Viral hepatitis (VH) remains one of the pressing problems in human infectious pathology. Advances in the field of virology and the study of the subtle mechanisms of CH pathogenesis have made it possible not only to re-evaluate the stages and variants of interaction between the virus and the host, but also to develop new approaches to the treatment of CH, including the development and implementation of effective etiotropic antiviral therapy. At the same time, the basic principles of CH therapy, developed by S. P. Botkin, E. M. Tareev, A. F. Blyuger and other leading domestic hepatologists and infectious disease specialists back in the 19th-20th centuries, remain relevant and mandatory at the present time.

Acute viral hepatitis (AVH)

The basis of therapy for OVH is the creation of a protective and gentle regimen and adherence to a diet. Patients with acute hepatitis are subject to hospitalization in infectious diseases hospitals both for epidemiological reasons and for diagnosis, assessment of severity and dynamic monitoring for the purpose of early diagnosis of the development of severe forms of hepatitis and complications. In the acute period of the disease, it is recommended to prescribe bed rest, and for patients with a risk of developing acute hepatic encephalopathy, strict bed rest is recommended. During periods of decline in jaundice and convalescence, patients switch to ward mode.

After discharge from the hospital, patients are registered with an infectious disease specialist at the clinic. During the outpatient observation period, recommendations for the regimen take into account the individual characteristics of the patient’s life. In all cases, it is recommended to limit active sports (for students - exemption from physical education), avoid night shift work, and limit labor-intensive physical work (with transfer to light types of work). Sports and physical exercises that involve prolonged or sudden effort are excluded. Physical exercise should also not cause a feeling of fatigue and should last no more than 10 minutes. Lifting weights over 3 kg and prolonged physical activity are not recommended - walking no more than one hour a day or no more than 2 km. Playing sports after hepatitis is allowed by a doctor if there are normal clinical and laboratory parameters no earlier than three months later.

Long business trips and climate change, which require adaptation, are undesirable. Visits to bathhouses, saunas, sunbathing on the beach and in solariums are limited. Unfavorable factors also include long-term driving, psycho-emotional stress, and prolonged work on the computer.

The issue of resuming sexual activity is decided individually, taking into account the presence or absence of the virus in the blood and the dynamics of normalization of laboratory parameters.

It should be emphasized that violation of the regimen, especially during the outpatient period, often underlies clinical and laboratory exacerbations of CH and contributes, in some cases, to the formation of chronic liver pathology.

Diet for CH, both acute and chronic, occupies an important place in basic therapy. Regularity of food intake, quality of products, their nutritional value and gentle nature are the basis of nutrition for liver diseases. In medical practice, this diet is designated as table No. 5 or 5a. If in a hospital setting the issue of nutrition for patients with CH is resolved by applying the appropriate regulatory documentation at catering units, then when supervising patients in an outpatient setting and home nutrition, it is necessary to discuss with the patient in as much detail as possible the basic principles and regularity of therapeutic nutrition, the range of products and an approximate list of dishes.

It is necessary to eat at strictly defined hours and at least 4-5 times a day (1st and 2nd breakfasts, lunch, afternoon snack and dinner).

You should avoid consuming foods that have a strong irritating effect on the mucous membrane of the stomach, duodenum and upper parts of the small intestine: seasonings and spices, smoked meats, dishes containing vinegar, vegetables rich in essential oils - radishes, onions, garlic, radish, sorrel and etc., as well as products containing refractory fats (mutton, goose, pork, etc.).

The consumption of tomatoes and sour sauerkraut is limited. Excluded: mushrooms (in any form), peas and beans (since increased gas formation is possible!), However, it is allowed to eat a small amount of green canned peas as an addition to salads, soups, etc. You should not eat raw, unripe and sour ones varieties of berries and fruits (sour, green apples, red currants, cranberries, etc.).

A small amount of dill and parsley, caraway seeds, and bay leaves are allowed.

It is not recommended to consume almost any food products intended for long-term storage (containing preservatives, concentrates, flavoring additives): canned food, freeze-dried foods, instant soups and broths, concentrated and dry juices and drinks, confectionery products designed for long-term storage.

The following are excluded from the diet:

Chocolate and its derivatives, confectionery products containing creams (cakes, pastries, ice cream);

Products made from puff pastry and butter dough;

All types of coffee, strong tea, cocoa;

Alcohol in any form;

Mayonnaise, ketchup, hot sauces, vinegar and pickled foods, all types of peppers, mustard, horseradish.

Fatty meats, poultry and fish are excluded from animal products; liver, kidneys and other offal; lard, bacon, loin, brisket, etc., smoked poultry, balyki, spicy, salted fish, seafood, crabs, crayfish.

It is useful to prepare dishes from minced meat, passed through a meat grinder twice - this reduces the mechanical load on the stomach and promotes more complete digestion of food.

You should limit the number of eggs you eat to three per week, and it is advisable to use them for cooking rather than consuming them whole or raw.

It is necessary to exclude whole milk and sharp varieties of cheese from dairy products. The intake of sour cream, curd cheese, fatty cottage cheese, fermented baked milk, and yogurt is limited. It is advisable to use low-fat dairy products.

It is recommended to consume fermented milk products: kefir, bifidok, bifidum-kefir, bifilife, acidophilus, etc. However, individual tolerance should be taken into account in the event of flatulence (increased fermentation processes and gas formation), abdominal pain, loose stools, nausea or other symptoms consumption of these products should be reduced or discontinued.

For liver diseases, it is necessary to limit the consumption of salt and salty foods.

In case of acute liver disease or during periods of exacerbation of chronic liver diseases, we recommend mandatory mechanical processing (mashed, finely chopped or twice minced products) and strict adherence to the schedule of fractional meals.

The diet must be varied - there should be no fasting days. When expanding the range of food, you should introduce a new product in small portions and no more than one product per day - if discomfort occurs, it will not be difficult to determine its cause and eliminate the unsuitable product.

Bread. Black and white, well baked, without burnt crusts, “yesterday’s”, no more than 500 g per day. Crackers (dried, not fried!), dry biscuits, dry biscuits.

Soups. Vegetable, fish, meat (in a weak broth) with the addition of various cereals and vegetables. Dairy and fruit soups, borscht, cabbage soup.

Dishes from meat, poultry, fish. Lean varieties of beef, veal, rabbit, chicken, turkey. Occasionally - meat (lean) pork. Meat, cleaned of films, tendons and fat, without bones. A bird without skin. Portions in pieces, or chopped, or in the form of minced meat, boiled or steamed, can be subsequently baked in the oven. Sausages: milk, doctor's, diet. Milk sausages. Low-fat fish: pike perch, cod, perch, bream, hake, etc. - boiled, baked, jellied, in pieces or in the form of minced meat.

Vegetable dishes. Potatoes, beets, carrots, pumpkin, white cabbage, zucchini, cucumbers, tomatoes (in limited quantities). It is better to avoid using tomato paste. Vegetables boiled, baked and raw. Alone and as side dishes.

Fruits and berries. Not sour apples (preferably baked), pears, apricots, peaches, bananas (preferably overripe), kiwi, persimmon, quince, plums, cherries, prunes, figs, dates, dried apricots (preferably in compote), apricots, raisins, pomegranates, watermelons, melons, strawberries, currants, grapes, blueberries. A small amount of nuts (except peanuts) in their natural form, very carefully peeled and chopped, is useful. You can eat fruits and berries in their natural form and in the form of compotes, jelly, jellies, and diluted juices.

Cereals and pasta. Various porridges made with water or half-diluted milk (whole, dry, condensed), boiled or steamed (water bath), baked. Small pasta, vermicelli or chopped pasta, etc. - boiled, baked.

Sweet dishes. Sugar, a little honey (1-2 teaspoons per day - if there is no predisposition to allergies!), marmalade, marshmallows, marshmallows, caramel, toffee, preserves, jams. The amount of sugar (and sugar-containing products) should be limited if possible or partially replaced with xylitol or sorbitol.

Snacks. Jellied fish, tongue, lean meat, boiled chicken (all without spices). Jellied meat and jelly are not recommended. Low-fat ham, soaked herring, black caviar in limited quantities, mild cheeses, salads of raw and boiled vegetables with vegetable oil or sour cream (limit dressing with sour cream of no more than 10% fat to 1-2 times a week).

Oil. Butter no more than 40 g per day, using it in cooking. Refined sunflower, salad, corn, Kuban, olive, etc. can be used for preparing dishes and dressings.

Drinks The volume of liquid should not exceed 2-2.5 liters per day, including first courses. The tea is not strong, fruit, berry, and vegetable juices are freshly prepared and must be diluted with boiled water in a ratio of 1:2, compotes, homemade jelly. Rosehip infusion is very useful. Mineral water (2-3 glasses a day, no more than 3 times a week) at room temperature, without gas. It is not recommended to drink water and other drinks chilled. You should not drink all kinds of carbonated (fruit) drinks and canned fruit drinks. Natural juices (preferably nectars) should be diluted with boiled water.

Basic therapy for OVH includes detoxification therapy and the use of enterosorbents. In mild and moderate forms of OVH, detoxification can be carried out orally - for this, the daily volume of fluid is increased by 1-1.5 liters by taking mineral water. In the presence of nausea and especially vomiting (during the acute period of hepatitis), parenteral (intravenous) detoxification therapy is carried out in a volume of 800-1200 ml per day. 5% glucose solution, saline solution, Plasmalit, Hemodez and its analogues, crystalloid solutions are used as infusion solutions. In all cases of detoxification therapy, diuresis should be monitored. In severe forms of acute hepatitis and especially in the development of acute hepatic encephalopathy, methods of forced diuresis are used with an increase in the volume of administered fluid to 2-2.5 liters per day. In the same situations, plasmapheresis is used.

Currently, there is an extensive arsenal of enterosorbents - drugs that can bind and remove toxins from the body: Filtrum-STI, Laktofiltrum, Polyphepan, Enterosgel, Normaze, Duphalac, etc.

Other hepatoprotective drugs can also be included in the pathogenetic therapy of VH: Heptral, Riboxin, Tykveol, Hofitol, Dipana, Phosphogliv, Karsil, Legalon, etc. Drugs of the glutoxim group can be used, selectively acting on virus-infected and unaffected cells and regulating the processes of thiol metabolism (Glutoxim, Molixan, etc.).

In cases of severe OVH, glucocorticoids are added to therapy (prednisolone 60-90 mg per os per day or 240-300 mg intravenously), protein preparations (albumin, plasma), amino acid mixtures (Hepasteril A and B, Hepasol A, Aminosteril N-Hepa etc.), antihemorrhagic agents (Vikasol, Dicynon, Aminocaproic acid, etc.), protease inhibitors (Kontrikal, Gordox and analogues), enterosorbents, among which Duphalac is the most preferred. Plasmapheresis remains an effective method of treating severe forms. Along with the generally accepted basic therapy, it is possible to prescribe etiotropic treatment - interferon inducers and immunomodulators (Amiksin, Neovir, Cycloferon, Imunofan, Polyoxidonium, etc.).

With the development of a cholestatic variant of the course, Ursofalk (ursodeoxycholic acid) is prescribed at 10-15 mg/kg body weight per day once in the evening for 15-30 days, enterosorbents (Polyphepan, Enterosgel, etc.), in some cases a positive effect is observed during repeated duodenal intubation, HBOT, inhalation administration of heparin in combination with laser therapy, and plasmapheresis sessions.

Considering the fact that in liver pathology there are always varying degrees of severity of intestinal microflora disturbances, it is recommended to prescribe bacterial preparations that normalize the intestinal microflora: Bifidumbacterin and its combinations, Lactobacterin, Hilak forte, etc. During the period of resolution of cholestasis (normalization of stool and urine color), you can recommend choleretic drugs of plant origin.

In the treatment of acute hepatitis C, it is desirable to prescribe a 3-6-month course of interferons with nucleosides according to the regimen used for the treatment of chronic hepatitis C. Early prescription of antiviral drugs significantly reduces the frequency or even eliminates the transition of acute hepatitis to protracted and chronic. It also seems justified to prescribe in the initial period of acute hepatitis C drugs that have a certain antiviral activity (glycyrrhizic acid drugs - Viusid, Phosphogliv, drugs from the amantadine group - Remantadine, PC-Merz, etc.).

Treatment of exacerbations of AVG occurring with an autoimmune component involves the administration of glucocorticoids. In this case, the immunosuppressive effect of adrenal hormones is used.

Chronic viral hepatitis (CVH)

For CVH, the same basic principles of therapy are followed as for OVH: regimen and diet are mandatory components of therapy.

Treatment of chronic hepatitis, as a rule, is carried out on an outpatient basis, requires an individual approach and includes a number of aspects, among which the deontological one should be highlighted. Thus, patients with chronic hepatitis C must be informed in detail on a certain range of issues related to their disease, in particular regarding the features of the clinical course, rules of behavior for the patient in everyday life, sanitary and epidemiological nature, possible outcomes, the use of therapeutic measures and means, in including specific antiviral drugs and associated difficulties and problems (duration and high cost of therapy, unwanted side effects, expected effectiveness of treatment). The result of such an interview between the doctor and the patient should be the patient’s conscious desire to be treated, as well as an optimistic attitude towards the upcoming long and persistent therapy.

Currently, a number of medications are used in world practice, the antiviral activity of which has been proven to one degree or another.

The first and main group of antiviral drugs used for the treatment of chronic hepatitis C (CHC) are alpha interferons (recombinant and natural) - such as: Human leukocyte interferon, Alfaferon, Wellferon, Viferon, Reaferon, Roferon-A, Intron A, Interal , Realdiron, Altevir, Alfarona, Eberon alpha R, etc. (Table 1). It is believed that their antiviral effect is based on inhibition of viral reproduction and stimulation of many factors of the body's immune system.

The second group of antiviral agents consists of reverse transcriptase inhibitors and, in particular, nucleoside analogues (lamivudine, acyclovir, ribavirin (Copegus, Ribamidil, Rebetol, Vero-Ribavirin), vidarabine, lobucavir, sorivudine, etc.), blocking the synthesis of viral DNA and RNA by replacing natural nucleosides and thereby inhibiting virus replication (Table 2).

The third series of drugs is represented by interferonogens (Cycloferon, Neovir, Amiksin, etc.), the mechanism of action of which is to induce the macroorganism to produce additional amounts of its own interferons (Table 4). Drugs from the amantadine group (Remantadine, PC-Merz, etc.) also have an antiviral effect.

Undoubtedly, hepatoprotectors are useful in the complex therapy of chronic hepatitis, the use of which, on the one hand, helps restore damaged structures and functions of the liver, and on the other hand, prevents the possible toxic effect of powerful antiviral drugs (Table 3).

Treatment of any disease, and especially the chronic form of hepatitis C, requires an exclusively individual approach, since the nature of the pathological process in each individual patient is determined by a number of components, such as: the patient’s age, the nature of the concomitant pathology, the duration of the disease, the genotype of the virus and the level of viral load, drug tolerance, the presence and severity of side effects associated with the therapy and, in the end (and in some cases, at the beginning) with the financial capabilities of a particular patient.

Nevertheless, it is appropriate to note that monotherapy with interferon drugs, initially used in patients with CHC according to the literature (1999-2000) - 3 million IU 3 times a week for 12 months, gave a positive result in 13-48% of cases (was present in means normalization of aminotransferase levels and disappearance of HCV RNA in the blood according to PCR data). This difference in results depended on the genotypes of the pathogens, whether they included, etc. positive unstable responses, i.e., the new appearance of RNA in the blood of patients during 6-12 months of observation after completion of treatment.

Currently, in order to increase the effectiveness of treatment of CHC, complex antiviral therapy is used - usually the combined use of alpha interferons and nucleoside analogues (ribavirin (Copegus, Rebetol, Ribamidil), vidarabine, lobucavir, sorivudine, etc.). For example, the combined use of Intron A 3-5 million IU 3 times a week and ribavirin daily at a dose of 1000-1200 mg for 12 months allowed us to obtain a stable, sustained response in 43% of patients, i.e. the absence of hepatitis C virus RNA in the blood, according to dynamic PCR data, for 12 months after cessation of therapy. However, it should be taken into account that nucleoside analogues themselves have a whole range of adverse reactions that manifest themselves with long-term use of the drugs. The patient should also be warned about these nucleoside reactions.

Existing recommendations for antiviral therapy provide for 2 options for the initial stage of treatment: daily administration of interferons at a dose of 3-5 million IU for 4 weeks, then every other day at the same dosage. Another option is to prescribe increased doses of interferons 6-10 million IU every other day in the first month, followed by a subsequent dose reduction. Among other factors, the insufficiently high positive stable effect of even such combination therapy was explained by some authors by the fact that the interferon therapy regimens used did not create a constant therapeutic concentration of the active substance in the blood and tissues, since the half-life of interferon introduced into the body is 8 hours, while It only takes a few hours between interferon injections for the virus to reach its original concentration again. Replacing the drug Intron A in the above treatment regimen for patients with CHC with peginterferon alfa-2a (Pegasys) at a dose of 1.5 mcg/kg in the form of 1 injection per week (the addition of polyethylene glycol to the interferon molecule leads to an extension of the half-life of the active substance in the body to 168 hours) allowed the authors to obtain a stable therapeutic response on average in 72% of all patients treated in this way, of which 94% with pathogen genotypes 2 and 3.

It should be added that the optimistic results obtained with the use of peginterferons at the initial stage of clinical trials subsequently, with wider use, somewhat reduced the percentage of positive results, and the high price of the drugs significantly reduced their practical use.

At the same time, convincing evidence has recently emerged that the positive effect of the therapy depends to a greater extent on the duration of the course, and not on the dosage of interferons. The effectiveness of schemes that gradually increase the dose of interferons after obtaining a negative PCR result for HCV RNA has also been shown.

The generally accepted standard treatment of CHC with interferon drugs and nucleoside analogues should be supplemented with accompaniment therapy, including various groups of drugs.

Pathogenetically justified in the treatment of CHC is the use of immunomodulatory drugs - interleukins (IL). Interleukin-1 beta (Betaleukin) rebuilds immunopoiesis, activates the neuroendocrine system, stimulates bone marrow hematopoiesis, activating neutrophil granulocytes, the proliferative and functional activity of T- and B-lymphocytes. It also induces the synthesis of growth factors and a number of cytokines, such as IL-2 and IL-4, enhances the expression of their receptors and causes an increase in the content of endogenous interferon alpha, and also suppresses the intracellular replication of the hepatitis C virus.

The most promising at present seems to be the use of Betaleukin in combination with interferons and nucleoside analogues.

Treatment of hepatitis C is a rather complex undertaking, therefore, when prescribing and conducting specific therapy, it is appropriate to be guided by the following principles:

It is necessary to carry out therapy by a doctor who has sufficient practical experience in managing such patients.

Treatment is undertaken only if the virus RNA is detected in the blood according to PCR data, its genotype and the level of viremia are determined (by a quantitative or semi-quantitative method - titer).

Conduct a comprehensive laboratory examination - a detailed analysis of peripheral blood, possibly a full range of liver function tests and other biochemical studies: blood sugar, amylase, iron, etc. if necessary in each specific case. In addition, it is desirable to determine the patient’s natural interferon level, study sensitivity to interferons and interferon inducers, as well as the morphofunctional state of the thyroid gland.

Assess the nature of concomitant pathology, for example: renal with impaired excretory function, cardiovascular, autoimmune diseases, thyroid pathology, mental illness, severe peripheral blood abnormalities (anemia, thrombocytopenia, leukopenia), etc., which may even be a contraindication for planned antiviral treatment.

Specific therapy is prohibited during pregnancy and breastfeeding.

Both acute (and even preferably) and chronic forms of viral hepatitis C are subject to treatment, including those when, in the presence of pathogen RNA in the blood, a consistently normal level of aminotransferases is recorded.

Considering the possibility of developing tolerance to the medications used and the formation of antibodies to them, from time to time at certain stages of treatment it is advisable to change the combination of medications.

The effectiveness of treatment depends more on the duration of treatment than on the dose of the drug (depending on the specific characteristics of the patient, the duration of treatment ranges from 6 to 18 months, on average 12 months).

In cases of hepatitis C caused by genotypes 1a and 1b, as well as when the process lasts more than 3 years and with repeated courses of antiviral therapy, the duration of treatment should be at least 12 months (and more often more), with therapy intensified at the last stage.

Monthly and, if necessary, more frequent monitoring of clinical and laboratory data, including a detailed analysis of peripheral blood, is required in order to correct possible side effects.

The patient should be remembered and informed that during therapy, chills, fever, myalgia, allergic and toxic-allergic phenomena, anorexia, depression, thyroiditis, baldness, anemia, leukopenia, thrombocytopenia, agranulocytosis, etc. are possible.

A priori, one should expect less effectiveness of treatment for hepatitis C, and sometimes its complete absence in the following cases: in persons with immunosuppression of various origins, in patients with obesity, in a combined chronic process caused by hepatitis C viruses (in particular, different types of it can be simultaneously identified genotypes), B and D, in patients with virus genotypes 1a and 1b, in cases of high concentration of HCV-RNA in the blood, with a long duration of the chronic process (many years. On the contrary, it has been noted that therapy is most effective with a duration of the chronic process of up to 2 years ), in patients where chronic hepatitis C occurs with elements of liver cirrhosis, in the presence of autoimmune diseases, in cases where therapy occurs while taking alcohol and drugs, and also when treatment is carried out only in one of the two sexual partners with viral hepatitis C (possibility of reinfection with a virus of the same genotype).

Adverse blood reactions that accompany long-term antiviral therapy often include anemia, leukocytopenia and thrombocytopenia. Correction of anemia can be successfully carried out with drugs that stimulate erythropoiesis, for example Epocrine. For leukopenia, the administration of Betaleukin (recombinant Interleukin-1 beta) can be recommended.

It should be noted that the possibilities of using other antiviral drugs that can replace interferons are currently being actively studied. An antiviral effect has been demonstrated in preparations containing salts of glycyrrhizic acid obtained from licorice root—Phosphogliv, Viusid, etc. (Table 3).

Antiviral treatment of chronic hepatitis B is indicated for persons with an active infectious process - in the presence of HBV DNA in the blood. Interferon-alpha preparations are used together with nucleosides: interferons 3-5 million IU 3 times a week intramuscularly or subcutaneously (Pegasys 180 mcg once a week) in combination with Zeffix daily 100 mg orally (Table 1, Table 2) . It is possible to use only Zeffix at a dose of 100 mg orally. At the same time, it is known that monotherapy with Zeffix relatively quickly leads to the formation of mutations in the HBV genome and loss of control over replication. On average, the course of such therapy is carried out for 12 months. When resistance to lamivudine (Zeffix) develops, the administration of entecavir (Baralude) at a dose of 1 mg daily is indicated (Table 2). Baraclude is also effective against the “wild” strain of the virus at a dose of 0.5 mg. Unlike nucleoside analogs, pegelated interferons do not cause virus mutation and are equally effective both as monotherapy and in combination with nucleoside analogs. Therapy can be supplemented by the administration of interferon inducers, immunostimulants such as Taktivin, Neominophagen C, Imunofan, etc. (Table 4). Treatment is carried out under monthly monitoring of liver function tests, clinical blood tests, and viral load.

Integrative forms (HBe-negative) of CHB, characterized, as a rule, by normal or low levels of transferase activity (ALT/AST) and low concentration of HB DNA (or absence of DNA), are not subject to antiviral therapy. In these cases, the goal of therapy is to carry out a set of measures that limit or eliminate the possibility of exacerbations of the disease, such as: adherence to diet, regimen, use of hepatoprotectors (Table 3).

It must be borne in mind that, in addition to the high cost, the treatment is quite aggressive, is accompanied by a number of side effects that require correction, and, unfortunately, not all patients give a stable positive result, i.e. permanently normal ALT levels , seroconversion of HBe - anti-HBe, disappearance of HBsAg, repeated negative results of viral DNA determination within a year from the moment of cessation of therapy.

An almost absolute contraindication for antiviral therapy for CHB is the presence of concomitant autoimmune diseases, diseases of the blood system, alcoholism, and pregnancy in the patient.

It should be emphasized that treatment of CHB should be carried out by a doctor who has sufficient practical experience in managing such patients.

Unfortunately, at present, there is no effective specific therapy for chronic forms of HDV infection. There are separate reports on the effectiveness of using high doses of interferons in these cases - 10 or more million IU per day.

Finally, you should dwell on the cost of the “medicine basket”. A practicing doctor cannot ignore the economic component of antiviral therapy, since both domestic and foreign antiviral drugs used in Russia are not yet included in the register of medications provided free of charge. It seems obvious that the majority of patients are simply not able to purchase expensive foreign drugs for a full course. In this regard, the study and generalization of experience with domestic antiviral drugs as the most accessible and quite effective is of practical importance.

S. N. Zharov, Doctor of Medical Sciences, Professor B. I. Sanin, Candidate of Medical Sciences, Associate Professor RGMU, Moscow

The liver is one of the largest and most complex human organs and plays a critical role in almost every function of the body. The liver is the “first line of defense,” a key link in the detoxification system, a powerful filter that cleanses the blood of harmful substances and thus protects the entire body. The liver is involved in many pathological processes. Its damage causes serious disturbances in metabolism, immune response, detoxification and antimicrobial defense.

The liver is the largest digestive gland. It produces bile, which, entering the duodenum, promotes the digestion and absorption of fats and fat-soluble vitamins. Violation of the outflow of bile not only negatively affects the digestive processes, but also adversely affects the state of the nervous system (it is not without reason that an irritable person is referred to as a “bilious person”), causes itching and changes in skin color.

The liver is involved in the processes of metabolism of proteins, amino acids, carbohydrates, biologically active substances (hormones, biogenic amines, vitamins), on which the appearance and elasticity of the skin largely depends. Its role in immune and protective reactions, including protecting the skin from external influences of microorganisms, is important. Suffice it to say that up to 95% of substances that are antigenic, i.e., are concentrated in the liver and then neutralized. properties alien to the body, and capable of affecting both internal organs and skin.

The liver consists of structural components - lobules. The number of lobules in the liver reaches 500 thousand. These structural and functional elements have the shape of a multifaceted prism 1.5–2 mm high. Each such lobule, consisting of many liver cells - hepatocytes, has its own system of bile ducts, nerve fibers and blood vessels.

The structure of the bloodstream of the liver is unusual. Unlike other organs, there are two supplying blood vessels: the portal vein, through which 70–80% of the total volume of blood flowing into the liver enters, and the hepatic artery, which delivers the remaining 20–30% of the blood.

The blood flowing to hepatocytes through these vessels is extremely rich in various nutrients. Liver cells spend a small part of them for their energy and construction needs, another part is used as raw material for the production of bile, and the third, having been processed and neutralized, is returned to the bloodstream.

The efferent vessels flow into the central vein, located in the middle of the lobule. Gradually enlarging, they form 2-3 hepatic veins, which flow into the inferior vena cava, which carries blood to the right atrium.

Bile, which is synthesized by hepatocytes, flows through a special system of ducts, which begins with bile capillaries located between the rows of liver cells. Merging, the capillaries form bile ducts, which enlarge and then unite into the common hepatic duct. After emerging from the porta hepatis, this duct merges with the cystic duct to form the common bile duct. The common bile duct carries bile into the duodenum.

Bile passes directly from the liver into the intestines only during the digestion of food. If the intestines are empty, the bile that the liver secretes continuously is sent through the cystic duct to the gallbladder, a pear-shaped reservoir that holds approximately 40–60 cm3 of bile. The topography of the liver and gall bladder is shown in Fig. 9.6.

Severe liver damage is caused by viral hepatitis - infectious diseases caused by several types of hepatotropic viruses.

Rice. 9.6.

Viral hepatitis– a group of infectious diseases with predominant liver damage. The disease is characterized by significant polymorphism of clinical manifestations (from subclinical to severe). In severe cases, general intoxication, jaundice, hemorrhages and other signs of liver failure are characteristic.

Etiology. Viral hepatitis can be caused by viruses A, B, C and other types.

The reservoir and only source of infection is a sick person or a virus carrier.

The mechanism of transmission of viral hepatitis A is fecal-oral. Routes of transmission: alimentary, water, contact and household. Susceptibility to the disease is high.

The mechanism of transmission of viral hepatitis B is parenteral. Transmission of infection occurs through blood transfusion (12–20 cases per thousand blood transfusions), microtrauma. Possible sexual and transplacental transmission routes.

The mechanism of transmission of viral hepatitis C is parenteral, characterized by a chronic course.

There is no cross immunity between different forms.

Pathogenesis. There are phases of introduction of pathogens: enteral (or nasopharyngeal) phase, regional lymphadenitis and influx of viruses into the liver through the lymphatic tract, primary viremia and hematogenous introduction of pathogens into the liver, phase of parenchymal diffusion, unstable localization in the liver and secondary viremia, persistent localization and release from the pathogen .

Necrosis of hepatocytes causes the release of liver enzymes into the blood.

Violation of the formation and excretion of bile is accompanied by an increase in bilirubin content and the appearance of bile acids in the urine, an increase in phosphatase and cholesterol in the blood.

The inflammatory process is characterized by an increase in the level of gamma globulins and changes in protein sediment samples.

Impaired liver function leads to the accumulation of aromatic compounds, ammonia, indole, PVC, and lactic acid in the blood. Endotoxemia can lead to encephalopathy and hemorrhagic syndrome.

Protein, enzymatic, electrolyte, and hormonal metabolism changes.

Clinic. The incubation period for viral hepatitis type A is 7–50 (usually 14–30) days, for viral hepatitis type B – 40–180 (usually 60–120) days, for viral hepatitis type C – 14–50 days.

The pre-gestational period in 70% of cases is accompanied by dyspeptic syndrome (poor appetite, nausea, vomiting, abdominal pain), an increase in temperature to 38–39 ° C, asthenovegetative, arthalgic, catarrhal syndromes and a mixed variant of the course are possible. Already at this stage of development of the disease, the liver enlarges.

The icteric period is observed for 2–6 weeks, but can last from 1 day to several months. At the same time, the body temperature normalizes, the urine darkens and the feces become discolored. There is an increase in the level of ALT and bilirubin in the blood, which reflects the severity of the process. In mild cases, the bilirubin level does not exceed 85 mmol/l, ALT – 10–12 nmol/l. In case of moderate severity, the bilirubin level does not exceed 170 mmol/l, ALT – 12 nmol/l and higher. In severe cases, the bilirubin level rises to 170–300 mmol/l, dysproteinemia is noted, and precoma and hepatic coma develop.

Acute liver failure (ALF) can be a serious complication of viral hepatitis.

In the fulminant form, bleeding, swelling of the brain and lungs, and the addition of sepsis become ominous signs of impending death.

In 5–12% of cases, chronic hepatitis develops, often occurring with scant symptoms (dyspepsia, moderate hepatomegaly, occasional mild jaundice). A severe, active variant of chronic viral hepatitis is also possible.

Treatment. Bed rest in the acute period is extremely important.

The diet excludes indigestible fats. Liquid – in a volume of 2–3 liters per day. Alkaline mineral waters eliminate dyspeptic symptoms.

In case of mild hepatitis, against the background of a diet and an appropriate regimen, multivitamin preparations, potassium orotate, methyluracil, and the essential amino acid methionine are indicated.

In the case of hepatitis of moderate severity against the background of a diet and an appropriate regimen, intravenous drip administration of a 5% glucose solution, 5–10% albumin solution, hemodez, rheopolyglucin and other infusion solutions, cytochrome C is indicated. For hepatitis B, patients with high levels ALT and HBV DNA, as well as with histological signs of necrosis and inflammation in the liver, interferon preparations (primarily pegylated) and nucleoside analogues (lamivudine (Epivir®), entecavir (Baraclude)) are prescribed. Pegylated interferons have a number of advantages over standard interferons - improved pharmacokinetic parameters, higher antiviral activity, low antigenicity, and ease of use. When polyethylene glycol (PEG) is conjugated with interferon a-2a, peginterferon a-2a (Pegasys®) is formed. Interferon a-2a is produced biosynthetically using recombinant DNA technology and is a derivative product of the cloned gene of human leukocyte interferon, introduced and expressed in cells E. coli.

There are six genotypes of the hepatitis C virus, which may respond differently to treatment. Before initiating treatment for hepatitis, careful screening is necessary to determine the most appropriate approach for the patient. The treatment of hepatitis C is based on combination antiviral therapy based on interferon and ribavirin. Interferon is not always well tolerated, not all genotypes respond equally well to it, and many people receiving it do not complete treatment. Telaprevir (Insivo), boceprevir (Victrelis®) are new antiviral drugs for the treatment of hepatitis C.

In the convalescence phase, hepatoprotectors are used.

For severe hepatitis, glucocorticoids 40–90 mg of prednisolone per day are prescribed.

For chronic active hepatitis, prednisolone 15–20 mg is used in combination with azathioprine 50–150 mg per day.

Prevention of acute viral hepatitis includes a number of measures, including vaccination. There is no vaccine against hepatitis C. The risk of infection can be reduced by avoiding activities such as:

• administering unnecessary and unsafe injections;
• transfusion of unsafe blood products;
• collection and disposal of unsafe sharp-edged objects and fragments;
• use of illicit drugs and sharing of injection equipment;
• unprotected sex with people infected with hepatitis C;
• sharing sharp-pointed personal objects that may be contaminated with infected blood;
• performing tattoos, piercings and acupuncture with contaminated equipment.

Non-infectious hepatitis (non-infectious jaundice) is an inflammatory disease of the liver caused by various reasons, including:

• toxic substances (alcohol, drugs, poisons);
• autoimmune aggression on the liver’s own cells and the epithelium of the bile canaliculi in some diseases;
• disorders of copper and iron metabolism.

At the first signs of hepatitis: pain in the right hypochondrium, heaviness or discomfort in the abdomen (on the right, where the liver is located), yellowness of the sclera of the eyes and skin, weakness and fatigue, loss of appetite, nausea, darkening of urine, change in the color of stool (becomes light) - It is important to see a doctor immediately.

To make a correct diagnosis, after an examination, the doctor refers the patient to additional studies:

• biochemical blood test;
• blood test for markers of viral hepatitis;
• Ultrasound of the liver and other abdominal organs;
• gastroscopy (EGD) - to assess the condition of the veins of the esophagus and determine the risk of bleeding;
• liver scintigraphy - a radioisotope study that allows you to evaluate the functioning of various parts of the organ;
• computed tomography - to assess changes in the liver and other abdominal organs;
• in some cases, a liver biopsy.

The diet for liver damage and the prevention of liver changes is based on the exclusion of fatty, fried foods, alcohol, limiting salt and protein, and avoiding alcohol.

Herbal medicine for hepatitis slows down inflammatory and degenerative processes in liver tissue. Plant-based remedies reduce the likelihood of complications, speed up recovery, reduce jaundice, ailments, pain in the right hypochondrium, and rashes accompanied by itching.

Peppermint has a calming, antispasmodic, antiseptic, analgesic and choleretic effect, enhances the secretion of the digestive glands, increases bile secretion, and promotes the regeneration of liver cells.

Fennel increases the secretion of the digestive glands, has a choleretic, antispasmodic and diuretic effect and some antibacterial effect, increases the secretion of pancreatic juice and bile excretion.

Calendula has an anti-inflammatory effect and at the same time enhances secretory activity, increases bile formation and excretion, and also activates regeneration processes.

Most often, liver damage occurs through chemical and immunological mechanisms. Chemical damage to the liver can be caused by natural substances and xenobiotics (medicines). Chemical damage can lead to apoptosis or even necrosis of liver cells. Apoptosis or "programmed cell death" is a physiological process of cellular turnover. Apoptosis is found during various liver injuries. Unlike necrosis, it develops in individual cells.

To improve liver function, medications that have a selective effect on the liver are used - hepatoprotectors. Their action is aimed at restoring the liver, increasing the organ’s resistance to pathogenic factors, and normalizing its basic functions. The algorithm for selecting hepatoprotectors is presented in Fig. 9.7.

Rice. 9.7.

Hepatoprotectors based on milk thistle. Medicinal plant milk thistle ( Silybum marianum) is an effective heaton protector. Milk thistle has been traditionally used in Europe for many centuries and is still a leader in liver protection.

Name Silybum comes from the ancient Greek word silly bon – tuft, denoting a thistle whose leaves are marked with white spots. An ancient legend says that these white spots are drops of milk that fell from Mary's breast when she nursed the infant Christ during the flight to Egypt. In the Middle Ages, the plant was grown in monasteries and used for medicinal purposes: the roots and leaves were recommended against tumors and erysipelas, as well as for treating the liver. Hepatoprotectors based on milk thistle are necessary for the treatment of liver diseases and for the prevention of various diseases that arise as a result of exposure of the body to adverse environmental factors. By improving liver function, these drugs thereby have a positive effect on the condition of the skin.

The main component of milk thistle is silymarin (silibinin).

Silibinin blocks the binding sites of a number of toxic substances and their transport systems due to its phenolic structure.

The metabolic effect of silibinin is to stimulate the synthesis of proteins (proteins) and accelerate the regeneration of damaged liver cells (hepatocytes).

Silymarin derivatives exhibit immunomodulatory activity in patients with alcoholic cirrhosis of the liver.

Milk thistle fruit extract (Karsil® and Lethalon® 140) is used for acute and chronic hepatitis, liver cirrhosis, and toxicometabolic liver damage. The drugs provide an antioxidant effect and suppress the peroxidation of polyunsaturated fatty acids in phospholipid membranes and enhance reparative processes. Silibinin contributes to a significant increase in the content of reduced glutathione in the liver, thereby increasing the organ’s protection from oxidative stress and maintaining its normal detoxification function.

Hepatoprotectors based on other plants. Other plants that protect the liver are smokeweed, sandy immortelle, and stinging nettle. Great plantain, prickly artichoke, yarrow, and common chicory have a hepatoprotective effect.

Gepabene (fumatory extract, dry extract of milk thistle fruits) has a choleretic, antispasmodic, and hepatoprotective effect. Normalizes the amount of secreted bile, relaxes the smooth muscles of the bile ducts and gallbladder, has antioxidant, membrane-stabilizing activity, stimulates protein synthesis, and promotes the regeneration of hepatocytes. It is also used as part of complex therapy for chronic hepatitis and chronic toxic liver damage.

It is important to remember that the drug is not used for hypersensitivity, acute inflammatory diseases of the liver and biliary tract.

Side effects are also possible: laxative effect, increased diuresis, allergic reactions. During treatment, you should follow a diet and refrain from drinking alcohol.

Artichoke leaf extract (Hofitol) is a hepatoprotector of plant origin with choleretic, diuretic and hypoazotemic effects.

Affects the functional activity of liver cells, stimulates the production of enzymes, regulates fat metabolism, and increases the antitoxic function of the liver.

The widespread use of hofitol in various fields of medicine is due to:

• effective and multifaceted effect on organs and tissues of the human body:
• no side effects;
• the ability to use the drug without age restrictions during pregnancy.

Hofitol is included in the standards for the diagnosis and treatment of patients with diseases of the digestive system, as well as in the assortment list of medicines and medical products required for pharmacies "List of vital and essential medicines." The drug has pronounced detoxification properties, normalizes lipid, protein, nitrogen and carbohydrate metabolism, and has a therapeutic effect on the liver and kidneys.

Caper prickly extract + Cassia occidentalis extract + Black nightshade fruit extract + Tamarix dioecious fruit extract + Terminalia chebula fruit extract (Liv.52® K) – a complex preparation that contains plants growing in India.

Liv.52® protects the liver parenchyma from toxic agents. Strengthens intracellular metabolism and stimulates regeneration. Acts as a therapeutic or prophylactic agent.

Used to improve liver function in infectious and toxic hepatitis, chronic hepatitis and other liver diseases. The drug also increases appetite, improves digestion, and promotes the removal of gases from the intestines.

When used, dyspeptic symptoms are possible.

Pumpkin seed oil (Pykveol®) has membrane-stabilizing properties. In addition, the drug reduces inflammation, slows down the development of connective tissue and accelerates the regeneration of damaged liver parenchyma.

Tykveol has a choleretic effect, normalizes the chemical composition of bile, reduces the risk of developing cholelithiasis and has a beneficial effect on its course.

Tykveol is used for chronic liver diseases of various etiologies: chronic liver damage (hepatitis, cirrhosis), cholecystocholangitis and biliary dyskinesia, in the postoperative period of cholecystectomy, for the prevention of cholelithiasis.

They also have a hepatoprotective effect components of hepatocyte cell membranes, extracted from the liver of cattle or pigs. Hepatosan is the only preparation of lyophilized hepatocytes from pig liver in the Russian Federation.

In all liver diseases, damage to hepatocyte membranes is observed. A cross section of the plasma membrane is shown in Fig. 9.8. Pathogenetically justified is the prescription of therapy that has a regenerating effect on the structure and function of cell membranes and ensures inhibition of the process of cell destruction. Means of this type of action are drugs containing essential phospholipids (EFL).

EPL substance is a highly purified extract from soybeans and contains predominantly phosphatidylcholine (PC) molecules with a high concentration of polyunsaturated fatty acids. The main active ingredient of EPL is 1,2-dilinoleoyl - phosphagidylcholine, the synthesis of which is impossible for the human body.

The membrane-stabilizing and hepatoprotective effect of EPL is achieved by directly integrating EPL molecules into the phospholipid structure of damaged liver cells, replacing defects and restoring the barrier function of the lipid biolayer of membranes. Exogenous EPL promotes the activation of transport proteins, which, in turn, has a supporting effect on metabolic processes in liver cells and helps to increase its detoxification and excretory potential.

The hepatoprotective effect of EPL is based on the inhibition of lipid peroxide oxidation (LPO), which is considered as one of the leading pathogenetic mechanisms for the development of liver damage.

Phospholipids (Essentiale® forte N) contain only highly purified EPL substance.

In clinical practice it is used in three main areas:

• for liver diseases and toxic lesions;
• with pathology of internal organs complicated by liver damage;
• as a method of “drug cover” when using drugs that cause liver damage (tetracycline, rifampicin, paracetamol, indomethacin, etc.).

Essentiale is prescribed for chronic hepatitis, liver cirrhosis, fatty degeneration, hepatic coma. It is also used for radiation syndrome and toxicosis in pregnant women, for the prevention of relapses of cholelithiasis, for preoperative preparation and postoperative treatment of patients, especially in cases of surgical interventions on the liver and biliary tract. At the same time, the use of Essentiale for active hepatitis requires caution, since in some cases it can contribute to increased cholestasis and inflammatory activity.

Contraindications: individual intolerance.

Side effects: very rarely, gastrointestinal upset may occur.

Multivitamins + phospholipids (Essliver® forte): contains essential phospholipids. The drug contains therapeutic doses of vitamins (B1, B2, B6, B12, tocopherol and nicotinamide).

The action of the drug is aimed at restoring hemostasis in the liver, increasing the organ’s resistance to the action of pathogenic factors, normalizing the functional activity of the liver, and stimulating reparative and regenerative processes.

The drug is used for acute and chronic hepatitis, liver cirrhosis, alcohol and drug intoxication, radiation syndrome, psoriasis.

Side effect: rarely - a feeling of discomfort in the abdomen.

Contraindications: hypersensitivity to the drug.

The peculiarity of the drug is the content of essential phospholipids of natural origin, which are easily absorbed by the body.

The domestic preparation glycyrrhizic acid + phospholipids (Phosphogliv®) - consists of phosphatidylcholine and trisodium salt of glycyrrhizic acid. Due to the EPL included in the drug, the severity of inflammatory reactions, necrosis of liver cells, and their fatty infiltration are reduced. Glycyrrhizic acid has an immunostimulating effect, stimulating phagocytosis and induction of γ-interferon. In addition, it has an antiviral effect, blocking the penetration of viruses into cells, and exhibits antioxidant properties. It is used for acute hepatitis, for relieving alcohol withdrawal syndrome, and in the pre- and postoperative period of cholecystectomy.

The technology for manufacturing the drug is based on know-how, which makes it possible to achieve the formation of nanospheres (micelles) from phospholipid molecules. For this purpose, homogenization modes under pressure of more than 1000 atm are used.

The drug is manufactured in two forms - for intravenous injection and in the form of capsules for oral use.

The hepatoprotector phosphogliv was awarded the State Prize of the Russian Federation in 2003.

Ademetionine (Gsptral®) – has hyspatoprotective, antidepressant, detoxication, regenerating, antioxidant, neuroprotective effects.

Replenishes methionine deficiency and stimulates its production in the body.

Indications: internal hepatic cholestasis, toxic liver damage, including alcoholic, viral, medicinal, encephalopathy, depressive and withdrawal syndrome.

Contraindications: hypersensitivity, pregnancy (I and II trimesters).

Side effects: when taken orally - heartburn, pain or discomfort in the epigastric region, dyspeptic symptoms, allergic reactions.

Ursodeoxycholic acid (Ursosan®) has a membrane-stabilizing effect and promotes the dissolution of cholesterol stones.

Indications: cholesterol gallstones in the gallbladder; chronic and acute hepatitis. The drug is effective for toxic (including alcohol, drugs) liver damage; biliary dyskinesia.

Side effects: diarrhea, calcification of gallstones, allergic reactions.

Contraindications: acute inflammatory diseases of the gallbladder and biliary tract.

The drug should be used to dissolve gallstones only in the presence of cholesterol (X-ray negative) stones no larger than 15–20 mm in size, with preserved patency of the cystic and common bile duct.

Non-steroidal anabolics dioxomethyltetrahydropyrimidine (Methyluracil), orotic acid (potassium orotate), sodium nucleinate, inosine (Riboxin) continue to be used for various liver pathologies due to low toxicity and low cost.

Riboxin is a purine derivative. The drug is used for acute and chronic hepatitis, liver cirrhosis.

Potassium orotate is a single biochemical precursor of all pyrimidine bases of nucleic acids. It has the greatest effect on protein synthetic function, while the duration of the “icteric” period is reduced. The detoxifying effect of the drug is often insufficient. Prescribed for acute viral hepatitis.

Methyluracil is an analogue of pyrimidine nucleotides, but is practically not included in the exchange as a precursor in the synthesis of nucleotides; accelerates the restoration of protein synthetic liver function, reduces symptoms of intoxication and dyspeptic symptoms.

Sodium nucleinate – activates protein synthesis. It is used mainly for acute hepatitis. The drug is low-toxic and very rarely causes side effects.

In recent years, the incidence of drug-induced liver injuries has increased. Among all drug-induced hepatitis, a large percentage falls on hepatitis caused by antibiotics (tetracycline, erythromycin, oleandomycin, etc.). The mechanisms of liver damage are diverse, which leads to various clinical forms of drug-induced injuries:

• isolated increase in transaminase levels;
• acute (virus-like) hepatitis occurring with jaundice;
• chronic persistent hepatitis;
• chronic active hepatitis;
• cholestatic hepatitis;
• granulomatous hepatitis;
• vascular and tumor lesions of the liver, etc.

Clinical manifestations of liver damage caused by drugs are nonspecific. Objective examination data are varied and are possible for chronic hepatitis of any other origin.

Medicines can induce the activity of monooxygenases in the hydroxylation reactions of aliphatic and aromatic compounds (barbiturates, meprobamate, ethanol, rifampicin, griseofulvin, hypoglycemic drugs), while others can inhibit. Cytochrome P450-dependent monooxygenases are a multienzyme electron transport system. All cytochromes P450 are heme-containing proteins. Heme iron is usually in an oxidized state (Fe3+). By being reduced to the Fe2+ state, cytochrome P450 is able to bind ligands such as oxygen or carbon monoxide. The stages of substrate hydroxylation by cytochrome P450 are shown in Fig. 9.9. The complex of reduced cytochrome P450 with CO has an absorption maximum of 450 nm, which was the basis for the name of these enzymes. There are many isoforms of cytochrome P450 that carry out oxidative and reductive metabolism of steroids, fatty acids, retinoids, bile acids, biogenic amines, leukotrienes, as well as exogenous compounds, including drugs, environmental pollutants, and chemical carcinogens.

Rice. 9.9.

A number of cytochromes P450 are activated with the participation of specific receptors. Only for P450 1A1 and, accordingly, the Ah receptor, a detailed mechanism of action is known. For the remaining P450s, as a rule, a specific receptor has been identified, but the mechanism of action has not been described in detail to date.

Inhibitors of microsomal oxidation bind to the protein part of cytochrome or heme iron - for example, spironolactone, erythromycin. Cimstidip slows down the elimination of diazepam and other benzodiazepines, increasing sedation and increasing toxicity. Microsomal oxidation can be assessed by drug pharmacokinetics and metabolic markers.

Aminazine, sulfonamides, indomethacin, mercazolil, isafenin, etc. cause hepatic necrosis.

Laboratory parameters in some patients are characterized by increased transaminase activity and a slight increase in the activity of cholestasis enzymes. In another part of the patients, the “cholestatic type” of liver damage appears in the foreground, reminiscent of that in primary biliary cirrhosis. With this type of lesion, changes in enzyme activity are observed, characteristic of patients with intrahepatic cholestasis. Drugs that cause drug-induced cholestasis are presented in Table. 9.5.

Table 9.5

Drug-induced cholestasis

The development of cholecystitis is promoted by stagnation of bile in the gallbladder. Disruption of the normal outflow of bile may be associated with dyskinesia caused by physical inactivity; nutritional factors (irregular meals at large intervals, large meals at night with a preference for meat, spicy, fatty foods, excess flour and sweet foods, etc.), emotional stress, cholelithiasis and other factors.

Pathogenesis. Pathogens penetrate the gallbladder through enterogenous (from the intestine), hematogenous (through the bloodstream), and lymphogenous (through lymphatic vessels) routes.

Depending on the nature of the inflammation, acute catarrhal, phlegmonous and gangrenous cholecystitis are distinguished. Chronic cholecystitis is characterized by a long course with periodic exacerbations. The exacerbation phase is characterized by an increase in the chronic inflammatory process of the gallbladder mucosa, which leads to an increase in body temperature and other signs of the inflammatory process.

Clinic. In the clinic of acute cholecystitis, pain syndrome with signs of inflammation and irritation of the peritoneum predominates.

For the clinical picture of chronic cholecystitis in the acute phase, pain is typical (occurs in the right hypochondrium, spreads to the right scapula, collarbone, shoulder). The occurrence of pain and its intensification is usually associated with a violation of the diet - heavy intake of fatty, spicy, fried foods, alcoholic drinks, etc. The intensity of the pain increases during the period of exacerbation, periodic pain persists during the period of remission in the form of minor, nagging pain. Pain may intensify with changes in body position and movement. On palpation, pain in the right hypochondrium and positive pain symptoms of cholecystitis are determined.

Patients complain of bitter belching, bitter and metallic taste in the mouth, nausea, bloating, stool disorders; Possible vomiting of bitterness.

Body temperature rises during the exacerbation phase. In a blood test in the acute phase, an increase in ESR, neutrophilic leukocytosis, a shift in the leukocyte formula to the left, and eosinophilia are determined.

Mandatory laboratory tests: once cholesterol, amylase, blood sugar, blood type and Rh -factor, coprogram, bacteriological, cytological and biochemical study of duodenal contents. Twice: general blood test, general urine test, bilirubin and its fractions, AST, ALT, ALP, GGLP, total protein and protein fractions, C-reactive protein. Mandatory instrumental studies: one-time ultrasound of the liver, gall bladder, pancreas, duodenal intubation (ECD or other options), esophagogastroduodenoscopy, chest x-ray.

Treatment. In case of acute acalculous cholecystitis and exacerbation of chronic bacterial cholecystitis, fasting and drinking (hot tea, warm mineral waters) are indicated in the first 2–3 days. Then, gentle fractional meals (5–6 times a day) are prescribed. The diet should be complete in calories with a normal protein content, some limitation of fats, primarily refractory ones, and a high content of carbohydrates.

Drug therapy(antibacterial treatment options using one of them).

• 1. Ciprofloxacin orally, 500–750 mg 2 times a day for 10 days.
• 2. Doxycycline orally or intravenously. On the 1st day, 200 mg per day is prescribed, on subsequent days 100–200 mg per day, depending on the severity of the disease.

Duration of taking the drug is up to 2 weeks.

• 3. Co-trimoxazole [sulfamethoxazole + trimethoprim] (Bactrim®, Biseptol®) 480–960 mg 2 times a day with an interval of 12 hours. The course of treatment is 10 days.
• 4. Cephalosporins for oral administration, for example, cefuroxime (Zinnat®) 250–500 mg 2 times a day after meals. The course of treatment is 10–14 days.

Symptomatic drug therapy(used according to indications).

• 1. Domperidone 10 mg 3–4 times a day or trimebutine (Trimedat®) 100–200 mg 3–4 times a day or Meteospasmil 1 drop. 3 times a day. The duration of the course is at least 2 weeks.
• 2. Artichoke leaf extract (Hofitol) 2-3 tablets. 3 times a day before meals or allohol, 2 tablets. 3-4 times a day after meals or other drugs that increase choleresis and cholekinesis.

The duration of the course is at least 3–4 weeks.

In chronic cholecystitis, choleretic drugs are used until the factors that caused stagnation in the gallbladder are eliminated. If the causes of obstruction of the outflow of bile cannot be eliminated (for example, prolapse of internal organs, bending of the gallbladder), choleretic drugs should be taken continuously for a long time. The choice of drug depends on the concomitant biliary dyskinesia and the severity of the process. In case of an acute inflammatory process and exacerbation of a chronic one, the only possible means are myotronic antispasmodics and anticholinergics (cholespasmolytics). These drugs are also the drugs of choice for hypermotor dyskinesia, which is typical for young people who eat erratically and lead a stressful lifestyle. Choleretics are not contraindicated for such patients. In case of hyiomotor dyskinesia (obese, elderly, gynodynamic patients) outside of exacerbation of chronic cholecystitis, it is possible to use choleretics and take cholekinetics very carefully only if gallstone disease (GSD) is excluded.

Choleretics – drugs that stimulate bile formation. True choleretics (cholesecretics) increase the secretion of bile due to an increase in its formation.

Preparations containing bile acids or native bile.

Ursodsoxycholic acid (Ursosan®) has high cholesterol-secreting activity and also increases the cholate/cholesterol ratio. When used, stool disturbances are possible, most often diarrhea, increased levels of transaminases in the blood serum. Contraindicated in case of exacerbation of cholecystitis, cholangitis, acute and chronic hepatitis, as well as obstruction of the bile ducts, exacerbation of gastric and duodenal ulcers, acute intestinal diseases, severe dysfunction of the night, pregnancy.

Cholenzyme: contains bile + pancreatic powder + small intestinal mucosa powder.

Preparations of herbal origin.

Calamus rhizomes + peppermint leaves + chamomile flowers + + licorice roots + dill fruits are included in Fitogastrol (gastrointestinal collection).

Preparations of immortelle - immortelle sandy flowers, immortelle sandy flowers sum of flavonoids (Flamin), immortelle sandy flowers + yarrow herb + peppermint leaves + coriander fruits (Cholagogue collection No. 2).

Plant choleretics - knotweed grass, centaury grass, coriander fruits, corn columns with stigmas, burdock roots, rowan fruits.

Tansy preparations – tansy flowers (tansy flowers), tansy flower extract (Tanacehol®), birch leaf extract + St. John's wort herb extract + milk thistle fruit extract + tansy flower extract (Sibektan®), calendula officinalis flowers + peppermint leaves + common tansy flowers + chamomile flowers + common yarrow herb (Cholagogue collection No. 3)).

Wormwood preparations - wormwood herb, belladonna tincture + + valerian officinalis rhizomes with roots tincture + wormwood bitter herb tincture (valerian tincture 10 ml, wormwood tincture 8 ml, belladonna tincture 2 ml).

Urolesan and urocholesan contain oregano herb extract + castor bean seed oil + wild carrot seed extract + peppermint leaf oil + fir oil + hop fruit.

The combined herbal medicine Cholagol contains turmeric flavonoids, frangulomodin, mint essential oil, eucalyptus essential oil, sodium salicylate, olive oil.

The choleretic effect is also exhibited by the fruits of barberry, the buds and leaves of birch, and the herb longifolia.

The mechanism of action of herbal preparations lies, in particular, in the direct stimulation of the secretory function of hepatocytes. This is how essential oils of juniper (juniper fruits), coriander, oregano, and caraway (caraway fruits) act. Magnesium ions included in herbal medicinal preparations can stimulate the secretion of cholecystokinin by duodenal epithelial cells, which is probably associated with the cholekinetic effect of preparations of arnica, birch, immortelle, rosehip (rosehip fruits, rosehip fruit syrup, low-vitamin rosehip fruits, rosehip seed oil), fennel. A reflex increase in the release of cholecystokinin causes bitterness. These are preparations of dandelion (dandelion officinalis roots), yarrow (common yarrow herb).

When combining plants with different mechanisms of cholekinetic action, the effect is enhanced. In addition to choleretic activity, many plants have antimicrobial, anti-inflammatory and antihypoxic effects, some have hepatoprotective properties.

Hydrocholeretics – drugs that increase the volume of bile by increasing its water component (bile dilution). This is how drinking mineral water works (balneotherapy).

Cholekinetics – agents that increase the tone of the gallbladder and relax the bile ducts and sphincter of Oddi. These include magnesium sulfate, xylitol, sorbitol, extracts from the rhizome of calamus, sandy immortelle flowers, lingonberry leaves, cornflower flowers, trifoliate leaves, knotweed herb. Cholekinetics are also: the herb of oregano, shepherd's purse, flowers of calendula officinalis, chamomile (liquid chamomile extract), fruits of coriander, common juniper, roots of dandelion, Tangut rhubarb. Cholekinetic properties are exhibited by creeping thyme herb (thyme herb, thyme liquid extract), the fruits of caraway seeds, common fennel, rose hips, and yarrow herb.

The cholekinetic effect is most pronounced in magnesium sulfate, which causes increased secretion of cholecystokinin when taken orally. As a result, the tone of the smooth muscles of the gallbladder increases, the bile ducts and sphincter of Oddi relax, and bile is released into the duodenum. Xylitol, sorbitol, and mannitol have a similar mechanism of action. These drugs also have a laxative effect. Cholekinetics should not be prescribed during exacerbation of cholecystitis and in the presence of gallstones. The use of cholekinetics is optimal for the so-called blind (or probeless) dubage (contraindicated in case of cholelithiasis). The patient drinks on an empty stomach, lying on his side, for 30 minutes in small sips of 100 ml of a 10% (if there is no effect - up to 25%) warm solution of magnesium sulfate, then lies in this position for 1.5–2 hours with a heating pad on the liver area. During the procedure, signs of dyspepsia, discomfort or pain in the right hypochondrium may appear. If after dyubazh the intestines are not released, it is necessary to do a cleansing enema. As a therapeutic procedure, dubazh is done once every 5-7 days, to prevent exacerbations of cholecystitis - once every 2-4 weeks. Instead of magnesium sulfate, you can use 200 ml of a 1–2% solution of Carlsbad salt, 100 ml of a 20% solution of sorbitol or xylitol.

Cholespasmolytics are drugs that relax the smooth muscles of the gallbladder and biliary tract.

Among the cholespasmolytics, M-cholinergic blockers are distinguished: atropine, bellalgin (belladonna leaves extract + benzocaine + metamizole sodium + + sodium bicarbonate), besalol (belladonna leaves extract + phenyl salicylate), metacin, platiphylline, as well as myotropic antispasmodics of synthetic and plant origin (bencyclane (halidor ), drotaverine, papaverine) and combination drugs (for example nikoshpan).

The algorithm for choosing antispasmodic therapy is presented in Fig. 9.10.

Rice. 9.10.

Antispasmodics of plant origin - extracts from the flowers of arnica montana, rhizomes and roots of valerian officinalis and elecampane, St. John's wort herb, lemon balm herb (lemon balm tincture), peppermint leaves, calendula officinalis flowers, cudweed herb, sage leaves, cholagol.

The distribution of choleretic drugs into groups is conditional, since most of them have a combination of the above effects, especially herbal remedies.

Common barberry ( Berberis vulgaris), fam. barberry ( Berbe-ridaceae ). A tincture is prepared from the leaves, take 15–30 drops 2–3 times a day before meals. Effects of the drug: choleretic, antispasmodic, antimicrobial, anti-inflammatory, diuretic, weak antihypoxic. With prolonged use, there is an increase in blood clotting. The drug is contraindicated during pregnancy.

Sandy immortelle ( Helichrysum arenarium), fam. Asteraceae ( Compositae ). An infusion is prepared from the flowers (1:10), take 1/3 cup 3-4 times a day before meals. The extract is prescribed 1 g 3 times a day before meals. The drug Flamin contains extracts of immortelle sandy; it is taken 0.05 g 3 times a day before meals. Immortelle combines choleretic, cholekinetic, anti-inflammatory, hepatoprotective, stimulating the secretion of digestive glands, antispasmodic, normalizing metabolism, and moderate antihypoxic effects. Long-term use may increase blood clotting. Contraindicated in gastritis with increased secretion; used with caution in gallstone disease.

Centaury small ( Centaurium minus), family gentianaceae ( Gentia-paseae ) is used as an infusion of herbs (1:10) 1/3 cup 3 times a day before meals. The effect of the drug is choleretic, cholekinetic, analgesic, gpatoprotector, stimulating the secretion of digestive glands, anti-inflammatory, antimicrobial, anthelmintic, immunotropic, antihypoxic. In therapeutic doses it is well tolerated. In case of overdose, dyspepsia occurs. Contraindications are hypersecretory gastritis, peptic ulcer of the stomach and duodenum, and are used with caution in case of cholelithiasis.

Corn ( Zea mays), fam. cereals ( Roaseae ). Corn silk is used, applied as an infusion (1:10) 1/3–1/2 cup 3 times a day before meals. Pharmacological effects: choleretic, cholespasmolytic, anti-inflammatory, hepatoprotective, moderate sedative, diuretic, litholytic, normalizes metabolism, hypoglycemic, hemostatic, moderate antihypoxic. Prescribed with caution for cholelithiasis; monitoring of blood clotting is necessary during long-term use.

Peppermint ( Mentha piperita), fam. Lamiaceae ( Lamiaceae ). Herbal infusion (1:10) is prescribed 1/3–1/2 cup 3 times before meals. Pharmacological effects: choleretic, cholespasmolytic, sedative, vasodilator, analgesic, expectorant, moderate bronchodilator and anti-inflammatory, antihypoxic. An allergic reaction to menthol rarely occurs; in children, bronchospasm is possible during inhalation. Peppermint preparations are contraindicated if you are intolerant to the components of the essential oil.

Common tansy ( Tanacetum vulgare), fam. asteraceae ( Asteraceae ). Infusion of flowers (1:10–1:30) take 1/3 cup 3 times a day before meals. Pharmacological effects: choleretic, cholekinetic, anti-inflammatory, antipyretic, antimicrobial, anthelmintic, pronounced antihypoxic. In case of overdose, nausea, vomiting, diarrhea, and convulsions occur. Contraindications are pregnancy, childhood (up to 5 years), hypersecretory gastritis.

Common chicory ( Cichorium intybus), fam. asteraceae ( Asteraceae ). A decoction of the roots (1:10) is taken 1/4–1/3 cup 3–4 times a day before meals. Pharmacological effects: choleretic, cholekinetic, antimicrobial, anti-inflammatory, diuretic, sedative, moderate cardiotonic and antihypoxic. In case of overdose, tachycardia rarely occurs.

Rosehip May ( Rosa majalis), fam. pink ( Rosaceae ). Rosehip fruit extract (Holosas) take 1 teaspoon 3 times a day before meals. Rosehip decoction (1:10) is taken 1/3–1/2 cup 3 times a day before meals. Pharmacological effects: choleretic, cholekinetic, hepatoprotective, anti-inflammatory, normalizing metabolism.

Spanish artichoke ( Cynara scolymus), fam. Asteraceae ( Compositae ). Dry artichoke extract contains the drug hofitol. The active ingredients are cynarin and caffeic, chlorogenic, and caffeinequinic acids. They ensure the maintenance of hepatocyte functions and cause choleretic and diuretic effects.

Milk thistle ( Silybum marianum), fam. asteraceae ( Asteraceae ). Fruits and herbs contain silybin, dehydrosilibin and other flavolignans, have a choleretic and cholespasmolic effect, milk thistle flavonoids provide hepatoprotective, antioxidant and anabolic effects (stimulate RNA polymerase), block the production of acetaldehyde. Side effects: diarrhea, increased diuresis. Milk thistle preparations (Karsil®, Silibinin®, Legalon®, Silymar®, Silymarin) are contraindicated for acute inflammatory liver diseases, hypersensitivity to drugs, during pregnancy and lactation they are used only for health reasons.

Celandine ( Chelidonium ), fam. poppy ( Papaveraceae ). The celandine alkaloid helidopine causes analgesic, antispasmodic, and choleretic effects.

Pumpkin ( Cucurbita ), fam. pumpkin ( Cucurbitaceae ). Pumpkin seeds (preparation Tykveol®) contain carotenoids, phospholipids, tocopherols, flavonoids, vitamins B, B2, C, PP, F, saturated and unsaturated fatty acids. The active substances have an antiulcer, hepatoprotective, choleretic effect, and inhibit the proliferation of prostate cells.

Combination medications are effective. The patient is given 3–4 prescriptions of preparations, which should be alternated every 1.5–2 months, which ensures long-term remission and prevention of the formation of gallstones. There are also proprietary combinations.

Allochol contains activated carbon + bile + stinging nettle leaves + garlic bulbs. Used for chronic hepatitis, cholangitis, acalculous cholecystitis, habitual constipation.

Holagol, 10 ml bottles, contains turmeric root dye, emodin, magnesium salicylate, essential oils, olive oil. The algorithm for choosing choleretic agents is presented in Fig. 9.11.

Rice. 9.11.

To improve digestion processes, digestive enzyme preparations are prescribed.

Pancreatin (festal, creon, panzinorm) is taken for 3 weeks before meals, 1-2 doses.

• Biochemistry: textbook for universities / ed. E. S. Severina. M., 2009.

Chapter 30. PHARMACOTHERAPY OF VIRAL INFECTIONS

Chapter 30. PHARMACOTHERAPY OF VIRAL INFECTIONS

Viruses that infect people are spread by people themselves through the respiratory tract (influenza) or feces (hepatitis A). A number of severe viral infections (hepatitis B and C, HIV infection) are spread through sexual contact and blood. Many viral infections have a long incubation period.

Some viruses are characterized by oncogenicity, for example, the Epstein-Barr virus is associated with the development of lymphoma, the human papilloma virus is associated with genital cancer, and the hepatitis C virus is associated with hepatocellular cancer.

Diagnosis of viral infections

By detecting the nucleic acid of the virus using PCR. This is the most sensitive and specific of the diagnostic methods, but it can only be used during the period of active replication of viral particles in the body.

Serological methods based on the detection of antibodies to viruses (have less sensitivity than PCR).

Detection of viruses by infecting cell cultures (not used in practical medicine).

Currently, new antiviral drugs are being actively introduced into clinical practice, but their creation still remains

complex. Due to the fact that virus reproduction occurs thanks to the enzyme systems of host cells, the number of virus-specific enzymes that should be affected by antiviral agents is very small. Most antiviral drugs disrupt host cell metabolism to some degree and therefore have a very narrow therapeutic window.

Below is a description of the most common viral diseases in clinical practice.

30.1. ACUTE RESPIRATORY VIRAL INFECTIONS AND FLU

Acute respiratory viral infections

ARVI is a large group of viral infections, the distinctive feature of which is the development of an inflammatory process in any part of the upper respiratory tract (nose, paranasal sinuses, throat, larynx, trachea and bronchi).

Etiology: picornoviruses, RS viruses, parainfluenza viruses, adenoviruses.

Mechanism of transmission of infection: airborne. Incubation period: 1-3 days.

Symptoms: unpleasant sensations in the nose and throat, sneezing, runny nose, malaise. There may be a cough, copious nasal discharge, and sputum production. The diagnosis is made based on the clinical features of the disease.

Flow: symptoms go away on their own after 4-10 days. Some patients may experience complications (bronchitis, inflammation of the paranasal sinuses) associated with the addition of a bacterial infection.

Treatment. Antibiotics and antivirals are not used for ARVI. Symptomatic treatment is indicated - NSAIDs, with the exception of acetylsalicylic acid, which can enhance the release of the virus and cause hemorrhagic complications in children (Reye's syndrome). According to indications, drugs are prescribed that reduce swelling of the nasal mucosa and antitussives. For patients with allergic diseases, antihistamines can be added to treatment. High doses of ascorbic acid are considered a popular treatment, but the effectiveness of this method has not been confirmed in clinical studies.

Flu

Influenza is an acute viral disease of the respiratory tract, characterized by intoxication (high body temperature, headache, malaise) and the development of an inflammatory process in the mucous membrane of the upper respiratory tract, most often the trachea. In severe cases, complications (pneumonia, hemorrhagic bronchitis) and death are possible. In addition, influenza is often complicated by sinusitis, otitis media, frontal sinusitis, and, less commonly, myocarditis. The flu is especially severe in the elderly and those weakened by chronic diseases, as well as in pregnant women. During epidemics, strokes and MI become more frequent among older people.

Etiology: the disease is caused by influenza A viruses (clinically expressed influenza, occurring in the form of epidemics), influenza B viruses (also causes severe forms of the disease) and C. In children, a similar clinical picture is observed when affected by paramyxo-, rhino- and ECHO viruses.

Mechanism of transmission of infection: airborne.

Incubation period: 48 hours

Symptoms The disease begins acutely, with an increase in body temperature to 39-39.5 ° C and chills. Patients complain of severe weakness, headache, pain in the eyes, and sometimes dizziness and vomiting. Somewhat later, dryness and soreness in the nasopharynx, dry cough, and nasal congestion appear. There may be pain in the back and legs. Hyperemia of the face and conjunctiva develops. There are serological diagnostic methods, but usually the diagnosis is made based on the clinical features of the disease.

Flow. The duration of the disease does not exceed 3-5 days. The persistence of fever and other symptoms for more than 5 days indicates the development of complications (bronchitis, pneumonia) and require additional examination. The main cause of death in patients is the rapid (within 48 hours) development of severe viral pneumonia with hemorrhagic complications and progressive heart failure.

Prevention. The transferred infection forms temporary immunity to a given serological type of pathogen, but the body remains susceptible to other serotypes. Serotypes of influenza A virus, which causes epidemics, regularly replace each other (antigenic drift). There are vaccines consisting of whole bodies of inactivated viruses or their components.

Due to the variability of the antigenic structure of the virus, the use of these vaccines for routine collective vaccination of the population does not give the desired result, although it reduces the incidence. Annual vaccination is especially important for older people and people with chronic diseases of the cardiovascular and respiratory systems. Amantadine and rimantadine are used to prevent influenza.

(Table 30-1).

Treatment. Early administration of antiviral drugs allows for rapid relief of fever and respiratory tract damage (see Table 30-1). In most cases, symptomatic treatment is indicated - bed rest and rest (up to 1-2 days after normalization of temperature), antipyretic drugs (preference is given to paracetamol), drugs that reduce swelling of the nasal mucosa, and antitussives.

Aspirin is contraindicated in children with influenza (Reye's syndrome).

Parainfluenza

An acute viral disease that affects the upper respiratory tract, especially the larynx, and occurs with mild intoxication.

Etiology. The disease is caused by RNA-containing paramyxoviruses of four serological types.

Clinical picture varies depending on the serotype of the pathogen.

The disease most often occurs with a moderate increase in temperature (high fever is typical for children), runny nose, dry cough, and hoarseness. May be complicated by the development of bronchitis and pneumonia. Parainfluenza viruses are the main cause of false croup in children. After an illness, partial immunity to a virus of a given serotype is formed, which reduces the severity of subsequent infections.

Treatment. There is no specific treatment. Therapeutic measures are limited to the prescription of symptomatic drugs.

30.2. CLINICAL PHARMACOLOGY OF ANTI-FLU DRUGS

There are two groups of anti-influenza drugs with proven clinical effectiveness: M2 channel blockers - amantadine, rimantadine, and viral neuroamindase inhibitors - zanamivir, oseltamivir.

Currently, rimantadine is considered the main drug for the treatment and prevention of influenza caused by virus A. It was developed in the USSR by modifying the structure of amantadine. Arbidol*, created on the basis of domestic developments, is also used in the Russian Federation. It should be noted that the use of many other drugs for the treatment and prevention of influenza, such as dibazole, oxolinic ointment *, tebrofen *, florenal *, interferon alpha-2 in the form of nasal drops, does not have sufficient grounds from the point of view of evidence-based medicine, since they effectiveness has not been studied in randomized clinical trials.

M2 channel blockers

Mechanism of action. The antiviral effect of amantadine and rimantadine is realized by blocking special M2 ion channels of the influenza A virus, which disrupts its ability to penetrate cells and release ribonucleoprotein. This inhibits the most important stage of viral replication.

Spectrum of activity. Amantadine and rimantadine are active only against the influenza A virus. During use, resistance may develop, the frequency of which can reach 30% by the 5th day of treatment.

Pharmacokinetics. Amantadine and rimantadine are almost completely, but relatively slowly absorbed from the gastrointestinal tract. Food does not affect bioavailability. Maximum concentrations in the blood are reached on average after 2-4 hours. Plasma protein binding of amantadine is 67%, rimantadine is 40%. The drugs are well distributed in the body. In this case, high concentrations are created in tissues and liquids that are in primary contact with the virus: in the mucus of the nasal passages, saliva, tear fluid. Concentrations of rimantadine in nasal mucus are 50% higher than in plasma. Drugs pass through the blood-brain barrier and placenta. Amantadine passes into breast milk. Rimantadine is approximately 75% biotransformed in the liver,

excreted by the kidneys mainly in the form of inactive metabolites. Amantadine is almost not metabolized and is excreted by the kidneys in its active form. The half-life of amantadine is 11-15 hours, in elderly people it can increase to 24-29 hours, in patients with renal failure - up to 7-10 days. The half-life of rimantadine is 1-1.5 days; in severe renal failure it can increase to 2-2.5 days. Both drugs are not removed by hemodialysis.

NLR. Gastrointestinal tract: abdominal pain, loss of appetite, nausea. CNS: when using amantadine in 14% of patients, rimantadine - in 3-6%, drowsiness, insomnia, headache, dizziness, visual disturbances, irritability, paresthesia, tremor, convulsions occur.

Indications. Treatment of influenza caused by virus A. Prevention of influenza (if the epidemic is caused by virus A). Efficiency -

70-90%.

Neuroamindase inhibitors

Mechanism of action. Neuroamindase is one of the key enzymes involved in the replication of influenza A and B viruses. When it is inhibited, the ability of viruses to penetrate healthy cells is impaired, the release of virions from an infected cell is inhibited and their resistance to the inactivating action of mucous secretions of the respiratory tract is reduced, and further spread of the virus is inhibited in the body. In addition, neuroaminidase inhibitors reduce the production of certain cytokines, preventing the development of a local inflammatory response and weakening the systemic manifestations of viral infection (fever).

Spectrum of activity. Influenza viruses A and B. The resistance rate of clinical strains is 2%.

Pharmacokinetics. Oseltamivir is well absorbed from the gastrointestinal tract. During absorption and during the first passage through the liver, it is converted into an active metabolite (oseltamivir carboxylate). Food does not affect bioavailability. Zanamivir has low oral bioavailability and is administered by inhalation. In this case, 10-20% of the drug penetrates the tracheobronchial tree and lungs. The binding of drugs to plasma proteins is low - 3-5%. The oseltamivir metabolite creates high concentrations in the main foci of influenza infection - the nasal mucosa, middle ear, trachea, bronchi, and lungs. Both drugs are excreted predominantly

mainly with urine. The half-life of zanamivir is 2.5-5 hours, oseltamivir carboxylate is 7-8 hours; in case of renal failure, its significant increase is possible, especially with oseltamivir

(until 18:00).

NLR. Gastrointestinal tract: abdominal pain, nausea, vomiting, diarrhea. CNS: headache, dizziness, insomnia, general weakness. Others: nasal congestion, sore throat, cough.

Indications. Treatment of influenza caused by viruses A and B. Prevention of influenza (oseltamivir only).

Contraindications. Hypersensitivity to zanamivir or oseltamivir. Severe renal failure (oseltamivir).

30.3. HERPES SIMPLE

Herpes simplex- a recurrent infection characterized by the appearance on the skin or on the surface of the mucous membranes of single or multiple clusters of small blisters filled with clear liquid and located on a slightly raised, inflamed base.

Etiology: There are two types of herpes pathogens known: Herpes simplex-1 usually causes damage to the lips, and Herpes simplex-2- damage to the skin and genital organs. The virus is capable of persisting (preserving) in a latent state in the nerve ganglia.

Mechanism of transmission of infection: contact (including during sexual intercourse).

Symptoms: rashes can appear on any area of ​​the skin or mucous membranes. Usually the appearance of rashes is preceded by itching. The rash is represented by single or multiple clusters of small blisters (from 0.5 to 1.5 cm in diameter). The rash is usually painful. After a few days, the bubbles dry out and crusts form. The diagnosis is usually made clinically; there are also serological diagnostic methods.

Flow: healing occurs in 8-12 days. The course of the disease may be complicated by the addition of a secondary bacterial infection.

Treatment. Local use of acyclovir or other anti-herpetic drugs. For secondary infections - local use of antibiotics. In severe forms of infection (generalized neonatal herpes), treatment is carried out under the following conditions:

in hospital with the use of intravenous injections of acyclovir. Systemic acyclovir is also prescribed for recurrent genital herpes.

Shingles

Shingles- acute damage to the central nervous system, primarily to the nerve ganglia, which is characterized by the appearance of herpetic rashes and neurological pain in areas of the skin located along the affected nerves.

Etiology: Shingles and chickenpox are caused by the same virus. Viral particles can persist for a long time in the nerve ganglia. The activation of the virus is caused by local damage to the nerve roots or the use of immunosuppressive drugs.

Symptoms: the disease begins with an increase in body temperature, general malaise and the appearance of pain in certain parts of the body (usually only on one side of the body). Later (on the 4th-5th day) characteristic rashes appear in these areas. Relapses are observed only in 4% of cases.

Treatment. Antiviral agents (see Table 30-1). Symptomatic - NSAIDs in combination with codeine.

30.4. CLINICAL PHARMACOLOGY OF ANTIHERPETIC DRUGS

The main antiherpetic drugs with effectiveness proven in randomized clinical trials include four structurally similar drugs from the group of nucleoside analogues - acyclovir, valacyclovir, penciclovir and famciclovir. Moreover, valacyclovir and famciclovir are initially inactive compounds that are converted in the human body to acyclovir and penciclovir, respectively. All of these drugs block DNA synthesis in reproducing herpes viruses, but do not affect viruses that are in a latent state.

For topical use, acyclovir, penciclovir, idoxuridine®, foscarnet sodium and tromantadine are used.

Mechanism of action. Acyclovir is considered the ancestor of antiherpetic drugs - blockers of viral DNA synthesis. The antiviral effect is exerted by the active metabolite of acyclo-

vira - acyclovir triphosphate, which is formed in cells affected by the herpes virus. By inhibiting viral DNA polymerase, acyclovir triphosphate blocks viral DNA synthesis. The drug has very low toxicity, since it does not affect the DNA polymerase of human cells and is inactive in healthy cells.

Penciclovir is activated in human cells affected by the virus, turning into penciclovir triphosphate, which disrupts the synthesis of viral DNA. Penciclovir has a long intracellular half-life (7-20 hours), which is significantly higher than that of acyclovir (less than 1 hour). However, it has less affinity for viral DNA polymerase than phosphorylated acyclovir.

In general, all three drugs (acyclovir, valacyclovir and famciclovir) have comparable clinical efficacy when taken orally.

Foscarnet sodium forms inactive complexes with DNA polymerase of herpetic viruses and CMV.

Spectrum of activity. Herpes simplex viruses (HSV) types 1 and 2 are most sensitive to acyclovir. Virus Varicella-zoster more than 20 times, and CMV is less than 470 times sensitive to acyclovir than HSV type 1. Penciclovir is very close to acyclovir in activity against HSV types 1 and 2 and the virus Varicella-zoster.

Pharmacokinetics. Three drugs are used for oral administration - acyclovir, valacyclovir and famciclovir, and only acyclovir is administered intravenously. Acyclovir has the lowest bioavailability when taken orally (15-20%), but even a daily dose (0.8-1.0 g) is sufficient to suppress HSV. Valacyclovir is the valine ester of acyclovir, intended for oral administration and has a higher bioavailability (54%). During absorption from the gastrointestinal tract and in the liver, it is converted into acyclovir. The bioavailability of famciclovir when taken orally on an empty stomach is 70-80%. In the gastrointestinal tract, it is converted to penciclovir, which is then phosphorylated in cells affected by the virus.

Penciclovir is used only externally, since when taken orally it has very low bioavailability (5%).

Acyclovir is well distributed in the body. Penetrates into saliva, intraocular fluid, vaginal secretions, and the fluid of herpetic vesicles. Passes through the BBB. When applied topically, it is slightly absorbed through the skin and mucous membranes.

Both acyclovir and penciclovir are excreted primarily by the kidneys, 60-90% unchanged. Acyclovir

excreted by glomerular filtration and tubular secretion. The drugs have approximately the same half-life - 2-3 hours, in young children - up to 4 hours. In case of renal failure (creatinine clearance less than 30 ml/min), the half-life increases significantly, which requires adjustment of doses and administration regimens.

NLR. Acyclovir is generally well tolerated by patients, and ADRs are rare. Local reactions: burning when applied to mucous membranes, especially when applied vaginally; phlebitis with intravenous administration. Systemic reactions from the gastrointestinal tract: abdominal pain or discomfort, nausea, vomiting, diarrhea. In 1-4% of patients with intravenous administration of acyclovir, lethargy, tremor, convulsions, hallucinations, delirium, and extrapyramidal disorders are observed. Symptoms usually appear in the first 3 days of treatment, are associated with a high concentration of acyclovir in the blood serum (more than 25 mcg/ml) and gradually disappear as it decreases. Due to crystallization of the drug in the renal tubules, 5% of patients with intravenous administration develop obstructive nephropathy, manifested by nausea, vomiting, lower back pain, and azotemia. Prevention measures: drink plenty of fluids. Help: drug withdrawal, infusion therapy. Valaciclovir is close in tolerability to acyclovir for oral administration. In terms of safety profile in adults, famciclovir is close to acyclovir. The most common ADRs are headache and nausea.

Indications. Infections caused by HSV types 1 and 2: infections of the skin and mucous membranes; ophthalmoherpes (aciclovir only); genital herpes; herpetic encephalitis; neonatal herpes. Infections caused by a virus Varicella-zoster: shingles; chicken pox; pneumonia; encephalitis. Prevention of CMV infection after kidney transplantation (acyclovir, valacyclovir).

Contraindications. Allergic reactions.

30.5. CHRONIC VIRAL HEPATITIS

Chronic viral hepatitis- a group of chronic diseases caused by hepatotropic (liver-damaging) viruses. The disease occurs with the development of chronic inflammation of the liver, which usually progresses to cirrhosis.

Etiology: most often hepatitis B and C viruses.

Mechanism of transmission of infection: the infection is transmitted through blood (violation of asepsis during medical procedures, injection drug addicts) or contact - through microdamage to the integumentary tissue (including sexual intercourse).

Symptoms: after a long (90-120 days) incubation period, the disease begins acutely (jaundice, dark urine). At the same time, in a certain part of patients, the virus persists and the activity of transaminases increases, indicating chronic inflammation of the liver. With hepatitis C, pronounced clinical symptoms and an icteric period are often absent, and the diagnosis of hepatitis is first established when irreversible changes develop in the liver.

In the later stages of the disease, liver cirrhosis and portal hypertension syndrome develop, which is characterized by the accumulation of fluid in the abdominal cavity (ascites) and the progression of liver failure. The hepatitis C virus often causes liver cancer.

Diagnosis is based on the use of serological methods and PCR. Using the PCR method, you can obtain information about the activity of the virus replication process.

Treatment. The decision to use antiviral agents (see Table 30-1) should be made by a specialist. Patients with chronic hepatitis should not be prescribed drugs with hepatotoxic effects or inducers of microsomal oxidation. Hepatoprotectors for chronic viral hepatitis are not effective.

30.6. CLINICAL PHARMACOLOGY OF DRUGS FOR THE TREATMENT OF CHRONIC VIRAL HEPATITIS

Ribavirin

A synthetic drug similar in structure to the nucleotide guanosine. It has a wide spectrum of activity against many DNA and RNA viruses and is highly toxic.

Mechanism of action. The mechanism of antiviral action is not fully understood. It is believed that ribavirin causes a decrease in the intracellular pool of guanosine triphosphate and, thus, indirectly reduces the synthesis of viral nucleic acids.

Spectrum of activity. Of clinical importance is activity against RNA viruses, as well as viruses that cause Lassa disease, hemorrhagic fever with renal syndrome and hepatitis C (in combination with interferons).

Pharmacokinetics. Bioavailability when taken orally is 45%, maximum concentration in the blood is achieved after 1-1.5 hours. When used in inhalation, high concentrations are observed in the secretions of the respiratory tract and significantly lower concentrations are observed in the blood plasma. The drug does not bind to proteins. May accumulate in red blood cells. Penetrates through the BBB. Biotransformed by phosphorylation in the liver, excreted mainly in the urine. The half-life when taken orally is 27-36 hours, when a stable concentration is reached - 6 days. After inhalation administration, 30-55% of the drug is excreted in the urine as a metabolite within 72-80 hours.

NLR. Hematological reactions: anemia, hemolytic anemia, leukopenia, neutropenia, granulocytopenia, thrombocytopenia. Control methods: clinical blood test every 2 weeks. CNS: asthenic syndrome, headache, insomnia, feeling tired, irritability. Local reactions: rash, skin irritation, conjunctivitis (for inhalation use due to prolonged contact with the drug in both patients and medical personnel). Heart: decreased blood pressure, bradycardia, asystole. Appropriate clinical and instrumental monitoring is required. Gastrointestinal tract: anorexia, nausea, metallic taste in the mouth, abdominal pain, flatulence. Liver: hyperbilirubinemia.

Indications. Infections caused by rhinosyncytial viruses (serologically confirmed only): severe bronchiolitis and pneumonia in newborns and young children at risk of death (congenital heart disease, immunodeficiency, bronchopulmonary dysplasia), against the background of severe cystic fibrosis or pulmonary hypertension. Hepatitis C (in combination with interferons). Hemorrhagic fever with renal syndrome.

Contraindications. Hypersensitivity to ribavirin. Severe liver and/or kidney failure. Anemia. Hemoglobinopathy. Severe heart failure. Pregnancy. Breastfeeding.

Lamivudine

Synthetic analogue of deoxycytidine nucleoside. It was created as an antiretroviral drug for the treatment of HIV infection. Then it was revealed that it has activity against some other viruses.

Mechanism of action. In cells affected by the virus, it is activated, turning into lamivudine triphosphate, which inhibits hepatitis B virus DNA polymerase and HIV reverse transcriptase.

Spectrum of activity. Activity against retroviruses (HIV) and the hepatitis B virus is of clinical importance. With monotherapy, resistance to lamivudine of both the hepatitis B virus and HIV can develop quite quickly.

Pharmacokinetics. Well and quickly absorbed from the gastrointestinal tract. Food does not significantly affect bioavailability, but increases the time to reach peak concentration in the blood and slightly decreases it (this has no clinical significance). The time to reach peak concentration is 0.5-2 hours. Distributed into many tissues and fluids, passes through the blood-brain barrier and placenta. Plasma protein binding is low - 36%. Partially biotransformed, excreted mainly by the kidneys (about 70%) unchanged. The half-life in adults is 2-11 hours, in children - about 2 hours, and increases with renal failure.

NLR. Gastrointestinal tract: abdominal pain or discomfort, nausea, vomiting, diarrhea. Liver: increased ALT activity, hepatomegaly with steatosis (possibly associated with impaired mitochondrial function - mitochondrial cytotoxicity). Nervous system: fatigue, headache, dizziness, weakness, insomnia, peripheral neuropathy, paresthesia (more often in children). Blood: neutropenia, anemia. Allergic reactions: rash.

Indications. Chronic hepatitis B. Treatment and prevention of HIV infection.

Contraindications. Hypersensitivity to lamivudine. Pregnancy. Breastfeeding.

Telbivudin

Antiviral drug, synthetic thymidine analogue of nucleoside.

Mechanism of action. Blocks the activity of the hepatitis B virus DNA polymerase enzyme. Inclusion of telbivudine-5-triphosphate

into the structure of the viral DNA causes its chain to break and suppress the replication of the hepatitis B virus.

Spectrum of activity. Its activity against the hepatitis B virus is of clinical significance. The drug has no effect on other RNA and DNA viruses, including HIV.

Pharmacokinetics. T1/2 is approximately 15 hours. Telbivudine is not a substrate, inhibitor or inducer of the cytochrome P-450 enzyme system. It is excreted primarily in the urine unchanged.

NLR. Gastrointestinal tract: nausea, diarrhea. Liver: increased activity of ALT, AST. Nervous system: fatigue, headache, peripheral neuropathy. Allergic reactions: rash.

Indications. Chronic hepatitis B with confirmed viral replication and active inflammatory process in the liver.

Interferons

Interferons are biologically active proteins that are synthesized by the cell during the protective reaction. They are secreted into the extracellular fluid and act on other cells through receptors, increasing resistance to intracellular microorganisms, primarily viruses. Based on their structure and biological properties, interferons are divided into three types: interferon alpha, interferon beta and interferon gamma. According to the method of production, leukocyte, lymphoblastoid and recombinant interferons are distinguished.

Recombinant alpha interferons are most widely used as antiviral drugs. All are recombinant forms of human interferon alpha-2 and their pharmacological actions are similar. Depending on the amino acid content, interferon alpha-2a and interferon alpha-2b are distinguished, which do not differ significantly in clinical effectiveness and safety. Currently, pegylated interferons have been developed, obtained by attaching polyethylene glycol to the interferon molecule. Pegylated interferons have a longer half-life and better clinical efficacy.

Leukocyte interferons are currently practically not used due to insufficient stability of the composition, the presence of other peptides and mediators of the immune system in the drug. In addition, it is impossible to completely eliminate the risk of contamination

lysis of leukocyte interferons by blood-borne viruses. Intranasal use of leukocyte interferons is unjustified due to the lack of evidence of their effectiveness in acute respiratory viral infections (ARVI) and influenza.

Classification of interferons

Lymphoblastoid: interferon alpha-p1.

Recombinant: interferon alpha-2a, interferon alpha-2b.

PEGylated: peginterferon alfa-2a, peginterferon alfa-2b.

Mechanism of action. The main mechanism of the antiviral action of interferons is to suppress the synthesis of viral proteins. Recombinant alpha interferons have the basic properties of natural human interferons. They have an antiviral effect, inducing a state of resistance to viral infections in cells and modulating the immune system response aimed at neutralizing viruses or destroying cells infected by them (Fig. 30-1).

Rice. 30-1. Intracellular mechanisms of the antiviral action of interferon

Spectrum of activity. Alpha interferons do not have specificity and inhibit the replication of various viruses. Main cli-

Activity against hepatitis B, C and D viruses is of critical importance.

Pharmacokinetics. Being proteins, interferons are destroyed in the gastrointestinal tract, which is why they can only be administered parenterally. When administered intramuscularly and subcutaneously, the bioavailability is 80%, the maximum concentration in the blood is achieved on average after 3.8 hours. Low concentrations of interferons have been noted in the secretions of the respiratory tract, eye tissues, and the central nervous system. They undergo rapid inactivation in the kidneys and, to a lesser extent, in the liver. The half-life is 2-4 hours, does not change in case of renal failure. The pharmacokinetics of peginterferons has been studied somewhat less. The maximum concentration in the blood is reached within 15-44 hours, and it is 10 times higher, and the area under the pharmacokinetic curve is 50 times greater than that of conventional interferon alpha. Half-life - 40 hours.

NLR. They have a dose-dependent nature. There are early ones, which occur more often in the first week of treatment, and late ones, which develop in the 2-6th week of taking the drug. Early (in the 1st week of treatment) - a flu-like syndrome with fever, myalgia, soreness of the eyeballs and usually does not require discontinuation of the drug. Late (at 2-6 weeks of treatment, usually the cause of interferon withdrawal) - anemia, thrombocytopenia, agranulocytosis, lethargy, depression, arrhythmias, transient cardiomyopathy, arterial hypotension, autoimmune thyroiditis, hyperlipidemia, alopecia.

Indications. Lymphoblastoid and recombinant interferon alpha - chronic hepatitis B. Acute hepatitis C. Chronic hepatitis C (sometimes in combination with ribavirin). Chronic hepatitis D.

Peginterferons - chronic hepatitis C.

Contraindications. Hypersensitivity to drugs. Psychosis (at the time of treatment or in history). Severe depression. Neutropenia or thrombocytopenia. Decompensated diseases of the cardiovascular system. Decompensated cirrhosis of the liver. Uncontrollable seizures. Organ transplantation (except liver). Pregnancy. Liver cirrhosis (except peginterferons).

30.7. HUMAN IMMUNODEFICIENCY VIRUS

HIV- an infection caused by a number of retroviruses and manifested by a variety of clinical conditions from asymptomatic

long carriage to severe and fatal disease - acquired immunodeficiency syndrome (AIDS). AIDS is a secondary immunodeficiency syndrome that develops in patients with HIV infection and is characterized by opportunistic infections 1, malignant neoplasms and neurological manifestations.

Etiology: HIV infection is caused by a retrovirus called HIV. This virus infects a subpopulation of CD4 T lymphocytes (T helper cells) and some other cells in the lungs, brain, skin and lymph nodes, causing their death.

Mechanism of transmission of infection: the infection is transmitted through body fluids that contain plasma or infected cells: blood, seminal fluid, vaginal secretions, saliva. Transmission of the infection from mother to child can occur directly through the placenta, during childbirth, or through breast milk.

Symptoms HIV infection is characterized by a long (up to several years) asymptomatic period, during which viruses practically do not multiply. The developed AIDS clinic is characterized by the appearance of opportunistic infections (Pneumocystis pneumonia, tuberculous and pneumococcal meningitis), tumors (Kaposi's sarcoma, brain lymphoma), and neurological symptoms (peripheral neuropathies, meningitis, seizures, progressive dementia).

To diagnose the disease, serological tests are used - determination of antibodies to HIV proteins using enzyme-linked immunosorbent assay (ELISA test). If the ELISA test results are positive, a more specific test, Western blotting, is performed to confirm the diagnosis. An indicator of the severity of the disease, which allows one to judge the prognosis and risk of complications, is the number of circulating CD4T lymphocytes (it is these cells that become the main target of the virus and die when it multiplies massively in the body).

Treatment. HIV quickly develops resistance to the action of all currently existing antiviral drugs; therefore, antiviral treatment can only slow down the progression of the disease.

1 Opportunistic infections are infections that occur when the physiological and immunological defense mechanisms of the body are damaged. Microorganisms that act as pathogens in opportunistic infections, as a rule, do not cause diseases in individuals with intact immunity.

The indication for treatment is a decrease in the number of circulating CD4T lymphocytes less than 350-500 10 6 /l and / or a high degree of viral replication (determined by PCR). In addition, high doses of antiviral drugs are used during childbirth in HIV-infected women, which reduces the risk of transmission of infection when the newborn moves through the birth canal.

For treatment, zidovudine, lamivudine, indinavir, stavudine, and didanosine are prescribed.

30.8. CLINICAL PHARMACOLOGY OF ANTIRETROVIRAL DRUGS

Antiretroviral drugs are used to treat and prevent HIV infection. There are three classes of these drugs.

Nucleoside HIV reverse transcriptase inhibitors (zidovudine, phosphazide, stavudine, didanosine, lamivudine, abacavir, combination drugs: zidovudine + lamivudine, zidovudine + lamivudine + abacavir).

Non-nucleoside HIV reverse transcriptase inhibitors: nevirapine and efavirenz* 3.

HIV protease inhibitors: amprenavir, saquinavir, indinavir, ritonavir, nelfinavir.

General indications for the use of antiretroviral drugs. Treatment of infection caused by HIV-1 and HIV-2 (zidovudine, phosphazide, stavudine, didanosine, zalcitabine, lamivudine, abacavir). Prevention of perinatal HIV infection (zidovudine, phosphazide). Chemoprophylaxis of HIV infection in newborns (zidovudine). Chemoprophylaxis of parenteral HIV infection (zido-vudine, phosphazide, stavudine, didanosine, lamivudine, abacavir).

Nucleoside inhibitors of human immunodeficiency virus reverse transcriptase

Mechanism of action. The structure of all nucleoside reverse transcriptase inhibitors is based on one of the natural nucleoside analogs (thymidine, adenine, cytidine or guanine), which determines the common property of the metabolites of each drug to block HIV reverse transcriptase and selectively inhibit viral DNA replication. Under the influence of appropriate fer-

ment drugs are transformed with the formation of triphosphates, which exhibit pharmacological activity. The ability of drugs in this group to inhibit HIV reverse transcriptase is hundreds of times higher than the ability to inhibit human DNA polymerase. Nucleoside reverse transcriptase inhibitors are active in HIV-infected T cells and macrophages and inhibit early stages of the viral life cycle.

Zidovudine

Thymidine analogue. The first antiretroviral drug.

Pharmacokinetics. It is well absorbed from the gastrointestinal tract; food (especially fatty foods) somewhat reduces bioavailability. The time to reach peak concentration in serum is 0.5-1.5 hours, in CSF - 1 hour. Plasma protein binding is low (30-38%). Penetrates through the BBB, placenta and seminal fluid. It undergoes biotransformation in the liver to an inactive metabolite and is excreted by the kidneys. Half-life - 1.1 hours, cellular - 3.3 hours.

NLR. Gastrointestinal tract: most often - nausea and vomiting, rarely - taste disturbances, abdominal pain, diarrhea, anorexia, flatulence. Liver: increased transaminase activity, steatosis. Hematological reactions: anemia, neutropenia, leukopenia, thrombocytopenia. Nervous system: weakness, fatigue, headache, insomnia, asthenic syndrome, drowsiness, depression, peripheral neuropathies, paresthesia.

Contraindications. Hypersensitivity to zidovudine. Leukopenia (neutrophil count less than 0.75 10 9 /l). Anemia (hemoglobin concentration less than 70 g/l).

Non-nucleoside inhibitors of immunodeficiency virus reverse transcriptase

The group of non-nucleoside reverse transcriptase inhibitors includes nevirapine and efavirenz* 3 . They inhibit the early stages of the virus life cycle and are therefore active against acutely infected cells.

Spectrum of activity. The activity of non-nucleoside reverse transcriptase inhibitors against HIV-1 is of clinical significance. At the same time, drugs of this group are inactive against HIV-2.

Indications. Combination treatment of infection caused by HIV-1 (nevirapine, efavirenz* 3). Prevention of transmission of HIV-1 infection from mother to newborn (nevirapine). Chemoprophylaxis of parenteral HIV infection (ifavirenz* 3).

Nevirapine

Mechanism of action. Causes destruction of the catalytic site of HIV-1 reverse transcriptase. Blocks the activity of RNA- and DNA-dependent polymerase. Does not inhibit HIV-2 reverse transcriptase or human α-, β-, γ- or σ-DNA polymerase. With monotherapy, viral resistance quickly and almost always develops. Active in acutely HIV-infected T cells, inhibits early stages of the virus life cycle. In combination with zidovudine, it reduces the concentration of viruses in the serum and increases the number of CD4 cells; slows down the progression of the disease.

Pharmacokinetics. Well absorbed from the gastrointestinal tract, bioavailability does not depend on food intake. The time to reach peak concentration in the blood is 4 hours. Plasma protein binding is 60%. It has high lipophilicity. It passes well through the BBB, the concentration in the CSF reaches 45% of the concentration in plasma. Passes through the placenta and accumulates in breast milk. Biotransformed in the liver, excreted mainly by the kidneys. The half-life is 20-45 hours.

NLR. Symptoms of hypersensitivity: rash (in 17% of patients), fever, arthralgia, myalgia. In rare cases, toxic epidermal necrolysis or Stevens-Johnson syndrome develops. Gastrointestinal tract: nausea, stomatitis. CNS: headache, fatigue, drowsiness. Hematological reactions: granulocytopenia. Liver: hepatitis (more often in patients with chronic viral hepatitis, as well as in alcohol abusers).

Contraindications. Hypersensitivity to nevirapine.

Immunodeficiency virus protease inhibitors

HIV protease inhibitors include saquinavir, indinavir, ritonavir, nelfinavir and amprenavir.

Mechanism of action. HIV protease is an enzyme necessary for the proteolytic cleavage of polyprotein precursors of the virus into individual proteins that make up HIV. Cleavage of viral polyproteins is essential for maturation

virus capable of infection. Protease inhibitors block the active site of the enzyme and disrupt the formation of viral capsid proteins. Drugs in this group suppress HIV replication, including resistance to reverse transcriptase inhibitors. As a result of inhibition of HIV protease activity, immature viral particles are formed that are unable to infect other cells.

Spectrum of activity. The activity of drugs in this group against HIV-1 and HIV-2 is of clinical importance.

Indications. Treatment of HIV infection as part of combination therapy. Chemoprophylaxis of parenteral HIV infection.

Saquinavir

The first drug of the group of protease inhibitors, introduced into clinical practice in 1995.

Pharmacokinetics. Absorbed from the gastrointestinal tract by 30%, but bioavailability is only 4%, which is due to the “first pass” effect through the liver. Food (especially fatty foods) significantly increases the bioavailability of saquinavir. The time to reach peak concentration in the blood is 4 hours. Plasma protein binding is 98%. It is well distributed, but practically does not pass through the BBB. Biotransformed in the liver, excreted mainly in feces. The half-life is 1-2 hours. With long-term use it accumulates.

NLR. Gastrointestinal tract: diarrhea, abdominal pain, nausea. Oral cavity: ulceration of the mucous membrane, pharyngitis. Hematological reactions: hemolytic anemia. Metabolic disorders: redistribution of subcutaneous fat, increased concentrations of cholesterol (including low-density lipoproteins), triglycerides, hyperglycemia (sometimes type II diabetes develops). Nervous system: headache, confusion, ataxia, weakness, dizziness, asthenic syndrome, convulsions, peripheral neuropathies, numbness of the extremities. Skin: rash, itching, Stevens-Johnson syndrome, dermatitis. Musculoskeletal system: pain in muscles and joints, osteoporosis.

Contraindications. Hypersensitivity to saquinavir. Liver failure.

Clinical pharmacology and pharmacotherapy: textbook. - 3rd ed., revised. and additional / ed. V. G. Kukesa, A. K. Starodubtseva. - 2012. - 840 p.: ill.

Factors that aggravate the course of hepatitis C:

The importance of a number of factors that can have a negative impact on the natural course of hepatitis C has been established:

• age over 40 years at the time of hepatitis C infection;
• male gender;
• race (not European);
• alcohol abuse;
• obesity;
• iron metabolism disorder;
• metabolic syndrome.

Recently, close attention has been paid to studying the influence of various metabolic parameters on the course of chronic hepatitis C, which is quite justified in connection with the understanding of hepatitis syndrome of any origin as a metabolic problem of the body. In chronic hepatitis C, additional interest in metabolic disorders is due to the ability of the hepatitis C virus to be an initiator or co-factor in the development of metabolic disorders that are significant for the course of the disease, in particular carbohydrate-fat metabolism. For example, it is known that insulin resistance influences the course of chronic hepatitis C, and in its development the role of hepatitis C virus genotype 1b in inhibiting the insulin cascade has been established. This circumstance explains the significantly more frequent detection of type 2 diabetes mellitus and insulin resistance in CHC compared with patients with chronic hepatitis B and persons without viral hepatitis. That is, type 2 diabetes mellitus and insulin resistance have pathogenetic connections with chronic hepatitis C. Also, there is evidence of a connection between the acceleration of the rate of progression of liver fibrosis in chronic hepatitis C combined with insulin resistance.

Pharmacotherapy of hepatitis C:

Antiviral therapy for hepatitis C is one of the most effective methods of treating this disease. The main goal of such therapy is to stop the development of the virus in the human body.

Recent international studies and practical data have shown that at present, combination antiviral therapy with interferon-alpha and ribavirin is most justified. The main objective of such antiviral therapy is the prevention of liver cirrhosis and hepatocellular carcinoma. The goal of treatment is to achieve a sustainable virological response - the absence of viremia (undetectable level of viral RNA in the blood) 24 weeks after the end of treatment. At the same time, all biochemical blood parameters are normalized and liver histology improves. Long-term observations have shown that in most patients who achieve a sustained virological response, the virus is no longer detectable.

Protease and polymerase inhibitors- oral medications whose action is directed directly at the hepatitis C virus. After lengthy clinical studies, they were approved for use. They have a so-called direct antiviral effect, while inhibiting (blocking) the key intracellular stages of virus reproduction. The advantage of this class of drugs, in contrast to combination antiviral therapy, is the form of administration (tablets or capsules), their high efficiency and good tolerability. The main disadvantage is the fairly high cost. However, recently more and more analogues (generics) of original antiviral drugs have appeared, which, as a rule, are not inferior in effectiveness to the original, and their price is tens of times cheaper.