Guidance for medical personnel on the safe handling of anticancer drugs. SLE: treatment with cytotoxic agents

Over the past 20-25 years, cytostatics have become an important part of the treatment of a large number of autoimmune diseases. Due to their action, such medications have found their application not only in the treatment of cancer, but also in dermatology, dentistry, dermatovenereology and other areas. Cytostatics - what are they, and what is their effect? You can learn about this from this article.

About cytostatics

Cytostatic drugs or cytostatics are a group of drugs that are capable of disrupting the growth, development and division of cells, including malignant types, when they enter the human body. Therapy of neoplasms with drugs of this kind is prescribed only by a qualified doctor. The drugs can be produced in the form of tablets, capsules, or administered intravenously to patients using a dropper or injections.

Literally all cytostatic drugs are chemicals with high biological activity. Similar drugs also have the option to:

inhibit cell proliferation;
attack cells that have a high miotic index.

Where are they applied?

Cytostatics have been widely used in the treatment oncological diseases different complexity and different parts body. The drugs are prescribed for the treatment of malignant tumors in cancer, leukemia, monoclonal gammopathy, etc. In addition, cytostatics prevent rapid cell division:

bone marrow;
skin;
mucous membranes;
epithelium of the gastrointestinal tract;
hair;
lymphoid and myeloid genesis.

In addition to the above, cytostatics are actively used in the treatment of diseases of the digestive system, such as cancer of the stomach, esophagus, liver, pancreas, rectum. Medications are used where chemotherapy does not produce the desired positive results.

Having considered detailed instructions before taking the drug, it becomes clear how cytostatics work, what they are, and in what cases they should be used. This type of drug is most commonly prescribed autoimmune therapy. Cytostatics have a direct effect on the cells of the bone marrow, while reducing the activity of the immune system, which results in a stable remission.

Types of cytostatics

A competent classification of cytostatics allows you to determine which drugs are needed in a particular case. Only a qualified doctor can prescribe drug therapy after receiving the results of the tests. Drugs of the cytostatic group are divided into such types as:

Alkylating drugs that have the ability to damage the DNA of rapidly dividing cells. Despite the effectiveness, drugs are difficult to tolerate by patients, and the negative consequences of therapy are pathologies of the liver and kidneys.
Alkaloids-cytostatics of plant type ("Etoposide", "Rozevin", "Kolhamin", "Vincristine").
Cytostatic antimetabolites are drugs that lead to tumor tissue necrosis and remission of cancer.
Cytostatic antibiotics - antitumor agents with antimicrobial properties.
Cytostatic hormones - drugs that inhibit the production of certain hormones. They can reduce the growth of malignant tumors.
Monoclonal antibodies are artificially created antibodies that are identical to real immune cells.

Mechanism of action

Cytostatics, the mechanism of action of which is aimed at inhibition of cell proliferation and death tumor cells, pursue one of the main goals - this is the impact on different targets in the cell, namely:

on DNA;
for enzymes.

Damaged cells, that is, mutated DNA, disrupt metabolic processes in the body and the synthesis of hormones. Of course, the mechanism for achieving inhibition of the growth of tumor tissues in different cytostatics may differ. This is because they have different chemical structures and can have different effects on metabolism. Depending on the group of cytostatic drugs, cells can be affected:

thymidylate synthetase activity;
thymidylate synthetase;
topoisomerase I activity;
mitotic spindle formation, etc.

Basic admission rules

Cytostatics are recommended to be taken during or after meals. During drug treatment cytotoxic drugs are forbidden to use alcoholic drinks. Doctors do not advise taking such drugs during pregnancy or lactation.

Side effects

Cytostatics - what it is, and what contraindications for use exist, the attending physician can explain in each case. The frequency of occurrence of side effects directly depends on such nuances as:

the type of medication you are taking;
dosage;
scheme and mode of administration;
therapeutic effect that preceded the drug;
general condition of the human body.

In most cases, side effects are due to the properties of cytostatic drugs. Therefore, the mechanism of tissue damage is similar to the mechanism of action on the tumor. The most characteristic and inherent in most cytostatic side effects are:

stomatitis;
inhibition of hematopoiesis;
nausea, vomiting, diarrhea;
alopecia of different types;
allergy ( skin rashes or itching)
heart failure, anemia;
nephrotoxicity or damage to the renal tubules;
reaction from the veins (phlebosclerosis, phlebitis, etc.);
headaches and weakness that is felt throughout the body;
chills or fever;
loss of appetite;
asthenia.

Overdose may cause nausea, vomiting, anorexia, diarrhea, gastroenteritis, or liver dysfunction. The negative impact of drug treatment with cytostatic drugs has on Bone marrow, healthy cells which accept incorrect elements and cannot be updated at the same speed. In this case, a person may experience a lack of blood cells, which leads to disruption of oxygen transport, and the level of hemoglobin decreases. This can be seen by the pallor of the skin.

Another side effect of taking cytostatics is the appearance of cracks, inflammatory reactions and ulcers on mucous membranes. During therapy, such areas in the body are sensitive to the ingress of microbes and fungi.

Reduce Side Effects

Due modern medicines and vitamins, you can reduce the negative impact of cytostatics on the body, while not reducing therapeutic action. Taking special preparations, it is quite possible to get rid of the gag reflex and maintain working capacity and good health all day.

It is recommended to take such drugs in the morning, after which during the day you should not forget about water balance. Drink 1.5 to 2 liters clean water per day. This can be explained by the fact that literally the entire list of cytostatic drugs is characterized by excretion with the help of the kidneys, that is, the elements of drugs settle in the bladder and irritate tissues. Thanks to the water drunk during the day, the body is cleansed, and the Negative consequences cytostatic therapy. Also frequent use liquids in small portions can minimize the risk of increasing allowable rate bacteria in the mouth.

In order to cleanse the body and improve the composition of the blood, doctors recommend doing a blood transfusion, as well as enriching it with hemoglobin artificially.

Contraindications

hypersensitivity to the drug or its components;
oppression of bone marrow functions;
diagnosed with chicken pox, shingles or other infectious diseases;
violation normal functioning kidneys and liver;
gout;
kidney disease.

Commonly prescribed cytotoxic drugs

The question of cytostatics, what they are and their role in the treatment of malignant tumors, has always been relevant. Commonly prescribed drugs are:

"Azathioprine" is an immunosuppressant that has a partial cytostatic effect. Prescribed by doctors when backlash in transplantation of tissues and organs, in various systemic diseases.
"Dipin" is a cytostatic drug that suppresses the growth of tissues, including malignant ones.
"Myelosan" is a drug that can inhibit the growth of blood elements in the body.
"Busulfan" - inorganic medicine, which has pronounced bactericidal, mutagenic and cytotoxic properties.
"Cisplatin" contains heavy metals and can inhibit DNA synthesis.
"Prospidin" is an excellent antitumor drug, which is most often taken for malignant neoplasms that have arisen in the larynx and pharynx.

Cytostatic drugs, the list of which is presented above, are prescribed only by prescription. 'Cause that's enough strong means. Before taking medications, it is worth studying what cytostatics are, what they are and what they are. side effects. The attending physician will be able to select the most effective cytostatic drugs, depending on the patient's condition and his diagnosis.

Catad_tema Breast cancer - articles

New principles of cytotoxic systemic therapy primary cancer mammary gland

L. Norton

Weill Medical College, Cornell University,
department clinical oncology Sloane-Kettering Cancer Center, New York, USA

More than forty years ago, trials of alkylating agents were first started, and since then, significant progress has been made in the field of systemic therapy for breast cancer (BC). At the heart of two major achievements, namely the use hormonal methods treatment and use of trastuzumab lies the paradigm of targeting molecules associated with the malignant phenotype. The first of these approaches involves the use of drugs that bind to the estrogen receptor (an example of such a drug is tamoxifen), or agents that deprive the receptor of the ability to interact with endogenous estrogen (eg, aromatase inhibitors). The second approach concerns the use of a monoclonal antibody to inactivate the HER-2 receptor, which sometimes (in 25% of cases) is overexpressed in a breast tumor. HER-2, a member of the epidermal growth factor receptor family, is involved in the tyrosine kinase cascade that originates at the cell membrane and provides transcriptional control of various growth-regulatory molecules. However, there are numerous other targets for anticancer drugs in the biology of cancer, even though most of these drugs are also active against normally dividing cells. For example, TAXOL targets microtubules, which are essential for many normal processes in organism. Why drugs that act on such universal processes have a specific anti-cancer effect is one of the greatest mysteries modern biology.

It is generally accepted that, with the exception of two concrete examples, hormonal therapy and the use of trastuzumab, much of our success in the field of cancer treatment is based on an empirical approach, and not at all on rational drug design. It seems to me that such a view is a typical example of the distortion of history and is unfair to our predecessors in the field of medical oncology. Approaches based on extrapolation of results obtained in other fields of knowledge are not a new concept, despite the fact that the scientific arsenal has been remarkably enriched over the past few years. Extrapolative and clinical research always tries to use the highest level of scientific understanding of its time, even if by modern standards this understanding seems primitive. Moreover, it is safe to say that today's science will also seem primitive in the near future, but this does not mean that we are unreasonable in our scientific research. We should be inspired by the realization that significant progress has been made without a satisfactory understanding of biology. Our capabilities will continually expand and our optimism will grow as our knowledge of the regulation of mitosis, apoptosis, stromal and vascular biology expands, immune mechanisms and thousands of other questions of great potential importance.

To date, we have established a number of key facts regarding systemic cytotoxic therapy:

Chemotherapy can kill cancer cells
Most cells are resistant to certain drugs
Some cells are resistant to all currently available drugs used at therapeutic doses
Combined chemotherapy increases the duration of remission
Sequential chemotherapy improves overall duration of disease control
Going into remission means controlling disease symptoms and improving survival
Use of adjuvant therapy increases disease-free period and overall survival
In conditions clinical application drug dose-response curve is not necessarily strictly ascending.

We have also defined whole line Areas where we need to improve our knowledge:

How exactly does chemotherapy work?
How can we predict remission?
What is the optimal treatment regimen (doses and administration schedule)?
How can we ensure maximum efficiency with minimum toxicity?
How do we the best way can we apply our knowledge of tumor and host biology to optimize clinical outcomes?

Based on kinetic models, it can be assumed that one of the disadvantages of cytotoxic treatment aimed at cell mitosis, is the rapid growth of tumor cells after subcurative therapy. As will be shown on the basis of computer simulations, this problem cannot be overcome by a simple dose escalation technique. Created in Lately mathematical models showed that the fractal geometry of cancer could be the source of serious complications in this respect. However, one can try to use the fractal structure factor as a positive one if, in addition to cytotoxic therapy, one turns to therapies aimed at suppressing angiogenesis and acting on the extracellular matrix. The theory suggests that a truly effective form of treatment may require combined treatment of multiple components of the malignant phenotype. For example, trastuzumab, the human variant of the mouse monoclonal antibody 4D5 (which binds to and inactivates the HER-2 receptor) binds to HER-2 with high affinity. At clinical use As a single agent, trastuzumab has weak activity in relation to breast cancer, giving no more than 20% remissions in cases with 2+ or higher, according to immunohistochemical analysis, HER-2 expression (so far, such studies have been carried out only on such patients). Since 25% of all primary patients have some degree of overexpression, it was reasonable to design the trial in such a way as to study the ability of trastuzumab to increase the effectiveness of conventional chemotherapy. To this end, a group of international researchers began a study on patients with metastatic breast cancer who had not previously received chemotherapy and who had an overexpression of HER-2. Patients not previously treated with anthracyclines under an adjuvant protocol were randomized to doxorubicin (or epirubicin), doxorubicin/cyclophosphamide (AC), or AC plus trastuzumab. Patients who received anthracycline-based adjuvant chemotherapy were divided into subgroups who received TAXOL once every three weeks or TAXOL in combination with trastuzumab. When patients completed protocol treatment, those who did not receive trastuzumab could then be referred for treatment with this drug in combination with any chemotherapeutic agent in a non-randomized, open-label trial. Patients in the TAXOLA group had a worse prognosis compared with those patients who were in the AS group according to status criteria. lymph nodes at the time of diagnosis, a higher percentage of patients who received adjuvant therapy (98% and 47%, respectively) (including high-dose chemotherapy with hematopoietic stem cell protection), as well as a shorter period free from signs of disease.

The study showed that the overall percentage of remissions in the AC group was 42%, and in the AC + trastuzumab group it was 56% (P = 0.0197). In the case of TAXOL, the corresponding figures increased from 17% to 41% (P=0.0002). In patients treated with AS plus trastuzumab (n=143), the mean (median) time to onset of disease progression was 7.8 months, while for patients treated with AS alone it was 6.1 months. (n=138) (P=0.0004). For the TAXOL group, the benefit associated with trastuzumab was even more impressive: 6.9 months (n=92) compared to 3.0 (n=96) (P=0.0001). (The short time to disease progression in the TAXOL-only group is probably due to the very poor prognosis of patients in this group. This makes the results obtained in the group of patients treated with TAXOL in combination with trastuzumab, in whom the prognosis was equally poor, still more interesting). Time to treatment failure also increased with the addition of trastuzumab from 5.6 to 7.2 months for AC and from 2.9 to 5.8 months for TAXOL; as follows from the data obtained, this led to a highly significant increase in overall survival of about 25%. When treated with a combination of trastuzumab / doxorubicin / cyclophosphamide, cardiotoxic complications were observed in 27% of patients (compared with 7% who received only AS). For TAXOL, the corresponding figures were 12% in combination with trastuzumab and 1% in the case of monotherapy; it should be remembered that almost all patients in the study group that received TAXOL had previously received anthracycline adjuvant therapy. The cardiotoxicity of TAXOL in combination with trastuzumab, which is significantly less pronounced than the cardiotoxicity of the combination of anthracycline + trastuzumab, may reflect the effect of "memory" of previously occurring subclinical anthracycline toxicity.

These results indicate significant progress in the treatment of patients with metastatic breast cancer with HER-2 overexpression, but their significance is not limited to this. The implications of the findings are important for creating better forms of treatment in the future. This test shows the importance of combined targeting, in this case microtubulin and HER-2. In addition, targeting membrane-associated tyrosine kinases from the epidermal growth factor receptor family is only one possible approach to therapeutically interfering with mitotic signaling. For example, a universal mechanism for controlling cell growth is the pathway determined by the ras gene. For this gene to function protein product must be processed in the cell by an enzyme called farnesyl transferase. In many tumors (approximately 30%), an abnormal Ras gene is present, this gene allows tumor cells to elude the normal mechanisms that control growth. To treat these tumors, a class of drugs called farnesyl transferase inhibitors (IFTs) have been developed that are remarkably nontoxic to normal cells. However, breast tumors only in some cases have abnormal Ras, so it was previously assumed that in most cases IPT would not have antitumor activity. However, scientists at the Sloan-Kettering Cancer Center have shown that, contrary to expectations, IFT does induce breast cancer cell death despite the presence of normal Ras, possibly because IPT increases p21 and p53. Of even greater interest is the pronounced synergy between IFT and TAXOL and antibodies to HER-2 and epidermal growth factor receptors. Undoubtedly, we are talking about an area of outstanding interest and relevant clinical trials are currently being planned.

Although the processes of regulation of mitosis still remain the main target of cytotoxic drug therapy, recent advances in vaccine technology may herald an era of effective immunotherapy. IN Cancer Center Sloan-Kettering, for example, we immunized three groups of breast cancer patients belonging to certain groups high risk, three different MUC1 peptides containing 30-32 amino acids (1_ repeats of the 20-amino acid repeat of MUC1). All patients showed a serological response to the peptides used for immunization, and antibodies were found in high titers, although the resulting sera reacted only minimally or did not react at all with MUC1 fixed on cancer cells. It has recently become clear that glycosylation of serine and threonine residues in MUC1 can alter or even increase the antigenicity of MUC1, and it has been possible to obtain glycosylated MUC1 glycopeptides in sufficient quantities for clinical vaccination trials currently underway. There are many other targets for a similar immunological attack on breast cancer cells, and we plan to start a multicenter trial of a polyvalent vaccine before the end of 2000.

We can expect that targeted immunotherapy will be most valuable within a cytoreduction-based approach that optimally utilizes the latest data regarding mitosis regulation and disruption. Respectively, modern research in clinical oncology are targeting some of the most important "unknown areas" as we explore the mechanisms of the cell that are so happily damaged by old and new forms of mitotic drug treatment. The knowledge gained from such research will not only help us create more effective drugs, but also help us choose the best effective forms treatments based on the rational construction of a cancer cell profile, as, for example, in the case of the determination of HER-2 and molecules close to it. These approaches, combined with advances in our understanding of tumor growth kinetics, will certainly lead to improved breast cancer therapy, which is our ultimate goal.

All cytostatic agents according to their origin and mechanism can be divided into: Alkylating compounds. Antimetabolites.
,3. Antitumor antibiotics.
> 4. Drugs plant origin.
Alkylation compounds got their name due to their ability to form covalent bonds of their alkyl radicals with heterocyclic atoms of purines and pyrimidines and, especially, guanine nitrogen in position 7. Alkylation of DNA molecules, the formation of crosslinks and breaks leads to violations of its matrix functions in the process of replication and transcription and, ultimately, to mitotic blocks and death of tumor cells. All alkylating agents are cyclonon-specific, ie. able to damage tumor cells in various phases from life cycle. They have a particularly pronounced damaging effect on rapidly dividing cells. Most alkylating agents are well absorbed from the gastrointestinal tract, but due to their strong local irritant action, many of them are administered intravenously.
Depending on the chemical structure, several groups of alkylating substances are distinguished: Chlorethylamine derivatives
Sarcolysin (Melphalan), Cyclophosphamide (Cyclophosphamide), Chlorambucil
(Lakeran). Ethyleneimine derivatives
Thiophosfamide. Derivatives of methanesulfonic acid
Busulfan (Mielosan).
Nitrosourea derivatives
Carmustine, lomustine. Organometallic compounds
Cisplatin, carboplatin. Triazene and hydrazine derivatives
procarbazine, dacarbazine.
Despite general mechanism actions, most of the drugs in this group differ from each other in the spectrum of antitumor activity. Among the alkylating substances there are drugs (cyclophosphamide, thiophosfamide) that are effective both in hemoblastoses and in some types of true tumors, for example, in breast and ovarian cancer. At the same time, there are alkylating substances with a narrower spectrum of antiblastoma action (derivatives of nitrosourea and methanesulfonic acid). Due to their high solubility in lipids, nitrosourea derivatives penetrate the blood-brain barrier, which leads to their use in the treatment of primary malignant brain tumors and brain metastases of other neoplasms. Platinum preparations are basic in many chemotherapy regimens for true tumors, but are highly emetogenic and nephrotoxic drugs.
All alkylating compounds are highly toxic, suppress hematopoiesis (neutropenia, thrombocytopenia), cause nausea and vomiting, ulceration of the oral mucosa and gastrointestinal tract.
Antimetabolites are substances that are structurally similar to natural products metabolism (metabolites), but not identical to them. Mechanism of action in general view can be imagined in the following way: modified molecules of purines, pyrimidines, folic acid enter into competition with normal metabolites, replace them in biochemical reactions but cannot perform their function. The processes of synthesis of nucleic bases of DNA and RNA are blocked. Unlike alkylating agents, they only act on dividing cancer cells, ie. are cycle-specific drugs.
Antimetabolites used in malignant neoplasms are represented by three groups: Folic acid antagonists Methotrexate. Purine antagonists Mercaptopurine. Pyrimidine antagonists
Fluorouracil (Fluorouracil), cytarabine (Cytosar).
Antimetabolites act on different stages synthesis of nucleic acids. Methotrexate inhibits dihydrofolate reductase and thymidyl synthetase, which leads to disruption of the formation of purines and thymidil and, accordingly, inhibition of DNA synthesis. Mercaptopurine prevents the incorporation of purines into polynucleotides. Fluorouracil is converted in tumor cells to 5-fluoro-2-deoxyuridylic acid, which inhibits thymidyl synthetase. A decrease in the formation of thymidylic acid leads to disruption of DNA synthesis. Cytarabine inhibits DNA polymerase, which also leads to impaired DNA synthesis. methotrexate, mercaptopurine, and cytarabine acute leukemia, fluorouracil - with true tumors (cancer of the stomach, pancreas, large intestine).
Complications caused by antimetabolites, in general, are the same as those of the drugs of the previous group.
big group antitumor drugs are antibiotics - the waste products of fungi, which are divided into 3 groups based on their chemical structure: Antibiotics-actinomycins Dactinomycin, mitomycin. Anthracycline antibiotics
Doxorubicin (Adriamycin), Rubomycin (Daunorubicin). Antibiotics-phleomycins Bleomycin.
The mechanism of cytotoxic action of anticancer antibiotics includes a number of components. First, antibiotic molecules wedged (intercalate) into DNA between adjacent base pairs, which prevents DNA chains from unwinding with subsequent disruption of replication and transcription processes. Secondly, antibiotics (anthracyclines group) generate toxic oxygen radicals that damage macromolecules and cell membranes tumor and normal cells (including myacardial cells, which leads to the development of a cardiotoxic effect). Thirdly, some antibiotics (in particular, bleomycin) inhibit DNA synthesis, causing the formation of its single breaks.
Most antitumor antibiotics are cycle-specific drugs. Like antimetabolites, antibiotics show some affinity for certain types of tumors. Side effects: nausea, vomiting, severe fever with dehydration, arterial hypotension, allergic reactions, oppression of hematopoiesis and immunity (except for bleomycin), cardiotoxicity.
In the treatment of oncological diseases, cytostatics of plant origin are used, which are classified according to the sources of production. Alkaloids of vinca rosea (vinca alkaloids)
Vinblastine, vincristine, vinorelbine. Colchicum alkaloids magnificent Kolhamin. Podophyllotoxins (a complex of substances from rhizomes with roots of podophyllum thyroid) Natural Podophyllin. Semi-synthetic
Etoposide (Vepezid), teniposide (Vumon). Yew tree terpenoids (taxosides)
Paclitaxel (taxol), docetaxel. Semi-synthetic analogs of camptothecin Irinotecan (CAMPTO), topotecan.
The mechanism of the cytostatic action of vinca alkaloids is reduced to the denaturation of tubulin, a microtubule protein, which leads to mitosis arrest. Vinca alkaloids differ in their spectrum of antitumor activity and side effects. Vinblastine is used mainly for lymphogranulomatosis, and vincristine - for lymphomas and a number of solid tumors as a component of combination chemotherapy. Toxic action vinblastine is characterized, first of all, by myelodepression, avicristine - neurological disorders and kidney damage. Vinorelbine belongs to the new vinca alkaloids.
Colhamin is applied topically (as an ointment) to treat skin cancer.
Herbal preparations also include podophyllin, which is used topically for papillomatosis of the larynx and Bladder. Currently, semi-synthetic podophyllin derivatives, epipodophyllotoxins, are used. These include etoposide (Vepezid) and teniposide (Vumon). Etoposide is effective in small cell lung cancer, atheniposide - in hemoblastoses.
IN last years in the treatment of many solid tumors, taxoids - paclitaxel, docetaxel, obtained from the Pacific and European yew, have become widely used. The drugs are used for lung cancer, rarely breast cancer, malignant tumors of the head and neck, tumors of the esophagus. The limiting point in their use is severe neutropenia.
Semisynthetic analogues of camptothecin - irinotecan, topotecan - represent a fundamentally new group of cytostatics - topoisomerase inhibitors responsible for DNA topology, its spatial structure, replication and transcription. Drugs inhibiting type I topoisomerase block transcription in tumor cells, which leads to growth inhibition. malignant neoplasms. Irinotecan is used for colon cancer, and topotecan is used for small cell lung cancer and ovarian cancer. The side effects of this group of agents are generally the same as those of other cytostatic agents.

Cytotoxic action is a damaging effect on the body, which results in the formation of deep functional and structural changes in cells leading to their lysis. Such an effect can be exerted by cytotoxic T cells, or T-killers, as well as medical cytotoxic drugs.

Mechanism of action of cytotoxic T cells

Many pathogenic microorganisms are located inside the affected cells and are inaccessible to humoral factors immune response. To eliminate these pathogens, a system of acquired immunity has been formed, which is based on the functioning of cytotoxic cells. Such cells have the unique ability to detect a particular antigen and destroy cells exclusively with that foreign agent. Exists great multitude clones of T-cells, each of which is "aimed" at a specific antigen.

In the case of penetration of the corresponding antigen into the body under the influence of T-helpers, T-killers are activated and clone cells begin to divide. T cells are able to detect an antigen only if it is expressed on the surface of the affected cell. T-killers detect the antigen together with the cell marker - MHC molecules ( main complex histocompatibility) class I. During the recognition of a foreign agent, the cytotoxic cell interacts with the target cell and destroys it to reduplication. In addition, the T-lymphocyte produces gamma-interferon, thanks to this substance, the pathogenic virus is not able to penetrate into neighboring cells.

The targets of T-killers are cells affected by viruses, bacteria, and cancer cells.

Cytotoxic antibodies capable of causing irreversible damage to the cytoplasmic membrane of the target cell are the main element of antiviral immunity.

Most killer T cells are part of the CD8+ subpopulation and detect antigen in complex with MHC class I molecules. Approximately 10% of cytotoxic cells belong to the CD4+ subpopulation and recognize antigen in complex with MHC class II molecules. Cancer cells lacking MHC molecules are not recognized by T-killers.

The lysis of cells with a foreign antigen is carried out by T-lymphocytes by introducing special perforin proteins into their membranes and injecting toxic substances into them.

Formation of T-killers

The development of cytotoxic cells is carried out in the thymus. The precursors of T-killers are activated by the MHC class I antigen-molecule complex, their reproduction and maturation occurs with the participation of interleukin-2 and poorly identified differentiation factors produced by T-helpers.

The formed cytotoxic cells circulate freely throughout the body, periodically they can return to the lymph nodes, spleen and other lymphoid organs. After receiving an activating signal from T-helpers, the reproduction of certain T-lymphocytes begins.

According to the cytotoxic type, pathologies such as autoimmune thyroiditis, anemia, drug allergy. Also, due to intracellular metabolic lesions, cytotoxic cerebral edema is possible.

Cytotoxic drugs

The cytotoxic effect can have certain medical preparations. Cytotoxics damage or destroy body cells. At the same time, rapidly multiplying cells are most sensitive to the effects of such drugs. Therefore, these drugs are used, as a rule, for the treatment of cancer. Also, such agents can be used as immunosuppressants. Manufacturers produce these drugs in tablet and injectable forms. Maybe combined application some drugs with different type impact on the body.

Healthy cells of the body, especially bone marrow cells, are also affected by cytotoxic effects.

Cytotoxics have Negative influence for production blood cells, resulting in increased susceptibility to infectious diseases, anemia, bleeding.

Cytotoxicants include:

alkylating agents (Chlorbutin, Dopan, Mielosan, Oxaliplatin, Lomustine);
antimetabolites (Cytabarin, Fluorouracil);
antibiotics that have an antitumor effect (Carminomycin, Mitomycin, Dactinomycin, Idarubicin);
drugs natural origin(Vinblastine, Taxol, Etoposide, Cohamin, Taxotere);
hormones and their antagonists (Tetrasterone, Tamoxifen, Triptorelin, Letrozole, Prednisolone);
monoclonal antibodies (Herceptin);
cytokines (Interferon);
enzymes (L-asparaginase);
antitubulins;
intercalants;
inhibitors of topoisomerase I (Irinotecan), topoisomerase II (Etoposide), tyrosine kinases (Tyverb).

Cytotoxic agents disrupt the vital activity of any cells, but cells with rapid division are primarily affected: tumor cells, cells of the bone marrow, gonads, epithelium of the gastrointestinal tract.

In this regard, cytotoxic substances, while inhibiting the growth of tumors, simultaneously have a depressing effect on the bone marrow, sex glands, gastrointestinal tract. As antiblastoma agents, cytotoxic substances are most often administered intravenously.

Alkylating agents disrupt the structure of DNA by forming covalent alkyl bonds between DNA strands, and thus prevent the division of tumor cells.

Alkylating agents include:

chlorethylamines - cyclophosphamide;

ethyleneimines - thiotepa;

nitrosourea derivatives - carmustine, lomustine;

platinum compounds ~ cisplatin, carboplatin, oxaliplatin.

Cyclophosphamide (cyclophosphamide) is effective in cancer of the breast, lung, ovaries, lymphocytic leukemia, lymphogranulomatosis.

In addition, cyclophosphamide is used as an immunosuppressive agent in rheumatoid arthritis, systemic lupus erythematosus, nephrotic syndrome.

Thiotepa (thiophosfamide) is used for cancer of the ovaries, breast, bladder.

Carmustine and lomustine penetrate well into the central nervous system and are used in brain tumors.

Cisplatin is effective in cancer of the lung, stomach, colon, bladder, breast, ovaries, uterus. The drug more often than other cytostatics causes vomiting; possible arterial hypotension, hematopoietic disorders, ototoxic effect, neuropathy, convulsive reactions.

Carboplatin and oxaliplatin are better tolerated by patients.

Antimetabolites are similar in chemical structure with some metabolites necessary for tumor cells. Interfering with the exchange of metabolites, these antiblastoma drugs disrupt the synthesis of nucleic acids and the growth of tumors.

Antimetabolites include:

1) drugs that affect the metabolism of folic acid - methotrexate;

2) purine analogues - mercaptopurine;

3) pyrimidine antagonists - fluorouracil, cytarabine, capecitabine.

Methotrexate inhibits dihydrofolate reductase and thus disrupts the metabolism of folic acid and, accordingly, the formation of purine and pyrimidine bases and DNA synthesis.

Used for acute lymphocytic leukemia, lung cancer, breast cancer.

In relatively low doses, methotrexate has an anti-inflammatory effect and is used in rheumatoid arthritis.

Mercaptopurine is prescribed for acute leukemia.

Fluorouracil (5-fluorouracil) in tumor cells is converted to 5-fluoro-2-deoxyuridine-5-phosphate, which inhibits thymidine synthetase and thus disrupts DNA synthesis. In addition, RNA polymerase is inhibited and protein synthesis of tumor cells is disrupted.

Fluorouracil is one of the main drugs for the treatment of cancer of the stomach, colon, breast, ovaries, and prostate.

Cytarabine is used for leukemia, lymphogranulomatosis; capecitabine for breast cancer.

Antitumor antibiotics disrupt the structure of DNA. For example, doxorubicin, bleomycin cause fragmentation (“breaks”) of DNA strands and thus prevent the division of tumor cells.

This group includes doxorubicin, daunorubicin, bleomycin, mitomycin, etc.

Doxorubicin is used for cancer of the lung, stomach, bladder, breast, ovaries, acute leukemia; daunorubicin - for acute myeloid leukemia; bleomycin - for lung cancer, kidney; mitomycin - for colon cancer.

Herbal ingredients include:

1) pink periwinkle alkaloids (Vinca rosea) - vincristine, vin-blastine, vinorelbine;

2) taxanes (semi-synthetic compounds from yew processing products) - paclitaxel, docetaxel;

3) derivatives of podophyllotoxin (a podophyllum thyroid alkaloid) - etoposide;

4) colchicum alkaloids - kolhamin.

Vinca alkaloids - vincristine and vinblastine disrupt the polymerization of tubulin and the formation of microtubules and thus prevent the division of tumor cells. They are used for lymphogranulomatosis, cancer of the lung, kidney, bladder, and Kaposi's sarcoma. Vinorelbine is effective in lung and breast cancer.

Paclitaxel (Taxol) and docetaxel (Taxotere), on the contrary, prevent the depolymerization of tubulin and also disrupt the division of tumor cells. They are used for cancer of the lung, breast, ovaries.

Etoposide disrupts the structure of DNA, causing fragmentation of its strands. Indications for use: cancer of the lung, breast, ovaries, Hodgkin's disease.

Colchicum alkaloid colchamine is used as an ointment for skin cancer. The drug causes destruction cancer cells without affecting healthy skin cells.