Mechanism of action of antivirals. The most effective antiviral drugs. Side effects of antiviral drugs

In autumn, winter and early spring it is very easy to catch a viral infection.

In total, there are more than 300 types of ARVI. The most common viruses in our region are:

flu;
parainfluenza;
rhinovirus and adenovirus;
respiratory syncytial infection virus.

Drugs are used to treat viral diseases various actions, therapy is carried out in three directions:

Causative – that is, aimed at eliminating the causative agent of the disease – the virus.
Pathogenetic – affects the mechanism of development and course of the disease.
Symptomatic – symptoms and manifestations of the disease are eliminated

Below is an overview of drugs with etiotropic action and classification of antiviral drugs.

How are antiviral drugs classified?

All etiotropic drugs used to treat different types of influenza and ARVI are divided into several groups according to their origin and mechanism of action.

Interferon inducers;
Cyclic amines;
Neuraminidase inhibitors;
Antiviral herbal medicines;
Other antiviral drugs.

The mechanism of action of drugs in each group during ARVI is different; it is important to know the features in order to correctly select and use the drug.

Interferon is a protein that cells begin to produce when infected with a virus. Their main purpose is to prevent the active reproduction of the virus in cells, thus interferons protect the body from the spread of infection and the development of disease.

To help the body cope more quickly, ease the course of the disease and speed up recovery, researchers tried to administer additional interferons taken from donor plasma.

Today, thanks to the research and work of genetic engineers, synthetic interferon is produced artificially.

Preparations containing interferons are discussed in detail below.

Human leukocyte interferon

Suitable for the treatment and prevention of influenza and ARVI, it is a powder intended for preparing a solution by combining with cooled boiled water. They begin to take this remedy when there is a threat of contracting the virus - with inevitable contact with an already infected person, or before visiting public places with large crowds of people.

You can continue taking it as long as there is a risk of infection. Apply leukocyte interferon in this manner:

Open the capsule with the powder and pour its contents into a glass.
Add water and stir until the powder is completely dissolved.
Take the resulting solution with a pipette and inject five drops into each nostril. The drug must be administered twice a day.

This dosage is prophylactic and does not have a therapeutic effect if infection with the virus occurs. At the first symptoms of influenza, the dose should be increased: five drops of the drug are administered into each nasal passage at intervals of 1-2 hours, but not less than five times a day. The duration of intensive treatment is 3 days.

The intensity of leukocyte antiviral drugs can be increased if they are administered by inhalation. Prepare inhalation as follows:

Open three ampoules of powder and dissolve them in 10 ml of warm water - the temperature should be approximately 37 degrees.
Place the solution in the inhaler and carry out the procedure.
Repeat twice a day for five days from the moment of infection.

If the virus has spread to the organs of vision and viral conjunctivitis has developed, the solution can be instilled into the eyes, 1-2 drops every two hours.

Grippferon

This is a combination drug that includes recombined human alpha interferon and auxiliary components. It is also suitable for the treatment and prevention of acute respiratory viral infections, influenza and other diseases caused by viruses. It is administered nasally, three drops every 3-4 hours.

Such drugs cannot be used during pregnancy or if you are hypersensitive to any of the components.

The main active ingredient of this product is also alpha-interferon, the difference is that it is produced in the form of rectal suppositories.

This form allows you to easily use the drug for treatment in young children who may refuse to drink drops or powders.

The dosage is determined depending on the purpose of treatment, the age and weight of the child; usually one suppository is administered once a day.

Interferon inducers

Drugs from this group have a stimulating effect on cells that produce interferon. By themselves, they do not neutralize viruses. But they can significantly alleviate the patient’s condition after infection with influenza or other viral diseases, as well as protect against infection during an epidemic.

Tiloron - Amiksin, Lavomax

This drug is a typical representative of antiviral drugs.

The regimen for taking Tiloron is as follows:

In the first two days of illness - 125 mg once a day orally.
In the following days - 125 mg once every 48 hours. In just one course of treatment, you should take 750 mg of the drug.
For prevention, you should take 125 mg of the drug once every seven days for 6 weeks.

Tiloron is not prescribed during pregnancy and breastfeeding, in case of hypersensitivity to the components of the drug. Side effects include nausea, temporary fever, and very rarely, urticaria and other allergic reactions.

Umifenovir - Arbidol, Arpeflu, Arbivir, Immusstat

The mechanism of action of this drug is different from the previous one. The drug not only stimulates the production of interferons, but also increases the body's immunity at the cellular level.

In the autumn-winter season, during an epidemic of influenza and ARVI, the drug is taken 0.1 mg once every three days for a month; in case of contact with infected patients, 0.2 mg of the drug should be taken per day for 10-14 days. For therapeutic purposes, the medicine is taken 0.2 mg four times a day for at least 3 days.

There are no side effects; in rare cases, allergic manifestations are observed.

Cyclic amine rimantadine – Rimantadine-KR, Rimavir

The mechanism of action of this substance is as follows: it penetrates viral cells through their membrane and destroys them, thereby suppressing the proliferation of microorganisms. The drug is available in the form of tablets or powder in sachets for one dose.

It is taken according to a special scheme:

The first day – 100 mg three times a day;
The second and third days - 100 mg twice a day;
The fourth and fifth days - 100 mg once a day.

For preventive purposes, take 50 mg of the drug once a day for 10-14 days. Contraindications to the use of this drug are pregnancy and breastfeeding, individual hypersensitivity to the active component of the drugs, severe renal and liver failure.

Neuraminidase inhibitors – Zanamivir, Relenza

Drugs in this group are effective only against the influenza virus. The mechanism of action is to suppress the synthesis of the enzyme neuraminidase. This enzyme releases the influenza virus from the affected cell and allows the infection to spread further. If the virus cannot overcome the cell membrane, after a while it dies inside the cell.

When treated with neuraminidase inhibitors, the disease is easier and goes away faster. But it should be borne in mind that these drugs have quite serious contraindications and side effects. The heaviest of them:

Hallucinations.
Disorders of consciousness.
Psychoses.

The drug is administered orally exclusively using a special device resembling an inhaler - a diskhaler. For treatment, two inhalations twice a day are recommended. The course of therapy lasts 5 days.

For preventive purposes, do two inhalations once a day for 1-4 weeks.

Antiviral herbal medicines – Flavazid, Proteflazid, Altabor, Immunoflazid

Altabor - the basis of this medicine is an extract of dried alder fruits. The substances contained in them are able to activate the cells’ production of their own interferon and suppress the synthesis of neuraminidase. In addition, Altabor is able to neutralize numerous types of bacteria.

The drug is available in tablet form. For prevention, you should slowly dissolve 2 tablets in your mouth 2-3 times a day. If infection has occurred and treatment is required, also dissolve 2 tablets 4 times a day. The course of taking the drug lasts 7 days.

Altabor can cause allergic reactions; it should not be taken if you are hypersensitive to active components. Official studies on the effect of the drug on the reproductive capacity and development of the fetus have not been conducted, therefore this drug is not recommended during pregnancy and lactation.

Immunoflazide, Proteflazide and Flavazide are almost the same in their composition; the mechanism of action of these three drugs is the same. The main components of these medicines:

Liquid extract of turf pike;
Liquid extract of ground reed grass.

The mechanism of action of the drugs is inhibition of the production of viral enzymes and stimulation of the synthesis of endogenous interferon. The drug stops the proliferation of viruses and increases the body's natural resistance to the disease. Only the pharmaceutical forms of release of drugs from this group differ.

Immunoflazid is produced in the form of syrup. Adults should take 9 ml twice a day for 5-14 days if infection has already occurred. To prevent infection with the virus, take 4.5 ml of syrup once a day. Well preventive treatment can last up to one month.

Proteflazid can be found in pharmacies in the form of drops. The drug dosage table is as follows:

The first seven days - 7 drops twice a day.
From the 2nd to the 21st day - 15 drops twice a day.
From the 22nd to the 30th days - 12 drops, also twice a day.

If necessary, the prophylactic course of taking the drug can be repeated after a few weeks.

Other antivirals

In addition to those listed above, there are also etiotropic drugs, the mechanism of action and composition of which do not fall under any one group. These are Inosine Pranobex, Amizon and Engistol.

Inosine pranobanks – Groprinosine, Inosine, Novirin

These drugs can neutralize most viruses and increase the body's defenses. The active substances of these drugs are able to penetrate the cell membrane and integrate into the cell structure. As a result, the genetic structure of the viruses is disrupted and they die.

These products are available in tablet form. The daily dose is calculated at the rate of 50 mg of the drug per 1 kg of body weight. The average dose is 6-8 tablets. They should be divided into 3-4 doses. You should not take more than 4 grams per day. drug. At acute flu and other acute respiratory viral infections, the duration of treatment is up to 14 days; if the disease is protracted, it can be extended up to 28 days.

Contraindications to the use of Groprinosin:

Gouty arthritis;
Hyperuricemia;
Individual intolerance to the components of the drug.

The most serious side effect of taking tablets containing inosine pranobex is an increase in the level of uric acid in the blood and urine. No symptomatic treatment is required in this case. Uric acid levels return to normal on their own as soon as the drug is stopped.

Possible side effects when taking Inosine:

General weakness.
Nausea and vomiting.
Cutting in the stomach area.
Constipation or diarrhea.
Dizziness and headaches.
Joint and muscle pain.
Increased excitability.
Sleep disorders.
Skin rash and itching.

In rare cases, severe allergic reactions are observed - anaphylactic shock and angioedema. There is no official data on how safe these medications are for the unborn child, so they are not used during pregnancy and feeding.

Engystol

This drug belongs to homeopathic remedies with antiviral effect. The Engystol intake table is as follows:

On initial stage diseases 1 tablet every 15 minutes for two hours;
Then 1 tablet three times a day;
For prevention, the drug is taken 1 tablet twice a day. Duration of treatment is from 14 to 21 days.

The medication is taken 20 minutes before meals or an hour after it. The tablet should be placed on the tongue and dissolved slowly. Engystol can be used during pregnancy and lactation as prescribed by a doctor. Allergic reactions are possible.

Homeopathic Sagrippin and Amizon

Sagrippin is a plant-based antiviral agent, it is used for the prevention of acute respiratory viral infections and in complex therapy, combining with antibiotics, antipyretics and antiallergic drugs.

Amizon is a non-narcotic analgesic. It has antipyretic, anti-inflammatory, analgesic and immunomodulatory effects. Take it one tablet three times a day for 5 to 7 days. Contraindications: first trimester of pregnancy and hypersensitivity to iodine-containing drugs.

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 chronic pathology heart, lungs, kidneys, etc. and the fact that the 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 limited quantity 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 and is accompanied by inhibition of their metabolism and biological functions, 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 the 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 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 influenza-like illness is specific. clinical picture, which is accompanied by corresponding symptoms, 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:

accompanying illnesses, which are contraindications to the use of the drug,
pregnancy,
breast-feeding,
early childhood,
neonatal period,
elderly and old 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 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 is used by adults with therapeutic purpose 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, the Ministry of Health and social security Japan received information about 54 deaths from taking Tamiflu, mainly 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 Ministry of Health and Welfare of Japan 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 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 inappropriate behavior the patient 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.

21. Antiviral drugs: classification, mechanism of action, use in various localizations of viral infection. Antitumor drugs: classification, mechanisms of action, features of purpose, disadvantages, side effects.

Antiviral agents:

a) antiherpetic drugs

Systemic action - acyclovir(Zovirax), valacyclovir (Valtrex), famciclovir (Famvir), ganciclovir (Cymevene), valganciclovir (Valcyte);

Local action - acyclovir, penciclovir (fenistil pencivir), idoxuridine (Oftan Idu), foscarnet (gefin), tromantadine (Viru-Merz serol);

b) medicines for the prevention and treatment of influenza

Membrane protein blockers M 2 - amantadine, remantadine (remantadine);

Neuraminidase inhibitors - oseltamivir(tamiflu), zanamivir (relenza);

c) antiretroviral drugs

HIV reverse transcriptase inhibitors

Nucleoside structure - zidovudine(Retrovir), didanosine (Videx), lamivudine (Zeffix, Epivir), stavudine (Zerit);

Non-nucleoside structure - nevirapine (Viramune), efavirenz (Stocrine);

HIV protease inhibitors - amprenavir (Agenerase), saquinavir (Fortovase);

Inhibitors of fusion (fusion) of HIV with lymphocytes - enfuvertide (fuzeon).

d) broad-spectrum antivirals

ribavirin(virazol, rebetol), lamivudine;

Interferon preparations

Recombinant interferon-α (grippferon), interferon-α2a (roferon-A), interferon-α2b (viferon, intron A);

Pegylated interferons - peginterferon- α2a (Pegasys), peginterferon-α2b (PegIntron);

Inducers of interferon synthesis - acridoneacetic acid (cycloferon), arbidol, dipyridamole (chimesin), yodantipyrine, tilorone (amixin).

Antiviral substances that are used as medicines can be represented by the following groups

Synthetic products

Nucleoside analogues- zidovudine, acyclovir, vidarabine, ganciclovir, tri-fluridine, idoxuridine

Peptide derivatives- saquinavir

Adamantane derivatives- midantan, remantadine

Indole carboxylic acid derivative -arbidol.

Phosphonoformic acid derivative- foscarnet

Thiosemicarbazone derivative- metisazon

Biological substances produced by the cells of a macroorganism – Interferons

A large group of effective antiviral agents is represented by derivatives of purine and pyrimidine nucleosides. They are antimetabolites that inhibit nucleic acid synthesis

IN last years attracted especially great attentionantiretroviral drugs,which include reverse transcriptase inhibitors and protease inhibitors. Increased interest in this group of substances is associated with their

used in the treatment of acquired immunodeficiency syndrome (AIDS 1). It is caused by a special retrovirus - the human immunodeficiency virus

Antiretroviral drugs effective against HIV infection are represented by the following groups.

/. Reverse transcriptase inhibitorsA. Nucleosides Zidovudine Didanosine Zalcitabine Stavudine B. Non-nucleoside compounds Nevirapine Delavirdine Efavirenz2. HIV protease inhibitorsIndinavir Ritonavir Saquinavir Nelfinavir

One of the antiretroviral compounds is the nucleoside derivative azidothymidine

called zidovudine

). The principle of action of zidovudine is that it, phosphorylated in cells and converted into triphosphate, inhibits the reverse transcriptase of virions, preventing the formation of DNA from viral RNA. This suppresses the synthesis of mRNA and viral proteins, which provides a therapeutic effect. The drug is well absorbed. Bioavailability is significant. Easily penetrates the blood-brain barrier. About 75% of the drug is metabolized in the liver (azidothymidine glucuronide is formed). Some zidovudine is excreted unchanged by the kidneys.

The use of zidovudine should be started as early as possible. Its therapeutic effect manifests itself mainly in the first 6-8 months from the start of treatment. Zidovudine does not cure patients, but only delays the development of the disease. It should be taken into account that retrovirus resistance develops to it.

Of the side effects, hematological disorders take the first place: anemia, neutropenia, thrombocytopenia, pancytemia. Possible headache, insomnia, myalgia, depression of renal function.

TOnon-nucleoside antiretroviral drugsinclude nevirapine (Viramune), delavirdine (Rescriptor), efavirenz (Sustiva). They have a direct, non-competitive inhibitory effect on reverse transcriptase. They bind to this enzyme in a different place compared to nucleoside compounds.

The most common side effect occurs skin rash, transaminase levels increase.

A new group of drugs has been proposed for the treatment of HIV infection -HIV protease inhibitors.These enzymes, which regulate the formation of structural proteins and enzymes of HIV virions, are necessary for the reproduction of retroviruses. If their quantity is insufficient, immature precursors of the virus are formed, which delays the development of infection.

A significant achievement is the creation of selectiveantiherpetic drugs,which are synthetic derivatives of nucleosides. Acyclovir (Zovirax) is one of the highly effective drugs in this group.

Acyclovir is phosphorylated in cells. In infected cells it acts in the form of triphosphate 2, disrupting the growth of viral DNA. In addition, it has a direct inhibitory effect on the viral DNA polymerase, which inhibits the replication of viral DNA.

Absorption of acyclovir from the gastrointestinal tract is incomplete. The maximum concentration is determined after 1-2 hours. Bioavailability is about 20%. 12-15% of the substance is bound to plasma proteins. It passes through the blood-brain barrier quite satisfactorily.

Saquinavir (invirase) has been more widely studied in the clinic. It is a highly active and selective inhibitor of HIV-1 and HIV-2 proteases. Despite the low bioavailability of the drug (~ 4%)", it is possible to achieve such concentrations in the blood plasma that suppress the proliferation of retroviruses. Most of the substance binds to blood plasma proteins. The drug is administered orally. Side effects include dyspepsia, increased activity of liver transaminases , lipid metabolism disorders, hyperglycemia.Viral resistance to saquinavir may develop.

The drug is prescribed mainly for herpes simplex

as well as with cytomegalovirus infection. Acyclovir is administered orally, intravenously (in the form of sodium salt) and locally. When applied topically, a slight irritant effect may be observed. At intravenous administration acyclovir sometimes causes renal dysfunction, encephalopathy, phlebitis, and skin rash. When administered enterally, nausea, vomiting, diarrhea, and headache are observed.

New antiherpetic drug valacyclovir

This is a prodrug; during its first passage through the intestines and liver, acyclovir is released, which provides an antiherpetic effect.

This group also includes famciclovir and its active metabolite gan-ciclovir, which are similar in pharmacodynamics to acyclovir.

Vidarabine is also an effective drug.

Having penetrated the cell, vidarabine is phosphorylated. Inhibits viral DNA polymerase. At the same time, the replication of large DNA-containing viruses is suppressed. In the body, it is partially converted into hypoxanthine arabinoside, which is less active against viruses.

Vidarbine is successfully used for herpetic encephalitis (administered by intravenous infusion), reducing mortality in this disease by 30-75%. Sometimes it is used for complicated herpes zoster. Effective for herpetic keratoconjunctivitis (prescribed topically in ointments). In the latter case, it is less irritating and less likely to inhibit corneal healing than idoxuridine (see below). Penetrates more easily into deeper layers of tissue (in the treatment of herpetic keratitis). It is possible to use vidarabine for allergic reactions to idoxuridine and if the latter is ineffective.

Side effects include dyspepsia (nausea, vomiting, diarrhea), skin rash, central nervous system disorders (hallucinations, psychosis, tremor, etc.), thrombophlebitis at the injection site.

Trifluridine and idoxuridine are used topically.

Trifluridine is a fluorinated pyrimidine nucleoside. Inhibits DNA synthesis. Used for primary keratoconjunctivitis and recurrent epithelial keratitis caused by a virus herpes simplex(type1 and 2). Trifluridine solution is applied topically to the mucous membrane of the eye. Transient irritation and swelling of the eyelids are possible.

Idoxuridine (kerecid, iduridine, ophtan-IDU), which is an analogue of thymidine, is integrated into the DNA molecule. In this regard, it suppresses the replication of individual DNA viruses. Idoxuridine is used topically for herpetic eye infections (keratitis). May cause irritation and swelling of the eyelids. It is of little use for resorptive action, since the toxicity of the drug is significant (suppresses leukopoiesis).

Atcytomegalovirus infection Ganciclovir and foscarnet are used. Gan-ciclovir (cymevene) is a synthetic analogue of 2"-deoxyguanosine nucleoside. The mechanism of action is similar to acyclovir. Inhibits the synthesis of viral DNA. The drug is used for cytomegalovirus retinitis. It is administered intravenously and into the conjunctival cavity. Side effects are often observed

many of them lead to severe functional impairment various organs and systems. Thus, 20-40% of patients experience granulocytopenia and thrombocytopenia. Adverse neurological effects are common: headache, acute psychosis, convulsions, etc. Anemia, allergic skin reactions, and hepatotoxic effects are possible. Experiments on animals have established its mutagenic and teratogenic effects.

A number of drugs are effective as anti-influenza agents. Antiviral drugs effective against influenza infection can be represented by the following groups./. M2 viral protein inhibitorsRemantadine Midantan (amantadine)

2. Inhibitors of the viral enzyme neuraminidaseZanamivir

Oseltamivir

3. Viral RNA polymerase inhibitorsRibavirin

4. Various drugsArbidol Oksolin

The first group belongs toM2 protein inhibitors.The membrane protein M2, which functions as an ion channel, is found only in influenza virus type A. Inhibitors of this protein disrupt the process of “undressing” the virus and prevent the release of the viral genome in the cell. As a result, virus replication is suppressed.

This group includes midantan (adamantanamine hydrochloride, amantadine, symmetrel). Well absorbed from the gastrointestinal tract. It is excreted mainly by the kidneys.

Sometimes the drug is used to prevent type A influenza. remedy ineffective. Midantan is more widely used as an antiparkinsonian drug.

Remantadine (rimantadine hydrochloride), which is similar in chemical structure to midantan, has similar properties, indications for use and side effects.

Viral resistance develops quite quickly to both drugs.

Second group of drugsinhibits the viral enzyme neuraminidase,which is a glycoprotein formed on the surface of influenza viruses type A and B. This enzyme helps the virus reach target cells in the respiratory tract. Specific neuraminidase inhibitors (competitive, reversible action) prevent the spread of the virus associated with infected cells. Virus replication is disrupted.

One inhibitor of this enzyme is zanamivir (Relenza). It is used intranasally or inhaled

The second drug, oseltamivir (Tamiflu), is used in the form of ethyl ester.

Drugs have been created that are used both for influenza and other viral infections. To the group of synthetic drugs,inhibiting the synthesis of nucleic acids,includes ribavirin (ribamidil). It is a guanosine analogue. The drug is phosphorylated in the body. Ribavirin monophosphate inhibits the synthesis of guanine nucleotides, and triphosphate inhibits viral RNA polymerase and disrupts the formation of RNA.

Effective against influenza types A and B, severe respiratory syncytial virus infection (administered by inhalation), hemorrhagic fever with renal syndrome and Lassa fever (intravenously). Side effects include skin rash, conjunctivitis

To the numberdifferent drugsrefers to arb idol. It is an indole derivative. It is used for the prevention and treatment of influenza caused by influenza viruses type A and B, as well as for acute respiratory viral infections. According to available data, arbidol, in addition to its moderate antiviral effect, has interferonogenic activity. In addition, it stimulates cellular and humoral immunity. The drug is administered orally. Well tolerated.

This group also includes the drug oxolin, which has a virucidal effect. It is moderately effective in preventing

The drugs listed are synthetic compounds. However, antiviral therapy is also usednutrients,especially interferons.

Interferons are used to prevent viral infections. This is a group of compounds belonging to low molecular weight glycoproteins, produced by the cells of the body when they are exposed to viruses, as well as a number of biologically active substances of endo- and exogenous origin. Interferons are formed at the very beginning of infection. They increase the resistance of cells to damage by viruses. Characterized by a wide antiviral spectrum.

More or less pronounced effectiveness of interferons has been noted for herpetic keratitis, herpetic lesions of the skin and genital organs, ARVI, herpes zoster, viral hepatitis B and C, and AIDS. Interferons are used locally and parenterally (intravenously, intramuscularly, subcutaneously).

Side effects include increased temperature, development of erythema and pain at the injection site, and progressive fatigue. In large doses, interferons can inhibit hematopoiesis (granulocytopenia and thrombocytopenia develop).

In addition to antiviral effects, interferons have anticellular, antitumor and immunomodulatory activities.

Antitumor agents: classification

Alkylating agents - benzoteph, myelosan, thiophosphamide, cyclophosphamide, cisplatin;

Antimetabolites folic acid- methotrexate;

Antimetabolites - analogues of purine and pyrimidine - mercaptopurine, fluorouracil, fludarabine (cytosar);

Alkaloids and other herbal products vincristine, paclitaxel, teniposide, etoposide;

Antitumor antibiotics - dactinomycin, doxorubicin, epirubicin;

Monoclonal antibodies to tumor cell antigens - alemtuzumab (Campas), bevacizumab (Avastin);

Hormonal and antihormonal agents - finasteride (Proscar), cyproterone acetate (Androcur), goserelin (Zoladex), tamoxifen (Nolvadex).

ALKYLING AGENTS

Regarding the mechanisms of interaction of alkylating agents with cellular structures, there is the following point of view. Using the example of chloroethylamines(A)It has been shown that in solutions and biological fluids they split off chlorine ions. In this case, an electrophilic carbonium ion is formed, which transforms into ethylenimonium(V).

The latter also forms a functionally active carbonium ion (g), which interacts, according to existing ideas, with nucleophilic structures of DNA (with guanine, phosphate, aminosulfhydryl groups-

Thus, alkylation of the substrate occurs

The interaction of alkylating substances with DNA, including cross-linking of DNA molecules, disrupts its stability, viscosity and subsequently integrity. All this leads to a sharp inhibition of cell activity. Their ability to divide is suppressed, many cells die. Alkylating agents act on cells in interphase. Their cytostatic effect is especially pronounced in relation to rapidly proliferating cells.

Most of

used mainly for hemoblastoses (chronic leukemia, lymphogranulomatosis (Hodgkin's disease), lympho- and reticulosarcomas

Sarcolysin (racemelfolan), active in myeloma, lymphoma and reticulosarcoma, is effective in a number of true tumors

ANTI-METABOLYTES

Drugs in this group are antagonists of natural metabolites. In the presence of tumor diseases, the following substances are mainly used (see structures).

Folate antagonists

Methotrexate (amethopterin)Purine antagonists

Mercaptopurine (leupurine, purinethol)Pyrimidine antagonists

Fluorouracil (fluorouracil)

Ftorafur (tegafur)

Cytarabine (Cytosar)

Fludarabine phosphate (fludara)

In terms of their chemical structure, anti-metabolites are only similar to natural metabolites, but not identical to them. In this regard, they cause disruption of nucleic acid synthesis 1

This negatively affects the process of tumor cell division and leads to their death.

When treating acute leukemia, improvement in the general condition and hematological picture occurs gradually. The duration of remission is several months.

The drugs are usually taken orally. Methotrexate is also available for parenteral administration.

Methotrexate is excreted by the kidneys, mainly unchanged. Some of the drug remains in the body for a very long time (months). Mercaptopurine is exposed in the liver x

The negative aspects of the action of the drugs are manifested in their inhibition of hematopoiesis, nausea, and vomiting. A number of patients experience liver dysfunction. Methotrexate affects the mucous membrane of the gastrointestinal tract and causes conjunctivitis.

Antimetabolites also include thioguanine and cytarabine (cytosine arabinoside), which are used for acute myeloid and lymphoid leukemia

ANTIBIOTICS WITH ANTI-TUMOR ACTIVITY

A number of antibiotics, along with antimicrobial activity, have pronounced cytotoxic properties due to inhibition of the synthesis and function of nucleic acids. These include dactinomycin (actinomycinD), produced by some speciesStreptomyces. Dactinomycin is used for uterine chorionepithelioma, Wilms tumor in children, and for lymphogranulomatosis (Fig. 34.2). The drug is administered intravenously, as well as into body cavities (if there is exudate in them).

The antibiotic olivomycin, produced byActinomycesolivoreticuli. It is used in medical practice sodium salt. The drug causes some improvement in testicular tumors - seminoma, embryonal cancer, teratoblastoma, lymphoepithelioma. reticulo-sarcoma, melanoma. It is administered intravenously. In addition, for ulceration of superficial tumors, olivomycin is used topically in the form of ointments.

Antibiotics of the anthracycline group - doxorubicin hydrochloride (formedStreptomyces speciesvarcaesius) and karm and nom and qing (producerActinoma- duracarminatasp. nov.) - attract attention due to its effectiveness in sarcomas of mesenchymal origin. Thus, doxorubicin (Adriamycin) is used for osteogenic sarcomas, breast cancer and other tumor diseases.

When using these antibiotics, loss of appetite, stomatitis, nausea, vomiting, and diarrhea are observed. Possible damage to the mucous membranes by yeast-like fungi. Hematopoiesis is inhibited. Cardiotoxic effects are sometimes noted. Hair loss often occurs. These drugs also have irritating properties. Their pronounced immunosuppressive effect should also be taken into account.

and autumn colchicum

VincaroseaL.)

The toxic effect of vincristine manifests itself in different ways. While inhibiting hematopoiesis with little or no effect, it can lead to neurological disorders (ataxia, disruption of neuromuscular transmission, neuropathy, paresthesia), kidney damage (polyuria, dysuria), etc.

Androgens

Estrogens

Corticosteroids

According to the mechanism of action on hormone-dependent tumors, hormonal drugs differ significantly from the cytotoxic drugs discussed above. Thus, there is evidence that under the influence of sex hormones, tumor cells do not die. Apparently, the main principle of their action is that they inhibit cell division and promote their differentiation. Obviously, to a certain extent, the impaired humoral regulation of cell function is restored.

Androgens5

PRODUCTS OF PLANT ORIGIN WITH ANTI-TUMOR ACTIVITY

Colchamine, an alkaloid of Colchicum splendidus, has pronounced antimitotic activity.

and autumn colchicum

Colchamine (demecolcine, omain) is used topically in ointments for skin cancer (without metastases). In this case, malignant cells die, and normal epithelial cells are practically not damaged. However, during treatment, an irritating effect (hyperemia, swelling, pain) may occur, which forces you to take breaks in treatment. After rejection of necrotic masses, wound healing occurs with a good cosmetic effect.

With a resorptive effect, colhamine quite strongly inhibits hematopoiesis, causes diarrhea, and hair loss.

Antitumor activity was also found in alkaloids from the plant Vinca rosea (VincaroseaL.) vinblastine and vincristine. They have an antimitotic effect and, like colhamine, block mitosis at the metaphase stage.

Vinblastine (Rozevin) is recommended for generalized forms of lymphogranulomatosis and chorionepithelioma. In addition, it, like vincristine, is widely used in combination chemotherapy for tumor diseases. The drug is administered intravenously.

The toxic effect of vinblastine is characterized by inhibition of hematopoiesis, dyspeptic symptoms, and abdominal pain. The drug has a pronounced irritating effect and can cause phlebitis.

therapy acute leukemia, as well as other hemoblastoses and true tumors. The drug is administered intravenously.

HORMONES AND HORMONE ANTAGONISTS USED IN CANCER DISEASES

Of the hormonal drugs 1, the following groups of substances are mainly used for the treatment of tumors:

Androgens- testosterone propionate, testenate, etc.;

Estrogens- synestrol, fosfestrol, ethinyl estradiol, etc.;

Corticosteroids- prednisolone, dexamethasone, triamninolone.

Androgensused for breast cancer. They are prescribed to women with preserved menstrual cycle and in the case when menopause does not exceed5 years. The positive role of androgens in breast cancer is to suppress estrogen production.

Estrogens are widely used in cancer prostate gland. In this case, it is necessary to suppress the production of natural androgenic hormones.

One of the drugs used for prostate cancer is fosfestrol (honvan)

CYTOKINES

ENZYMES EFFECTIVE IN TREATING TUMOR DISEASES

It was found that a number of tumor cells do not synthesizeL-asparagine, which is necessary for the synthesis of DNA and RNA. In this regard, it became possible to artificially limit the entry of this amino acid into the tumor. The latter is achieved by introducing the enzymeL-asparaginase, which is used in the treatment of acute lymphoblastic leukemia. Remission lasts several months. Side effects include liver dysfunction, inhibition of fibrinogen synthesis, and allergic reactions.

One of the effective groups of cytokines are interferons, which have immunostimulating, antiproliferative and antiviral effects. In medical practice, recombinant human interferon-os is used in the complex therapy of some tumors. It activates macrophages, T-lymphocytes and killer cells. Has a beneficial effect in a number of tumor diseases (chronic myeloid leukemia, sarcoma Ka

sewing, etc.). The drug is administered parenterally. Side effects include fever, headache, myalgia, arthralgia, dyspepsia, suppression of hematopoiesis, dysfunction of the central nervous system, thyroid dysfunction, nephritis, etc.

MONOCLONAL ANTIBODIES

Monoclonal antibody drugs include trastuzumab (Herceptin). Its antigens areHER2-receptors of breast cancer cells. Overexpression of these receptors, detected in 20-30% of patients, leads to proliferation and tumor transformation of cells. The antitumor activity of trastuzumab is associated with blockadeHER2 receptors, which leads to a cytotoxic effect

A special place is occupied by bevacizumab (Avastin), a monochannel antibody drug that inhibits vascular endothelial growth factor. As a result, the growth of new vessels (angiogenesis) in the tumor is suppressed, which disrupts its oxygenation and the supply of nutrients to it. As a result, tumor growth slows down.

The most common side effects of antiviral drugs

Use of antiviral drugs for diabetes mellitus

Is it possible to combine treatment with antiviral drugs and alcohol?

Use of antiviral and anti-inflammatory drugs ( paracetamol, ibuprofen)

For what diseases are antiviral drugs used? - ( video)

Antiviral drugs for diseases caused by the herpesvirus family - ( video)

Antiviral drugs for intestinal viral infections

Use of antiviral drugs for prophylactic purposes. Antiviral drugs for children, pregnant and breastfeeding women

The site provides reference information for informational purposes only. Diagnosis and treatment of diseases must be carried out under the supervision of a specialist. All drugs have contraindications. Consultation with a specialist is required!

What are antiviral drugs?

Antiviral drugs are medicines aimed at combating various types of viral diseases ( herpes, chicken pox, etc.). Viruses are a separate group of living organisms that can infect plants, animals and humans. Viruses are the smallest infectious agents, but also the most numerous.

Viruses are nothing more than genetic information ( short chain of nitrogenous bases) in a shell of fats and proteins. Their structure is as simplified as possible; they do not have a nucleus, enzymes, or energy supply elements, which makes them different from bacteria. That is why they have microscopic sizes, and their existence was hidden from science for many years. The existence of viruses passing through bacterial filters was first suggested in 1892 by the Russian scientist Dmitry Ivanovsky.

The number of effective antiviral drugs today is very small. Many drugs fight the virus by activating the body’s own immune forces. There are also no antiviral drugs that could be used in the case of a variety of viral infections; most existing drugs are narrowly aimed at treating one, maximum two diseases. This is due to the fact that viruses are very diverse; various enzymes and defense mechanisms are encoded in their genetic material.

History of the creation of antiviral drugs

The creation of the first antiviral drugs occurred in the middle of the last century. In 1946, the first antiviral drug, thiosemicarbazone, was proposed. It turned out to be ineffective. In the 50s, antiviral drugs appeared to combat the herpes virus. Their effectiveness was sufficient, however a large number of side effects almost completely eliminated the possibility of its use in the treatment of herpes. In the 60s, amantadine and remantadine were developed, drugs that are still used today.

All drugs until the beginning of the 90s were obtained empirically, using observations. Efficiency ( mechanism of action) these drugs were difficult to prove due to the lack of necessary knowledge. Only in recent decades have scientists obtained more complete data on the structure of the virus and its genetic material, as a result of which it became possible to produce more effective drugs. However, even today many drugs remain with clinically unproven effectiveness, which is why antiviral drugs are used only in certain cases.

A great success in medicine was the discovery of human interferon, a substance that carries out antiviral activity in the human body. It was proposed to be used as a medicine, after which scientists developed methods for purifying it from donor blood. Of all the antiviral drugs, only interferon and its derivatives can claim to be broad-spectrum drugs.

In recent years, the use of natural preparations for the treatment of viral diseases ( for example echinacea). Also today, the use of various immunomodulatory drugs that provide prevention against viral diseases is popular. Their action is based on increasing the synthesis of its own interferon in the human body. A special problem of modern medicine is HIV infection and AIDS, therefore the main efforts of the pharmaceutical industry today are aimed at finding a treatment of this disease. Unfortunately, the necessary cure has not yet been found.

Production of antiviral drugs. The basis of antiviral drugs

There are a wide variety of antiviral drugs, but all of them have disadvantages. This is partly due to the complexity of developing, manufacturing and testing drugs. Antiviral drugs need to be tested, naturally, on viruses, but the problem is that viruses outside cells and outside other organisms do not live long and do not manifest themselves in any way. They are also quite difficult to identify. Unlike viruses, bacteria are cultivated in nutrient media, and their effectiveness can be judged by slowing down their growth antibacterial drugs.

Today, antiviral drugs are obtained in the following ways:

Chemical synthesis. The standard method of producing drugs is to obtain drugs through chemical reactions.
Obtained from plant materials. Some parts of plants, as well as their extracts, have an antiviral effect, which is used by pharmacists in the production of medicines.
Obtained from donor blood. These methods were relevant several decades ago, but today they have been practically abandoned. They were used to produce interferon. From 1 liter of donor blood, only a few milligrams of interferon could be obtained.
Use of genetic engineering. This method is the latest in the pharmaceutical industry. Using genetic engineering, scientists change the structure of genes certain types bacteria, as a result of which they produce the necessary chemical compounds. They are subsequently purified and used as an antiviral agent. This is how, for example, some types of antiviral vaccines, recombinant interferon and other drugs are obtained.

Thus, the basis of antiviral drugs can be both inorganic and organic matter. However, in recent years, recombinant ( obtained through genetic engineering) drugs. They, as a rule, have exactly the qualities that the manufacturer puts into them; they are effective, but are not always available to the consumer. The price of such drugs can be very high.

Antiviral drugs, antifungals and antibiotics, differences. Can they be taken together?

Differences between antiviral, antifungal and antibacterial agents ( antibiotics) are implied in their name. All of them are created against different classes of microorganisms that cause diseases that differ in clinical manifestations. Naturally, they will be effective only if the pathogen has been correctly identified and the correct group of drugs has been selected for it.

Antibiotics are directed against bacteria. Bacterial lesions include purulent lesions of the skin, mucous membranes, pneumonia, tuberculosis, syphilis, and many other diseases. Majority inflammatory diseases (cholecystitis, bronchitis, pyelonephritis and many others) is caused precisely by a bacterial infection. They are almost always characterized by standard clinical signs (pain, fever, redness, swelling and dysfunction) and have minor differences. Diseases caused by bacteria constitute the largest group and have been studied most fully.

Fungal infections usually occur when the immune system is weakened and mainly affect the surface of the skin, nails, hair, and mucous membranes. The best example of fungal infections is candidiasis ( thrush). For the treatment of fungal infections should be used exclusively antifungal drugs. The use of antibacterial drugs is a mistake, since fungi very often develop precisely when the balance of the bacterial flora is disturbed.

Finally, antiviral drugs are used to treat viral diseases. You can suspect you have a viral disease by the presence of flu-like symptoms ( headache, body aches, fatigue, mild fever). This onset is typical for many viral diseases, including chickenpox, hepatitis and even intestinal viral diseases. Viral diseases cannot be treated with antibiotics; they cannot even be used to prevent the addition of a bacterial infection. However, it is worth considering that in the presence of simultaneous viral and bacterial infections, doctors prescribe drugs from both groups.

The listed groups of drugs are considered potent drugs and are sold only with a doctor's prescription. To treat viral, bacterial or fungal diseases, you should consult a doctor and not self-medicate.

Antiviral drugs with proven effectiveness. Are modern antiviral drugs effective enough?

There are currently a limited number of antiviral drugs available. The number of active ingredients with proven effectiveness against viruses is about 100 items. Of these, only about 20 are widely used in the treatment of various diseases. Others have either a high price or a large number of side effects. Some drugs have never undergone clinical trials, despite many years of practice. For example, only oseltamivir and zanamivir have proven effectiveness against influenza, despite the fact that pharmacies sell a large number of anti-influenza drugs.

Antiviral drugs that have proven effectiveness include:

valacyclovir;
vidarabine;
foscarnet;
interferon;
remantadine;
oseltamivir;
ribavirin and some other drugs.

On the other hand, today you can find many analogues in pharmacies ( generics), due to which hundreds of active ingredients of antiviral drugs turn into several thousand commercial names. Only pharmacists or doctors can understand so many drugs. Also, under the name of antiviral drugs, ordinary immunomodulators are often hidden, which strengthen the immune system, but have a rather weak effect on the virus itself. Thus, before using antiviral drugs, you should consult with your doctor about the need for their use.

In general, you need to be very careful when using antiviral drugs, especially those sold over the counter in pharmacies. Most of them do not have the necessary medicinal properties, and the benefits of their use are equated by many doctors to placebo ( a dummy substance that has no effect on the body). Viral infections are treated infectious disease doctors ( sign up) , in their arsenal there are the necessary drugs that definitely help against various pathogens. However, treatment with antiviral drugs should be carried out under the supervision of doctors, since most of them have significant side effects ( nephrotoxicity, hepatotoxicity, nervous system disorders, electrolyte disturbances and many others).

Can I buy antiviral drugs at the pharmacy?

Not all antiviral drugs can be purchased at the pharmacy. This is due to the serious influence of drugs on human body. Their use requires permission and supervision from a physician. This applies to interferons, drugs against viral hepatitis, and systemic antivirals. To purchase a prescription drug, you need a special form with the seal of the doctor and medical institution. In all infectious diseases hospitals, antiviral drugs are provided without a prescription.

However, there are various antiviral medications that can be purchased without a prescription. For example, ointments against herpes ( containing acyclovir), eye and nasal drops containing interferon and many other products are available over the counter. Immunomodulators and herbal antiviral drugs can also be purchased without a prescription. They are usually equated to dietary supplements ( dietary supplement).

Antiviral drugs according to their mechanism of action are divided into the following groups:

drugs acting on extracellular forms of the virus ( oxolin, arbidol);
drugs that prevent the virus from entering the cell ( remantadine, oseltamivir);
drugs that stop the reproduction of the virus inside the cell ( acyclovir, ribavirin);
drugs that stop the assembly and exit of the virus from the cell ( mixed breed);
interferons and interferon inducers ( alpha, beta, gamma interferon).

Drugs acting on extracellular forms of the virus

This group includes a small number of drugs. One of these drugs is oxolin. It has the ability to penetrate the shell of a virus located outside cells and inactivate its genetic material. Arbidol affects the lipid membrane of the virus and makes it unable to merge with the cell.

Interferon has an indirect effect on the virus. These drugs can attract cells to the area of infection immune system, which manage to inactivate the virus before it penetrates into other cells.

Drugs that prevent the virus from entering the body's cells

This group includes the drugs amantadine and remantadine. They can be used against the influenza virus, as well as against the tick-borne encephalitis virus. These drugs have in common the ability to disrupt the interaction of the virus envelope ( in particular M protein) with a cell membrane. As a result, foreign genetic material does not enter the cytoplasm of the human cell. In addition, a certain obstacle is created during the assembly of virions ( virus particles).

It is advisable to take these drugs only in the first days of the disease, since at the height of the disease the virus is already inside the cells. These drugs are well tolerated, but due to the peculiarities of the mechanism of action, they are used only for preventive purposes.

Drugs that block the activity of the virus inside the cells of the human body

This group of drugs is the widest. One way to stop the virus from reproducing is to block DNA ( RNA) – polymerases. These enzymes, brought into the cell by the virus, produce large numbers of copies of the viral genome. Acyclovir and its derivatives inhibit the activity of this enzyme, which explains their antiherpetic effect. Ribavirin and some other antiviral drugs also inhibit DNA polymerases.

This group also includes antiretroviral drugs that are used to treat HIV. They inhibit the activity of reverse transcriptase, which converts viral RNA into cell DNA. These include lamivudine, zidovudine, stavudine and other drugs.

Drugs that block the assembly and release of the virus from cells

One of the representatives of the group is metisazon. This drug blocks the synthesis of the viral protein that makes up the virion envelope. The drug is used to prevent chickenpox, as well as to reduce complications of chickenpox vaccination. This group is promising in terms of creating new drugs, since the drug metisazon has pronounced antiviral activity, is easily tolerated by patients and is prescribed orally.

Interferons. Use of interferons as medicine

Interferons are low molecular weight proteins that the body produces independently in response to infection with a virus. There are different types of interferons ( alpha, beta, gamma), which differ in various properties and the cells that produce them. Interferons are also produced during some bacterial infections, but these compounds play the greatest role in the fight against viruses. Without interferons, the immune system cannot function and the body cannot protect itself from viruses.

Interferons have the following qualities that allow them to exhibit an antiviral effect:

suppress the synthesis of viral proteins inside cells;
slow down the assembly of the virus inside the body’s cells;
block DNA and RNA polymerases;
activate cellular and humoral immunity systems against viruses ( attract leukocytes, activate the complement system).

After the discovery of interferons, speculation arose about their possible use as a medicine. The fact that viruses do not develop resistance to interferons is especially important. Today they are used in the treatment of various viral diseases, herpes, hepatitis, AIDS. The big disadvantages of the drug are serious side effects, high cost and difficulty in obtaining interferons. Because of this, interferons are very difficult to purchase in pharmacies.

Interferon inducers ( kagocel, trekrezan, cycloferon, amiksin)

The use of interferon inducers is an alternative to the use of interferons. Such treatment is usually several times cheaper and more accessible to consumers. Interferon inducers are substances that increase the body's production of its own interferon. Interferon inducers have a weak direct antiviral effect, but have a pronounced immunostimulating effect. Their activity is mainly due to the effects of interferon.

The following groups of interferon inducers are distinguished:

natural remedies ( amiksin, poludanum and others);
synthetic drugs ( polyoxidonium, galavit and others);
herbal preparations ( echinacea).

Interferon inducers increase the production of their own interferon by imitating the signals received when the body is infected with viruses. In addition, their long-term use leads to depletion of the immune system and can also lead to various side effects. Because of this, this group of drugs is not registered as official medicines, but is used as dietary supplements. The clinical effectiveness of interferon inducers has not been proven.

Antiviral drugs have a specific, selective effect. They are usually divided into types according to the virus on which they have the greatest impact. The most common classification involves dividing drugs according to their spectrum of action. This division facilitates their use in certain clinical situations.
Types of antiviral drugs by spectrum of action

Pathogen	Most commonly used drugs
*Herpes virus*	acyclovir; valacyclovir; famciclovir.
*Influenza virus*	remantadine; amantadine; arbidol; zanamivir; oseltamivir.
*Varicella zoster virus*	acyclovir; foscarnet; metisazon.
*Cytomegalovirus*	ganciclovir; foscarnet.
AIDS virus(HIV)	stavudine; ritonavir; indinavir.
*Hepatitis virus* *B and* C	alpha interferons.
*Paramyxovirus*	ribavirin.

Antiherpetic drugs ( acyclovir ( Zovirax) and its derivatives)

Herpes viruses are divided into 8 types and are relatively large viruses containing DNA. Manifestations of herpes simplex are caused by viruses of the first and second types. The main drug in the treatment of herpes is acyclovir ( Zovirax). It is one of the few drugs with proven antiviral activity. The role of acyclovir is to stop the growth of viral DNA.

Acyclovir, entering a cell infected with a virus, undergoes a series of chemical reactions ( phosphorylated). The modified substance of acyclovir has the ability to inhibit ( stop development) viral DNA polymerase. The advantage of the drug is its selective action. In healthy cells, acyclovir is inactive, and against ordinary cellular DNA polymerase its effect is hundreds of times weaker than against the viral enzyme. The drug is used locally ( as a cream or eye ointment), and systemically in the form of tablets. But, unfortunately, only about 25% of the active substance is absorbed from the gastrointestinal tract when used systemically.

The following drugs are also effective in treating herpes:

Ganciclovir. The mechanism of action is similar to acyclovir, but has a stronger effect, due to which the drug is also used in the treatment of tick-borne encephalitis. Despite this, the drug does not have a selective effect, which is why it is several times more toxic than acyclovir.
Famciclovir. The mechanism of action is no different from acyclovir. The difference between them is the presence of a different nitrogenous base. In terms of effectiveness and toxicity, it is comparable to acyclovir.
Valaciclovir. This medicine is more effective than acyclovir when used in tablet form. It is absorbed from the gastrointestinal tract in a fairly large percentage, and after undergoing a series of enzymatic changes in the liver it is converted into acyclovir.
Foscarnet. The drug has a special chemical structure ( formic acid derivative). It does not undergo changes in the cells of the body, due to which it is active against strains of the virus that are resistant to acyclovir. Foscarnet is also used for cytomegalovirus, herpetic and tick-borne encephalitis. It is administered intravenously, which is why it has a large number of side effects.

Anti-flu drugs ( arbidol, remantadine, Tamiflu, Relenza)

There are many variants of influenza viruses. There are three types of influenza viruses ( A, B, C), as well as their division according to variants of surface proteins - hemagglutinin ( H) and neuraminidase ( N). Due to the fact that it is very difficult to determine the specific type of virus, anti-influenza drugs are not always effective. Anti-influenza drugs are usually used for severe course infections, since with lungs clinical manifestations The body copes with the virus on its own.

The following types of anti-influenza drugs are distinguished:

Inhibitors of viral protein M ( remantadine, amantadine). These drugs prevent the virus from entering the cell, therefore, they are mainly used as a prophylactic rather than a therapeutic agent.
Inhibitors of the viral enzyme neuraminidase ( zanamivir, oseltamivir). Neuraminidase helps viruses destroy mucous secretions and penetrate the cells of the mucous membrane of the respiratory tract. Drugs in this group prevent the spread and replication ( reproduction) virus. One such drug is zanamivir ( release). It is used in aerosol form. Another drug is oseltamivir ( Tamiflu) – applied internally. It is this group of drugs that is recognized by the medical community as the only one with proven effectiveness. The drugs are tolerated quite easily.
RNA polymerase inhibitors ( ribavirin). The principle of action of ribavirin does not differ from acyclovir and other drugs that inhibit the synthesis of viral genetic material. Unfortunately, drugs of this kind have mutagenic and carcinogenic properties, so they must be used with caution.
Other drugs ( arbidol, oxolin). There are many other medications that can be used for the influenza virus. They have a weak antiviral effect, some additionally stimulate the production of their own interferon. However, it is worth noting that these drugs do not help everyone and not in all cases.

Drugs aimed at combating HIV infection

Treatment of HIV infection is one of the most serious problems in medicine today. The drugs that are available to modern medicine can only contain this virus, but not get rid of it. The human immunodeficiency virus is dangerous because it destroys the immune system, causing the patient to die from bacterial infections and various complications.

Drugs to combat HIV infection are divided into two groups:

reverse transcriptase inhibitors ( zidovudine, stavudine, nevirapine);
HIV protease inhibitors ( indinavir, saquinavir).

A representative of the first group is azidothymidine ( zidovudine). Its role is that it prevents the formation of DNA from viral RNA. This suppresses the synthesis of viral proteins, which provides a therapeutic effect. The drug easily penetrates the blood-brain barrier, which is why it can cause disorders of the central nervous system. Drugs of this kind need to be used for a very long time; the therapeutic effect appears only after 6–8 months of treatment. The disadvantage of the drugs is the development of viral resistance to them.

A relatively new group of antiretroviral drugs are protease inhibitors. They reduce the formation of enzymes and structural proteins of the virus, which is why immature forms of the virus are formed as a result of the life activity of the virus. This significantly delays the development of infection. One such drug is saquinavir. It inhibits the multiplication of retroviruses, but it also has the potential to develop resistance. That is why doctors use combinations of drugs from both groups in the treatment of HIV and AIDS.

Are there broad-spectrum antiviral drugs?

Despite the claims of drug manufacturers and advertising information, there are no broad-spectrum antiviral drugs. The drugs that exist today and are recognized by official medicine are characterized by a targeted, specific effect. The classification of antiviral drugs implies their division according to the spectrum of action. There are some exceptions in the form of drugs that are active against 2 - 3 viruses ( for example, foscarnet), but nothing more.

Antiviral drugs are prescribed by doctors in strict accordance with the clinical signs of the underlying disease. So, with the influenza virus, antiviral drugs intended for the treatment of herpes are useless. Drugs that can actually increase resistance ( resistance) of the body to viral diseases, are actually immunomodulators and have a weak antiviral effect. They are used primarily for prevention rather than treatment of viral diseases.

Interferons are also considered an exception. These drugs are allocated to a special group. Their action is unique, since the human body uses its own interferon in the fight against any viruses. Thus, interferons are indeed active against almost all viruses. However, the complexity of interferon therapy ( duration of treatment, need to be taken as part of courses, a large number of side effects) make it impossible to use it against mild viral infections. That is why interferons are used today mainly for the treatment of viral hepatitis.

Antiviral drugs - immunostimulants ( amiksin, kagocel)

Very common on sale today various drugs, stimulating the immune system. They have the ability to stop the growth of viruses and protect the body from infections. Such drugs are harmless, but do not have a direct effect against the virus. For example, Kagocel is an interferon inducer, which, after administration, increases the interferon content in the blood several times. It is used no later than the 4th day from the onset of infection, since after the fourth day the level of interferon increases on its own. Amixin has a similar effect ( tiloron) and many other drugs. Immunostimulants have many disadvantages that make their use inappropriate in most cases.

The disadvantages of immunostimulants include:

weak direct antiviral effect;
limited period of use ( before the height of the disease);
the effectiveness of the drug depends on the state of the human immune system;
with prolonged use, the immune system is depleted;
lack of clinically proven effectiveness of this group of drugs.

Herbal antiviral drugs ( echinacea preparations)

Herbal antiviral drugs are one of the best options in the prevention of viral infections. This is due to the fact that they do not have side effects like conventional antiviral drugs, and also do not have the disadvantages of immunostimulants ( immunodepletion, limited effectiveness).

One of the best options for preventive use are preparations based on echinacea. This substance has a direct antiviral effect against herpes and influenza viruses, increases the number of immune cells and helps destroy various foreign agents. Echinacea preparations can be taken in courses lasting from 1 to 8 weeks.

Homeopathic antiviral remedies ( ergoferon, anaferon)

Homeopathy is a branch of medicine that uses highly diluted concentrations of the active substance. The principle of homeopathy is to use those substances that are expected to cause symptoms similar to the patient's disease ( the so-called principle of “treating like with like”). This principle is the opposite of the principles official medicine. In addition, normal physiology cannot explain the mechanisms of action of homeopathic remedies. It is assumed that homeopathic remedies help in recovery by stimulating the neurovegetative, endocrine, and immune systems.

Few suspect that some antiviral remedies sold in pharmacies are homeopathic. Thus, the drugs ergoferon, anaferon and some others belong to homeopathic remedies. They contain various antibodies to interferon, to histamine and to some receptors. As a result of their use, the connection between the components of the immune system improves and the speed of interferon-dependent protective processes increases. Ergoferon also has a slight anti-inflammatory and antiallergic effect.

Thus, homeopathic antiviral drugs have a right to exist, but it is advisable to use them as a preventive or auxiliary remedy. Their advantage is the almost complete absence of contraindications. However, treating severe viral infections with homeopathic remedies is prohibited. Doctors rarely prescribe homeopathic medicines to your patients.

Use of antiviral drugs

Antiviral drugs are quite diverse and differ in the method of administration. Various dosage forms should be used for their intended purpose according to the instructions. You should also observe the indications and contraindications for the use of drugs, since the benefits and harm to the patient’s health depend on this. For certain groups of patients ( pregnant women, children, patients with diabetes) you should be especially careful when using antiviral agents.
The group of antiviral drugs has a large number of side effects, so their distribution and use are carefully controlled by the Ministry of Health. If the use of an antiviral drug causes side effects, you should immediately consult a doctor. He decides on the advisability of continuing treatment with this drug.

Indications for the use of antiviral agents

The purpose of using antiviral drugs comes from their name. They are used for various types of viral infections. In addition, some drugs from the antiviral category have additional effects that allow them to be used in various clinical situations not associated with viral infection.

Antiviral drugs are indicated for the following diseases:

flu;
herpes;
cytomegalovirus infection;
HIV AIDS;
viral hepatitis;
tick-borne encephalitis;
chicken pox;
enterovirus infection;
viral keratitis;
stomatitis and other lesions.

Antiviral drugs are not always used, but only in severe cases when there is no possibility of independent recovery. Thus, influenza is usually treated symptomatically, and special anti-influenza drugs are used only in cases of exceptional cases. Chicken pox ( chickenpox) in children goes away on its own after 2–3 weeks of illness. Usually, the human immune system quite successfully fights this type of infection. The limited use of antiviral drugs is explained by the fact that they cause many side effects, while the benefits of their use, especially in the middle of the disease, are low.

Some antiviral agents have their own characteristics. Thus, interferons are used for oncological diseases (melanoma, cancer). They are used as chemotherapy agents to shrink tumors. Amantadine ( midantan), used to treat influenza, is also suitable for the treatment of Parkinson's disease and neuralgia. Many antiviral agents also have an immunostimulating effect, but the use of immunostimulants is generally discouraged by the medical community.

Contraindications to the use of antiviral agents

Antiviral drugs have various contraindications. This is due to the fact that each drug has its own metabolic mechanisms in the body and affects organs and systems differently. In general, the most common contraindications to antiviral drugs include diseases of the kidneys, liver, and hematopoietic system.

Among the most common contraindications to this group of drugs are:

Mental disorders ( psychosis, depression). Antiviral drugs may adversely affect psychological condition person, especially during the first time of use. In addition, patients with mental disorders are at very high risk of inappropriate use of medications, which is very dangerous for medications with a large number of side effects.
Hypersensitivity to one of the components of the drug. Allergies pose a challenge to the use of any medication, not just antivirals. It can be suspected if there are other allergies ( for example, on plant pollen) or allergic diseases ( bronchial asthma). To prevent such reactions, it is worth undergoing special allergy tests.
Hematopoietic disorders. Taking antiviral drugs can lead to a decrease in the number of red blood cells, platelets, and white blood cells. That is why most antiviral drugs are not suitable for patients with hematopoietic disorders.
Severe pathology of the heart or blood vessels. When using drugs such as ribavirin, foscarnet, interferons, the risk of cardiac arrhythmia and an increase or decrease in blood pressure increases.
Cirrhosis of the liver. Many antiviral drugs undergo various transformations in the liver ( phosphorylation, formation of less toxic products). Liver diseases associated with liver failure ( for example, cirrhosis) reduce their effectiveness, or, conversely, increase the duration of their presence in the body, making them dangerous for the patient.
Autoimmune diseases. The immunostimulating effect of some drugs limits the possibility of their use in autoimmune diseases. For example, interferons cannot be used for diseases of the thyroid gland ( autoimmune thyroiditis). When using them, the immune system begins to more actively fight the cells of its own body, which is why the disease progresses.

In addition, antiviral drugs are generally contraindicated in pregnant women and children. These substances can affect the rate of growth and development of the fetus and child, lead to various mutations ( The mechanism of action of many antiviral drugs is to stop the synthesis of genetic material, DNA and RNA). As a result, antiviral drugs can lead to teratogenic effects ( formation of deformities) and mutagenic effects.

Forms of release of antiviral drugs ( tablets, drops, syrup, injections, suppositories, ointments)

Antiviral drugs today are available in almost all dosage forms available to modern medicine. They are intended for both local and systemic use. A variety of forms are used so that the drug can have the most pronounced effect. At the same time, the dosage of the drug and the method of its use depend on the dosage form.

Modern antiviral drugs are available in the following dosage forms:

tablets for oral administration;
powder for the preparation of solution for oral administration;
powder for injection ( complete with water for injections);
ampoules for injections;
suppositories ( candles);
gels;
ointments;
syrups;
nasal sprays and drops;
eye drops and other dosage forms.

The most convenient form of use is oral tablets. However, it is typical for this group of drugs that the drugs have low availability ( absorbability) from the gastrointestinal tract. This applies to interferons, acyclovir, and many other drugs. That is why the best dosage forms for systemic use are injection solution and rectal suppositories.

Most dosage forms allow the patient to independently accurately control the dose of the drug. However, when using some dosage forms ( ointment, gel, powder for the preparation of injection solution) you need to dose the drug correctly to avoid side effects. That is why the use of antiviral drugs in such cases should be carried out under the supervision of medical personnel.

Antiviral drugs for systemic and local use

There are a large number of forms of antiviral drugs that can be used both locally and systemically. This may even apply to the same active substance. For example, acyclovir is used either as an ointment or gel ( for topical application), and in tablet form. In the second case, it is used systemically, that is, it affects the entire body.

Local use of antiviral agents has the following features:

has a local effect ( on an area of skin, mucous membrane);
as a rule, gel, ointment, nasal or eye drops, and aerosols are used for topical application;
characterized by a pronounced effect in the area of application and lack of effect in distant places;
has a lower risk of side effects;
has virtually no effect on distant organs and systems ( liver, kidneys and others);
used for influenza, genital herpes, lip herpes, papillomas and some other diseases;
used for mild viral infections.

The systemic use of antiviral agents is characterized by the following features:

used in case of generalized infection ( HIV, hepatitis), as well as in severe cases of the disease ( for example, with influenza complicated by pneumonia);
has an effect on all cells in the human body, as it reaches them through the bloodstream;
for systemic use, oral tablets, injections, and rectal suppositories are used;
has a higher risk of side effects;
In general, it is used in cases where local treatment alone is ineffective.

It should be taken into account that dosage forms cannot be used for local use systematically and vice versa. Sometimes, to achieve the best therapeutic effect Doctors recommend combining drugs, which allows for a multifaceted effect on the viral infection.

Instructions for the use of antiviral drugs

Antiviral drugs are quite powerful drugs. In order to achieve the desired effect from them and avoid side effects, you should follow the instructions for use of the drugs. Each medicine has its own instructions. The dosage form of the drug plays the greatest role in the use of antiviral drugs.

The following are the most common ways of using antiviral drugs, depending on the dosage form:

Pills. Tablets are taken orally during or after meals 1 to 3 times a day. The appropriate dosage is determined by taking the whole tablet or half of it.
Injections. Must be performed by medical personnel, as incorrect administration can lead to complications ( including post-injection abscess). The drug powder is completely dissolved in liquid for injection and administered intramuscularly ( less often intravenously or subcutaneously).
Ointments and gels. Apply a thin layer to the affected surface of the skin and mucous membranes. Ointments and gels can be used 3–4 times a day or even more often.
Nasal and eye drops. Correct use of drops ( for example, influenzaferon) implies their administration in the amount of 1 – 2 drops in each nasal passage. They can be used 3 to 5 times a day.

When using an antiviral drug, the following parameters should be observed in accordance with the accompanying instructions and doctor’s recommendations:

Drug dosage. Most important parameter, observing which you can avoid overdose. Antiviral drugs are usually taken in small concentrations ( from 50 to 100 mg of active ingredient).
Frequency of use during the day. Antiviral tablets are taken 1 to 3 times a day, preparations for topical use ( drops, ointments) can be used 3 – 4 times a day or more often. When applied topically, overdose phenomena are very rare.
Duration of use. The duration of the course is determined by the doctor and depends on the severity of the disease. Discontinuation of treatment with antiviral drugs should be carried out after examination by a doctor.
Storage conditions. The storage temperature specified in the instructions must be observed. Some medications need to be stored in the refrigerator, others at room temperature.

Courses of antiviral drugs

Some antiviral drugs are used as part of long courses. Long-term use of drugs is necessary, first of all, for the treatment of viral hepatitis and HIV/AIDS. This is due to the high resistance of hepatitis and HIV viruses to drugs. Anti-hepatitis medications are taken for 3 to 6 months, anti-HIV medications for more than a year. Interferon and some other drugs are also used as part of course therapy.

The duration of treatment for most antiviral drugs is no more than 2 weeks. During this time, flu, herpes, enterovirus infection and other viral diseases are usually cured. Another way to use antiviral drugs is prevention. If prophylactic purposes are pursued, the duration of taking antiviral drugs is from 3 to 7 days.

The most common side effects of antiviral drugs

Side effects from the use of antiviral drugs are really common. Naturally, the nature of the side effects largely depends on the drug itself, as well as its dosage form. Systemic medications tend to create more side effects. Side effects are not common to all drugs, but we can summarize and highlight the most common adverse reactions of the body to taking antiviral drugs.

The most common side effects of antiviral drugs are:

Neurotoxicity ( negative effect on the central nervous system). Expressed by headache, fatigue,

Despite the achievements of modern medicine, viral infections remain one of the main causes of morbidity and mortality in the population. Viruses (from Latin virus, poison) are the smallest infectious agents consisting of nucleic acid (DNA or RNA), structural proteins and enzymes (Fig.

1). The genetic material of viruses is “packaged” in a special case - capsid (from Latin capsa, case). Capsid is protein coat, which protects the virus from external influences and ensures the adsorption of the virus on the membrane and its penetration into the cell.

Supercapsid

Nucleic Acid Capsid

The process of reproduction (multiplication) of viruses includes the following stages (Fig. 2):

1. Adsorption occurs through the interaction of glycoprotein capsid spike receptors with cellular receptors. The specific interaction of viral proteins with the surface receptors of the infected cell explains the “tropism of viruses” to a certain type of cell of the macroorganism. Adsorption also depends on ionic attraction (Scheme 2, /).

2. Penetration of the virus into the cell (viropexis) occurs in two ways: by injection of viral RNA (DNA) or by vacuolization (Scheme 2.2).

3. Deproteinization (“stripping”) of viral particles leads to the release of the viral genome. The destruction of the capsid occurs under the action of lysosomal enzymes of the cell. Modified viral particles lose their infectious properties (Scheme 2.3).

4. Replication - the formation of daughter copies of virus genomes (Scheme 2.4).

5. Assembly of daughter populations of the virus (Scheme 2, 5).

6. Release of daughter virions - the final stage of the reproductive cycle (Scheme 2, 6).

Classification of antiviral agents

I. Drugs acting on extracellular forms of the virus:

Oksolin;

Arbidol-lens.

II. Viropexis inhibitors (M2 channel blockers):

Amantadine (midantan, symmetrel, verigit-K, adamantine, amandine, amantane, antadin);

Rimantadine (rimantadine, meradan, algirem, polyrem).

III. Neuraminidase inhibitors:

Zanamivir (Relenza);

Oseltamivir (Tamiflu).

IV. Drugs that inhibit viral reproduction:

1. Inhibitors of DNA (RNA) polymerase of viruses:

Acyclovir (acigerpin, acyclovir, vivorax, herpevir, herperax, herpesin, zovirax, xorovir, lovir, medovir, supraviran, cycloviral, sedico, citivir);

Ganciclovir (cymevene);

Vidarabine;

Ribavirin (virazol, rebetol, ribavirin Meduna, ribamidil), etc.

2. Reverse transcriptase inhibitors:

A) . Abnormal nucleoside:

Abacavir (Ziagen);

Didanosine (Videx);

Lamivudine (Zeffix, Epivir Tri Ti SM);

Stavudin (zerit) -,

Zalcytobin (hivid);

Zidovudine (retrovir AZ and Ti, timazide, azidothymidine).

b) Preparations of non-nucleoside structure:

Efavirenz;

Nevirapine (viramune).

3. Protease inhibitors:

Aprenavir (Agenerase);

Indinavir sulfate (Crixivan);

Saquinavir (invirase, fortovase).

V. Virus maturation inhibitors:

Metisazone (marborane, kemoviran, viruzone)

VI. Interferons and interferon inducers.

Antiviral agents will be considered in accordance with the proposed classification.

I. Drugs acting on extracellular forms of the virus

The main use of the first group of antiviral drugs is the treatment and prevention of influenza and acute respiratory viral infections (ARVI). ARVI is a group of diseases that are similar in clinical and epidemiological characteristics. Acute respiratory viral infections account for about 75% of all infectious pathologies. The widespread spread of ARVI is facilitated by airborne infection, lack of persistent immunity to repeated infections, as well as a wide variety and frequent mutations of ARVI pathogens. Among the 200 known pathogens, influenza viruses undoubtedly play the leading role. Influenza is registered everywhere and represents the greatest epidemic danger. Every year, every tenth adult on the planet gets sick with the flu. During epidemic outbreaks, influenza is accompanied by high mortality, especially in young children and the elderly. Occupying the main place in the structure of acute respiratory viral infections, influenza reduces the reactivity of the immune system and is often complicated by pneumonia, otitis media, pyelonephritis and damage to other organs.

There are three types of influenza virus - A, B, C. These are RNA-containing viruses of the Orthomixoviridae family (Fig. 3). Large epidemics and pandemics are caused by the type A virus. The unpredictability of epidemics is due to the antigenic variability of viruses, leading to partial or complete changes in group and strain determinants - hemagneticin and neuraminidase. Hemagglutinin and neuraminidase are glycoprotein spikes that penetrate the supercapsid of the virus. These spikes are necessary for the adhesion of the virus to the membrane and its penetration into the cell (Fig. 3a). In this case, hemagglutinin ensures the fusion of the capsid with the cell membrane and lysosome membranes, and neuraminidase recognizes and interacts with cell surface receptors. In addition, neuraminidase, by cleaving neuraminic acid from daughter virions and the cell membrane, ensures the release of viruses from the cell (Fig. 3d). The M protein plays an important role in the morphogenesis of the virus. On the one hand, the M protein surrounds the nucleocapsid and protects the genome of the virus; on the other hand, the M protein is integrated into the cell membrane and modifies

478- her. On membrane areas modified by the M protein, the assembly of daughter populations of the virus occurs, followed by the formation of M channels and the release of daughter virions from the cell.

Among chemotherapeutic agents for the prevention of influenza and ARVI, the intranasal use of oxopine ointment is still popular. The drug is also effective for adenoviral keratoconjunctivitis, herpetic keratitis, viral skin lesions (herpes zoster), rhinitis viral etiology.

Mechanism of action: oxolin binds to the guanine bases of the nucleic acids of the viral particle located outside the cell - a virucidal effect.

When applied topically, oxolinic ointment can cause irritation. Oxolinic ointment for nasal and external use is available in 0.25% - 1.0 and 3% - 1.0.

Modern anti-influenza drugs include the interferon inducer arbidop-pans. Arbidol is active against influenza A and B viruses and reduces the risk of ARVI by 7.5 times.

The mechanism of action of the drug is complex and consists of the following links:

* suppresses the fusion of the lipid shell of the virion with the membranes of human cells - “prevents the penetration of the virus into the host cell.

Inhibits the translation of virus-specific proteins in infected cells - “suppresses the reproduction of viruses.

The antiviral effect of the drug is enhanced by its interferonogenic and immunomodulatory activity. It has been proven that arbidol stimulates cellular and humoral immunity. The antioxidant activity of arbidol is also important. Good therapeutic effect and the absence of side effects allows Arbidol-lance to be prescribed for the prevention and treatment of influenza and acute respiratory viral infections for adults and children from two years of age. To prevent influenza and acute respiratory viral infections, the drug is used in an age-specific dose during the epidemic 2 times a week for three weeks, in contact with patients - daily for 10-14 days. Taking arbidol for medicinal purposes should be started in the first hours of the disease 4 times a day (every 6 hours) for 3-5 days. The drug is available in the form of capsules of 0.1 for adults and film-coated tablets of 0.05 for children.

II. Viropexis inhibitors (M2 channel blockers)

M protein blockers are represented by adamantane derivatives: amantadine and rimantadine (Table 1).

In the mechanism of antiviral action of adamantane derivatives, the key reaction is their interaction with the M protein of the influenza virus. This, in turn, disrupts the following two stages of viral particle reproduction:

1. Suppress the fusion of the virus shell with endosome membranes - “impair the deproteinization of viral particles -” prevent the transfer of the virion’s genetic material into the cytoplasm of the host cell -> inhibit the early stage of specific virus reproduction (Fig. 1, c-/).

2. They disrupt the integration of M protein into the host cell membrane - “prevent modification of the membrane -” inhibit the assembly of daughter virions.

bgcolor=white>Dosage forms

	A drug	Range actions	Side effects
1.	Amantadine (gludantan, midantan)	Tablets 0.05 and 0.1, capsules 0.05	Viruses	Headache, insomnia, irritability, hallucinations, anorexia, xerostomia, peripheral edema, orthostatic hypotension.
2.	Rimantadine (rimantadine, algirem)	Tablets 0.05, capsules 0.05, syrup for children 0.2% - 100 ml.	Virus influenza type A, tick-borne encephalitis virus.	Allergies, drowsiness, depression, tremors, increased excitability.
3.	Adapro-	Tablets 0.05, capsules 0.05	Influenza viruses type A (H3/N2) and type B.	Allergic dyspepsia.

Midantan, a well-known antiparkinsonian drug, is not used as an antiviral drug in our country. Based on amantadine, rimantadine was created, which has greater activity and is less toxic compared to its predecessor. Rimantadine is well absorbed when taken orally and penetrates into the secretions of the respiratory tract better than amantadine. The antiviral effect of rimantadine is longer than that of midantan. Rimantadine is produced in Russia under the brand name Rimantadine in 50 mg tablets. Remantadine suppresses reproduction large number strains of influenza A viruses and reduces the toxic effect of influenza B virus on the body. The drug is active against tick-borne encephalitis viruses. In this regard, rimantadine is used not only for influenza, but also for the prevention of tick-borne encephalitis of viral etiology. For prophylactic use

The effectiveness of rimantadine for influenza is 70-90%. For prevention, take 0.05 once a day for 10-15 days.

For therapeutic purposes, rimantadine is prescribed no later than 48 hours from the appearance of the first signs of the disease, and then resistance to it develops. This is due to the fact that the main mechanism of action of the drug is due to impaired penetration of the virus into cells and blockade of the nuclear phase of reproduction. At later stages of virus reproduction, rimantadine has a much lesser effect. Therefore, at the height of the disease, when the virus “has time” to integrate into the genome of the host cell, the drug is not effective. The treatment regimen is as follows: 1st day 300 mg once, 2nd day 200 mg and 3rd day 100 mg. 0.1 g 3 times on the first day; on the 2nd and 3rd days - 0.1 g 2 times a day and on the 3rd day - 0.1 g 1 time a day. The duration of the course should not exceed 5 days to avoid the emergence of resistant forms of the virus. For children from 1 to 7 years of age, rimantadine is replaced with agyrem (syrup). The drug is a combination of rimantadine with sodium alginate, which ensures a constant concentration of rimantadine in the blood and reduces its toxic effect.

In most cases, rimantadine is well tolerated. 3-6% of patients may experience adverse reactions from the central nervous system or gastrointestinal tract. Rimantadine should be used with caution in the elderly, with severely impaired liver function, as well as in people with increased seizure activity (for example, epilepsy).

III. Neuraminidase inhibitors

A new direction in the development of anti-influenza drugs is the creation of viral neuraminidase inhibitors (Table 2). As mentioned earlier, neuraminidase (sialidase) is one of the key enzymes involved in the replication of influenza viruses types A and B. When neuraminidase is inhibited, the ability of viruses to penetrate healthy cells is impaired. Thanks to a special mechanism of action, neuraminidase inhibitors prevent the spread of infection from a sick person to a healthy person. In addition, neuraminidase inhibitors are able to reduce the production of cytokines (IL-1 and tumor necrosis factor), preventing the development of a local inflammatory reaction and weakening systemic manifestations of a viral infection such as fever, pain in muscles and joints, and loss of appetite. Let us add that neuraminidase inhibitors reduce the resistance of viruses to the protective effect of respiratory tract secretions, which prevents further spread of the virus in the body.

The first representatives of neuraminidase inhibitors are oseptamivir and zanamivir. Zanamivir is a structural analogue of sialic acid, a natural substrate of viral neuraminidase, and has the ability to compete with it for binding to the active centers of the enzyme. Thus, the mechanism of action of zanamivir is based on the principle of competitive antagonism. Due to high toxicity and low bioavailability when taken orally, the drug is used by inhalation. Zanamivir is recommended for the treatment of uncomplicated influenza in persons over 12 years of age with the onset of clinical symptoms no more than 36 hours.

The oral neuraminidase inhibitor oseltamivir (Tamiflu) is active against all clinically significant strains of influenza virus, including avian influenza virus (H5N1). Viruses do not become resistant to the drug. Moreover, according to clinical studies, the sensitivity of influenza viruses to Tamiflu increases over time. Oseltamivir is a prodrug and, under the influence of intestinal and liver esterases, is converted into an active carboxylate metabolite, which is well distributed to the main foci of influenza infection.

Mechanism of action: carboxylate binds to the hydrophobic “pocket” of the active site of the influenza virus neuraminidase - it blocks the latter’s ability to cleave off sialic acid residues from the surface of the infected cell - the penetration and exit of new virions from the cell is inhibited (Fig. 1, a, d).

In Russia, oseltamivir is registered as a drug for seasonal prevention of influenza in adults and children over 1 year of age. Conducted clinical studies indicate that the use of the drug allows:

Reduce symptom severity by 38%;

Reduce the duration of the disease by 37%;

Reduce the likelihood of developing the disease in adults and adolescents who are in close contact with someone who has the flu by 89%.

The recommended prophylactic dose of the drug is 75 mg per day for 4-6 weeks, and the therapeutic dose is 75-150 mg twice a day for 5 days. The drug is well tolerated, has high bioavailability and systemic action. To date, oseltamivir is the only drug officially recommended by WHO in the event of an influenza pandemic. Thus, oseltamivir fully confirms the status of the main antiviral drug assigned to the drug by WHO on August 23, 2007. Oseltamivir is produced by F. Hoffmann-LaRoche (Switzerland) under the brand name Tamiflu in 75 mg capsules.

Thus, an important advantage of neuraminidase inhibitors over M channel blockers (amandatin, rimantadine) is their activity against two types of influenza virus - A and B.

IV. Drugs that inhibit viral reproduction

Drugs that suppress virus reproduction are represented by a large group of highly effective drugs. According to their chemical structure, these medicinal substances are derivatives of nucleosides. Recall that nucleosides include purine and pyrimidine bases. In turn, nucleosides arranged in a certain order form nucleic acids(DNA and RNA).

Due to their similar chemical structure, drugs from the group of abnormal purine and pyrimidine bases are integrated into the nucleic acids of viruses and disrupt their function. In addition, nucleoside analogues inhibit the DNA polymerase of virions, which blocks the replication of daughter viral particles. Thus, the mechanism of action of abnormal nucleosides is based on the principle of competitive antagonism.

Inhibitors of DNA (RNA) polymerase of viruses

1. Inhibitors of PH K-polymerase viruses

Ribavirin is active against many RNA and DNA viruses. The drug has a complex, not fully understood mechanism of action. It is assumed that it blocks the RNA polymerase of viruses, which disrupts the synthesis of messenger RNA ribonucleoproteins. Thus, ribavirin inhibits the early stages of viral transcription. When administered by inhalation, the drug creates high concentrations in the secretions of the respiratory tract. Considering the toxicity of ribavirin and the limited data on its clinical effectiveness, the drug should be prescribed only if positive results serological tests confirming the presence of respiratory syncytial virus infection (RSV). At the same time, the drug has shown effectiveness in the treatment of viral hepatitis. It is used inhalation using a nebulizer, only in a hospital setting. Before the procedure, the contents of the bottle are dissolved in 300 ml of sterile water for injection (the concentration of the solution used is 20 mg/ml). Inhalations are carried out for 12-18 hours daily, the course of treatment is 3-7 days.

2. Viral DNA polymerase inhibitors

DNA-containing viruses are the causative agents of herpes viral infections. Herpesvirus diseases (from the Greek Herpes - creeping) are among the common viral infections of humans. Most famous representatives This group - herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2) - cause lesions of the mucous membranes. Primary infection with herpes virus type 3 (Varicella zoster, HZV) occurs as chickenpox (varicella), and relapses cause shingles (zoster). A fourth type of herpes virus, better known as Epstein-Barr virus (EBV), causes infectious mononucleosis. A characteristic feature of herpes virus type 5 (SHMV) is its ability to form giant or cytomegalic cells. Therefore, herpes virus type 5 is called cytomegalovirus. Thus, herpesviruses cause acute and latent infections, and also have a certain oncogenic potential.

Most modern antiherpetic drugs (antiherpes) are abnormal nucleosides. Antiherpes inhibit viral DNA polymerase more actively than host cell polymerase. Lesions caused by herpes simplex virus type 1 usually go away on their own and require only local measures. It is recommended to start therapy at the prodrome stage (itching). In this case, the development of the bubble stage can be completely prevented. To treat infections caused by herpes simplex viruses and Varicella zoster virus, the following antiherpetic agents are prescribed for local and external use.

Table 3

Antiherpetic agents for local and external use

In the treatment of herpetic keratitis, the thymidine analogue idoxuridine (oftan idu) has proven effective. When applied topically, the drug may cause irritation and allergic reactions. Available in plastic dropper bottles in the form of a solution for eye drops 0.1% - 10 ml.

Acyclovir is a universal representative of abnormal nucleosides. The drug is indicated for the treatment of herpetic infections and the prevention of relapses of the disease. Undoubtedly

486- The advantage of acyclovir is its wide spectrum of antiherpetic activity. Thus, the drug is prescribed for infection with EBV, HSV-1 and HSV-2. Acyclovir is effective against herpes zoster and cytomegalovirus infection. However, severe side effects that develop during the resorptive action of acyclovir limit its use.

Vapacicpovir (Valtrex) is close in its main characteristics to acyclovir, but differs from it in greater bioavailability when taken enterally. Valaciclovir is a prodrug and in the human body is converted into acyclovir, which provides the antiherpetic effect of the drug. Valacyclovir is active against all types of herpes viruses.

Another representative of antiherpetic agents, famciclovir (famvir), after oral administration, quickly turns into the active metabolite penciclovir. The advantage of penciclovir is its activity against recently identified strains of herpes simplex viruses that are resistant to acyclovir. In addition, the administration of famciclovir significantly reduces the severity and duration of postherpetic neuralgia in patients with herpes zoster. The drug is well tolerated.

Currently, penciclovir, also known as fenistil and pencivir, is becoming increasingly popular. Being a synthetic analogue of acyclic guanine nucleoside, penciclovir has high specificity against herpes-infected cells. Like acyclovir, penciclovir is activated in the cell by phosphorylation, but the latter in its activated form is more stable and therefore the duration of action of penciclovir is longer than that of acyclovir. As a result of longer exposure to the infected cell, penciclovir is effective at any stage of herpes simplex, including blistering. At the same time, the drug reduces the time of crust formation by 30%, and the healing process occurs 1-2 days faster (on average - 4 days). Quickly relieves pain and other symptoms of labial herpes (itching, burning, redness, tingling, etc.). Penciclovir is active against herpes simplex viruses (Herpes simhlex) and herpes virus type 3 (Varicella zoster).

In some cases, vidarabine is prescribed to treat complicated infections caused by the Varicella zoster virus. The drug is successfully used for herpetic encephalitis and herpetic keratoconjunctivitis. With topical application of Vidarabine,

irritation, pain, photophobia, allergic reactions. The drug is neurotoxic and causes leukopenia and thrombocytopenia.

Table 4

Abnormal nuclesosides with antiherpetic activity

A drug	Form	Range actions	Side effects
Acyclovir (acyclovir-AKOS, acyclovir-acri, herperax, zovirax, cycloviral SELICO)	Table 0.2 and 0.4. Ointment	HSV-1, HSV-2, HZV, CMV, EBV.	When taken orally - dispepsil and allergic reactions, leukopenia, thrombocytopenia, hematuria, phlebitis at the injection site, etc.
Valaciclovir (Val-Trex)	Tablets 0.5. Lyophilized powder for injection 0.25 in vials.	HSV-1, HSV-2, HZV, CMV. VEB.	Possible renal failure, hemolytic anemia, allergic reactions
Famciclovir	Tablets 0.25	HSV-1, HSV-2, HZV, CMV, EBV.	Headache, nausea, allergic reactions.
Ganciclovir (cymevene)	Capsules 0.25	HSV-1, HSV-2, CMV, EBV.	Neutropenia, thrombocytopenia, arrhythmia, edema, convulsions, depression, dyspepsia, etc.

The mainstay of treatment for cytomegalovirus infection is ganciclovir or foscarnet sodium. Ganciclovir, a drug similar in chemical structure to acyclovir, is a synthetic analogue of guanine. Ganciclovir is active against all types of herpes viruses, but is prescribed only for cytomegalovirus infection, since taking ganciclovir often leads to severe dysfunction of various organs and systems.

Inhibitors of viral DNA polymerase include sodium foscarnet, an antiviral agent for external use. It has a virusostatic effect on herpes simplex viruses of the first and second types and influenza A viruses. It is active against oncogenic viruses, hepatitis B virus and some retroviruses. When applied topically, the drug does not cause side effects.

Reverse transcriptase inhibitors

Reverse transcriptase is an enzyme involved in the reproduction of viruses of the Retroviridae family. Reverse transcriptase (or revertase) ensures the reverse direction of the flow of genetic information - not from DNA to RNA, but, on the contrary, from RNA to DNA, which is why the family got its name (Fig. 4). Retroviruses include the human immunodeficiency virus (HIV). HIV infection is caused by two lymphotropic retroviruses, HIV-1 and HIV-2. Human immunodeficiency virus type 1, formerly called HTLV-3 or LAV, is considered the main causative agent of the disease. The late manifest stage of HIV infection is AIDS (acquired immunodeficiency syndrome). HIV infection is characterized by progressive impairment of the immune response as a result of prolonged circulation of the virus in lymphocytes, macrophages and human nervous tissue cells.

The tropism of the virus towards cells of the immune system is ensured by glycoprotein spikes built into the supercapsid. It is well known that these glycoproteins interact with CD4 receptors located on the membrane immunocompetent cells. After adsorption and penetration into the cell, HIV “undresses”, and the virion RNA is released into the cytoplasm. Retrovirus RNA does not exhibit infectious properties, but serves as a template for the synthesis of a DNA molecule using RNA-dependent DNA polymerase (reverse transcriptase, revertase), which is part of the viral particle. The synthesized double molecule of viral DNA is transported into the cell nucleus and, with the help of cellular integrases, is integrated into the DNA of the host cell. The integrated DNA molecule is transcribed by the cellular DNA-dependent RNA polymerase to produce viral RNA. Part of the RNA molecules is used to form mature virions, the other part of the viral RNA is a matrix for the synthesis of structural proteins and enzymes of daughter virions on the ribosomes of host cells. It is important that viral proteins are synthesized

are formed in the form of long polymer chains of precursor proteins, which are “cut” into individual structural proteins by viral proteases.

Rice. 4. Human immunodeficiency virus reproduction cycle

Thus, during the process of retrovirus reproduction, two virus-specific enzymes are formed (reverse transcriptase and proteases), which are the target for the action of drugs used in the treatment of HIV infection.

1. Abnormal nucleosides - reverse transcriptase inhibitors

Among the drugs used in the treatment of HIV infection, viral reverse transcriptase inhibitors have attracted much attention. As can be seen from Fig. 5, nucleoside derivatives of this group of drugs are phosphorylated when they enter an infected cell.

Non-nucleoside reverse transcriptase inhibitors Fig. 5. Mechanism of action of antiretroviral drugs

The resulting active metabolites inhibit the reverse transcriptase of virions by the principle of competitive antagonism. As a result, the formation of daughter RNA of the virus from proviral DNA is disrupted. The latter suppresses the synthesis of mRNA and viral proteins, which provides a therapeutic effect.

Nucleoside reverse transcriptase inhibitors are presented in Table 5.

Table 5

Nucleoside HIV reverse transcriptase inhibitors

A drug	Side effects	Release form
Stavudin	Cytotoxic effect, inhibition of bone marrow cells.	Capsules of 0.03 and 0.04. Powder for preparing a solution for oral administration in 260 ml bottles.
Zidovudin (Retrovir)	Inhibition of hematopoiesis, dyspepsia, central nervous system damage > allergic reactions.	Solution for infusion 0.2 in 20 ml bottles. Capsules 0.1. Oral solution, 200 ml.
Abacavir	Allergic reactions, arthralgia, myalgia, edema, lymphadenopathy, dyspepsia	Film-coated tablets 0.3. Oral solution in 240 ml bottles.
Didanosin	Dyspeptic symptoms, pancreatitis, central nervous system lesions, suppression of hematopoiesis.	Tablets for chewing or preparing a suspension for oral administration, 0.1. Capsules of 0.25 and 0.4.
Lamivudin	Dyspeptic symptoms, headache.	Film-coated tablets 0.15. Oral solution in 240 ml bottles.

Representatives of the first generation, stavudine and zidovudine, have low selectivity of action against viral enzymes and inhibit DNA polymerases of human cells. As a result, the synthesis of myochondrial DNA of human cells is inhibited, which leads to damage to almost all organ systems. Thus, stavudine and zidovudine are characterized by suppression of hematopoiesis and the development of leukopenia, thrombocytopenia and anemia. Pancytopenia and bone marrow hypoplasia are possible. From the digestive system, anorexia, taste perversion, abdominal pain, diarrhea, hepatomegaly, fatty liver, increased levels of bilirubin and liver transaminases are possible. Damage to the central nervous system is manifested by depression and seizures.

Pamivudine has a highly selective effect on viral reverse transcriptase. The drug does not inhibit bone marrow cells and has a less pronounced cytotoxic effect. In addition, lamivudine is characterized by high bioavailability (80-88%) and is active against HIV strains resistant to zidovudine. Lamivudine is used to treat viral hepatitis B.

2. Non-nucleoside reverse transcriptase inhibitors

Non-nucleoside inhibitors of HIV reverse transcriptase are not phosphorylated in host cells and non-competitively inhibit the RNA-dependent DNA polymerase of virions due to direct interaction with the catalytic center of the enzyme (see Fig. 5).

Protease inhibitors

Inhibitors of viral proteases inhibit HIV proteases by the principle of competitive antagonism. As a result, viral enzymes lose the ability to cleave the precursor polyproteins necessary for viral replication. This leads to the formation of inactive viral particles. HIV protease inhibitors include the drugs listed in Table 6.

Unfortunately, available antiviral drugs do not radically cure patients, but only delay the development of the disease. Therefore, the most effective use of antiretroviral drugs is in the first 6-8 months from the onset of the disease. It is advisable to combine protease inhibitors with nucleoside and/or non-nucleoside HIV reverse transcriptase inhibitors. Preparations of endogenous and exogenous interferon have proven their effectiveness in complex treatment of AIDS.

V. Viral maturation inhibitors

A prominent representative of this group of products is metisazon. Metisazone inhibits the assembly of virions because it blocks the synthesis of the viral structural protein. The drug is active against smallpox viruses and is used for the prevention smallpox, as well as to reduce complications of smallpox vaccination. Since smallpox is now rare, the drug is almost never used. At the same time, mestiza - 493 -

zones is of interest due to its special mechanism of action and pronounced antiviral activity. It is possible that new highly effective antiviral agents will be synthesized based on metisazone, and it will become the founder of a new group of drugs. This is all the more interesting because there is data on the effectiveness of the drug in the treatment of recurrent genital herpes. The drug is well tolerated and administered orally.

VI. Interferons and interferon inducers

Interferon preparations are widely used for the treatment and prevention of viral infections. Interferons were discovered relatively recently. In 1957, Isaacs and Lindenmann discovered that cells infected with the influenza virus began to produce and secrete environment a special protein that prevents the proliferation of viruses. Subsequently, this protein was named interferon (Latin inter - between, death + ferre - to bear). The following definition is currently generally accepted:

Interferons are low molecular weight proteins of the cytokine group, synthesized by human cells in the process of a protective reaction to foreign agents.

Interferons (IFNs) have a pronounced species specificity and are one of the most important factors in the body’s defense during a primary viral infection. Not only viruses, but also bacteria, mitogenic and antigenic effects are capable of inducing IFN synthesis. More than 20 interferons are known, differing in structure and biological properties. All human cells are capable of synthesizing interferons, but their main source is immune cells. Therefore, there are three main types of interferons:

1. a-interferon (leukocyte) - produced by leukocytes;

2. f)-interferon (fibroblastic) - produced by fibroblasts;

3. γ-interferon (lymphocytic or immune) - synthesized by lymphocytes.

Based on their functional activity, interferons are divided into two types. Type I includes α-IFN and β-IFN.

IFN-a is intended for free circulation and protection of organs distant from the sites of pathogen penetration.

IFN-R acts locally, preventing the spread of the virus from the sites of its introduction.

This group of glycoproteins are characterized by pronounced antiviral activity.

The mechanism of action of interferons includes the following points:

1. Suppression of transcription of viral proteins.

2. Inhibition of translation of viral proteins.

3. Suppression of protein metabolism.

4. Disruption of assembly and maturation of the viral particle.

An important property of interferons is their ability to activate in human cells the synthesis of protective enzymes that block the replication of viral DNA and RNA. The complex mechanism of action provides interferons with a wide range of antiviral activity. Moreover, it is believed that resistance to interferon does not arise in viruses. The immunomodulatory activity of interferons enhances their antiviral effect, and this effect is most pronounced in the representative of type II interferons - IFN-γ.

All interferons, along with an antiviral effect, have antitumor and immunomodulatory effects. The spectrum of pharmacological activity of IFN determines the main indications for their use: complex therapy of infectious diseases, oncological pathology, immunodeficiencies of various origins and other conditions accompanied by a decrease in the production of interferon by the cells of the macroorganism. A pronounced suppression of interferonogenesis is also characteristic of chronic viral infections. In addition, studies have found that in children and older people, especially in the cold season, interferon is formed more slowly and in smaller quantities. There are two ways to increase the concentration of interferons in the body:

1. Administration of exogenous interferon preparations (IFN itself).

2. Administration of interferon synthesis inducers (endogenous interferon preparations).

Alpha-interferon preparations are mainly used as antiviral agents. At the same time, all three types of human interferons have now been obtained by genetic engineering. Preparations of recombinant and natural interferons include:

1. Interferon alpha - 2b;

2. Interferon beta - 1a;

3. Interferon - lb;

4. Combination drugs containing several IFNs;

5. Complex preparations, including, along with IFN, cytokines and other biologically active substances.

To treat viral infections, the interferon-based medications listed in Table 8 are used. Exogenous interferon preparations are widely used for the treatment and prevention of influenza. IFN is successfully used in the complex therapy of herpetic infections, viral hepatitis and AIDS. Note that interferon therapy is not without its drawbacks. So parenteral administration IFN drugs for severe viral infections lead to serious side effects. In addition, interferons are not widely available for widespread use in practical medicine, since they are poorly represented on the pharmaceutical market in Russia, and the cost of such drugs is very high.

Table 8

Interferon preparations

X"	A drug	Release form
1.	Alphainterferon (interlock, CHLI)	Ampoules and vials of 2 ml in dry form (activity 1000 MR, 4 doses)
2.	Viferon	Ointment
3.	Grippferon	A bottle containing 5 or 10 ml of recombinant IFN a-2b with an activity of at least 10,000 IU/ml.
4.	Reaferon (real-diron)	Ampoules with lyophilized powder containing 0.5; 1; 3; 5 million ME.
5.	Human Leukocyte IFN for Injection	Ampoules with lyophilized powder for injection (a-IFN mixture, activity 0.1, 0.25, 0.5 or 1 million IU).
6.	Intron-A	Vials with lyophilized powder for injection containing 1, 3, 5, 10 and 30 million IU of human recombinant IFN a-2b Ointment containing 5 million IU per 1 g.

An alternative to interferon therapy are interferon inducers.

Interferon inducers are substances of natural and synthetic origin that cause the production of endogenous IFN in the cells of the macroorganism. Despite the variety of interferon inducers, their pharmacological activity is largely due to the effects of IFN:

1) Induction of interferon synthesis;

2) Immunomodulatory effect;

3) Stimulation of nonspecific defense mechanisms of the body;

4) Antiviral effect.

Endogenous interferon preparations or interferon inducers include the following medicinal substances:

I. Preparations of natural origin:

Aktipol, Arbidol-lens, Poludan, Amiksil.

II. Preparations of synthetic origin:

Copaxone-teva, Isoprinosine, Galavit, Gepon, Derinat, Immunomax, Lykopid, Polyoxidonium, Decaris.

III. Herbal medicines:

Echinocea hexa l (immunal, immunorm,)

Herbal remedies of combined composition: Original Bittner balm, Sinupret, Tonsilgon.

Due to similar immunopharmacological mechanisms of action, interferon inducers have common indications for use with IFN. Endogenous interferon preparations are prescribed for the treatment and prevention of viral infections. In addition, IFN inducers are used in complex therapy of infectious diseases of other etiologies and for the correction of weakened immunity (including immunodeficiency states).

Pharmacotherapy of viral hepatitis occupies a special place. Thus, the number of carriers of viral hepatitis in the world exceeds 1 billion. Considering the large social significance of this infectious disease, a few words about modern chemotherapy drugs used to treat viral hepatitis. Viral hepatitis is a group of polyetiological anthroponotic liver lesions with different mechanisms and routes of pathogen transmission. For the first time, it was the outstanding Russian physician S.P. Botkin (1888) who proposed separating infectious hepatitis from other liver lesions. Currently, 8 types of viral pathogens have been isolated and studied.

th hepatitis. The viruses presented in Table 9 are the most fully characterized.

Table 9

Viral hepatitis

Viral	Pathogen	Transmission path	Forecast
Hepatitis A (Botkin's disease)	RNA-containing virus of the genus Hepatovirus family. Picornaviridae.	Fecal oral.	Good
Hepatitis B	DNA-containing virus of the genus Orthohepadnavirus family. Hepadnaviridae.		Cirrhosis and primary liver carcinoma.
Hepatitis D (delta hepatitis)	Defective RNA-containing virus of the genus Deltavirus family. Togaviridae.	Transfusion, sexual and transplacental.	Depends on the course of viral hepatitis B.
Hepatitis C	RNA virus of the genus Flaviridae family. Flaviridae	Mainly parenteral.	Cirrhosis and primary liver carcinoma
Hepatitis E	RNA-containing virus of the genus Calicivirus family. Caliciviridae..	Fecal oral.	Good

Over the past 30 years, the main principle of treatment of viral hepatitis has been intensive and long-term interferon therapy. Its effect is expressed in reducing intoxication, the number and severity of complications and neutralizing the causative virus. In some cases, interferon inducers are prescribed. At the present stage, therapy

viral hepatitis includes the prescription of such etiotropic drugs as vidarabine, pamivudine and ribavirin (see earlier). An important part of the complex therapy of viral hepatitis is symptomatic treatment. In general, rational pharmacotherapy of viral hepatitis remains a challenge. Therefore, the possibilities of immunoprophylaxis of the disease attract great attention.

And in conclusion, a few words about other treatment options for the most common viral infections. Thus, in the treatment of various forms of herpes infection, almost all known interferon inducers of local and systemic action are used. For example, for herpes infection, gpicyrrhizic acid (epigen intim) is used. Glycyrrhizic acid stimulates the formation of IFN and interacts with the structures of the virus, changing the phases of the viral cycle. The drug improves tissue regeneration and has anti-inflammatory and analgesic effects. Glycyrrhizic acid is active against DNA and RNA viruses, including herpes simplex viruses, herpes zoster viruses, human papillomaviruses and cytomegaloviruses. The drug is well tolerated.

Currently, the Allopharm company has developed and introduced into production the innovative drug allomedine. The main active component of the new drug is the peptide alloferon-3. Preclinical studies have established that active substances - peptides from the group of allostatins - increase the body's antiviral and antitumor immunity. Clinical trials have shown that the use of alloferons for recurrent herpes increases the relapse-free period to six months or more. The use of the drug at the onset of the disease eliminates unpleasant symptoms within a few hours and stops herpetic eruptions. Let us add that allomedine is also indicated for the treatment of viral papilloma. The drug is available in the form of Allomedin gel.

It is worth mentioning the domestic drug antigrippin (ZAO Antiviral, St. Petersburg, Russia), which is a balanced mixture of acetylsalicylic acid, ascorbic acid, rutin, metamizole, diphenhydramine, potassium gluconate. For influenza and ARVI with therapeutic and for preventive purposes adaptogens are widely used - general strengthening agents of plant origin (ginseng preparations, eleutherococcus, Chinese lemongrass, zamaniha, aralia, rhodiola, echinacea, kalanchoe). To treat influenza caused by viruses type A and B, synthetic

a biological drug from the class of bicyclotenes, deityforin. As a therapeutic and prophylactic agent for influenza A and B, adapromine is used - 0.2 g 1 time per day for 4 days, for emergency prevention in the outbreak 0.1 g 1 time per day for 5-10 days.

For respiratory infections, immunomodulators are widely used: ribomunil, broncho-muchal, IRS-19, chmudon, etc. They increase the concentration of IFN-γ and interleukin-2 (IL-2), which contributes to the development of a more stable immune response. The development of the disease can be prevented by the intranasal use of interferon preparations such as Alfainterferon (interlock, CLI), Viferon, Grippferon and Reaferon (realdiron). No side effects were identified with topical application of IFN. A separate group of anti-influenza drugs consists of homeopathic remedies: aflubin, allicor, flu-hel, influcid, tonsilgon, traumeel, flu, engystol, EDAS 903 granules, EDAS 131 drops, nazentropfen S, “AGRI” for adults and children.

Pleconaril, recently developed in the USA, is a promising antiviral drug. In vitro studies and animal experiments have revealed its activity against enteroviruses and rhinoviruses. Data from the first placebo-controlled studies indicate the effectiveness of the drug against respiratory infections and enteroviral meningitis.

Despite a fairly extensive list of drugs, viral diseases remain poorly controlled infections. This is due to the lack radical ways therapy and the development of viral resistance. The maximum effectiveness of antiviral therapy is achieved with a complex nature of treatment.

Name drug	Average therapeutic doses and concentrations for adults; Routes of drug administration	Forms
Idoxuridine	Into the cavity conjunctiva 2 drops of 0.1% solution	0.1% solution
Oksolin	Into the conjunctival cavity 1 - 2 drops of 0.1 - 0.2% solution, 0.25% ointment; for lubrication nasal mucosa 0.25 - 0.5% ointment; externally 1 - 3% ointment	Powder; 0.25%; 0.5%; 1%; 2% and 3% ointment
Acyclovir	Orally 0.2 g; intravenously 5-10 mg/kg; cutaneous 5% ointment	Tablets 0.2 g; 5% ointment in tubes of 5 g; 3% eye ointment in tubes of 4.5 or 5 g; in bottles of 0.25 g
Ganciclovir	Intravenous infusion 0.005-0.006 g/kg	Lyophilized powder in bottles of 0.546 g of ganciclovir sodium (corresponds to 0.5 g ganciclovir base)
Ribavirin	Orally 0.2 g	Tablets 0.2 g
Zidovudine	Orally 0.1-0.2 g	Capsules 0.1 g
Arbidol	Orally 0.1-0.2 g	Tablets 0.025; 0.05 and 0.1 g
Amiksin	Orally 0.125-0.25 g	Tablets 0.125 g