The mechanism of action of antiviral. The most effective antiviral drugs. Side effects of antiviral drugs

In the fall, 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.

For the treatment of viral diseases, drugs of various actions are used, therapy is carried out in three directions:

Etiotropic - that is, aimed at eliminating the causative agent of the disease - a virus.
Pathogenetic - there is an effect on the mechanism of development and the course of the disease.
Symptomatic - symptoms and manifestations of the disease are eliminated

Below is a review of etiotropic drugs and the classification of antiviral agents.

How are antiviral drugs classified?

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

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

The mechanism of action for ARVI drugs of each group is different, it is important to know the features in order to choose and use the remedy correctly.

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

To help the body cope with it faster, ease the course of the disease and speed up recovery, the researchers tried to introduce 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 designed to prepare a solution by combining it with chilled boiled water. They begin to take this remedy when there is a threat of infection with a virus - with inevitable contact with an already infected person, or before visiting public places with a large crowd of people.

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

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

This dosage is prophylactic and has no therapeutic effect if virus infection has occurred. At the first symptoms of influenza, the dose should be increased: five drops of the drug are injected into each nasal passage at intervals of 1-2 hours, but not less than five times a day. The duration of the 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 about 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 combined preparation, which includes recombined human alpha-interferon and auxiliary components. It is also suitable for the treatment and prevention of ARVI, influenza and other diseases caused by viruses. It is administered nasally, three drops every 3-4 hours.

Such drugs cannot be used during pregnancy and with individual intolerance to any of the components.

The main active ingredient of this agent 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, and also protect against infection during an epidemic.

Tiloron - Amiksin, Lavomax

This agent is a typical representative of antiviral drugs.

Tiloron's regimen is as follows:

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

Tiloron is not prescribed during gestation and feeding of a child, with hypersensitivity to the components of the drug. Side effects include nausea, a temporary increase in body temperature, very rarely, urticaria and other allergic reactions.

Umifenovir - Arbidol, Arpeflu, Arbivir, Immustat

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 acute respiratory viral infections, the drug is taken at 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 drug is taken at 0.2 mg four times a day for at least 3 days.

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

Cyclic amine rimantadine - Rimantadine-KR, Rimavir

The mechanism of action of this substance is as follows: it penetrates the cells of viruses through their envelopes and destroys them, thus suppressing the reproduction of microorganisms. The drug is available in the form of tablets or powder in sachets for a single dose.

They take it according to a special scheme:

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

For prophylactic 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, renal and hepatic failure in severe form.

Neuraminidase inhibitors - Zanamivir, Relenza

The 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 cross the cell membrane, after a while it dies inside the cell.

With treatment with neuraminidase inhibitors, the disease progresses more easily and passes faster. But it should be borne in mind that these drugs have quite serious contraindications and side effects. The most difficult of them:

Hallucinations.
Disorders of consciousness.
Psychoses.

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

For prophylactic purposes, two inhalations are done once a day for 1-4 weeks.

Antiviral phytopreparations - Flavazid, Proteflazid, Altabor, Immunoflazid

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

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

Altabor can cause allergic reactions; it is not taken in case of hypersensitivity to active ingredients. Official studies on the effect of the drug on reproductive capacity and fetal development have not been carried out, therefore this drug is not recommended during gestation and lactation.

Immunoflazid, Proteflazid and Flavazid almost do not differ in their composition, the mechanism of action of these three drugs is the same. The main components of these medicines are:

Sod pike liquid extract;
Ground reed grass liquid extract.

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

Immunoflazid is produced in the form of a syrup. Adults should take it 9 ml twice a day for 5-14 days if the infection has already occurred. For the prevention of virus infection, syrup is taken 4.5 ml once a day. The course of preventive treatment can last up to one month.

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

The first seven days - 7 drops twice per knock.
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 antiviral agents

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

Inosine pranobanks - Groprinosine, Inosine, Novirin

These drugs are able to 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 makeup of viruses is disrupted and they die.

These funds are produced in the form of tablets. 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 broken down into 3-4 doses. You can not take more than 4 grams per day. drug. In acute influenza and other acute respiratory viral infections, the duration of the course 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 effects of pranobanks inosine tablets are increased levels of uric acid in the blood and urine. No symptomatic treatment is required in this case. The uric acid level returns to normal on its own as soon as the drug is stopped.

Possible side effects when taking Inosine:

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

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

Engystol

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

At the initial stage of the disease, 1 tablet every 15 minutes for two hours;
Further, 1 tablet three times a day;
For prophylaxis, the drug is taken 1 tablet twice a day. Duration of admission is from 14 to 21 days.

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

Sagrippin homeopathic 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. So, according to the World Health Organization (WHO), the number of SARS cases per year reaches 1.5 billion cases (and this is every third inhabitant of the planet), which is 75% of infectious pathology in the world, and during epidemics - about 90% of all cases. The latter leads to the fact that it is this pathology that occupies the first place in the structure of the causes of high morbidity and temporary disability.

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

In Ukraine, about 10-14 million people annually suffer from influenza and ARVI, which is 25-30% of the total morbidity, 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.

So, in June 2007 in Toronto (Canada), the VI World Symposium "Option for the control of Influenza VI" considered 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 the exchange of information on the prevention of an influenza pandemic). This forum was held within the framework of traditional worldwide anti-influenza events, the last twenty years have been held 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 participants of the symposium was as follows:

The world is on the verge of another flu pandemic.
Each 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 amount 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, in the indicated directions, activities began to be carried out and information was accumulated, which made it necessary to carry out the appropriate necessary organizational and preventive measures at the global and national levels. One of the leading directions in this case is active educational work among various specialties of medical workers in pharmaco-therapeutic and preventive measures. The latter would avoid unnecessary hype around this problem, especially with regard to information on efficacy and safety.

Properties of antiviral drugs

In this regard, there is a need to once again turn to the questions of the main clinical and pharmacological properties of antiviral drugs.

Today, there are a limited number of antiviral drugs with proven clinical efficacy, namely:

Antiherpetic;
Protitomegalovirus;
Anti-influenza;
Against HIV infection;
Antiviral drugs that have an extended spectrum of activity.

Another point that is difficult in the treatment of antiviral drugs is the ability of viruses to mutate. Accordingly, the sensitivity of the altered virus to certain drugs decreases, as does the effectiveness of pharmacotherapy. Elucidation of the features of the process of viral reproduction, their structure and differences in 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 composition of the envelope of the influenza virus includes the proteins hemagglutinin (H) and neuraminidase (N) due to which the virus binds to the target cell and the destruction of sialic acids upon exiting 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 a similar offspring. In a generalized form, viral replication at the level of a single cell consists of several successive stages of the multiplication cycle. First, the virus attaches to the surface of the cell, then penetrates through its outer membranes. Already in the host cell, the virion is undressed 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 tissue or organ level, the reproduction cycles are often asynchronous, and the virus enters healthy cells from the affected cells. Reproduction of the virus in the cell lasts about 6-8 hours and is characterized by an increase in the number of virions exponentially, when up to 10,000 new ones are formed from one virus. This process extends to a significant number of host cells, is accompanied by inhibition of their metabolism and biological functions, and manifests itself in the corresponding pathological symptoms.

A significant obstacle to the effective treatment of a viral infection is that the replication of viruses largely occurs in the manifestation of the symptoms of the disease, the course of this pathological process is complicated against the background of 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 viral replication. The earlier the treatment begins, the more positive its consequences.

On this basis, the fundamental division of modern antiviral drugs used for the treatment of influenza by the mechanism of action into the following groups is based:

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

Antiviral medicines that affect the virus

The first group includes preparations of amantadine, rimantadine, zanamivir, oseltamivir, arbidol, amizone 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. Inhibition of neuraminidase inhibits the release of virions from infected cells, increases their aggregation on the cell surface and slows down the spread of the virus in the body. Under the influence of neuraminidase inhibitors, the resistance of viruses to the harmful effects of the 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, there is no fusion of the lipid viral envelope with the cell membrane and endosome membranes in the early stages of virus reproduction. Arbidol tends to penetrate unchanged into infected and uninfected cells of the human body, localized in the cytoplasm and nucleus of the cell. In addition to the direct effect on the virus, arbidol also has antioxidant, immunomodulatory, interferonogenic effects.

The 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 into the host cell is disrupted and ribonucleoprotein is not released. Also, these drugs act at the stage of assembly of virions, it is possible that due to changes in hemagglutinin processing.

The drug, the active ingredient of which 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 cells affected by the virus, slows down the synthesis of viral i-RNA (violation of transcription and translation) and leads to inhibition of the replication of RNA and DNA-genomic viruses. Also, the drug is characterized by the induction of interferon production. The immunomodulatory properties of the antiviral drug are due to the drug's ability to enhance the differentiation of T-lymphocytes, stimulate the proliferation of T- and B-lymphocytes induced by myogen, increase the functional activity of T-lymphocytes, as well as their ability to form lymphokines. The synthesis of interleukin-1, microbicidal activity, expression of membrane receptors and the ability to respond to lymphokines and hemataxic 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 treatment and for the prevention of acute and chronic viral infections. It has also been proven that the drug is able to potentiate the antiviral effect of interferon, acyclovir and other antiviral drugs.

It was found that the use of Groprinosin helps to reduce the severity of the 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 medicines that affect the immune system

The second group includes drugs that are representatives of 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 the biochemical defense mechanisms of cells that have an antiviral effect: α (more than 20 representatives), β and γ. The synthesis of interferon 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 lies in the fact that it disrupts the penetration of the viral particle into the cell, inhibits the synthesis of m-RNA and the translation of viral proteins (adenylate synthetase, protein kinase), 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 on different stages of its reproduction. For the prevention and treatment of influenza, human leukocyte interferon and interferon-alpha2-c are used.

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

Alfatron,
Laferbion,
Lipoferon,

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

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

The pandemic (California, swine flu) is not sensitive to adamantane drugs due to the S31N mutation in the M gene. For the treatment of patients with this pandemic influenza, WHO recommends the use of oseltamivir and zanamivir. Effective is the appointment of these drugs no later than 48 hours after the onset of the disease.

Side effects of antiviral drugs

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

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

In the structure of side effects of antiviral drugs that arose during the medical use of drugs that were intended to treat influenza in Ukraine, the largest number of manifestations were allergic reactions and, especially, disorders of the skin and its appendages, as well as complications from 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 (at the age of 28 days-23 months - 3.0%, 2-11 years old - 11.4%, 12-17 years old - 7 , 5%), in 78% of cases - occurred in adults: at the age of 18-30 years - 22.5%, 31-45 years old - 24.6%, 46-60 years old - 23.7%, 61-72 years - 6.0%, 73-80 years old - 1.2%, over 80 years old - 0.3%. In terms of gender characteristics, adverse reactions predominantly occurred in women (72.8%), in men - in 27.2% of cases.

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

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

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

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

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

It is an axiom that absolutely safe medicines have not been, are not and will not be. Any drug can cause adverse reactions. According to the 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 feasibility of using an antiviral drug is determined by the risk / benefit ratio. Only if the benefits outweigh the risks, the drug should be used according to the instructions for use. This is the current objective information on the safety and efficacy 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 studies of this antiviral drug, it was found that most often when it was used by adults for therapeutic purposes, there were such side effects as nausea and vomiting. Diarrhea, bronchitis, abdominal pain, dizziness, headache, cough, insomnia, weakness, nosebleeds, conjunctivitis were much less common. Patients who took Oseltamivir for the prevention of influenza experienced pain of various localization, rhinorrhea, dyspepsia, and upper respiratory tract infections.

Children were more likely to vomit. Among the side effects that were observed in less than 1% of children treated with Oseltamivir were abdominal pain, nosebleeds, hearing impairment and conjunctivitis (they appeared suddenly, stopped despite continued treatment, and in the vast majority of cases were not the reason for stopping treatment) , nausea, diarrhea, bronchial asthma (including exacerbations), acute otitis media, pneumonia, sinusitis, bronchitis, dermatitis, lymphadenopathy.

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

In patients with influenza who received Oseltamivir, isolated cases of hepatitis and an increase in the level of liver enzymes were observed; rarely there were cases of gastrointestinal bleeding, but the manifestations of hemorrhagic colitis disappeared when the course of influenza weakened or after the drug was discontinued.

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

Since 2004, regulatory agencies began to receive reports that patients with influenza (mainly children and adolescents) who took Tamiflu had seizures, delirium, behavioral changes, confusion, hallucinations, anxiety, nightmares, which rarely resulted in accidental injury or death.

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

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

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

In March 2008, the FDA (USA) added information to physicians on the neuropsychiatric disorders associated with the use of Tamiflu in patients with influenza in the "disclaimer" section.

In Ukraine, back in August 2007, in the instructions for the medical use of Tamiflu in patients with influenza, it was noted that taking it can lead to the development of psychoneurotic disorders (convulsions, delirium, including a change 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 patients with influenza who did not use this drug... Therefore, the manufacturer recommended to monitor the behavior of patients, especially children and adolescents, in whom adverse reactions from the central nervous system were most often recorded. In case of any manifestations of inappropriate behavior of the patient, you should immediately consult a doctor.

It should be emphasized that according to the WHO Center for International Monitoring of Side Effects (March 2010), only in 270 cases out of 3566 a causal relationship between the registered cases of adverse reactions and the action of Tamiflu was proved.

21. Antiviral drugs: classification, mechanism of action, use in various localizations of viral infection. Antineoplastic agents: classification, mechanisms of action, peculiarities of appointment, disadvantages, side effects.

Antiviral agents:

a) antiherpetic drugs

Systemic action - acyclovir(Zovirax), Valacyclovir (Valtrex), Famciclovir (Famvir), Ganciclovir (Cymeven), Valganciclovir (Valcite);

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 agents

HIV reverse transcriptase inhibitors

Nucleoside structure - zidovudine(retrovir), didanosine (videx), lamivudine (zeffix, epivir), stavudine (zerit);

Non-nucleoside structure - nevirapine (viramune), efavirenz (stokrin);

HIV protease inhibitors - amprenavir (agenrase), saquinavir (fortovase);

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

d) broad-spectrum antiviral agents

ribavirin(virazol, rebetol), lamivudine;

Interferon preparations

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

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

Interferon synthesis inducers - acridoneacetic acid (cycloferon), arbidol, dipyridamole (curantil), iodantipyrine, tilorone (amiksin).

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

Synthetic products

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

Derivatives of peptides- saquinavir

Adamantane derivatives- midantan, remantadine

Indolecarboxylic acid derivative -arbidol.

Phosphonoformic acid derivative- foscarnet

Thiosemicarbazone derivative- metisazon

Biological substances produced by 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 the synthesis of nucleic acids

In recent years,antiretroviral drugs,which include reverse transcriptase inhibitors and protease inhibitors. The increased interest in this group of substances is associated with their

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

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

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

One of the antiretroviral compounds is the nucleoside derivative azidothymidine

dubbed 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 inhibits 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). Part of zidovudine is excreted unchanged by the kidneys

Zidovudine should be started as early as possible. Its therapeutic effect is manifested 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 borne in mind that retrovirus resistance is developing to it.

Of the side effects in the first place are hematological disorders: anemia, neutropenia, thrombocytopenia, pancythemia. Headache, insomnia, myalgia, and suppression of renal function are possible.

TOnon-nucleoside antiretroviral drugsinclude nevirapine (viramune), delavirdine (rescriptor), efavirenz (sustiva). They have a direct, noncompetitive inhibitory effect on reverse transcriptase. They bind to this enzyme at a different location than nucleoside compounds.

Of the side effects, skin rash most often occurs, the level of transaminase rises.

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

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

In cells, acyclovir is phosphorylated. In infected cells, it acts as triphosphate 2, disrupting the growth of viral DNA. In addition, it has a direct inhibitory effect on the DNA polymerase of the virus, 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%. Plasma proteins bind 12-15% of the substance. Quite satisfactorily passes through the blood-brain barrier.

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 reproduction of retroviruses. Most of the substance binds to plasma proteins. The drug is administered orally. Side effects are noted for dyspeptic disorders, increased activity of hepatic transaminases. , lipid metabolism disorders, hyperglycemia Possible development of viral resistance to saquinavir.

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 topically. When applied topically, there may be a slight irritant effect. With intravenous administration of acyclovir, renal dysfunction, encephalopathy, phlebitis, and skin rash sometimes occur. With enteral administration, nausea, vomiting, diarrhea, and headache are noted.

New antiherpetic drug valacyclovir

It is a prodrug; when it first passes through the intestines and liver, acyclovir is released, which provides an antiherpetic effect.

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

Vidarabine is also an effective drug.

Penetrating into the cell, vidarabine is phosphorylated. Inhibits viral DNA polymerase. This suppresses the replication of large DNA-containing viruses. In the body, it partially turns into arabinoside, which is less active against viruses, hypoxanthine.

Vidarbin is successfully used for herpes encephalitis (administered by intravenous infusion), reducing mortality in this disease by 30-75%. It is sometimes used for complicated shingles. Effective for herpetic keratoconjunctivitis (prescribed topically in ointments). In the latter case, it causes less irritation and less inhibits corneal healing than idoxuridine (see below). Easily penetrates 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 dyspeptic symptoms (nausea, vomiting, diarrhea), skin rash, disorders of the central nervous system (hallucinations, psychosis, tremors, etc.), thrombophlebitis at the injection site.

Trifluridine and idoxuridine are used topically.

Trifluridine is a fluorinated pyrimidine nucleoside. Inhibits DNA synthesis. It is used for primary keratoconjunctivitis and recurrent epithelial keratitis caused by the herpes simplex virus (type1 and 2). A solution of trifluridine is applied topically to the mucous membrane of the eye. A transient irritant effect, swelling of the eyelids is possible.

Idoxuridine (kerecid, iduridin, ophthalmicIDU), which is an analogue of thi-midine, is incorporated into the DNA molecule. In this regard, it inhibits the replication of certain DNA-containing viruses. Idoxuridine is used topically for herpes eye infections (keratitis). May cause irritation, swelling of the eyelids. It is of little use for resorptive action, since the toxicity of the drug is significant (it suppresses leukopoiesis).

Atcytomegalovirus infectionuse ganciclovir and foscarnet. Gan-cyclovir (cymevene) is a synthetic analogue of 2'-deoxyguanosine nucleoside. The mechanism of action is similar to acyclovir. It 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 dysfunctions of various organs and systems. So, 20-40% of patients have granulocytopenia, thrombocytopenia. Adverse neurological effects are frequent: headache, acute psychosis, convulsions, etc. Development of anemia, skin allergic reactions, hepatotoxic effects are possible. In experiments on animals, its mutagenic and teratogenic effects have been established.

A number of drugs are effective as anti-influenza drugs. Antiviral drugs effective for influenza infection can be represented by the following groups./. Inhibitors of viral protein M2Remantadine Midantan (amantadine)

2. Inhibitors of the viral enzyme neuraminidaseZanamivir

Oseltamivir

3. Inhibitors of viral RNA polymeraseRibavirin

4. Various drugsArbidol Oxolin

The first group refers toinhibitors of the M2 protein.The membrane protein M2, which functions as an ion channel, is found only in the type A influenza virus. 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, replication of the virus 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 influenza type A. As a remedy, it is ineffective. More commonly, midanthan is used as an antiparkinsonian agent.

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

Viral resistance is rapidly developing to both drugs.

The second group of drugsinhibits the viral enzyme neuraminidase,which is a glycoprotein formed on the surface of influenza A and B viruses. This enzyme facilitates the entry of the virus to target cells in the respiratory tract. Specific neuraminidase inhibitors (competitive, reversible action) prevent the spread of the virus associated with infected cells. Replication of the virus is disrupted.

One of the inhibitors of this enzyme is zanamivir (relenza). It is used intranasally or by inhalation

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

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

It is effective for influenza type A and B, severe respiratory syncytial viral infection (administered by inhalation), hemorrhagic fever with renal syndrome and for weasel fever (intravenously). Side effects include skin rash, conjunctivi

Amongdifferent drugsrefers to the arb idol. It is an indole derivative. It is used for the prevention and treatment of influenza caused by influenza A and B viruses, as well as in acute respiratory viral infections. According to available data, arbidol, in addition to a moderate antiviral effect, has interferonogenic activity. In addition, it stimulates cellular and humoral immunity. The drug is injected inside. It is 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. At the same time, for antiviral therapy, they also usebiogenic substances,especially interferon s.

Interferons are used to prevent viral infections. This is a group of compounds related to low molecular weight glycoproteins, produced by the cells of the body when 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 the infection. They increase the resistance of cells to attack by viruses. They are characterized by a wide antiviral spectrum.

A more or less pronounced efficacy of interferons was noted for herpetic keratitis, herpetic lesions of the skin and genitals, acute respiratory viral infections, with shingles, viral hepatitis B and C, and AIDS. Interferons are used locally and parenterally (intravenously, intramuscularly, subcutaneously).

Side effects include fever, the development of erythema and soreness at the injection site, and progressive fatigue is noted. In large doses, interferons can inhibit hematopoiesis (granulocytopenia and thrombocytopenia develop).

In addition to antiviral action, interferons have anti-cellular, antitumor and immunomodulatory activities.

Antineoplastic agents: classification

Alkylating agents - benzotef, mielosan, thiophosphamide, cyclophosphamide, cisplatin;

Folic acid antimetabolites - methotrexate;

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

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

Antineoplastic antibiotics - dactinomycin, doxorubicin, epirubicin;

Monoclonal antibodies to tumor cell antigens - alemtuzumab (campas), bevacizumab (avastin);

Hormonal and anti-hormonal agents - finasteride (proscar), cyproterone acetate (androcur), goserelin (zoladex), tamoxifen (nolvadex).

ALKYLATING AGENTS

The following point of view exists regarding the mechanisms of interaction of alkylating agents with cellular structures. Chloroethyl amines as an example(a)it was shown that in solutions and biological fluids they split off chlorine ions. In this case, an electrophilic carbonium ion is formed, which transforms into ethyleneimonium(v).

The latter also forms a functionally active carbonium ion (g), interacting, according to the available concepts, with the nucleophilic structures of 2 DNA (with guanine, phosphate, aminosulfhydryl groups -

Thus, the alkylation of the substrate occurs

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

Most of

used mainly for hematological malignancies (chronic leukemia, lymphogranulomatosis (Hodgkin's disease), lymph and reticulosarcomas

Sarcolysin (racemelfolan), active in myeoloma disease, lymph and reticulosarcomas, is effective in a number of true tumors

ANTIMETABOLITES

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

Folic acid antagonists

Methotrexate (ametopterin)Purine antagonists

Mercaptopurine (leupurine, purinethol)Pyrimidine antagonists

Fluorouracil (fluorouracil)

Ftorafur (tegafur)

Cytarabine (cytosar)

Fludarabine Phosphate (Fludar)

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

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

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

Drugs are usually taken by mouth. Methotrexate is also available for parenteral administration.

Methotrexate is excreted by the kidneys, mainly unchanged. Part 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. In a number of patients, liver dysfunction is observed. Methotrexate affects the mucous membrane of the gastrointestinal tract, causing conjunctivitis.

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

ANTIBIOTICS WITH ANTITUMOR 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 chorionepithelioma of the uterus, Wilms' tumor in children, with lymphogranulomatosis (Fig. 34.2). The drug is administered intravenously, as well as in the body cavity (if there is exudate in them).

The antibiotic olivomycin, produced byActinomycesolivoreticuli. In medical practice, its sodium salt is used. The drug causes some improvement in testicular tumor - seminoma, embryonic 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 (formedStreptomycespeuceticusvarcaesius) and karma and nom and qing (producerActinoma- duracarminatasp. nov.) - attract attention due to their effectiveness in sarcomas of mesenchymal origin. So, doxorubicin (adriamycin) is used for osteosarcomas, breast cancer and other neoplastic diseases.

With the use of these antibiotics, there are impaired appetite, stomatitis, nausea, vomiting, diarrhea. Damage to the mucous membranes by yeast-like fungi is possible. Hematopoiesis is inhibited. Sometimes there is a cardiotoxic effect. Hair loss is not uncommon. These drugs also have irritating properties. One should also take into account their pronounced immunosuppressive effect.

and autumn crocus

VincaroseaL.)

The toxic effect of vincristine is manifested in different ways. With practically little suppression of hematopoiesis, it can lead to neurological disorders (ataxia, impaired neuromuscular transmission, neuromuscular gia, paresthesia), kidney damage (polyuria, dysuria), etc.

Androgens

Estrogens

Corticosteroids

In terms of the mechanism of action on hormone-dependent tumors, hormonal drugs differ significantly from the cytotoxic drugs discussed above. So, 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, there is a restoration of the disturbed humoral regulation of cell function.

Androgens5

PLANT PRODUCTS WITH ANTITUMOR ACTIVITY

Kolchamine, an alkaloid of the colchicum of the magnificent

and autumn crocus

Kolkhamin (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, edema, pain) may occur, which forces you to take breaks in treatment. After the rejection of necrotic masses, wound healing occurs with a good cosmetic effect.

With a resorptive action, kolchamin rather strongly inhibits hematopoiesis, causes diarrhea, hair loss.

Antitumor activity was also found in the alkaloids of the pink periwinkle plant (VincaroseaL.) vinblastine and vincristine. They have an antimitotic effect and, like kolchamin, block mitosis in the metaphase stage.

Vinblastine (rosevin) is recommended for generalized forms of lymphogranulomatosis and for chorionepithelioma. In addition, it, like vincristine, is widely used in combination chemotherapy of neoplastic 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 irritant effect and can cause phlebitis.

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

HORMONAL DRUGS AND HORMONE ANTAGONISTS USED IN TUMOR DISEASES

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

Androgens- testosterone propionate, testenate, etc.;

Estrogens- sinestrol, fosfestrol, ethinylestradiol, etc.;

Corticosteroids- prednisolone, dexamethasone, triamninolone.

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

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

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

CYTOKINES

ENZYMS EFFECTIVE IN TREATMENT OF TUMOR DISEASES

It was found that a number of tumor cells do not synthesizeL-asparagine, which is essential for the synthesis of DNA and RNA. In this regard, it became possible to artificially limit the intake of this amino acid into tumors. The latter is achieved by the introduction of an enzymeL-asparaginase, which is used in the treatment of acute lymphoblastic leukemia. The remission lasts several months. Of the side effects, violations of the liver function, inhibition of fibrinogen synthesis, and allergic reactions were noted.

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 (with chronic myeloid leukemia, Ka sarcoma

poshi, etc.). The drug is administered parenterally. Side effects include fever, headache, myalgia, arthralgia, dyspeptic symptoms, inhibition 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, determined 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 preparation 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.

Most common side effects of antiviral drugs

The use of antiviral drugs for diabetes

Can antiviral medication be combined with alcohol?

The 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

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

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

What are antiviral drugs?

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

Viruses are nothing more than genetic information ( short chain nitrogenous bases) in a shell of fats and proteins. Their structure is simplified as much as possible, they do not have a nucleus, enzymes, energy supply elements, which makes them different from bacteria. That is why they are microscopic in size, and their existence has been hidden from science for many years. For the first time, the existence of viruses passing through bacterial filters was 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. Also, there are no antiviral drugs that could be used in the case of various viral infections, most of the existing drugs are narrowly targeted for the treatment of one, maximum of two diseases. This is due to the fact that viruses are very diverse, various enzymes and defense mechanisms are encoded in their genetic material.

The history of the creation of antiviral drugs

The creation of the first antiviral drugs falls on 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 fight the herpes virus. Their effectiveness was sufficient, however, a large number of side effects almost completely excluded the possibility of its use in the treatment of herpes. In the 60s, amantadine and rimantadine were obtained, drugs that are still used today.

Until the beginning of the 90s, all drugs were obtained empirically, using observations. Efficiency ( mechanism of action) of these medicines was difficult to prove due to the lack of necessary knowledge. Only in recent decades have scientists received more complete data on the structure of the virus, on their genetic material, as a result of which it became possible to produce more effective drugs. However, even today, many drugs remain with clinically unconfirmed efficacy, 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 use it as a medicine, after which scientists obtained methods for purifying it from donated blood. Of all antiviral drugs, only interferon and its derivatives can claim to be broad-spectrum drugs.

In recent years, the use of natural drugs for the treatment of viral diseases has become popular ( eg echinacea). Also today, the use of various immunomodulatory drugs is popular, which provide prophylaxis against viral diseases. 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 for this disease. Unfortunately, the required medicine has not yet been found.

Production of antiviral drugs. The basis of antiviral drugs

There are a wide variety of antiviral drugs, but they all have disadvantages. This is partly due to the complexity of drug development, manufacturing and testing. 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. It is also quite difficult to distinguish them. Unlike viruses, bacteria are cultivated on nutrient media, and by the slowdown in their growth, one can judge the effectiveness of antibacterial drugs.

To date, antiviral drugs are obtained in the following ways:

Chemical synthesis. The standard manufacturing method for drugs is to produce drugs through chemical reactions.
Obtaining from vegetable raw materials. Some parts of plants, as well as their extracts, have antiviral effect, which is used by pharmacists in the production of medicines.
Obtaining from donated blood. These methods were relevant several decades ago, today they are practically abandoned. They were used to obtain interferon. Only a few milligrams of interferon could be obtained from 1 liter of donated blood.
The use of genetic engineering. This method is the latest in the pharmaceutical industry. With the help of genetic engineering, scientists change the structure of the genes of certain types of bacteria, as a result of which they produce the necessary chemical compounds. They are further 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, both inorganic and organic substances can serve as the basis for antiviral drugs. However, in recent years, recombinant ( genetically engineered) drugs. They, as a rule, have exactly the qualities that the manufacturer implies in them, are effective, but not always available to the consumer. The price of such drugs can be very high.

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

Differences between antiviral, antifungal and antibacterial agents ( antibiotics) are in their name. All of them are created against various classes of microorganisms that cause diseases, differing from each other 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 target bacteria. Bacterial lesions include purulent lesions of the skin, mucous membranes, pneumonia, tuberculosis, syphilis, and many other diseases. Most 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 of the integument, swelling and dysfunction) and have minor differences. Diseases caused by bacteria constitute the largest group and the most thoroughly studied.

Fungal lesions occur, as a rule, with weakened immunity and mainly affect the surface of the skin, nails, hair, mucous membranes. The best example of a fungal infection is candidiasis ( thrush). For the treatment of fungal infections, only antifungal drugs should be used. 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, moderate fever). This onset is common in many viral diseases, including chickenpox, hepatitis, and even intestinal viral diseases. Viral diseases cannot be treated with antibiotics, they cannot be used even for the purpose of preventing the addition of a bacterial infection. However, it should be borne in mind that in the presence of a simultaneous viral and bacterial lesion, doctors prescribe drugs from both groups.

The listed groups of drugs are considered potent drugs and are sold only with a doctor's prescription. For the treatment of viral, bacterial or fungal diseases, you need to see 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 substances with proven effectiveness against viruses is about 100 names. Of these, only about 20 are widely used in the treatment of various diseases. Others have either a high price tag or a large number of side effects. Some of the drugs have never passed clinical trials, despite the long-term practice of use. For example, only oseltamivir and zanamivir have proven effective against influenza, despite the fact that many drugs against influenza are sold in pharmacies.

Antiviral drugs that have proven effectiveness include:

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

On the other hand, today in pharmacies you can find many analogues ( generics), due to which a hundred active ingredients of antiviral drugs are transformed 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 enhance immunity, 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 freely in pharmacies. Most of them do not have the desired healing properties, and the benefits of their use are equated by many doctors to a 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 pronounced side effects ( nephrotoxicity, hepatotoxicity, nervous system disorders, electrolyte disturbances and many others).

Can you buy antiviral drugs at the pharmacy?

Not all antiviral drugs are available over the counter. This is due to the serious effect of drugs on the human body. Their use requires permission and supervision by a physician. This applies to interferons, drugs against viral hepatitis, antiviral drugs of systemic action. To buy a prescription drug, you need a special form with the stamp of a doctor and a medical institution. In all infectious diseases hospitals, antiviral drugs are dispensed without a prescription.

However, there are various antivirals that can be purchased over the counter. So, for example, ointments against herpes ( containing acyclovir), eye and nasal drops containing interferon and many other products are available commercially. Immunomodulators and herbal antivirals are also available over the counter. They are equated, as a rule, with dietary supplements ( Dietary supplement).

According to the mechanism of action, antiviral drugs are divided into the following groups:

drugs acting on extracellular forms of the virus ( oxolin, arbidol);
drugs that prevent the penetration of the virus into the cell ( remantadine, oseltamivir);
drugs that stop the reproduction of the virus inside the cell ( acyclovir, ribavirin);
drugs that stop the assembly and release of the virus from the cell ( metisazon);
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 envelope of the virus outside the cells and inactivate its genetic material. Arbidol acts on the lipid membrane of the virus and makes it incapable of fusion with the cell.

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

Drugs that prevent the penetration of the virus into the cells of the body

This group includes drugs amantadine, remantadine. They can be used against influenza virus as well as against tick-borne encephalitis virus. These drugs combine the ability to disrupt the interaction of the envelope of the virus ( 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 when assembling 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 prophylactic purposes.

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

This group of drugs is the broadest. One of the ways to stop the reproduction of the virus is by blocking DNA ( RNA) - polymerases. These enzymes, introduced into the cell by the virus, produce a large number of copies of the viral genome. Acyclovir and its derivatives inhibit the activity of this enzyme, which explains their antiherpetic effect. The inhibition of DNA polymerases is also carried out by ribavirin and some other antiviral drugs.

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

Interferons. The use of interferons as a medicine

Interferons are low molecular weight proteins that the body produces on its own in response to a virus infection. There are different types of interferons ( alpha, beta, gamma), which differ in different properties and the cells that produce them. Interferons are also produced in some bacterial infections, but these compounds play the greatest role in the fight against viruses. Without interferons, the action of the immune system and the body's defense against viruses are impossible.

Interferons have the following properties that allow them to exhibit antiviral effects:

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

After the discovery of interferons, there were suggestions about their possible use as a medicine. Especially important is the fact that viruses do not develop resistance to interferons. Today they are used in the treatment of various viral diseases, herpes, hepatitis, AIDS. The major disadvantages of the drug are serious side effects, high cost and difficulties in obtaining interferons. Because of this, interferons are very difficult to obtain from pharmacies.

Interferon inducers ( kagocel, trerezan, 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.

There are the following groups of interferon inducers:

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

Interferon inducers increase the production of their own interferon by mimicking 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 efficacy 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 effect. The most common classification involves the division of drugs according to the spectrum of action. This division facilitates their use in certain clinical situations.
Types of antiviral drugs by spectrum of action

Causative agent	Most commonly used drugs
*Herpes virus*	acyclovir; valacyclovir; famciclovir.
*Flu 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, they are relatively large viruses containing DNA. The 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, getting into a cell infected with a virus, undergoes a series of chemical reactions ( phosphorylated). The altered acyclovir substance 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 in relation to ordinary cellular DNA polymerase, its effect is hundreds of times weaker than against a viral enzyme. The drug is used topically ( 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 it has a stronger effect, due to which the drug is also used in the treatment of tick-borne encephalitis. Despite this, the drug is devoid of selective action, which is why it is several times more toxic than acyclovir.
Famciclovir. The mechanism of action does not differ from acyclovir. The difference between them lies in the presence of another nitrogenous base. In terms of effectiveness and toxicity, it is comparable to acyclovir.
Valacyclovir. This drug is more effective than acyclovir when used in tablet form. It is absorbed from the gastrointestinal tract in a fairly large percentage, and after passing through a series of enzymatic changes in the liver it turns 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 viral strains that are resistant to acyclovir. Foscarnet is also used for cytomegalovirus, herpes and tick-borne encephalitis. It is administered intravenously, because of this, it has a large number of side effects.

Anti-influenza 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 the 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 in severe infections, since with mild clinical manifestations, the body copes with the virus on its own.

There are the following types of anti-influenza drugs:

Inhibitors of viral protein M ( remantadine, amantadine). These drugs prevent the penetration of the virus into 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 enter the cells of the mucous membrane of the respiratory tract. The drugs of this group prevent the spread and replication ( reproduction) virus. One of these drugs is zanamivir ( relenza). It is used as an aerosol. 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 efficacy. The drugs are easily tolerated.
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 drugs that can be used to treat the flu virus. They have a weak antiviral effect, some additionally stimulate the production of their own interferon. However, it should be noted that these drugs do not help everyone and not in all cases.

Drugs aimed at combating HIV infection

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

HIV drugs are divided into two groups:

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

The representative of the first group is azidothymidine ( zidovudine). Its role is that it interferes with the formation of DNA from viral RNA. This inhibits the synthesis of viral proteins, which provides a therapeutic effect. The drug easily penetrates the blood-brain barrier, which can cause disturbances in 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 drugs is the development of resistance to them from the virus.

Protease inhibitors are a relatively new group of antiretroviral drugs. They reduce the formation of enzymes and structural proteins of the virus, due to which, as a result of the vital activity of the virus, its immature forms are formed. This significantly delays the development of the infection. One of these drugs is saquinavir. It inhibits the multiplication of retroviruses, but it also potentially develops resistance. This is why doctors use combinations of drugs from both groups to treat HIV and AIDS.

Are there broad spectrum antivirals?

Despite claims from drug manufacturers and advertisements, there is no broad spectrum of antiviral drugs. The drugs that exist today and are recognized by official medicine are characterized by a targeted, specific action. 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, in fact, are immunomodulators and have a weak antiviral effect. They are used mainly for prevention, rather than for the 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, the need to take it 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)

Various drugs that stimulate the immune system are very common on the market today. They have the ability to stop the growth of viruses and protect the body from infections. Such drugs are harmless, but they do not have a direct effect on the virus either. So, 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 the infection, since after the 4th day the level of interferon increases by itself. Amiksin ( tiloron) and many other drugs. Immunostimulants have many disadvantages that make their use in most cases impractical.

The disadvantages of immunostimulants include:

weak direct antiviral effect;
limited periods of application ( before the height of the disease);
the effectiveness of the drug depends on the state of the human immune system;
with prolonged use, depletion of immunity occurs;
lack of clinically proven efficacy in this group of drugs.

Herbal antiviral drugs ( echinacea preparations)

Herbal antivirals are one of the best options for preventing viral infections. This is due to the fact that they do not have side effects, like conventional antiviral drugs, and are also devoid of the disadvantages of immunostimulants ( depletion of immunity, limited effectiveness).

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

Homeopathic antiviral drugs ( ergoferon, anaferon)

Homeopathy is a branch of medicine that uses highly diluted concentrations of the active ingredient. The principle of homeopathy is to use those substances that can presumably cause symptoms similar to those of the patient ( the so-called principle of "treating like with like"). This principle is the opposite of the principles of official medicine. Moreover, normal physiology cannot explain the mechanisms of action of homeopathic remedies. It is assumed that homeopathic remedies help in recovery by stimulating the neuro-vegetative, endocrine, and immune systems.

Few suspect that some of the over-the-counter antivirals are homeopathic. So, drugs ergoferon, anaferon and some others belong to homeopathic remedies. They contain various antibodies to interferon, histamine and some receptors. As a result of their use, the connection between the components of the immune system improves, the rate of defense processes dependent on interferon increases. Ergoferon also has a small anti-inflammatory and anti-allergic effect.

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

The use of antiviral drugs

Antiviral drugs are quite diverse and differ in the way they are used. Various dosage forms should be used as directed 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 mellitus) 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 closely monitored 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 the use of 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 infection with the virus.

Antiviral agents 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.

It is customary to use antiviral agents not always, but only in severe cases, when there is no possibility for self-recovery. So, influenza is usually treated symptomatically, and special anti-influenza drugs are used only in exceptional cases. Chicken pox ( chickenpox) in children goes away on its own after 2 - 3 weeks of illness. Usually, human immunity is quite successful in fighting this kind of infection. The limited use of antiviral drugs is due to 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. So, interferons are used for cancer ( melanoma, cancer). They are used as chemotherapeutic agents to shrink tumors. Amantadine ( midantan), used to treat influenza, is also suitable for treating Parkinson's disease and neuralgia. Many antiviral agents also have immunostimulatory effects, however, the use of immunostimulants is generally discouraged by the medical community.

Contraindications to the use of antiviral agents

Antiviral agents 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 in different ways. In general, the most common contraindications for antiviral drugs include diseases of the kidney, liver, and the hematopoietic system.

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

Mental disorders ( psychosis, depression). Antiviral drugs can negatively affect the psychological state of a person, especially during the first time of use. In addition, there is a very high risk of misuse of drugs for patients with mental disabilities, which is very dangerous for drugs with many side effects.
Hypersensitivity to one of the components of the drug. Allergy is a problem for any medication, not just antiviral drugs. It can be suspected in the presence of other allergies ( for example, pollen) or allergic diseases ( bronchial asthma). To prevent such reactions, it is worth taking special tests for the presence of allergies.
Hematopoietic disorders. Taking antiviral drugs can lead to a decrease in the number of red blood cells, platelets, leukocytes. 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 arrhythmias, 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 disease associated with liver failure ( e.g. cirrhosis) reduce their effectiveness, or, conversely, increase the duration of their stay in the body, making them dangerous for the patient.
Autoimmune diseases. The immunostimulating effect of some drugs limits their use in autoimmune diseases. So, for example, interferons cannot be used for thyroid diseases ( autoimmune thyroiditis). When they are used, 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 usually 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 agents is to stop the synthesis of genetic material, DNA and RNA). As a result, antiviral drugs can lead to teratogenic effects ( the formation of deformities) and mutagenic action.

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

Antiviral drugs are produced today 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 dose of the drug and the method of its use depend on the dosage form.

Modern antiviral drugs are available in the following dosage forms:

oral tablets;
powder for preparation of solution for oral administration;
powder for injection ( complete with water for injection);
ampoules for injection;
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, for this group of drugs, it is characteristic that drugs have low availability ( absorbability) from the gastrointestinal tract. This applies to interferons, acyclovir, and many other drugs. That is why, for systemic use, the best dosage forms are injection 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 preparation of injection solution) you need to properly dose the drug to eliminate side effects. That is why the use of antiviral agents in such cases should be carried out under the supervision of medical personnel.

Antiviral drugs for systemic and local use

There are many forms of antiviral drugs that can be used both topically and systemically. This may even apply to the same active ingredient. For example, acyclovir is used as an ointment or gel ( for topical application) and in the form of tablets. 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 the 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;
practically does not affect distant organs and systems ( liver, kidneys and others);
used for influenza, genital herpes, herpes of the lips, papillomas and some other diseases;
used for mild viral infection.

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 disease ( for example, with influenza complicated by pneumonia);
has an effect on all cells in the human body, as it enters them through the bloodstream;
for systemic use, tablets for oral administration, injections, rectal suppositories are used;
has a higher risk of side effects;
in general, it is used in cases where only local treatment is ineffective.

It should be borne in mind that dosage forms for local use cannot be used in a systemic manner and vice versa. Sometimes, in order to achieve the best therapeutic effect, doctors recommend combining drugs, which allows a multifaceted effect on a viral infection.

Instructions for the use of antiviral drugs

Antiviral drugs are pretty strong medicines. In order to achieve the desired effect from them and to avoid side effects, you should follow the instructions for use of the drugs. Each drug has its own instructions. The greatest role in the use of antiviral drugs is played by the dosage form of the drug.

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

Pills. The tablets are taken orally during or after meals 1 to 3 times a day. The appropriate dosage is selected by taking the whole tablet or half of it.
Injections. Should be performed by medical personnel, since incorrect administration threatens the development of complications ( including post-injection abscess). The powder of the drug is completely dissolved in liquid for injection and injected 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 application of drops ( for example, influenza) implies their introduction in the amount of 1 - 2 drops in each nasal passage. They can be used 3 to 5 times per day.

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

Dosage of the drug. The most important parameter, observing which you can exclude an overdose. Antivirals are usually taken in low 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, drugs for topical use ( drops, ointments) can be used 3-4 times a day or more. When applied topically, overdose phenomena are very rare.
Duration of use. The duration of the course is set by the doctor and depends on the severity of the disease. Termination 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 refrigerated, others at room temperature.

Antiviral drug courses

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, HIV / AIDS. This is due to the high resistance of the hepatitis and HIV viruses to drugs. Drugs against hepatitis are taken from 3 to 6 months, against HIV - more than a year. Also, the use as part of a course therapy is accepted in relation to interferon and some other drugs.

The duration of treatment with 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 of using antiviral drugs is prevention. If preventive goals are pursued, the duration of taking antiviral drugs is from 3 to 7 days.

Most common side effects of antiviral drugs

Side effects from the use of antiviral drugs are really common. Naturally, the nature of side effects largely depends on the drug itself, as well as its dosage form. Systemic drugs tend to have more side effects. Side effects are not common to all drugs, but the most common adverse reactions of the body to antiviral drugs can be summarized and highlighted.

The most common side effects of antiviral drugs are as follows:

Neurotoxicity ( negative effect on the central nervous system). Expressed in 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 "packed" in a special case - capsid (from Latin capsa, case). Capsid is a protein coat that 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 the capsid spike glycoprotein 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 cells of the macroorganism. Adsorption also depends on ionic attraction (Scheme 2, /).

2. The penetration of the virus into the cell (viropexis) occurs in two ways: by injecting 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 cell enzymes. Modified viral particles lose their infectious properties (Scheme 2,3).

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

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

6. The release of daughter virions is the final stage of the reproductive cycle (Scheme 2, 6).

Classification of antiviral agents

I. Drugs acting on extracellular forms of the virus:

Oxolin;

Arbidol-lens.

II. Viropexis inhibitors (M2 channel blockers):

Amantadine (midantan, symmetrel, verigit-K, adamantine, amandine, amantan, antadine);

Remantadine (rimantadine, meradan, algirem, polirem).

III. Neuraminidase inhibitors:

Zanamivir (Relenza);

Oseltamivir (Tamiflu).

IV. Drugs that inhibit the reproduction of the virus:

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

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

Ganciclovir (Cymeven);

Vidarabine;

Ribavirin (Virazol, Rebetol, Meduna's ribavirin, Ribamidil), etc.

2. Reverse transcriptase inhibitors:

a) . Abnormal nucleoside:

Abacavir (ziagen);

Didanosine (videx);

Lamivudine (zeffix, epivir Tri Ti Sm);

Stavudine (zerit) -,

Zalcitobin (hivid);

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

b) Preparations of non-nucleoside structure:

Efavirenz;

Nevirapine (viramune).

3. Protease inhibitors:

Aprenavir (agenrase);

Indinavir sulfate (crixivan);

Saquinavir (invirase, fortovaz).

V. Inhibitors of viral maturation:

Metisazon (marboran, kemoviran, viruzona)

Vi. Interferons and interferon inducers.

Antiviral agents will be considered according to the proposed classification.

I. Drugs acting on extracellular forms of the virus

The main application of the first group of antiviral agents 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 pathology. The widespread spread of ARVI is facilitated by the airborne route of infection, the lack of persistent immunity to repeated infections, as well as a wide variety and frequent mutations of the causative agents of ARVI. Among the 200 known causative agents of the disease, influenza viruses undoubtedly play the leading role. Influenza is registered everywhere and represents the greatest epidemic danger. Every year on the planet, one in ten adults falls ill with the flu. During epidemic outbreaks, influenza is accompanied by high mortality, especially in young children and the elderly. Occupying a major 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 other organ damage.

There are three types of influenza virus - A, B, C. These are RNA-containing viruses of the Orthomixoviridae family (Fig. 3). Major epidemics and pandemics are caused by the type A virus. The unpredictability of epidemics is due to the antigenic variability of viruses, leading to a partial or complete change in the group and strain determinants - hemagpyutinin and neuraminidase. Hemagglutinin and neuraminidase are glycoprotein spikes that pierce the supercapsid of the virus. These thorns are necessary for the adhesion of the virus to the membrane and its penetration into the cell (Fig. 3, a). In this case, hemagglutinin ensures the fusion of the capsid with the cell membrane and lysosomal membranes, and neuraminidase recognizes and interacts with surface cell receptors. In addition, neuraminidase, cleaving off 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 viral genome, on the other hand, the M-protein integrates into the cell membrane and modifies

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

Intranasal administration of oxopine ointment is still popular among chemotherapeutic agents for the prevention of influenza and ARVI. The drug is also effective in treating adenoviral keratoconjunctivitis, herpetic keratitis, viral skin lesions (shingles), and rhinitis of viral etiology.

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

When applied topically, oxolinic ointment can be irritating. Oxolinic ointment for nasal and external use is produced at 0.25% - 1.0 and 3% - 1.0.

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

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

* inhibits the fusion of the lipid membrane of the virion with the membranes of human cells - "prevents the penetration of the virus into the host cell.

Inhibits translation of virus-specific proteins in infected cells - "inhibits the reproduction of viruses.

The antiviral effect of the drug enhances its interferonogenic and immunomodulatory activity. It has been proven that arbidol stimulates cellular and humoral immunity. The antioxidant activity of arbidol is also important. A good therapeutic effect and the absence of side effects allows prescribing arbidol-lance for the prevention and treatment of influenza and ARVI in adults and children from two years of age. For the prevention of influenza and acute respiratory viral infections, the drug is used in an age 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 0.1 capsules for adults and tablets, coated at 0.05 for children.

II. Viropexis inhibitors (M2 channel blockers)

Blockers of M, -protein are represented by adamantane derivatives: amantadine and rimantadine (Table 1).

In the mechanism of the 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 envelope with endosome membranes - "violate the deproteinization of viral particles -" prevent the transfer of the virion genetic material into the cytoplasm of the host cell -> inhibit the early stage of specific viral reproduction (Fig. 1, c- /).

2. Violate the incorporation of M-protein into the host cell membrane - "prevent membrane modification -" inhibit the assembly of daughter virions.

bgcolor = white> Dosage Forms

	A drug	Spectrum actions	Side
1.	Amantadine (gludantan, midantan)	Tablets of 0.05 and 0.1, capsules of 0.05	Viruses	Headache, insomnia, irritability, hollucination, anorexia, xerostomy, peripheral edema, orthostatic hypotension.
2.	Rimantadine (remantadine, algirem)	Tablets of 0.05, capsules of 0.05, syrup for children 0.2% -100 ml.	Virus influenza type A, tick-borne encephalitis virus.	Allergies, drowsiness, depression, tremors, hyperexcitability.
3.	Adapro-	0.05 tablets, 0.05 capsules	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. On the basis of amantadine, rimantadine was created, which is more active and less toxic than its predecessor. Rimantadine is well absorbed when taken orally and better than amantadine, it penetrates the secretions of the respiratory tract. The antiviral effect of rimantadine is longer than that of mandantan. Rimantadine is produced in Russia under the brand name Remantadine in 50 mg tablets. Remantadine inhibits the reproduction of a large number of 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. When used prophylactically

the effectiveness of rimantadine for influenza is 70-90%. For prophylaxis, take 0.05 1 time per day, for 10-15 days.

For therapeutic purposes, rimantadine is prescribed no later than 48 hours after the first signs of the disease appear, and then resistance develops to it. This is due to the fact that the main mechanism of action of the drug is due to a violation of the penetration of the virus into cells and a blockade of the nuclear phase of reproduction. At the later stages of virus reproduction, rimantadine acts to a much lesser extent. 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: 1 day 300 mg once, 2 day 200 mg and 3 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 once a day. The duration of the course should not exceed 5 days in order to avoid the appearance of resistant forms of the virus. For children from 1 to 7 years old, remantadine is replaced by apygirem (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. In 3-6% of patients, there may be adverse reactions from the central nervous system or gastrointestinal tract. Rimantadine should be used with caution in the elderly, with severe liver dysfunction, as well as in persons with increased convulsive readiness (for example, with epilepsy).

III. Neuraminidase inhibitors

A new direction in the development of anti-influenza drugs is the creation of inhibitors of viral neuraminidase (Table 2). As mentioned earlier, neuraminidase (sialidase) is one of the key enzymes involved in the replication of influenza A and B viruses. Inhibition of neuraminidase disrupts the ability of viruses to penetrate healthy cells. Due to their special mechanism of action, neuraminidase inhibitors prevent the spread of infection from a sick person to a healthy one. 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 such systemic manifestations of viral infection as fever, pain in muscles and joints, and loss of appetite. We add that neuraminidase inhibitors reduce the resistance of viruses to the protective action of respiratory 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 the high toxicity and low bioavailability when taken orally, the drug is used by inhalation. Zanamivir is recommended for the treatment of uncomplicated influenza in people over 12 years of age with clinical symptoms not exceeding 36 hours.

The oral neuraminidase inhibitor oseltamivir (tafiflu) is active against all clinically significant influenza virus strains, including avian influenza (H5N1) virus. There is no resistance of viruses to the drug. Moreover, according to clinical studies, over time, the sensitivity of influenza viruses to Tamiflu increases. Oseltamivir is a prodrug and, under the influence of intestinal and liver esterases, is converted into an active metabolite carboxylate, which is well distributed to the main foci of influenza infection.

Mechanism of action: the carboxylate binds to the hydrophobic "pocket" of the active site of the neuraminidase of the influenza virus - e blocks the ability of the latter to split off sialic acid residues from the surface of the infected cell - "the penetration and release of new virions from the cell is inhibited (Fig. 1, a; d).

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

Reduce the severity of symptoms 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 a sick 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 by the WHO on August 23, 2007. Oseltamivir is manufactured by F. Hoffmann-LaRoche (Switzerland) under the Tamiflu trademark 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 the reproduction of the virus

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

Due to their similar chemical structure, drugs from the group of abnormal purine and pyrimidine bases are incorporated into the nucleic acids of viruses and disrupt their function. In addition, nucleoside analogs inhibit virion DNA polymerase, 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 viral DNA (RNA) polymerase

1. Inhibitors of PH K-polymerase viruses

Ribavirin is active against many RNA and DNA viruses. The drug has a complex, not completely elucidated mechanism of action. It is assumed that it blocks viral RNA polymerase, which disrupts the synthesis of messenger RNA ribonucleoproteins. Thus, ribavirin blocks the early stages of viral transcription. When administered by inhalation, the drug creates high concentrations in the secretions of the respiratory tract. Given the toxicity of ribavirin and limited data on its clinical efficacy, the drug should be prescribed only in case of positive serological test results confirming the presence of respiratory syncytial viral infection (RSV). At the same time, the drug has shown efficacy in the treatment of viral hepatitis. It is used by 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. Inhibitors of viral DNA polymerase

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

Most modern antiherpetic drugs (anti-herpes) are abnormal nucleosides. Antiherpetics inhibit viral DNA polymerase more actively than host cell polymerase. Herpes simplex virus type 1 lesions usually resolve on their own and require only local interventions. It is recommended to start therapy at the prodrome stage (itching). In this case, the development of the bubble stage can be completely prevented. For the treatment of infections caused by herpes simplex viruses and the Varicella zoster virus, the following antiherpetic agents are prescribed for local and external use.

Table 3

Antiherpetic drugs for local and external use

In the treatment of herpetic keratitis, the thymidine analogue idoxuridine (oftan go) has proven its effectiveness. 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 herpes infection and the prevention of recurrence of the disease. Undoubted

486- the advantage of acyclovir is a wide range of antiherpetic activity. So, the drug is prescribed for infection with EBV, HSV-1 and HSV-2. Acyclovir is effective for shingles and cytomegalovirus infection. However, severe side effects that develop with the resorptive action of acyclovir limit its use.

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

Another representative of antiherpetic drugs, famciclovir (famvir), after oral administration, quickly turns into an 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, prescribing famciclovir significantly reduces the severity and duration of postherpetic neuralgia in patients with shingles. The drug is well tolerated.

Penciclovir, also known as fenistil and pencivir, is becoming increasingly popular. Being a synthetic analogue of acyclic guanine nucleoside, penciclovir has a high specificity against herpes-infected cells. Like acyclovir, penciclovir is activated in the cell by phosphorylation, but the latter in the activated form is more stable and therefore the duration of action of penciclovir is longer than that of acyclovir. As a result of a longer exposure to an infected cell, penciclovir is effective at any stage of herpes simplex, including vesicular. 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 simplex virus type 3 (Varicella zoster).

In some cases, vidarabine is prescribed for the treatment of 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, causing leukopenia and thrombocytopenia.

Table 4

Abnormal nucleosides with antiherpetic activity

A drug	The form	Spectrum actions	Side effect
Acyclovir (acyclovir-AKOS, acyclovir-acri, herperax "zovirax, cyclo-viral SELICO)	Tab. 0.2 and 0.4. Ointment	VPG-1, VPG-2, HZV, tsmv, VEB.	When taken orally, dispep strength and allergic reactions, leukopenia, thrombocytopenia, hematuria, phlebitis at the injection site, etc.
Valacyclovir (val-treks)	Tablets 0.5. Lyophilized powder for injection 0.25 in vials.	VPG-1, VPG-2, HZV, tsmv. VEB.	Possible renal failure, hemolytic anemia, allergic reactions
Famciclovir	Pills 0.25	VPG-1, VPG-2, HZV, tsmv, VEB.	Headache, nausea, allergic reactions.
Ganciclovir (cymeven)	Capsules 0.25	VPG-1, VPG-2, CMV, VEB.	Neutropenia, thrombocytopenia, arrhythmia, edema, convulsions, depression, dyspepsia, etc.

The mainstay of treatment for cytomegalovirus infection is ganciclovir or sodium foscarnet. 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 it is prescribed only for cytomegalovirus infection, since taking ganciclovir often leads to severe dysfunctions of various organs and systems.

Inhibitors of DNA polymerase viruses include sodium foscarnet, an antiviral agent for external use. Has a virostatic effect on herpes simplex viruses of the first and second types and influenza A. 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 reverse transcriptase) provides a 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 referred to as HTLV-3 or LAV, is believed to be 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 disorders of the immune response as a result of prolonged circulation of the virus in lymphocytes, macrophages and cells of human nervous tissue.

The tropism of the virus to the cells of the immune system is provided by glycoprotein spikes built into the supercapsid. It is well known that these glycoproteins interact with CD4 receptors located on the membrane of immunocompetent cells. After adsorption and penetration into the cell, HIV “strips”, and the virion RNA is released into the cytoplasm. RNA of a retrovirus does not exhibit infectious properties, but serves as a template for the synthesis of a DNA molecule using an RNA-dependent DNA polymerase (reverse transcriptase, reverse transcriptase), which is part of the viral particle. The synthesized double molecule of viral DNA is transported into the cell nucleus and, using cellular integrases, is incorporated into the DNA of the host cell. The integrated DNA molecule is transcribed by cellular DNA-dependent RNA polymerase to form viral RNA. Some of the RNA molecules are 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 the host cells. It is important that viral proteins synthesize

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

Rice. 4. The cycle of reproduction of the human immunodeficiency virus

Thus, in the process of reproduction of a retrovirus, two virus-specific enzymes (reverse transcriptase and proteases) are formed, which are the targets 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, inhibitors of the reverse transcriptase of the virus have attracted much attention. As seen from Fig. 5, nucleoside derivatives of this group of drugs, entering the infected cell, are phosphorylated.

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

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

Nucleoside reverse transcriptase inhibitors are shown in Table 5.

Table 5

HIV nucleoside reverse transcriptase inhibitors

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

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. Possible pancytopenia and bone marrow hypoplasia. On the part of the digestive system, anorexia, taste perversion, abdominal pain, diarrhea, hepatomegaly, fatty degeneration of the liver, increased levels of bilirubin and hepatic transaminases are possible. The defeat of the central nervous system is manifested by depression and seizures.

Pamivudine has a high selectivity of action on the reverse transcriptase of the virus. 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 zidovudine-resistant HIV strains. Lamivudine is used to treat viral hepatitis B.

2. Non-nucleoside reverse transcriptase inhibitors

Non-nucleoside inhibitors of HIV reverse transcriptase in the cells of the microorganism are not phosphorylated and noncompetitively 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 by the principle of competitive antagonism inhibit HIV proteases. As a result, viral enzymes lose their ability to break down the precursor polyproteins required for viral replication. This leads to the formation of inactive viral particles. HIV protease inhibitors include the drugs listed in Table 6.

Unfortunately, the available antiviral agents do not cure patients radically, but only delay the development of the disease. Therefore, the most effective use of antiretroviral drugs in the first 6-8 months from the onset of the disease. The combined use of protease inhibitors with nucleoside and / or non-nucleoside inhibitors of HIV reverse transcriptase is expedient. Endogenous and exogenous interferon preparations have proven their effectiveness in the complex therapy of AIDS.

V. Inhibitors of viral maturation

A striking representative of this group of funds is mestizo. Metisazone inhibits the assembly of virions, as it blocks the synthesis of the viral structural protein. The drug is active against smallpox viruses and is used to prevent smallpox, as well as to reduce the complications of smallpox vaccination. Since smallpox is now rare, the drug is almost never used. At the same time, mestizo- 493 -

zones is of interest due to the special mechanism of action and pronounced antiviral activity. It is possible that new highly effective antiviral agents will be synthesized on the basis of metisazone, and it will become the founder of a new group of drugs. This is all the more interesting because there is evidence of 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 begin to produce and release into the environment a special protein that prevents the virus from multiplying. Subsequently, this protein was called interferon (Latin inter - between, death + ferre - to bear). Currently, the following definition is 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 in case of primary viral infection. Not only viruses, but also bacteria, mitogenic and antigenic effects are able to induce the synthesis of IFN. 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 (fibroblast) - produced by fibroblasts;

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

According to their functional activity, interferons are combined into two types. Type I includes a-IFN and R-IFN.

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

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

This group of glycoproteins is characterized by pronounced antiviral activity.

The mechanism of action of interferons includes the following points:

1. Suppression of transcription of viral proteins.

2. Suppression of translation of viral proteins.

3. Suppression of protein metabolism.

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

An important property of interferons is their ability to activate the synthesis of protective enzymes in human cells 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 viruses do not develop resistance to interferon. The immunomodulatory activity of interferons enhances their antiviral effect, and this effect is most pronounced in a representative of type II interferons - IFN-y.

All interferons, along with antiviral effect, have antitumor and immunomodulatory effects. The spectrum of pharmacological activity of IFN determines the main indications for their appointment: complex therapy of infectious diseases, oncological pathology, immunodeficiencies of various genes and other conditions, accompanied by a decrease in interferon production 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 the elderly, 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. Introduction of preparations of exogenous interferon (actually IFN).

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

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

1. Interferon alpha - 2b;

2. Interferon beta - 1a;

3. Interferon - lb;

4. Combined preparations containing several IFNs;

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

For the treatment of viral infections, the drugs listed in Table 8 are used based on interferons. Exogenous interferon preparations are widely used for the treatment and prevention of influenza. IFN is successfully used in the complex therapy of herpes infection, viral hepatitis and AIDS. Note that interferon therapy is not without its drawbacks. Thus, parenteral administration of IFN preparations for severe viral infections leads to serious side effects. In addition, interferons are not readily 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 vial containing 5 or 10 ml of recombinant a-2b IFN with an activity of at least 10,000 IU / ml.
4.	Reaferon (real-diron)	Lyophilized powder ampoules containing 0.5; 1; 3; 5 million ME.
5.	Human leukocyte IFN for injection	Ampoules with lyophilized powder for injection (mixture of a-IFN, activity 0.1; 0.25; 0.5 or 1 million IU).
6.	Intron-A	Vials of lyophilized powder for injection containing 1, 3, 5, 10 and 30 million IU of human recombinant a-2b IFN Ointment containing 5 million IU in 1 g.

Interferon inducers are an alternative to interferon therapy.

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). Immunomodulating action;

3). Stimulation of nonspecific defense mechanisms of the body;

4). Antiviral action.

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

I. Preparations of natural origin:

Aktipol, Arbidol-lense, Poludan, Amiksil.

II. Preparations of synthetic origin:

Copaxone-Teva, Isoprinosine, Galavit, Gepon, Derinat, Immunomax, Likopid, Polyoxidonium, Dekaris.

III. Phytopreparations:

Echinocea hexa l (immunal, immunorm,)

Combined phytopreparations: Original Bittner's balm, Sinupret, Tonsilgon.

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

Pharmacotherapy of viral hepatitis takes a special place. Thus, the number of carriers of viral hepatitis in the world exceeds 1 billion. Given the great 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 anthroponous lesions of the liver with various mechanisms and routes of transmission of the pathogen. For the first time, the outstanding domestic therapist S.P.Botkin (1888) proposed to separate infectious hepatitis from other liver lesions. Currently, 8 types of viral pathogens have been isolated and studied.

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

Table 9

Viral hepatitis

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

Over the past 30 years, the main principle of the 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 appointment of etiotropic drugs such as vidarabine, pamivudine and ribavirin (see earlier). An important link in the complex therapy of viral hepatitis is symptomatic treatment. In general, rational pharmacotherapy of viral hepatitis remains a challenge. Therefore, much attention is attracted by the possibilities of immunoprophylaxis of the disease.

And in conclusion, a few words about other possibilities of therapy for the most common viral infections. So, in the treatment of various forms of herpes infection, almost all known local and systemic interferon inducers are used. For example, for herpes infection, hpyrrhizic acid (epigenetic intima) 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, human papilloma and cytomegalovirus. The drug is well tolerated.

Currently, the Allopharm company has developed and introduced into production an innovative drug Allomedin. The main active ingredient of the new drug is the allooferon-3 peptide. Preclinical studies have established that active substances - peptides from the allostatin group - increase the antiviral and antitumor immunity of the body. 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. We add that allomedin is also indicated for the treatment of viral papilloma. The drug is available in the form of Allomedin gel.

We should mention the domestic drug antigrippin (CJSC "Antiviral", St. Petersburg, Russia), which is a balanced mixture of acetylsalicylic acid, ascorbic acid, rutin, metamizole, diphenhydramine, calcium gluconate. With influenza and ARVI, adaptogens are widely used for therapeutic and prophylactic purposes - fortifying agents of plant origin (preparations of ginseng, eleutherococcus, Chinese magnolia vine, zamanihi, aralia, rhodiola, echinacea, kalanchoe). For the treatment of influenza caused by viruses of type A and B, synthetic

deutiforin is a chemical drug from the bicyclotene class. As a therapeutic and prophylactic agent for influenza A and B, adapromin is used - 0.2 g once a day for 4 days, for emergency prophylaxis in the outbreak, 0.1 g once a day for 5-10 days.

For respiratory infections, immunomodulators are widely used: ribomunil, broncho-tormented, 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. To prevent the development of the disease, the intranasal use of such interferon drugs as Alfainterferon (interlock, ChLI), Viferon, Grippferon and Reaferon (realdiron) allows. With local application of IFN, side effects have not been identified. A separate group of anti-influenza drugs is made up of homeopathic remedies: aflubin, allikor, influenza-hel, iflucid, tonsilgon, traumeel, flu, engystol, EDAS 903 granules, EDAS 131 drops, nasentropfen C, "AGRI" for adults and children.

Pleconaril, recently developed in the United States, is a promising antiviral drug. In in vitro studies and in experiments on animals, its activity against enteroviruses and rhinoviruses was revealed. The data from the first placebo-controlled studies indicate the effectiveness of the drug in respiratory infections and enteroviral meningitis.

Despite a fairly extensive list of drugs, viral diseases remain poorly controlled infections. This is due to the lack of radical therapy and the development of viral resistance. The maximum effectiveness of antiviral therapy is achieved with a comprehensive 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
Oxolin	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	Inside 0.2 g; intravenously 5-10 mg / kg; skin 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 vials of 0.546 g of ganciclovir sodium (corresponds to 0.5 g of ganciclovir base)
Ribavirin	Inside 0.2 g	0.2 g tablets
Zidovudine	Inside 0.1-0.2 g	0.1 g capsules
Arbidol	Inside 0.1-0.2 g	Tablets of 0.025; 0.05 and 0.1 g
Amiksin	Inside 0.125-0.25 g	0.125 g tablets