How antiviral drugs work. Antiviral drugs
ina. In this regard, many chemical compounds that inhibit the replication of viruses also inhibit the vital activity of the cells of the host organism and have a pronounced toxic effect. Infection with viruses leads to the activation of a number of virus-specific biochemical reactions in host cells. It is these reactions that can serve as targets in the creation of selectively acting antiviral agents.
The process of virus replication occurs in stages. Fixation (adsorption) of the virus to specific cell wall receptors is a preparatory stage for replication. The virions then enter the host cell (viropexis). The cell engulfs viruses attached to its envelope by endocytosis. Lysosomal enzymes of the cell dissolve the viral envelope, and the virus deproteinizes (releases the nucleic acid). The acid penetrates the cell nucleus, starting to control the process of virus reproduction. The so-called early enzyme proteins are synthesized in the cell, which are necessary for the formation of nucleic acids of daughter viral particles. Then the viral nucleic acid is synthesized. The next stage is the formation of "late" (structural) proteins and the subsequent assembly of the viral particle. The last stage of the interaction between the virus and the cell is the release of mature virions into the external environment.
Antiviral agents are drugs that inhibit the processes of adsorption, penetration and reproduction of viruses.
For the prevention and treatment of viral infections, chemotherapy drugs, IFN and IFN inducers are used.
Antivirals
The classification of chemotherapeutic drugs used to treat viral infections is based on the effects produced at various stages of the interaction of a viral particle and host cells (Table 39-1, Fig. 39-1).
γ - Globulin (immunoglobulin G) contains specific antibodies to the surface antigens of the virus. The drug is administered intramuscularly 1 time in 2-3 weeks for the prevention of influenza and measles (during the epidemic). Another human IgG preparation, sandoglobulin, is administered intravenously once a month for the same indications. When using drugs, the development of allergic reactions is possible.
Table 39-1
Classification of antiviral agents
Interaction stage | Group | Preparations |
Adsorption and penetration of the virus into the cell | Ig preparations | γ-Globulin Sandoglobulin |
Adamantane derivatives | Amantadine Rimantadine |
|
Deproteinization of the virus | Adamantane derivatives | Amantadine, rimantadine |
Formation of active proteins from an inactive polyprotein | Nucleoside analogs | Aciclovir, ganciclovir famciclovir, valaciclovir |
Ribavirin, Idox- ridin Vidarabine |
||
Zidovudine, lamivudine didanosine, zalcitabine |
||
Phosphoric formic acid derivatives | Foscarnet sodium |
|
Synthesis of structural proteins of the virus | Peptide derivatives | Saquinavir, indinavir |
Rimantadine (rimantadine*) and amantadine (midantan*) are tricyclic symmetrical adamantaneamines. They are used for early treatment and prevention of influenza type A 2 (Asian flu). Assign inside. The most pronounced side effects of drugs include insomnia, speech disorders, ataxia, and some other disorders of the central nervous system.
Ribavirin (virazole*, ribamidil*) is a synthetic analogue of guanosine. In the body, phosphorylation occurs and the drug is converted into monophosphate and triphosphate. Ribavirin monophosphate is a competitive inhibitor of inosine monophosphate dehydrogenase that inhibits the synthesis of guanine nucleotides. Triphosphate inhibits viral RNA polymerase and interferes with the formation of messenger RNA, thus inhibiting the replication of both RNA-containing and DNA-containing viruses.
Rice. 39-1. Mechanisms of action of antiviral agents
Ribavirin is used for influenza type A and type B, herpes, hepatitis A, hepatitis B (in acute form), measles, as well as infections caused by respiratory syncytial virus. The drug is administered orally or inhaled. When using the drug, bronchospasm, bradycardia, respiratory arrest (with inhalation) are possible. In addition, skin rash, conjunctivitis, nausea, and abdominal pain are noted. Ribavirin is teratogenic and mutagenic.
Idoxuridine (kerecid*) is a synthetic analogue of thymidine. The drug is integrated into the DNA molecule and inhibits the replication of some DNA-containing viruses. Apply idoxuridine topically for herpetic keratitis. For the treatment of herpetic keratitis, the drug is applied to the cornea (0.1% solution or 0.5% ointment). The drug sometimes causes contact dermatitis of the eyelids, clouding of the cornea and allergic reactions. Idoxuridin is not used as a resorptive agent due to its high toxicity.
V and d a r and b and n (adenine arabinoside) is a synthetic analogue of adenine. When it enters the cell, the drug is phosphorylated and a triphosphate derivative is formed that inhibits viral DNA polymerase; this leads to suppression of replication of DNA-containing viruses. The affinity of vidarabine for viral DNA polymerase is significantly higher than for mammalian cell DNA polymerase. This determines the non-toxicity of the drug, compared with other nucleoside analogues.
Vidarabine is used for herpetic encephalitis (administered intravenously) and for herpetic keratitis (topically in the form of ointments). Of the side effects, dyspeptic disorders, skin rashes, disorders of the central nervous system (ataxia, hallucinations, etc.) are noted.
Acyclovir (zovirax*, virolex*) is a synthetic analogue of guanine. When it enters a virus-infected cell, the drug is phosphorylated under the action of viral thymidine kinase and converted into acyclovir monophosphate. Monophosphate under the influence of thymidine kinase of the host cell passes into acyclovir diphosphate, and then into the active form - acyclovir triphosphate, which inhibits viral DNA polymerase and disrupts the synthesis of viral DNA.
The selectivity of the antiviral action of acyclovir is associated, firstly, with its phosphorylation of only viral thymidine-
zoy (in healthy cells, the drug is inactive), and secondly, with high sensitivity (hundreds of times higher than to a similar enzyme of macroorganism cells) of viral DNA polymerase to acyclovir.
Acyclovir selectively inhibits the replication of the herpes simplex virus and herpes zoster. In case of damage to the skin and mucous membranes (herpes of the lips, genital organs), a cream containing 5% acyclovir is used; in ophthalmology with herpetic keratitis - eye ointment (3%). With extensive infection of the skin and mucous membranes with the herpes simplex virus, acyclovir is prescribed orally. When taken orally, approximately 20% of the drug is absorbed from the gastrointestinal tract. Intravenously, the drug is used for the prevention and treatment of herpetic lesions in patients with immunodeficiency, as well as for the prevention of herpes infection during organ transplantation in patients with severely impaired immune systems.
When taking acyclovir orally, dyspeptic disorders, headache, and allergic reactions are sometimes observed. With intravenous administration of the drug, reversible neurological disorders are possible (confusion, hallucinations, agitation, etc.). Sometimes determine violations of the functions of the liver and kidneys. When used topically, sometimes there is a burning sensation, peeling or dryness of the skin.
Ganciclovir is a synthetic analogue of the 2-deoxyguanosine nucleoside. Ganciclovir and acyclovir have a similar structure. Unlike acyclovir, ganciclovir has a greater effect and, in addition, acts not only on herpes viruses, but also on cytomega-
lovirus. In cells infected with cytomegalovirus, ganciclovir, with the participation of the phosphotransferase of the virus (cytomegalovirus thymidine kinase is inactive), turns into monophosphate, and then into triphosphate, which inhibits the DNA polymerase of the virus. The triphosphate is incorporated into the viral DNA; this leads to the termination of its elongation and inhibition of virus replication. Since phosphotransferase is also found in the cells of the human body, ganciclovir is able to disrupt DNA synthesis in healthy cells, which leads to a high toxicity of the drug.
Ganciclovir is used to treat cytomegalovirus retinitis, cytomegalovirus infection in AIDS patients and in immunosuppressed cancer patients, as well as to prevent cytomegalovirus infection after organ transplantation. The drug is administered orally and intravenously.
The main side effects of ganciclovir: neutropenia, anemia, thrombocytopenia. Sometimes there are violations of the cardiovascular system (arrhythmias, arterial hypotension or hypertension) and the nervous system (convulsions, tremors, etc.).
The drug may interfere with liver and kidney function.
Famciclovir is a synthetic analogue of purine. In the body, the drug is metabolized to form an active metabolite, penciclovir. In cells infected with herpes viruses and cytomegalovirus, penciclovir is sequentially phosphorylated and viral DNA synthesis is inhibited; this leads to inhibition of viral replication.
Famciclovir is prescribed for herpes zoster and postherpetic neuralgia. When using the drug, headache, nausea, and allergic reactions are sometimes noted.
Valaciclovir (Valtrex*) is the valyl ester of acyclovir. Valaciclovir, when it enters the liver, is converted to acyclovir. Next, acyclovir is phosphorylated, after which the drug has an antiherpetic effect. Valaciclovir, unlike acyclovir, has a high oral bioavailability (approximately 54%).
Z and d about v ud and n (azidothymidine *, retrovir *) is a synthetic analogue of thymidine that suppresses HIV replication. In virus-infected cells, zidovudine is converted by viral thymidine kinase to monophosphate and then to diphosphate and triphosphate under the influence of host cell enzymes. Zidovudine triphosphate inhibits viral DNA polymerase (reverse transcriptase), preventing the formation of DNA from viral RNA. As a result
there is an inhibition of the synthesis of messenger RNA and, accordingly, viral proteins.
The selectivity of the antiviral effect of the drug is associated with a greater sensitivity to the inhibitory effect of zidovudine of HIV reverse transcriptase (20-30 times) than DNA polymerase of macroorganism cells.
The drug is well absorbed in the gastrointestinal tract, but its biotransformation occurs when it first enters the liver. Bioavailability is 65%. Zidovudine passes through the placental and BBB. t 1/2 is one hour. The drug is excreted by the kidneys.
Zidovudine is administered orally at 0.1 g 5-6 times a day.
Zidovudine causes hematological disorders: anemia, leukopenia, thrombocytopenia. When using the drug, headache, agitation, insomnia, diarrhea, skin rashes and fever are observed.
Lamivudine, didanosine, isalcitabine are similar to zidovudine in terms of the spectrum of pharmacological action.
Sodium foscarnet is a derivative of phosphoric formic acid. The drug inhibits the DNA polymerase of viruses. Foscarnet is used to treat cytomegalovirus retinitis in patients with
AIDS.
In addition, the drug is used for herpes infection (in case of ineffectiveness of acyclovir). The manifestation of antiviral activity of foscarnet occurs in the absence of a phosphorylation reaction by viral thymidine kinase, therefore, the drug inhibits the DNA polymerase of the herpes virus even in acyclovir-resistant strains characterized by thymidine kinase deficiency.
Foscarnet is administered intravenously. The drug has a nephrotoxic and hematotoxic effect. When using foscarnet, fever, nausea, vomiting, diarrhea, headaches, convulsions sometimes occur.
The group of agents that disrupt the synthesis of structural proteins of the virus includes drugs that inhibit HIV proteases. According to the chemical structure, HIV protease inhibitors are derivatives of peptides.
Non-nucleoside inhibitors of HIV reverse transcriptase have been synthesized. These include nevirapine and others.
The mechanism of action of the HIV protease is the splitting of the polypeptide chain of the structural protein of HIV into separate fragments necessary for the construction of the viral envelope. Inhibition of this enzyme leads to disruption of the formation of structural elements of the viral capsid. Virus replication slows down. The selectivity of the antiviral action of drugs in this group is due to the fact that the structure of the HIV protease differs significantly from similar human enzymes.
In medical practice, saquinavir (Invirase*), nelfinavir (Viracept*), indinavir (Crixivan*), lopinavir and some other drugs are used. Drugs are prescribed orally. When using drugs, dyspeptic disorders, increased activity of hepatic transaminases are sometimes noted.
Interferons
IFN is a group of endogenous low molecular weight glycoproteins produced by body cells when exposed to viruses and some biologically active substances of endogenous and exogenous origin.
In 1957, an interesting fact was discovered: cells infected with the influenza virus begin to produce and release into the environment a special protein (IFN) that prevents the reproduction of virions in cells. Therefore, IFN is considered one of the most important endogenous factors in the body's defense against primary viral infection. Subsequently, the immunomodulatory and antitumor activity of IFN was discovered.
There are 3 main types of IFN: IFN-α (and its varieties α 1 and α 2), IFN-β and IFN-γ. IFN-α is produced by leukocytes, IFN-β is produced by fibroblasts, and IFN-γ is produced by T-lymphocytes that synthesize lymphokines.
The mechanism of antiviral action of IFN: they stimulate the production of enzymes by ribosomes of the host cells that inhibit the translation of viral messenger RNA and, accordingly, the synthesis of viral proteins. As a result, the reproduction of viruses is suppressed.
IFNs have a wide spectrum of antiviral activity. IFN-α preparations are mainly prescribed as antiviral agents.
I F N - leukocyte IFN of human donor blood. Used for the prevention and treatment of influenza, as well as other acute respiratory viral infections. The solution of the drug is instilled into the nasal passages.
Interlock* - purified IFN-α obtained from human donated blood (using biosynthetic technologies). Eye drops are used to treat viral eye diseases (keratitis, conjunctivitis) caused by a herpes infection.
Reaferon* - recombinant IFN-α 2 (obtained by genetic engineering). Reaferon is used to treat viral and neoplastic diseases. The drug is effective in viral hepatitis, conjunctivitis, keratitis, and chronic myeloid leukemia. There are data on the use of reaferon in the complex therapy of multiple sclerosis. The drug is administered intramuscularly, subconjunctivally and locally.
Intron A* - recombinant IFN-α 2b. The drug is prescribed for multiple myeloma, Kaposi's sarcoma, hairy cell leukemia and other cancers, as well as hepatitis A, chronic hepatitis B, acquired immunodeficiency syndrome. Intron is administered subcutaneously and intravenously.
Betaferon* (IFN-β 1b) is a non-glycosylated form of human IFN-β, a lyophilized protein product obtained by DNA recombination. The drug is used in the complex therapy of multiple sclerosis. Enter subcutaneously.
When using IFN, hematological disorders (leukopenia and thrombocytopenia), skin allergic reactions, flu-like conditions (fever, chills, myalgia, dizziness) sometimes develop.
IFN inductors (interferonogens) are substances that stimulate the formation of endogenous IFN (when administered to the body). As a rule, the interferonogenic action and immunomodulatory activity of drugs are combined.
Some drugs of a lipopolysaccharide nature (prodigiosan), low molecular weight polyphenols, fluorenes, etc. have interferonogenic activity. Immunomodulatory activity, accompanied by induction of IFN, was found in dibazol, a benzimidazole derivative.
IFN inductors include poludan* and neovir*.
Poludan* - polyadenyluridic acid. The drug is prescribed for adults with viral eye diseases (eye drops and injections under the conjunctiva).
Neovir* - sodium salt of 10-methylenecarboxylate-9-acridine. The drug is used to treat chlamydial infection. Enter intramuscularly.
21. Antiviral drugs: classification, mechanism of action, use in various localizations of a viral infection. Antitumor drugs: classification, mechanisms of action, features of purpose, disadvantages, side effects.
Antivirals:
a) anti-herpetic drugs
Systemic action - acyclovir(zovirax), valaciclovir (valtrex), famciclovir (famvir), ganciclovir (cymeven), valganciclovir (valcyte);
Local action - acyclovir, penciclovir (Fenistil pencivir), idoxuridine (Oftan Idu), foscarnet (Gefin), tromantadine (Viru-Merz Serol);
b) medicines for the prevention and treatment of influenza
Membrane protein blockers M 2 - amantadine, rimantadine (rimantadine);
Neuraminidase inhibitors - oseltamivir(tamiflu), zanamivir (relenza);
c) antiretrovirals
HIV reverse transcriptase inhibitors
Nucleoside structure - zidovudine(Retrovir), didanosine (Videx), lamivudine (Zeffix, Epivir), stavudine (Zerite);
Non-nucleoside structure - nevirapine (viramun), efavirenz (stokrin);
HIV protease inhibitors - amprenavir (agenase), saquinavir (fortovase);
Inhibitors of fusion (fusion) of HIV with lymphocytes - enfuvertide (fuzeon).
d) broad-spectrum antivirals
ribavirin(virazole, rebetol), lamivudine;
Interferon preparations
Recombinant interferon-α (grippferon), interferon-α2a (roferon-A), interferon-α2b (viferon, intron A);
Pegylated interferons - peginterferon- α2a (pegasys), peginterferon-α2b (PegIntron);
Interferon synthesis inductors - acridoneacetic acid (cycloferon), arbidol, dipyridamole (curantil), iodantipyrin, tilorone (amiksin).
Antiviral substances that are used as medicines can be represented by the following groups
Synthetics
Nucleoside analogs- zidovudine, aciclovir, vidarabine, ganciclovir, tri-fluridine, idoxuridine
Peptide derivatives- saquinavir
Adamantane derivatives- midantan, rimantadine
Derivative of indolecarboxylic acid -arbidol.
Derivative of phosphonoformic acid- foscarnet
Thiosemicarbazone derivative- metisazon
Biological substances produced by macroorganism cells – 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, particular attention has been drawn toantiretroviral 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 in HIV infection are represented by the following groups.
/. Reverse transcriptase inhibitorsA. Nucleosides Zidovudine Didanosine Zalcitabine Stavudine B. Non-nucleoside compounds Nevirapine Delavirdine Efavirenz2. HIV protease inhibitorsIndinavir Ritonavir Saquinavir Nelfinavir
One of the antiretroviral compounds is a nucleoside derivative azidothymidine
called zidovudine
). The principle of action of zidovudine is that, by being phosphorylated in cells and turning into triphosphate, it 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 soon 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 develops to it.
Of the side effects, hematological disorders come first: anemia, neutropenia, thrombocytopenia, pancythemia. Possible headache, insomnia, myalgia, inhibition of kidney function.
Tonon-nucleoside antiretroviral drugsinclude nevirapine (viramune), delavirdine (rescriptor), efavirenz (sustiva). They have a direct non-competitive inhibitory effect on reverse transcriptase. They bind to this enzyme at a different site compared to nucleoside compounds.
Of the side effects, a skin rash most often occurs, the level of transaminase increases.
A new group of drugs has been proposed for the treatment of HIV infection -HIV protease inhibitors.These enzymes, which regulate the formation of structural proteins and enzymes of HIV virions, are necessary for the reproduction of retroviruses. With insufficient amounts of them, immature precursors of the virus are formed, which delays the development of infection.
A significant achievement is the creation of selectiveantiherpetic drugs,which are synthetic derivatives of nucleosides. Among the highly effective drugs in this group is acyclovir (Zovirax).
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 blood plasma that inhibit the reproduction of retroviruses. Most of the substance binds to plasma proteins. The drug is administered orally. Side effects include dyspeptic disorders, increased activity of hepatic transaminases , lipid metabolism disorders, hyperglycemia.Development of resistance of viruses to saquinavir is possible.
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, sometimes there is a violation of kidney function, encephalopathy, phlebitis, skin rash. With enteral administration, nausea, vomiting, diarrhea, headache are noted.
New antiherpetic drug valaciclovir
This 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 ganciclovir, similar in pharmacodynamics to acyclovir.
Vidarabine is also an effective drug.
Once inside the cell, vidarabine is phosphorylated. Inhibits viral DNA polymerase. This inhibits the replication of large DNA-containing viruses. In the body, it is partially converted into a less active against viruses hypoxanthine arabinoside.
Vidarbin is successfully used in herpetic encephalitis (administered by intravenous infusion), reducing mortality in this disease by 30-75%. Sometimes it is used for complicated shingles. Effective in herpetic keratoconjunctivitis (assigned topically in ointments). In the latter case, it causes less irritation and less inhibition of corneal healing than idoxuridine (see below). Easier to penetrate into the deeper layers of tissue (in the treatment of herpetic keratitis). It is possible to use vidarabine in case of allergic reactions to idoxuridine and if the latter is ineffective.
Of the side effects, dyspeptic symptoms (nausea, vomiting, diarrhea), skin rash, CNS disorders (hallucinations, psychosis, tremor, etc.), thrombophlebitis at the injection site are possible.
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. Possible transient irritant effect, swelling of the eyelids.
Idoxuridin (kerecid, iduridin, oftan-IDU), which is an analogue of thymidine, is integrated into the DNA molecule. In this regard, it inhibits the replication of certain DNA-containing viruses. Idoxuridine is used topically for herpetic 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 (suppresses leukopoiesis).
Atcytomegalovirus infectionuse ganciclovir and foscarnet. Ganciclovir (cymeven) is a synthetic analogue of the 2"-deoxyguanosine nucleoside. Its 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. Often adverse neurological effects: headache, acute psychosis, convulsions, etc. 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 agents. Antiviral drugs effective for influenza infection can be represented by the following groups./. M2 viral protein inhibitorsRemantadine Midantan (amantadine)
2. Inhibitors of the viral enzyme neuraminidaseZanamivir
Oseltamivir
3. Viral RNA polymerase inhibitorsRibavirin
4. Miscellaneous drugsArbidol Oksolin
The first group refers toM2 protein inhibitors.Membrane protein M2, which functions as an ion channel, is found only in influenza type A 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, viral replication is suppressed.
This group includes midantan (adamantanamine hydrochloride, amantadine, symmetrel). Well absorbed from the gastrointestinal tract. It is excreted mainly by the kidneys.
Sometimes the drug is used to prevent influenza type A. It is ineffective as a therapeutic agent. More widely, midantan is used as an antiparkinsonian agent.
Similar properties, indications for use and side effects have rimantadine (rimantadine hydrochloride), similar in chemical structure to midantan.
Virus 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 inhibitors of neuraminidase (competitive, reversible action) prevent the spread of the virus associated with infected cells. Virus replication is disrupted.
One of the inhibitors of this enzyme is zanamivir (Relenza). It is used intranasally or inhaled
The second drug, oseltamivir (Tamiflu), is used in the form of ethyl ester.
Drugs have been created that are used both for influenza and other viral infections. To the group of synthetic drugs,inhibiting the synthesis of nucleic acids,includes ribavirin (ribamidil). It is a guanosine analogue. 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 virus infection (administered by inhalation), hemorrhagic fever with renal syndrome and Laska fever (intravenously). Side effects include skin rash, conjunctivitis
To the numberdifferent drugsrefers to arb idol. It is an indole derivative. It is used for the prevention and treatment of influenza caused by influenza A and B viruses, as well as for 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 administered orally. Well tolerated.
This group also includes the drug oxolin, which has a virucidal effect. It is moderately effective in preventing
These preparations are synthetic compounds. However, antiviral therapy is also usednutrients,especially interferons.
Interferons are used to prevent viral infections. This group of compounds belonging to low molecular weight glycoproteins is 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 virus attack. They have a broad antiviral spectrum.
More or less pronounced effectiveness of interferons in herpetic keratitis, herpetic lesions of the skin and genital organs, acute respiratory viral infections, herpes zoster, viral hepatitis B and C, and AIDS has been noted. Apply interferons locally and parenterally (intravenously, intramuscularly, subcutaneously).
Of the side effects, fever, the development of erythema and soreness at the injection site are possible, progressive fatigue is noted. In high doses, interferons can inhibit hematopoiesis (granulocytopenia and thrombocytopenia develop).
In addition to antiviral action, interferons have anti-cellular, antitumor and immunomodulatory activity.
Anticancer drugs: classification
Alkylating agents - benzotef, myelosan, thiophosfamide, cyclophosphamide, cisplatin;
Folic acid antimetabolites - methotrexate;
Antimetabolites - analogues of purine and pyrimidine - mercaptopurine, fluorouracil, fludarabine (cytosar);
Alkaloids and other herbal remedies vincristine, paclitaxel, teniposide, etoposide;
Antitumor antibiotics - dactinomycin, doxorubicin, epirubicin;
Monoclonal antibodies to tumor cell antigens - alemtuzumab (campas), bevacizumab (avastin);
Hormonal and antihormonal agents - finasteride (Proscar), cyproterone acetate (Androkur), goserelin (Zoladex), tamoxifen (Nolvadex).
ALKYLING AGENTS
Regarding the mechanisms of interaction of alkylating agents with cellular structures, there is the following point of view. On the example of chloroethylamines(a)it has been shown that in solutions and biological fluids they split off chloride ions. In this case, an electrophilic carbonium ion is formed, which passes into ethyleneimonium(in).
The latter also forms a functionally active carbonium ion (g), which interacts, according to existing ideas, with the nucleophilic structures of 2 DNA (with guanine, phosphate, aminosulfhydryl groups -
Thus, substrate alkylation occurs
The interaction of alkylating substances with DNA, including the cross-linking of DNA molecules, disrupts its stability, viscosity, and subsequently integrity. All this leads to a sharp inhibition of cell activity. Their ability to divide is suppressed, many cells die. Alkylating agents act on cells in interphase. Their cytostatic effect is especially pronounced in relation to rapidly proliferating cells.
Most of
It is mainly used for hemoblastoses (chronic leukemia, lymphogranulomatosis (Hodgkin's disease), lympho- and reticulosarcomas
Sarcolysin (racemelfolan), active in myeloma, lympho- and reticulosarcomas, effective in a number of true tumors
ANTIMETABOLITES
The drugs in this group are antagonists of natural metabolites. In the presence of neoplastic 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 (fludara)
In terms of chemical structure, anti-metabolites are only similar to natural metabolites, but not identical to them. In this regard, they cause a violation 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 in the general condition and the hematological picture occurs gradually. The duration of remission is estimated at several months.
The drugs are usually taken orally. Methotrexate is also available for parenteral administration.
Methotrexate is excreted by the kidneys, mainly unchanged. Part of the drug is retained in the body for a very long time (months). Mercaptopurine is exposed in the liver x
The negative aspects of the action of drugs are manifested in the oppression of hematopoiesis, nausea, and vomiting. Some patients have impaired liver function. 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 uterine chorionepithelioma, Wilms tumor in children, and for 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 tumors - seminoma, embryonic cancer, teratoblastoma, lymphoepithelioma. reticulosarcoma, melanoma. Enter it intravenously. In addition, with ulceration of superficially located tumors, olivomycin is applied topically in the form of ointments.
Antibiotics of the anthracycline group - doxorubicin hydrochloride (formedStreptomyces peuceticusvarcaesius) and karm and nom and qing (producerActinoma- duracarminatasp. new.) - are attracting attention due to their effectiveness in sarcomas of mesenchymal origin. So, doxorubicin (adriamycin) is used in osteogenic sarcomas, breast cancer and other tumor diseases.
When using these antibiotics, there is a violation of appetite, stomatitis, nausea, vomiting, diarrhea. Possible damage to the mucous membranes of yeast-like fungi. Hematopoiesis is inhibited. Sometimes there is a cardiotoxic effect. Hair loss often occurs. These drugs also have irritating properties. Their pronounced immunosuppressive effect should also be taken into account.
and autumn colchicum
VincaroseaL.)
The toxic effect of vincristine manifests itself in different ways. Suppressing hematopoiesis almost a little, it can lead to neurological disorders (ataxia, impaired neuromuscular transmission, neuropathy, paresthesia), kidney damage (polyuria, dysuria), etc.
Androgens
Estrogens
Corticosteroids
According to the mechanism of action on hormone-dependent tumors, hormonal drugs differ significantly from the cytotoxic drugs discussed above. Thus, there is evidence that under the influence of sex hormones, tumor cells do not die. Apparently, the main principle of their action is that they inhibit cell division and promote their differentiation. Obviously, to a certain extent, the disturbed humoral regulation of cell function is restored.
Androgens5
MEDICINES OF PLANT ORIGIN WITH ANTI-TUMOR ACTIVITY
Colchamine, an alkaloid of Colchicum splendid, has a pronounced antimitotic activity.
and autumn colchicum
Colhamin (demecolcin, 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 irritant effect (hyperemia, swelling, pain) may occur, which makes it necessary to take breaks in treatment. After rejection of necrotic masses, wound healing occurs with a good cosmetic effect.
With a resorptive effect, colchamine quite strongly inhibits hematopoiesis, causes diarrhea, and hair loss.
Antitumor activity was also found in the alkaloids of the plant periwinkle pink (VincaroseaL.) vinblastine and vincristine. They have an antimitotic effect and, like colhamine, block mitosis at the metaphase stage.
Vinblastine (Rozevin) is recommended for generalized forms of lymphogranulomatosis and for chorionepithelioma. In addition, it, like vincristine, is widely used in combination chemotherapy for tumor diseases. The drug is administered intravenously.
The toxic effect of vinblastine is characterized by inhibition of hematopoiesis, dyspeptic symptoms, and abdominal pain. The drug has a pronounced irritant effect and can cause phlebitis.
therapy of acute leukemia, as well as other hemoblastoses and true tumors. The drug is administered intravenously.
The toxic effect of vincristine manifests itself in different ways. Suppressing hematopoiesis almost a little, it can lead to neurological disorders (ataxia, impaired neuromuscular transmission, neuropathy, paresthesia), kidney damage (polyuria, dysuria), etc.
HORMONAL DRUGS AND HORMON ANTAGONISTS USED IN CANCER DISEASES
Of the hormonal preparations 1, the following groups of substances are mainly used for the treatment of tumors:
Androgens- testosterone propionate, testenat, etc.;
Estrogens- sinestrol, fosfestrol, ethinylestradiol, etc.;
Corticosteroids- Prednisolone, dexamethasone, triamninolone.
According to the mechanism of action on hormone-dependent tumors, hormonal drugs differ significantly from the cytotoxic drugs discussed above. Thus, there is evidence that under the influence of sex hormones, tumor cells do not die. Apparently, the main principle of their action is that they inhibit cell division and promote their differentiation. Obviously, to a certain extent, the disturbed humoral regulation of cell function is restored.
Androgensused in breast cancer. They are prescribed to women with a preserved menstrual cycle and in the case when menopause does not exceed5 years. The positive role of androgens in breast cancer is to suppress the production of estrogens.
Estrogens have been 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 (honwang)
CYTOKINES
ENZYMES EFFECTIVE IN THE TREATMENT OF CANCER DISEASES
It was found that a number of tumor cells do not synthesizeL-asparagine, which is necessary for the synthesis of DNA and RNA. In this regard, it became possible to artificially limit the supply of this amino acid to tumors. The latter is achieved by introducing the enzymeL-asparaginase, which is used in the treatment of acute lymphoblastic leukemia. Remission continues for 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. It has a beneficial effect in a number of tumor diseases (with chronic myeloid leukemia, Ka sarcoma
sew, etc.). Enter the drug parenterally. Side effects include fever, headache, myalgia, arthralgia, dyspepsia, hematopoiesis suppression, central nervous system dysfunction, thyroid dysfunction, nephritis, etc.
MONOCLONAL ANTIBODIES
Monoclonal antibodies include trastuzumab (Herceptin). Its antigens areHER2 receptors of breast cancer cells. Hyperexpression 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 drug that inhibits vascular endothelial growth factor. As a result, the growth of new vessels (angiogenesis) in the tumor is suppressed, which disrupts its oxygenation and the supply of nutrients to it. As a result, tumor growth slows down.
Content
Most viral diseases present with flu-like symptoms of varying degrees of severity. Depending on the specific pathology, different antiviral agents can be used. Their classifications are based on the mechanism and spectrum of action, origin and some other criteria.
Classification of antiviral agents according to the mechanism of action
Groups of antiviral drugs according to this classification are distinguished taking into account at what stage of the interaction of the virus with the cell the drug begins to act. There are 4 options for how antiviral agents affect the body:
|
The mechanism of action of antiviral agents |
Names of medicines |
|
Blocking the entry and release of the virus genome from the capsule inside the host cell. |
|
|
Inhibition of the process of assembly of viral particles and their release from the cytoplasm of the cell. |
|
|
Blocking the synthesis of viral RNA or DNA |
|
|
Inhibition of virion assembly |
Metisazon. |
Types of antiviral drugs by spectrum of action
The difference between antiviral drugs is the selectivity of their action. With this in mind, drugs are divided into types depending on the virus that they can affect the most. The classification of antiviral agents, taking into account the spectrum of their action, is presented in the table:
|
Fund group |
Title examples |
|
Anti-influenza |
|
|
Broad spectrum drugs |
These include interferons and interferonogens. |
|
Drugs affecting the human immunodeficiency virus |
|
|
Antiherpetic |
|
|
Against the chickenpox virus |
|
|
Anticytomegalovirus |
|
|
Against the hepatitis B and C virus |
interferons alpha. |
|
Antiretroviral |
|
Origin
Different substances have antiviral properties, so preparations based on them are also classified by origin. It distinguishes the following types of drugs:
|
Fund group |
Name examples |
|
Nucleoside analogs |
|
|
lipid derivatives |
|
|
Thiosemicarbazone derivatives |
Metisazon |
|
Adamantane derivatives |
|
|
Biological substances produced by macroorganism cells |
Interferons. |
Classification according to Mashkovsky M.D.
The founder of Soviet pharmacology proposed his own classification. According to it, antiviral agents for children and adults were divided into the following groups:
|
Group name |
Peculiarities |
Title examples |
|
Interferons |
Interferons are cytokines, presented in the form of proteins that exhibit antitumor, immunomodulatory and antiviral properties. |
|
|
Interferon inducers |
The antiviral effect of these drugs is to stimulate the production of their own interferon. |
|
|
Immunomodulators |
When taking a therapeutic dose of immunomodulators, the function of the immune system is restored. |
|
|
Derivatives of adamantane and other groups |
Influence the aggregation of human platelets. |
|
|
Nucleosides |
These are glycosylamines containing a nitrogenous base. |
|
|
Herbal preparations |
Obtained from plants. |
|
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The site provides reference information for informational purposes only. Diagnosis and treatment of diseases should be carried out under the supervision of a specialist. All drugs have contraindications. Expert advice is required!
What are antivirals?
Antivirals are medicines aimed at combating various types of viral diseases ( herpes, chicken pox, etc.). Viruses are a separate group of living organisms that can infect plants, animals and humans. Viruses are the smallest infectious agents, but also the most numerous.Viruses are nothing more than genetic information ( short chain of nitrogenous bases) in a shell of fats and proteins. Their structure is simplified as much as possible, they do not have a nucleus, enzymes, energy supply elements, which is how they differ from bacteria. That is why they have microscopic dimensions, 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 to date is very small. Many drugs carry out the fight against the virus on the principle of activating the body's own immune forces. Also, there are no antiviral drugs that could be used in case of a variety of viral infections, most of the existing drugs are narrowly aimed at treating one, maximum two diseases. This is due to the fact that viruses are very diverse, with various enzymes and defense mechanisms 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, aimed at combating the herpes virus. Their effectiveness was sufficient, but a large number of side effects almost completely ruled out the possibility of its use in the treatment of herpes. In the 60s, amantadine and rimantadine were produced, drugs that are still used today.All preparations before the beginning of the 90s were obtained empirically, with the help of observations. Efficiency ( mechanism of action) of these medicinal products was difficult to prove due to the lack of necessary knowledge. Only in recent decades, scientists have 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 agents are used only in certain cases.
A great success in medicine was the discovery of human interferon, a substance that performs antiviral activity in the human body. It was proposed to use it as a medicine, after which scientists received methods for purifying it from donated blood. Of all antiviral drugs, only interferon and its derivatives can claim the title of broad-spectrum drugs.
In recent years, the use of natural preparations for the treatment of viral diseases has become popular ( e.g. echinacea). Also today, the use of various immunomodulatory drugs that provide prophylaxis against viral diseases is popular. Their action is based on an increase in 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 necessary cure has not yet been found.
Production of antiviral drugs. The basis of antiviral drugs
There is a wide variety of antiviral drugs, but all of them have disadvantages. This is partly due to the complexity of developing, manufacturing and testing drugs. Antiviral drugs need to be tested, of course, on viruses, but the problem is that viruses outside cells and outside other organisms do not live long and do not manifest themselves in any way. They are also quite difficult to distinguish. Unlike viruses, bacteria are cultivated on nutrient media, and by slowing down their growth, one can judge the effectiveness of antibacterial drugs.To date, antiviral drugs are obtained in the following ways:
- Chemical synthesis. The standard way to manufacture drugs is to obtain drugs through chemical reactions.
- Obtaining from vegetable raw materials. Some parts of plants, as well as their extracts, have an antiviral effect, which is used by pharmacists in the manufacture 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 desired chemical compounds. In the future, they are purified and used as an antiviral agent. This is how, for example, some types of antiviral vaccines, recombinant interferon and other drugs are obtained.
Antivirals, antifungals and antibiotics, differences. Can they be taken together?
Differences between antiviral, antifungal and antibacterial agents ( antibiotics) are included in their name. All of them are created against different classes of microorganisms that cause diseases that differ 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 are directed against 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 by a bacterial infection. They are almost always characterized by standard clinical features ( pain, fever, redness, swelling and dysfunction) and have minor differences. Diseases caused by bacteria constitute the largest group and have been studied most fully.
Fungal infections occur, as a rule, with a weakened immune system and affect mainly the surface of the skin, nails, hair, and mucous membranes. The best example of fungal infections is candidiasis ( thrush). For the treatment of fungal infections, only antifungal drugs should be used. The use of antibacterial drugs is a mistake, since fungi very often develop precisely in case of an imbalance in the bacterial flora.
Finally, antiviral drugs are used to treat viral diseases. You can suspect that you have a viral disease by the presence of flu-like symptoms ( headache, body aches, fatigue, mild fever). This onset is characteristic of 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 simultaneous viral and bacterial lesions, doctors prescribe drugs from both groups.
The listed groups of drugs are considered potent drugs and are sold only by prescription. For the treatment of viral, bacterial or fungal diseases, you need to consult a doctor and do not self-medicate.
Antivirals with proven efficacy. Are modern antiviral drugs effective enough?
Currently, there is a limited number of antiviral drugs. The number of active substances with proven effectiveness against viruses is about 100 items. Of these, only about 20 are widely used in the treatment of various diseases. Others have either a high price or a large number of side effects. Some of the drugs have never passed clinical trials, despite many years of practice. For example, only oseltamivir and zanamivir have proven efficacy against influenza, despite the fact that a large number of anti-flu drugs are sold in pharmacies.Antiviral drugs that have proven effectiveness include:
- valaciclovir;
- vidarabine;
- foscarnet;
- interferon;
- rimantadine;
- oseltamivir;
- ribavirin and some other drugs.
In general, when using antiviral drugs, especially those sold freely in pharmacies, you need to be very careful. Most of them do not have the desired healing properties, and the benefits of their use are equated by many doctors with placebo ( a dummy substance that has no effect on the body). Treating viral infections infectious diseases doctors enroll) , 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 severe side effects ( nephrotoxicity, hepatotoxicity, nervous system disorders, electrolyte disorders, and many others).
Is it possible to buy antiviral drugs in a pharmacy?
Not all antiviral drugs can be purchased at a pharmacy. This is due to the serious effect of drugs on the human body. Their use requires permission and supervision by a doctor. This applies to interferons, drugs against viral hepatitis, antiviral agents of systemic action. To buy a prescription drug, you need a special form with the seal of a doctor and a medical institution. In all infectious diseases hospitals, antiviral drugs are issued without a prescription.However, there are various antiviral agents that can be purchased without a prescription. So, for example, ointments against herpes ( containing acyclovir), interferon-containing eye and nasal drops, and many other products are commercially available. Immunomodulators and herbal antiviral drugs can also be purchased without a prescription. They are equated, as a rule, with biologically active additives ( dietary supplement).
Antiviral drugs according to the mechanism of action are divided into the following groups:
- drugs that act on extracellular forms of the virus ( oxolin, arbidol);
- drugs that prevent the entry of the virus into the cell ( rimantadine, 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 that act on extracellular forms of the virus
This group includes a small number of drugs. One of these drugs is oxolin. It has the ability to penetrate the shell of the virus outside the cells and inactivate its genetic material. Arbidol affects the lipid membrane of the virus and makes it unable to merge with the cell.Interferon has an indirect effect on the virus. These drugs can attract cells 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, rimantadine. They can be used against influenza virus as well as tick-borne encephalitis virus. These drugs are united by the ability to disrupt the interaction of the virus envelope ( in particular M-protein) with cell membrane. As a result, foreign genetic material does not enter the cytoplasm of a human cell. In addition, a certain obstacle is created during the assembly of virions ( virus particles).It is advisable to take these drugs only in the first days of the disease, since at the height of the disease the virus is already inside the cells. These drugs are well tolerated, but due to the peculiarities of the mechanism of action, they are used only for preventive purposes.
Drugs that block the activity of the virus inside the cells of the human body
This group of drugs is the widest. One of the ways to stop the reproduction of the virus is to block the DNA ( RNA) - polymerase. 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. Ribavirin and some other antiviral drugs also inhibit DNA polymerases.This group also includes antiretroviral drugs that are used to treat HIV. They inhibit the activity of reverse transcriptase, which converts viral RNA into cell DNA. These include lamivudine, zidovudine, stavudine, and other medicines.
Drugs that block the assembly and release of the virus from cells
One of the representatives of the group is metisazon. This agent blocks the synthesis of the viral protein that makes up the virion envelope. The drug is used to prevent chickenpox, as well as to reduce the complications of vaccination against chickenpox. This group is promising in terms of creating new drugs, since the drug metisazon has a pronounced antiviral activity, is easily tolerated by patients and is administered orally.Interferons. The use of interferons as a drug
Interferons are low molecular weight proteins that the body produces on its own in response to infection with a virus. There are different types of interferons ( alpha, beta, gamma), which differ in their 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, it is impossible for the immune system to function and protect the body from viruses.Interferons have the following qualities that allow them to exhibit an antiviral effect:
- inhibit the synthesis of viral proteins inside cells;
- slow down the assembly of the virus inside the cells of the body;
- block DNA and RNA polymerase;
- activate systems of cellular and humoral immunity against viruses ( attract leukocytes, activate the complement system).
interferon inducers ( kagocel, trekrezan, cycloferon, amixin)
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 inductors are substances that increase the body's production of its own interferon. Interferon inductors have a weak direct antiviral effect, but have a pronounced immunostimulatory effect. Their activity is due mainly to the effects of interferon.There are the following groups of interferon inducers:
- natural preparations amixin, poludan and others);
- synthetic drugs ( polyoxidonium, galavit and others);
- herbal preparations ( echinacea).
Antiviral drugs have a specific, selective effect. They are usually divided into types according to the virus on which they have the greatest impact. The most common classification involves 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
Pathogen | Most commonly used drugs |
herpes virus |
|
flu virus |
|
Varicella zoster virus |
|
Cytomegalovirus |
|
AIDS virus(HIV) |
|
hepatitis virus B and C |
|
paramyxovirus |
|
antiherpetic drugs ( acyclovir ( zovirax) and its derivatives)
Herpes viruses are divided into 8 types, they are relatively large viruses containing DNA. Manifestations of herpes simplex cause 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 modified substance acyclovir has the ability to inhibit ( stop development) viral DNA polymerase. The advantage of the drug is the selective action. In healthy cells, acyclovir is inactive, and in relation to ordinary cellular DNA polymerase, its action 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 with systemic use.
The following drugs are also effective in the treatment of herpes:
- Ganciclovir. Similar in mechanism of action to acyclovir, but has a stronger effect, due to which the drug is also used in the treatment of tick-borne encephalitis. Despite this, the drug 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 is the presence of a different nitrogenous base. In terms of efficacy and toxicity, it is comparable to acyclovir.
- Valaciclovir. 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 undergoing 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 strains of the virus that are resistant to acyclovir. Foscarnet is also used for cytomegalovirus, herpetic and tick-borne encephalitis. It is administered intravenously, because of this, it has a large number of side effects.
Anti-influenza drugs ( arbidol, rimantadine, tamiflu, relenza)
There are many variants of influenza viruses. There are three types of influenza viruses ( A, B, C), as well as their division according to variants of surface proteins - hemagglutinin ( H) and neuraminidase ( N). Due to the fact that it is very difficult to determine the specific type of virus, anti-influenza drugs are not always effective. Anti-influenza drugs are usually used for severe infections, as with mild clinical manifestations, the body copes with the virus on its own.There are the following types of anti-influenza drugs:
- Inhibitors of the viral protein M ( rimantadine, 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 break down mucous secretions and penetrate the cells of the respiratory tract mucosa. The drugs of this group prevent the spread and replication ( reproduction) virus. One such drug is zanamivir ( relenza). It is used in the form of 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 effectiveness. The drugs are well 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 a mutagenic and carcinogenic property, so they must be used with caution.
- Other drugs ( arbidol, oxolin). There are many other drugs that can be used for the flu virus. They have a weak antiviral effect, some additionally stimulate the production of their own interferon. However, it is worth noting that these drugs do not help everyone and not in all cases.
Medicines to fight HIV infection
Treatment of HIV infection is one of the most serious problems in medicine today. The drugs that are available to modern medicine can only contain this virus, but not get rid of it. The human immunodeficiency virus is dangerous because it destroys the immune system, as a result of which the patient dies from bacterial infections and various complications.Drugs to fight HIV infection are divided into two groups:
- reverse transcriptase inhibitors ( zidovudine, stavudine, nevirapine);
- HIV protease inhibitors ( indinavir, saquinavir).
A relatively new group of antiretroviral drugs are protease inhibitors. 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 infection. One such drug is saquinavir. It inhibits the multiplication of retroviruses, but it also has the potential to develop resistance. That is why doctors use combinations of drugs from both groups in the treatment of HIV and AIDS.
Are there broad spectrum antivirals?
Despite the claims of drug manufacturers, as well as advertising information, there are no broad-spectrum antiviral drugs. The drugs that exist today and are recognized by official medicine are characterized by a directed, 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 active against 2-3 viruses ( e.g. 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, they are immunomodulators and have a weak antiviral effect. They are used mainly for the prevention, and not 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 for admission as part of courses, a large number of side effects) make it impossible to use against mild viral infections. That is why interferons are now used mainly for the treatment of viral hepatitis.
Antiviral drugs - immunostimulants ( amixin, kagocel)
Today, various drugs that stimulate the immune system are very common on the market. 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. 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 fourth day the level of interferon increases on its own. Amixin has a similar effect ( tilorone) 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 application time before the onset of illness);
- the effectiveness of the drug depends on the state of the human immune system;
- with prolonged use, immunity is depleted;
- lack of clinically proven efficacy in this group of drugs.
herbal antivirals ( echinacea preparations)
Herbal antivirals are one of the best options in 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 ( immune depletion, limited efficacy).One of the best options for preventive use is echinacea-based preparations. This substance has a direct antiviral effect against herpes and influenza viruses, increases the number of immune cells and contributes to the destruction of various foreign agents. Echinacea preparations can be taken in courses lasting from 1 to 8 weeks.
Homeopathic antivirals ( ergoferon, anaferon)
Homeopathy is a branch of medicine that uses highly diluted concentrations of the active substance. The principle of homeopathy is to use those substances that are expected to cause symptoms similar to the diseases of the patient ( the so-called principle of "treating like with like"). This principle is opposite to the principles of official medicine. In addition, normal physiology cannot explain the mechanisms of action of homeopathic remedies. It is assumed that homeopathic remedies help in recovery by stimulating the neurovegetative, endocrine, and immune systems.Few suspect that some antiviral agents sold in pharmacies are homeopathic. So, drugs ergoferon, anaferon and some others are homeopathic remedies. They contain various antibodies to interferon, to histamine and to some receptors. As a result of their use, the connection of the components of the immune system improves, the speed of protective processes dependent on interferon increases. Ergoferon also has a slight anti-inflammatory and anti-allergic effect.
Thus, homeopathic antiviral drugs have the right to exist, but it is advisable to use them as a prophylactic or adjuvant. 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 remedies 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 for their intended purpose according to the instructions. Indications and contraindications for the use of drugs should also be observed, since the benefits and harms to the health of the patient depend on this. For certain groups of patients ( pregnant women, children, diabetic patients) should be especially careful when using antiviral agents. The group of antivirals has a large number of side effects, so their distribution and use are carefully controlled by the Ministry of Health. If the use of an antiviral drug causes side effects, you should immediately consult a doctor. He decides on the advisability of continuing treatment with this drug.
Indications for the use of antiviral agents
The purpose of 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 a 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.
Some antiviral agents have their own characteristics. Thus, interferons are used in oncological diseases ( melanoma, cancer). They are used as chemotherapeutic agents to shrink tumors. Amantadine ( midantan), used to treat influenza, is also suitable for the treatment of Parkinson's disease and neuralgia. Many antiviral agents also have an immunostimulatory effect, but the use of immunostimulants is generally frowned upon 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 antivirals include diseases of the kidneys, liver, and hematopoietic system.Among the most common contraindications to this group of drugs are:
- Mental disorders ( psychosis, depression). Antiviral drugs can adversely affect the psychological state of a person, especially during the first time of use. In addition, for patients with mental disorders, the risk of misuse of drugs is very high, which is very dangerous for drugs with a lot of side effects.
- Hypersensitivity to one of the components of the drug. Allergy is a problem for the use of any medication, not just antivirals. It can be suspected in the presence of other allergies ( e.g. pollen) or allergic diseases ( bronchial asthma). To prevent such reactions, it is worth passing 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, white blood cells. That is why most antiviral drugs are not suitable for patients with hematopoietic disorders.
- Severe pathology of the heart or blood vessels. When using drugs such as ribavirin, foscarnet, interferons, the risk of cardiac arrhythmia, an increase or decrease in blood pressure, increases.
- Cirrhosis of the liver. Many antiviral drugs undergo various transformations in the liver ( phosphorylation, the formation of less toxic products). Liver disease associated with liver failure ( such as 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 the possibility of their use in autoimmune diseases. For example, interferons cannot be used in 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.
Forms of release of antiviral drugs ( tablets, drops, syrup, injections, suppositories, ointments)
Antiviral drugs are now produced in almost all dosage forms available to modern medicine. They are intended for both local and systemic use. A variety of forms is 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 application depend on the dosage form.Modern antiviral drugs are available in the following dosage forms:
- oral tablets;
- powder for 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.
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 injection solution) you need to dose the drug correctly to eliminate side effects. That is why the use of antiviral agents in such cases should be performed under the supervision of medical personnel.
Antiviral drugs for systemic and topical use
There are a large number of forms of antiviral drugs that can be used both locally and systemically. This may even apply to the same active substance. For example, acyclovir is used both as an ointment or gel ( for local 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, as well as aerosols are used for topical application;
- characterized by a pronounced effect in the area of application and no effect in remote 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 lips, papillomas and some other diseases;
- used for mild viral infections.
- used in case of generalized infection ( HIV, hepatitis), as well as in severe disease ( e.g. influenza complicated by pneumonia);
- has an effect on all cells in the human body, as it enters them through the bloodstream;
- for systemic use, oral tablets, injections, rectal suppositories are used;
- has a higher risk of side effects;
- generally used when topical treatment alone is ineffective.
Instructions for the use of antiviral drugs
Antiviral drugs are quite strong drugs. In order to achieve the desired effect from them and avoid side effects, you should follow the instructions for using the drugs. Each drug has its own instructions. The dosage form of the drug plays the greatest role in the use of antiviral agents.The following most common ways of using antiviral agents are distinguished, depending on the dosage form:
- Tablets. Tablets are taken orally during or after meals 1 to 3 times a day. A suitable dosage is selected by taking a whole tablet or half of it.
- Injections. Should be performed by medical personnel, as improper administration threatens the development of complications ( including post-injection abscess). The powder of the drug is completely dissolved in the liquid for injection and is administered intramuscularly ( rarely 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 and even more often.
- Nasal and eye drops. Proper use of drops such as influenza) implies their introduction in the amount of 1 - 2 drops in each nasal passage. They can be used 3 to 5 times a day.
- Dosage of the drug. The most important parameter, observing which you can exclude an overdose. Antivirals are usually taken in small concentrations ( from 50 to 100 mg of active ingredient).
- Frequency of use during the day. Tablets of antiviral agents are taken 1 to 3 times a day, drugs for topical use ( drops, ointments) can be used 3-4 times a day and more often. When applied topically, overdose phenomena are observed very rarely.
- Duration of use. The duration of the course is set by the doctor and depends on the severity of the disease. Stopping treatment with antiviral drugs should be carried out after examination by a doctor.
- Storage conditions. It is necessary to observe the storage temperature indicated in the instructions. Some drugs need to be stored in the refrigerator, others at room temperature.
Courses of antiviral drugs
Some antiviral drugs are used as part of long-term 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 hepatitis and HIV viruses to drugs. Hepatitis drugs are taken from 3 to 6 months, against HIV - more than a year. Also, the use as part of course therapy is accepted for interferon and some other drugs.The duration of treatment with most antiviral drugs is no more than 2 weeks. During this time, influenza, herpes, enterovirus infection and other viral diseases are usually cured. Another way to use antiviral drugs is prophylaxis. If prophylactic goals are pursued, the duration of taking antiviral drugs is from 3 to 7 days.
Most Common Side Effects of Antivirals
Side effects from the use of antiviral agents are indeed common. Naturally, the nature of side effects to a large extent depends on the drug itself, as well as its dosage form. Systemic drugs tend to create more side effects. Side effects are not common to all drugs, but it is possible to summarize and highlight the most common adverse reactions of the body to taking antiviral drugs.The most common side effects of antiviral drugs are:
- Neurotoxicity ( negative effect on the central nervous system). It is expressed by headache, fatigue,
Content
1. Introduction………………………………………………………3
2. The history of the creation of antiviral drugs………….4
3. Classification of antiviral agents………………...7
4. Mechanism of biological activity…………………….14
5. Conclusion…………………………………………………. 21
6. References…………………………………………22
Viral diseases are widespread. Among them are known herpetic infections, adenovirus infections, hepatitis B, influenza and parainfluenza, smallpox, rabies, tick-borne encephalitis, enterovirus diseases (poliomyelitis, hepatitis A, gastroenteritis, etc.), AIDS and other diseases. Often viral diseases are accompanied by severe complications that require special therapy. Viruses reproduce only in living tissues. Having penetrated inside the host cell, they begin to multiply and rebuild the system of metabolic processes of ribosomes of cells to build new viral RNA or DNA. This creates difficulties in directly affecting the virus without damaging the cell itself.
The problem of influenza and other acute respiratory viral infections is complex and complex in its solution. Prevention of these diseases should be timely, and emergency chemoprophylaxis can be taken after vaccination against influenza in the pre-epidemic period, especially for those who were not vaccinated against influenza before the epidemic.
The history of the creation of antiviral drugs
The first drug proposed as a specific antiviral agent was thiosemicarbazone, the virucidal effect of which was described by G. Domagk (1946). The drug of this group, thiocetosone, has some antiviral activity, but is not effective enough; it is used as an anti-tuberculosis agent. Derivatives of this group 1, 4-benzoquinone-guanyl-hydrazinothio-semicarbazone under the name "faringosept" (faringosept, Romania) are used in the form of "perlingual" (orally resorbable) tablets for the treatment of infectious diseases of the upper respiratory tract (tonsillitis, stomatitis, etc. .)
Later, metisazon was synthesized, which effectively suppresses the reproduction of smallpox viruses, and in 1959, the nucleoside idoxuridine, which turned out to be an effective antiviral agent that suppresses the herpes simplex virus and vaccinia (vaccination disease). Side effects with systemic use have limited the possibility of widespread use of idoxuridine, but it has survived as an effective topical agent in ophthalmic practice for herpetic kerotitis. Following idoxuridine, other nucleosides began to be obtained, among which highly effective antiviral drugs were identified, including acyclovir, ribamidin (ribovirin) and others. In 1964 amantadine (midantin) was synthesized, then rimantadine and other adamantane derivatives proved to be effective antiviral agents. An outstanding discovery was the discovery of endogenous interferon and the establishment of its antiviral activity. Modern technology of DNA recombination (genetic engineering) has opened up the possibility of widespread use of interferons for the treatment and prevention of viral and other diseases.
An outstanding event was the discovery of endogenous interferon and the establishment of its antiviral activity. Until 1957, interferons were regarded as a curious biological phenomenon. The period 1957 - 1967 was devoted to the study of the general patterns of production and action of interferon. In the process of this work, the universality of the phenomenon of the formation of this protein by the cells of all vertebrates (from fish to humans) was established, and the main methods for its production and purification were developed.
In 1967, the leading role of high-molecular-weight double-stranded RNAs in the induction of interferon was proved, and the search for the most active drugs with prospects for clinical use was begun. Over the next thirteen years (1967 - 1980), the anti-tulurogenic effect of interferon and its inducers was studied, and the principles of superinduction of interferon were experimentally substantiated .
The 80s were marked by such major events in the study of interferon and its inducers:
1) the doctrine of the interferon system was finally formed;
2) interferon preparations promising for clinical use have been obtained using genetic engineering methods;
3) the multiplicity of interferon genes has been proven (in humans, their number approaches 30);
4) indications and contraindications for the clinical use of interferons and their inducers are determined.
In the 1980s and 1990s, it was established that the action of a number of immunostimulating and antiviral agents (Prodigozan, Poludan, Arbidol, etc.) is associated with their interferogenic activity, i.e., the ability to stimulate the formation of endogenous interferon.
Domestic researchers have developed a number of synthetic and natural (plant origin) drugs for systemic and local use in viral diseases (bonafton, arbidol, oxolin, deutiformin, tebrofen, alpizarin, etc.). It has now been established that the action of a number of immunostimulating and antiviral agents is associated with their interferon activity, i.e. ability to stimulate the formation of endogenous interferon.
According to the sources of production and chemical nature, antiviral drugs are divided into the following groups:
interferons of endogenous origin and obtained by genetic engineering, their derivatives and analogues (human leukocyte interferon,gripferon , ophthalmoferon , herpferon );
synthetic compounds (amantadine , arbidol , bonafton and etc.);
substances of plant originalpizarin , flacoside and etc.).
Table. Classification of antiviral drugs
But more accessible for understanding, antiviral drugs can be divided, depending on the type of disease, into groups:
1. Anti-influenza drugs (rimantadine, oxolin, etc.)
2. Antiherpetic and anticytomegalovirus (tebrofen, riodoxone, etc.)
3. Drug affecting the human immunodeficiency virus (azidothymidine, phosphanoformate)
4. Broad-spectrum drugs (interferons and interferonogens)
Mashkovsky M.D. created the following classification of antiviral drugs:
A) interferon
interferon. Leukocyte interferon from human donor blood.
interlock. Purified β-interferon obtained from donated blood.
reaferon. Recombinant b 2 -interferon produced by a bacterial strain of Pseudomonas, in the genetic apparatus of which the human leukocyte b 2 -interferon gene is inserted.
intron A. Recombinant interferon alfa-2c.
betaferon. Recombinant human in 1-interferon.
Interferon inducers poludan. Powder or porous mass of white color, has immunostimulatory activity, i.e. the ability to stimulate the production of endogenous interferon and has an antiviral effect.
neovir. The action is the same as that of a half-dan.
B) Derivatives of amantadine and other groups of synthetic compounds
Remantadin. It is used as an antiparkinsonian agent, indicates a preventive effect against influenza infection caused by certain strains of viruses.
Adapromin. Close to rimantadine.
Deutiforin. Similar to rimantadine.
Arbidol. An antiviral drug that has an inhibitory effect on influenza A and B viruses.
Bonafton. It has antiviral activity against the herpes simplex virus and some adenoviruses.
Oksolin. It has virucidal activity, is effective in viral diseases of the eyes, skin, viral rhinitis; has a preventive effect on influenza.
Tebrofen. It is used as an ointment for viral eye diseases, as well as for skin diseases of viral or suspected viral etiology. It can also be used to treat flat warts in children.
Riodoxol. It has antiviral optimality and has an antifungal effect.
9. Florenal. Opens a neutralizing effect against viruses.
10 Metisazon. It suppresses the reproduction of the virus of the main group: it has a preventive activity against the smallpox virus and facilitates the course of post-vaccination complications, delays the spread of the skin process, and contributes to a faster drying of effeorations. There is evidence of the effectiveness of metisasone in the treatment of recurrent genital herpes.
B) Nucleosides
Idoxuridin. Used for keratitis in ophthalmology.
Acyclovir. Effective against herpes simplex and herpes zoster viruses. It has an immunostimulating effect.
Ganciclovir. Compared with acyclovir, ganciclovir is more effective and, in addition, acts not only on the herpes virus, but also on cytomegalovirus.
Famciclovir. It has the same functions as ganciclovir.
Ribamidil. Ribamidil, like acyclovir, has antiviral activity. Inhibits the synthesis of viral DNA and RNA.
Zidovudine. An antiviral drug that inhibits the replication of retroviruses, including the human immunodeficiency virus (HIV).
D) Antiviral drugs of plant origin
1. 1. Flacoside. Obtained from velvet leaves of the Amur rue family. The drug is effective against DNA viruses.
2. Alpidarin. Obtained from the herb Koneermena alpine and yellowing kopeechnik, of the legume family. Effective against DNA-containing viruses of the herpes group. The inhibitory effect on the reproduction of the herpes simplex virus manifests itself mainly in the early stages of the development of the virus.
3. Cholepin. Purified extract from a part of the mepedecia penny plant, legume family. It has antiviral activity against DNA-containing viruses of the herpes group.
4. Ligosin. Used for herpetic skin diseases.
5. Gossypol. A product obtained from the processing of cotton seeds or from the roots of the cotton plant, the Malvaceae family. The drug has activity against various strains of viruses, including dermatotropic strains of the herpes virus. Has a weak effect on gram-positive bacteria.
Mechanisms of biological activity
1 Anti-influenza drugs
All drugs of this group protect human cells from the penetration of the influenza virus into them, because. block the binding sites of the virus to the surface of the cell membrane. They do not affect viruses that have penetrated inside the cell, therefore they are used for individual or mass prevention of influenza in persons who are in contact with patients or during an epidemic. All drugs (except oxolin) are prescribed orally. They are well absorbed from the gastrointestinal tract. In a very small percentage, they bind to blood plasma proteins, penetrate well into all tissues and fluids, including cerebrospinal fluid. Elimination is carried out partly by the liver, and mainly by the kidneys (90%). Therefore, in patients with impaired renal function, repeated doses of drugs can lead to cumulation and be accompanied by undesirable effects.
2 Antiherpetic and anti-cytomegalovirus drugs
Antiherpetic (tebrofen, riodoxol, idoneuridine, vidarabine, acyclovir, valaciclovir). Anticytomegalovirus (ganciclovir, phosphonoformate).
All of these drugs block replication, i.e. disrupt the synthesis of nucleic acids of the virus. Vidarabine is used topically, and in case of disseminated herpes infection (encephalitis), it is administered intravenously by drip. But the drug is poorly soluble, so its infusion in a large amount of liquid lasts about 12 hours, which is undesirable for a patient with encephalitis, cerebral edema. The use of vidarabine across the blood-brain barrier is approximately 30% of the concentration of the drug in plasma.
3 Medicines affecting human immunodeficiency virus (HIV) (zidovusine, phosphonoformate)
After the penetration of lymphotropic HIV into a lymphocyte, viral DNA is synthesized on a matrix (viral RNA) under the influence of reverse transcriptase (revertase), which leads to damage to lymphocytes. The mechanism of action of aredothymidine and phosphonoformite is to block the named enzyme. In general, drugs are effective in carriers of the virus before signs of the disease appear. In addition to these drugs, new antiretroviral drugs have now appeared: dideoxymycetin and dideoxycidin. Azidovudine is administered orally or administered intravenously. Bioavailability from the gastrointestinal tract 60%. Communication with blood plasma proteins 35%. Azidothymidine easily penetrates into various tissues and fluids, including cerebrospinal fluid. It undergoes biotransformation in the liver, its main metabolite 5 | -o-glucuronide. Excretion - with the help of the kidneys unchanged (90%) and in the form of metabolites.
4 Broad-spectrum antivirals (interferons)
Under the influence of interferon inducers (numerous synthetic and natural agents), induction is carried out, the result of which is the depression of interferon genes, which are localized in the 2nd, 9th and, possibly, in the 5th and 13th human chromosomes. In response to induction, the formation and synthesis of interferon in the cells of the human body occurs.
The main indicator of the activity of interferon inducers is the production of the so-called "serum" interferon in the blood.
Antivirals
Poludan polyadenyluridic acid. The drug is used in adults with viral eye diseases. Assign in the form of eye drops and injections under the conjunctiva.
A specific anti-influenza drug is rimantadine, which has a pronounced therapeutic and prophylactic effect on all variants of the influenza A virus. Due to toxic side effects, it is recommended for use in children from the age of seven and adults. For prevention during an epidemic, take 1-2 tablets rimantadine per day up to 20 days, and in the focus of the disease 5-7 days until the patient recovers.
Another means of specific prevention of influenza is the domestic antiviral drug arbidol. It inhibits the adsorption and penetration of influenza viruses into the cell, being also an immunomodulator, an interferon inducer and an antioxidant. Arbidol effective for both influenza A and influenza B, as well as for some
SARS. Unlike rimantadine arbidol refers to low-toxic drugs and has no contraindications for use in adults and children. It is recommended
Pharmaceutical Committee of the Russian Federation for the treatment and prevention of acute respiratory viral infections.
RIMANTADINE (Remantadine)
Domestic anti-influenza drug developed on the basis of amantadine.
Spectrum of activity: influenza virus type A, and the activity is 5-10 times higher than that of amantadine.
Indications Treatment of influenza caused by type A virus.
Influenza prophylaxis if the epidemic is caused by type A virus Prophylactic administration is necessary only for those who have not received influenza vaccination, or if less than 2 weeks have passed since vaccination. The efficiency is 70-90%.
OXOLIN OINTMENT effective for viral diseases of the eyes, skin, and viral rhinitis. Use the drug for individual prevention of influenza. During the influenza epidemic, especially when in contact with patients, its ointment is used to lubricate the nasal mucosa in the morning and evening. In this case, sometimes there is a passing burning sensation of the mucous membrane.
ZANAMIVIR (Relenza)
The first representative of inhibitors of viral neuraminidase - a new class of anti-influenza drugs. It is used to treat influenza caused by viruses types A and B.
Spectrum of activity: Influenza viruses types A and B.
Indications: Treatment of influenza caused by viruses A and B.
OSELTAMIVIR (Tamiflu)
It is similar in chemical structure and action to zanamivir. Designed for ingestion.
Indications: Treatment and prevention of influenza A and B.
Acyclovir (Zovirax, Valtrex)
He is the ancestor of the group of viral DNA polymerase inhibitors.
- Infections caused h.simplex:
- genital herpes;
mucosal herpes;
herpetic encephalitis;
neonatal herpes.
- shingles;
chicken pox;
pneumonia;
encephalitis.
VALACIKLOVIR (Valtrex)
It is a valine ester of acyclovir intended for oral administration. In the process of absorption in the gastrointestinal tract and in the liver, it turns into acyclovir.
- Infections caused h.simplex: genital herpes, mucocutaneous herpes.
Shingles ( H.zoster) in immunocompromised patients.
Prevention of cytomegalovirus infection after kidney transplantation.
FAMCICLOVIR (Famvir)
Structurally close toacyclovir , is a prodrug.
Indications: Infections caused by H.simplex: genital herpes, mucosal herpes, Shingles (H.zoster) in immunocompromised patients.
Ganciclovir ( cymevene ) structurally similar to acyclovir, but more effective. This drug works not only on the virusherpes, but also on cytomegalovirus often leading to severe complicationsAIDS e. Possible side effects. Ganciclovir is contraindicated in pregnancy and breastfeeding.
Valaciclovir and famaciclovir are similar in their clinical and pharmacological characteristics to acyclovir. But they cannot be administered intramuscularly.
Interferon in addition to antiviral and antimicrobial actions, it can activate reduced immunity (increases the phagocytic activity of macrophages and spontaneous toxicity of natural killers), cause an antitumor effect, and affect many body functions, including the functions of the central nervous system.
Features of the course of a viral infection involves the following therapeutic provisions:
drugs should be distinguished by the reliability of the antiviral action with minimal damaging effects on the cells of the macroorganism;
methods of using antiviral agents are limited by insufficient knowledge of their pharmacokinetics;
the effectiveness of antiviral chemotherapy drugs ultimately largely depends on the body's defenses, the strength of the immune system;
for practical medicine, methods for determining the sensitivity of viruses to the chemotherapy drugs used are practically inaccessible.
LITERATURE
1. Bonafton - 14 S. Kivokurtseva L. N., Bulot A. D., Bobrova N. S. “Labeled biologically active substances” (Moscow), 1982, No. 4, 54-59. (RZhKh, 1zh188, 1983).
2. Lawrence D.R., Benitt P.N. Clinical pharmacology. - Moscow, 1993
3. Mashkovsky M.D. Medicines. - 15th ed., Rev. And extra. - M .: RIA "New Wave": Publisher Naumenkov, 2007.-1206s.
4. Mashkovsky M.D. Medications. T.2. - Kharkov "Torsing", 1997.423s.
5. Mikhailov Clinical pharmacology. - M. "Medicine", 1983, 258s.
etc.................
