretion of the drug is carried out mainly in the urine, through glomerular filtration and tubular secretion, practically unchanged. T ½ is approximately 3 hours.

Acyclovir is actively taken up by cells and converted into acyclovir monophosphate with the participation of the viral enzyme thymidine kinase. The drug's affinity for this enzyme is 200 times higher than for mammalian thymidine kinase. Under the action of cellular enzymes, acyclovir monophosphate is converted into acyclovir triphosphate. The concentration of the latter in virus-affected cells is 40-200 times higher than in healthy cells, so this metabolite successfully competes with endogenous deoxy-GTP. Acyclovir triphosphate competitively inhibits viral, and to a much lesser extent, human DNA polymerases. In addition, it is integrated into viral DNA and, due to the absence of a hydroxyl group in the 3" position of the ribose ring, stops its replication. The DNA molecule, which includes the acyclovir metabolite, binds to DNA polymerase and irreversibly inactivates it.

Resistance to the drug may occur due to: 1) decreased activity of viral thymidine kinase; 2) violation of its substrate specificity, for example, while maintaining activity towards thymidine, it ceases to phosphorylate acyclovir); 3) changes in viral DNA polymerase. Changes in viral enzymes occur due to point mutations, i.e. insertions and deletions of nucleotides in the corresponding genes. Both wild strains and strains isolated from patients after treatment with antiviral agents can exhibit resistance. In the herpes simplex virus, resistance most often occurs due to a decrease in the activity of viral thymidine kinase, and less often: due to changes in the DNA polymerase gene. In patients with weakened immune systems, infection caused by such strains cannot be cured. Resistance to the drug of the varicella zoster virus occurs due to mutation of the viral thymidine kinase and, less commonly, viral DNA polymerase.

S.D. Herpes simplex virus, especially type 1; herpes zoster virus; Epstein-Barr virus. Activity against cytomegalovirus is so low that it is neglected.

P.P. Herpetic lesions of the skin and mucous membranes; ocular herpes; genital herpes; herpetic encephalitis and meningitis; chicken pox; herpetic pneumonia; herpes zoster.

P.E. Local irritation: lacrimation, redness of the eyeballs, possible burns when applying skin ointments and creams to the mucous membranes; headache, dizziness; diarrhea; with intravenous administration - kidney damage to anuria, severe neurotoxicity; allergies; skin rashes; hyperhidrosis; decrease in blood pressure. In general, when used correctly, the drug is well tolerated.

Valaciclovir is a prodrug, in the body of a sick person acyclovir is formed from it, therefore, see the action and use of the drug itself. Differences: 1) it binds to carrier proteins in the intestines and kidneys; 2) when administered orally, valacyclovir bioavailability increases to 70%; 3) is available only in tablets, administered orally up to 3 times a day.

Ganciclovir - available in capsules of 0.5; in bottles containing a powdery substance in an amount of 0.546.

In general, the drug acts and is used similar to acyclovir. Differences: 1) compared to acyclovir triphosphate, the concentration of ganciclovir triphosphate in cells is 10 times higher and decreases in them much more slowly, which makes it possible to create higher MICs during treatment; 2) due to the ability to create higher intracellular MIC S.D. + cytomegalovirus; 3) P.P. It is used mainly for cytomegalovirus infection (HIV - marker); 4) more toxic, P.E. Inhibition of hematopoiesis, severe neurotoxicity from headache to convulsions, nausea, vomiting, diarrhea; 5) prescribed up to 3 times a day.