Clinical examination of patients with neoplasms includes not only therapeutic and preventive measures, but also their early diagnosis, i.e. detection of the tumor at the stage when it is still accessible to radical treatment.
Modern tumor chemotherapy is based on combined use (simultaneous or sequential) anticancer drugs different chemical groups. For certain indications, chemotherapy is combined with surgical removal of the tumor and radiation therapy. Modern antitumor agents, as a rule, provide only remission of the disease. Tumor cells are able to become resistant to drugs, most of which have low selectivity for tumor cells, and their use is accompanied by side effects. Contraindications for the appointment of the majority anticancer drugs are oppression of hematopoiesis, acute infections, dysfunction of the liver, kidneys, etc. According to the mechanism of action antitumor agents are divided into the following groups:
1) alkylating agents;
2) antimetabolites;
3) hormonal agents;
4) antibiotics;
5) enzymes;
6) substances of plant origin:
7) various synthetic agents.
2.5.2.9.1. Alkylating agents
To this group anticancer drugs representatives of 4 chemical groups include:
1. Chlorethylamines - chloroethylaminouracil (dopan). melphalan (sarcolysin), cyclophosphamide (cyclophosphamide), chlorambucil (chlorbutin).
2. Ethylene imines - thiotepa (thiophosfamide), benzotef, imiphos.
3. Derivatives of methanesulfonic acid - busulfan (myelosan).
4. Derivatives of nitrosourea - N-nitrosomethylurea.
Mechanism of cytotoxic action alkylating agents due to the ability of some of their molecules (dichloroethylamine ethyleneimine, etc.) to interact with the nucleophilic structures of DNA, which leads to alkylation and disruption of its structure, stability and integrity. Ultimately, DNA alkylation disrupts the vital activity of cells, their ability to divide. especially pronounced cytostatic the effect is manifested in relation to rapidly proliferating cells. Maybe alkylating compounds act not only on nucleic acids, but are also capable of inhibiting some enzymes involved in cell division.
Majority alkylating compounds is used for hemoblastoses ( Hodgkin's disease, lymph and reticulosarcoma, chronic leukemia). One of the drugs in this group is chloromethyl (embikhin), capable of alkylating action to suppress the development of hyperplastic tissues. The drug is used only intravenously, as it has a strong local irritant action. An indicator of the effectiveness of treatment is a positive clinical and corresponding hematological effect. In the process of treatment, it is necessary to control the blood picture, since a deep inhibition of bone marrow function is possible, up to aplasia. Close to embihin in chemical structure and action dopan and chlorbutin administered internally. The latter has selectivity for lymphoid tissue, and is used as immunosuppressant. Sarcolysin are highly active in true tumors (seminoma, malignant neoplasms jaw bones, etc.). With seminoma sarcolysin gives a positive result even in the presence of metastases. Found widespread use cyclophosphamide. As a result of chemical transformations (in the liver), it is activated and acquires cytostatic properties. The drug is able to cause more or less long-term remissions in hemoblastosis, it is often prescribed for various types of cancer of the maxillofacial region.
Ethyleneimines ( thiophosfamide , benzotef , imiphos ) how alkylating agents block the mitotic division of tumor and healthy cells due to the formation of cross-links between DNA chains. These compounds are able to block the function of RNA and enzyme proteins in phase G. The main indications for use are true tumors and hemoblastoses. Imiphos, the only drug from this group, is able to inhibit the excessive reproduction of erythroblasts. The tropism for the red germ of the bone marrow is due to its selective accumulation in hemoglobin-containing erythroblasts.
Mielosan - derivative of metasulfonic acid - is prescribed for exacerbations of chronic myeloid leukemia.
Nitrosourea derivatives - nitrosomethylurea has antitumor activity, sometimes gives an effect when cells are resistant to other drugs. Used for cancer Hodgkin's disease, lymphosarcoma, melanoma skin.
Alkylating compounds are able to act not only on tumor cells, but also on normal, especially actively proliferating tissues (bone marrow, germ cells, mucous membrane of the alimentary canal, etc.). As a result, it is possible leukopenia, thrombocytopenia, anemia. In extreme cases, it is necessary to stop the introduction of these drugs, or reduce the dose. If necessary, they resort to blood transfusion, the introduction of erythrocyte, leukocyte or platelet mass, prescribe means stimulating hematopoiesis. To prevent the development of infections associated with immune suppression, use antibiotics. Sometimes with the introduction of some anticancer drugs intravenously (embihin) phlebitis occurs, nausea, vomit, rarely seen diarrhea.
2.5.2.9.2. Antimetabolites
Anticancer drugs of this group are antagonists of natural metabolites. Antimetabolites similar in their chemical structure amino acids, vitamins, coenzymes or products of their metabolism. Although their structures are close to natural metabolites, they are not identical; being included in metabolic processes, they can act as competitive inhibitors.
TO antimetabolites include the following drugs: methotrexate (folic acid antagonist), mercaptopurine (purine antagonist) fluorouracil (fluorouracil ), tegafur (ftorafur ) are pyrimidine antagonists.
Inhibition of DNA and RNA synthesis, disruption of the structure due to the replacement of natural metabolites - purines and pyrimidines - with structural analogues, leads to a slowdown in the division of tumor cells. Unfortunately, the same mechanism can inhibit the division of cells of healthy tissues, especially rapidly proliferating ones (cells of the bone marrow, intestinal epithelium, etc.).
A prerequisite for the synthesis of nitrogenous bases of nucleic acids is the presence of folic acid, from which the active form, tetrahydrofolic acid, is formed. Methotrexate is a structural analogue of folic acid, active in small doses. Methotrexate used in chorionepithelioma, leukemia, breast cancer. It is perhaps the most common anticancer agent used in tumors of the head and neck and, in particular, in Burkitt's tumor, which affects the bones of the jaws. Of the side effects, they develop quite early stomatitis or conjunctivitis, later - changes in the blood ( leukopenia, thrombocytopenia), liver dysfunction.
Often methotrexate combined with others antimetabolites (mercaptopurine), antibiotics (bleomycin) or corticosteroids for increase cytostatic effect and reduce the resistance of tumor cells.
Mercaptopurine - homologue of adenine (6-aminopurine). Its mechanism cytostatic action is due to a violation of the synthesis of DNA and RNA due to the blockade of the inclusion of adenine in their structure. Mercaptopurine metabolized in the liver, excreted in the urine. The main indications are acute leukemia, chorionepithelioma of the uterus. Its use may be accompanied by inhibition of hematopoiesis, impaired liver function, nausea, and vomiting.
Fluorouracil and ftorafur (pyrimidine antagonists) are usually used for true tumors, inoperable forms of cancer of the stomach and intestines. Very toxic ftorafur- less). Some patients give regression of tumors. Sometimes used for malignant tumors of the head and neck. The effectiveness of chemotherapy increases when combined with radiation.
2.5.2.9.3. Hormonal remedies
For treatment neoplasms use androgens (testosterone propionate , testenate ), estrogens ( diethylstilbestrol , hexestrol or sinestrol , fosfestrol and etc.), corticosteroids (hydrocortisone , prednisolone , dexamethasone , triamcinolone ) or corticotropin .
It is possible to reduce the growth of hormone-dependent tumors with the help of hormones of the opposite sex. So, the development of prostate cancer is inhibited by estrogens, and breast cancer in women - androgens. The latter in high doses are mainly prescribed for breast cancer women with a preserved menstrual cycle (to suppress estrogen production). In women during menopause (more than 5 years) with breast cancer apply. on the contrary, estrogens; maybe they suppress production gonadotropic pituitary hormones capable of stimulating the growth of tumor cells.
A prerequisite for hormone therapy is its continuity. In this case, the development of side effects associated with signs of feminization (the appearance of female secondary sexual characteristics) in men and masculinization in women is possible.
Among androgens most commonly used drostanolone (medrotesterone propionate), which, however, has to be administered daily (for 2-3 years). In recent years, longer-acting drugs have been used ( testenate ) - 1 injection every 2 weeks. Estrogens inhibit stimulation androgens growth of tumors in men (cancer and prostate adenoma). Fosfestrol , Unlike diethylstilbestrol and sinestrol , deprived estrogenic activity. However, in the body, after the elimination of phosphoric acid, it forms diethylstilbestrol. It is important that the cleavage of the ether bond phosphestrol occurs under the influence of phosphatase, the activity of which in the tumor tissue of the prostate is higher than in healthy.
The production of hormones of the adrenal cortex is stimulated by adrenocorticotropin, which allows it to be used in cancer patients along with or instead of glucocorticoids. By inhibiting the proliferation process, glucocorticoids inhibit the production of formed elements of the hematopoietic system, mainly in the cells of the lymphoreticular formation. It must be remembered that glucocorticoids able to suppress immune responses, while reducing the body's resistance to infection.
2.5.2.9.4. Antitumor antibiotics
Some antibiotics, as well as antimicrobial activity, capable of cytostatic properties, inhibiting the synthesis of nucleic acids. Mechanism of action due to inhibition of DNA replication, which leads to a disruption in the formation of RNA. Without adequate relaying of the genetic code to RNA, synthesis is impossible enzymatic and other proteins. The main disadvantage antitumor antibiotics is the low selectivity of action in relation to tumor cells. Therefore, they are capable of causing dysfunction of the hematopoietic organs, digestion, and have a toxic effect on parenchymal organs. Most of them inhibit the growth and reproduction of microorganisms in the intestine, which ultimately contributes to the development of candidiasis and requires a joint appointment. antifungal agents. Antitumor antibiotics appropriate to combine with corticosteroids, and also used against the background of radiation therapy.
The most commonly used drugs are dactinomycin (actinomycin D) and its analogue chrysomallin. The main indications are uterine chorionepithelioma, Wilms tumors, Hodgkin's disease. Has a similar activity daunorubicin (rubomycin ), capable of inducing remissions in uterine chorioepithelioma, acute leukemia, reticulosarcoma. It has anti-blastoma activity olivomycin ; it is prescribed for fetal cancer, reticulosarcoma, melanoma. Both last antibiotic can also interfere with the functions of the gastrointestinal tract, cause stomatitis, provoke candidiasis, suppress the immune system. Antibiotic bleomycin (bleocin ) is active in squamous skin cancer, Hodgkin's disease and some other tumors. Bleomycin(like olivomycin) affects the hematopoietic system to a lesser extent, which allows its use in patients with reduced hematopoietic function.
Very active antibiotics anthracycline groups -
doxorubicin
(adriamycin
) and carubicin
(carminomycin
), especially in sarcomas of mesenchymal origin. 2.5.2.9.5. Enzyme preparations used in tumors
The best known drug in this group is asparaginase
(L-asparaginase
) produced by different strains of Escherichia coli. The drug has anti-leukemic activity. Mechanism antitumor actions due to the ability to disrupt metabolism amino acids asparagine, which is necessary for tumor cells. The main indications for L-asparaginase(alone or in combination) are lymphoblastoma leukemia, lymph and reticulosarcoma. In some cases, the drug is more effective than other antitumor agents. Possible side effects: fever, vomit, dysfunction of the liver and pancreas, sometimes there is a tendency to hemorrhages. 2.5.2.9.6. Anticancer agents of plant origin
Among herbal preparations, the most commonly used alkaloids are: demecolcin
(kolhamin
), colchicine
(colchicum) and vinblastine
or vincristine
(periwinkle pink). Colchicine It is highly toxic and is therefore only used topically. Kolhamin 7-8 times less toxic (although it inhibits hematopoiesis, it is also possible hair loss, diarrhea), which makes it possible to obtain resorptive effects. They are usually prescribed for esophageal cancer, stomach, skin (as an ointment). Vinblastine and vincristine, like Kolkhamin, selectively inhibit mitosis at the metaphase stage. Apply when Hodgkin's disease, lymphosarcoma maxillofacial region, chorionepithelioma. Their reception leads to disorders of hematopoiesis, dyspepsia. Vincristine to a lesser extent affects hematopoiesis, but can cause neurological disorders (neuralgia, paresthesia).
Antitumor has activity podophyllin , which is a mixture of substances from the roots of podophyllum thyroid. It is mainly used topically as an adjuvant for tumors of the larynx and bladder.
2.5.2.9.7. Various synthetic products
Procarbazine (a derivative of methylpyridine) is able to selectively accumulate in tumor cells, inducing the process of autoxidation. As a result, the concentration of free radicals increases in the cytoplasm, which have a damaging effect on macromolecules. Procarbazine inhibits hematopoiesis, leads to the development of neurological symptoms.
With papillomatosis of the upper respiratory tract, lung cancer, cancer of the larynx is used prospidium chloride (prospidin ). The drug is well tolerated, does not significantly affect hematopoiesis, but sometimes causes an increase in blood pressure, dizziness, paresthesia.
Preparations:
Methotrexate
Assign inside, intramuscularly, intravenously intraarterially, into the spinal canal.
Available in coated tablets, 0.0025 g each; ampoules of 0.005, 0.05 and 0.1 g.
Mercaptopurine.
Assign inside.
Kolhamin (demecolcin)
Apply inside and out.
Available in tablets of 0.002 g; in the form of an ointment 0.5%.
Vinblastine
Enter intravenously 1 time per week.
Produced in ampoules and vials of 0.005 g in lyophilized form with the application solvent.
MEDICINES USED IN MALIGNANT NEOPLASMS CHAPTER 42 ANTITUMOR DRUGSMEDICINES USED IN MALIGNANT NEOPLASMS CHAPTER 42 ANTITUMOR DRUGS
Antitumor (antiblastoma) drugs are drugs that delay the development of true tumors (cancer, sarcoma, etc.) and hemoblastoses (leukemia, etc.).
The treatment of malignant neoplasms with anticancer drugs is referred to as "chemotherapy". Chemotherapy is used to reduce the likelihood of tumor metastasis, as well as to treat cancers that are inaccessible to surgical intervention.
Drugs of various origins (synthetic preparations, antibiotics, hormones, enzymes) are used as antiblastoma drugs in medical practice. Anti-blastoma drugs are classified as follows:
Cytotoxic agents;
Hormonal and antihormonal agents;
Cytokines;
Enzymes;
radioactive isotopes.
The basis of modern drug therapy of malignant neoplasms is cytotoxic and cytotoxic agents. The mechanism of cytostatic action is realized either through direct interaction with DNA, or through enzymes responsible for the synthesis and functions of DNA. However, this mechanism does not provide true selectivity of the antitumor effect, since not only malignant, but also actively proliferating cells of normal tissues are vulnerable to cytostatic damage, which creates the basis for the development of complications.
42.1. CYTOTOXIC AGENTS
According to the origin and mechanism of action, the following groups of cytostatic agents are distinguished:
Alkylating compounds;
Antimetabolites;
Antitumor antibiotics;
Herbal preparations.
Alkylating compounds
Alkylating compounds got their name in connection with their ability to form covalent bonds of their alkyl radicals with heterocyclic atoms of purines and pyrimidines and, especially, with the 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 eventually to mitotic blocks and death of tumor cells. All alkylating agents are cyclonon-specific, i.e. capable of damaging tumor cells at different phases of the life cycle. They have a particularly pronounced damaging effect on rapidly dividing cells. Most alkylating agents are well absorbed in the gastrointestinal tract, but due to the strong local irritant effect, many of them are administered intravenously.
Depending on the chemical structure, several groups of alkylating substances are distinguished:
chloroethylamine derivatives:
Sarcolysin, melphalan, cyclophosphamide (cyclophosphamide*), chlorambucil (leukeran*);
Ethyleneimine derivatives:
Thiotepa (thiophosfamide*);
methanesulfonic acid derivatives:
Busulfan (Myelosan*);
nitrosourea derivatives:
Carmustine, lomustine;
organometallic compounds:
Cisplatin, carboplatin;
triazene and hydrazine derivatives:
procarbazine, dacarbazine.
Despite the common mechanism of action, most of the drugs in this group differ from each other in terms of the spectrum of antitumor activity. Among the alkylating substances there are drugs (cyclophosphamide, thiotepa) that are effective both in hemoblastoses and in
some types of true tumors, such as 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 BBB, which determines 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.
All alkylating compounds are highly toxic, suppress hematopoiesis (neutropenia, thrombocytopenia), cause nausea and vomiting, ulceration of the oral mucosa and gastrointestinal tract.
Antimetabolites
Antimetabolites- substances that have structural similarities with natural metabolic products (metabolites), but are not identical to them. The mechanism of their action in general can be represented as follows: modified molecules of purines, pyrimidines, folic acid compete 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 at different stages of nucleic acid synthesis
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
in tumor cells it turns into 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 are used for acute leukemia, fluorouracil - for true tumors (cancer of the stomach, pancreas, colon).
Complications caused by antimetabolites are generally the same as those of the drugs of the previous group.
Antibiotics
A large group of anticancer drugs are antibiotics- waste products of fungi, which are divided into 3 groups based on their chemical structure:
actinomycin antibiotics:
Dactinomycin, mitomycin;
anthracycline antibiotics:
doxorubicin (adriamycin*), daunorubicin (rubomycin hydrochloride*);
phleomycin antibiotics:
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 strands from unwinding with subsequent disruption of replication and transcription processes. Secondly, antibiotics (the group of anthracyclines) generate toxic oxygen radicals that damage macromolecules and cell membranes of 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, hematopoietic and immune suppression (except for bleomycin), cardiotoxicity.
Cytostatics of plant origin
Used in the treatment of cancer herbal cytostatics, which are classified according to the sources of receipt:
alkaloids of vinca rosea (vinca alkaloids):
Vinblastine, vincristine, vinorelbine p; colchicum alkaloids magnificent:
Demecolcin (colhamine*);
podophyllotoxins (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 analogues 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 mainly used for lymphogranulomatosis, and vincristine is used for lymphomas and a number of solid tumors as a component of combined chemotherapy. The toxic effect of vinblastine is characterized, first of all, by myelodepression, and vincristine by neurological disorders and kidney damage. The new vinca alkaloids include vinorelbine ** .
Demecolcin (Colhamin*) is used topically (as an ointment) to treat skin cancer.
Herbal preparations also include podophyllin *, used topically for papillomatosis of the larynx and bladder. Currently, semi-synthetic podophyllin derivatives, epipodophyllotoxins, are used. These include etopozid (vepezid *) and tenipozid (vumon *). Etoposide is effective in small cell lung cancer, and teniposide is effective in hemoblastoses.
In recent years, in the treatment of many solid tumors, taxosides - 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.
Semi-synthetic analogues of camptothecin - irinotecan, topotecan - represent a fundamentally new group of cytostatics - topoisomerase inhibitors responsible for DNA topology, its spatial structure, replication and transcription. The drugs, inhibiting type I topoisomerase, block transcription in tumor cells, which leads to inhibition of the growth of 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.
42.2. HORMONAL AND ANTI-HORMONAL DRUGS
The emergence and development of a number of malignant neoplasms is associated with a violation of the natural balance of hormones in the body, and therefore the introduction of the latter, and sometimes, on the contrary, their exclusion in one way or another, can change the growth of some neoplasms. This creates the prerequisites for the use of hormones, as well as their synthetic analogues and antagonists, as antitumor agents.
The drugs of this group delay the division of malignantly degenerated cells and promote their differentiation.
Hormonal drugs and their synthetic analogues
Androgens
Testosterone Propionate, Prolotestone*.
Androgens are used for breast cancer in women with preserved menstrual function and in the case when menopause does not exceed 5 years. The therapeutic effect of androgens in breast cancer is associated with the suppression of estrogen production.
When using androgens, virilization, dizziness, nausea and other side effects may occur.
Estrogens
Diethylstilbestrol, fosfestrol (honwang*), chlorthalidone (Chlortrianisene*).
The ability of estrogens to suppress the production of natural androgenic hormones is used in prostate cancer. Estrogens are also used for breast cancer in women who have been menopausal for more than 5 years. In this case, the effect of estrogens is associated with the suppression of gonadotropic hormones of the pituitary gland, which indirectly stimulate tumor growth.
To reduce the risk of complications (gynecomastia, edema, vomiting, thrombosis and thromboembolism) that occur when taking estrogenic drugs such as hexestrol (Sinestrol *) and diethylstilbestrol, drugs with a “transport function” are offered that deliver the active substance directly to the tumor tissue. These drugs include fosfestrol.
Gestagens
Medroxyprogesterone acetate (Depo-Provera*). Progestogens are used for uterine cancer and breast cancer.
Antihormonal agents
Antiandrogens
Cyproterone acetate (Androkur*), flutamide.
Antiandrogens include a number of compounds of a steroidal or non-steroidal structure that can suppress the physiological activity of endogenous androgens. Their mechanism of action is associated with competitive blockade of androgen receptors in target tissues.
Mostly used means of this group for prostate cancer.
With prolonged use of these drugs, the development of gynecomastia and impaired liver function is possible.
Antiestrogens
Tamoxifen citrate (Nolvadex*).
Antiestrogenic agents specifically bind to estrogen receptors in breast tumors and eliminate the stimulating effect of endogenous estrogens.
Antiestrogen agents are used for estrogen-dependent breast tumors in women in the menopausal period. When using tamoxifen, gastrointestinal disorders, dizziness, skin rash are possible.
Gonadotropin-releasing hormone analogues
Goserelin (Zoladex*).
When creating a stable concentration of these drugs in the blood, the secretion of gonadotropic hormones of the pituitary gland decreases, which leads to a decrease in the release of estrogens and androgens.
The drugs are used for hormone-dependent prostate cancer, breast cancer in women of reproductive age and uterine cancer.
Adrenal hormone antagonists
Aminoglutethimide**, Letrozole (Femara*). In the postmenopausal period, estrogens are formed from androgens synthesized in the adrenal cortex and in other tissues (Fig. 42-1).
Rice. 42-1. Mechanism of action of adrenal hormone inhibitors
Aminoglutethimide ** inhibits the synthesis of glucocorticosteroids, mineralocorticosteroids and estrogens. The drug is used for Itsenko-Cushing's syndrome, progressive breast cancer in postmenopausal women. When using the drug, lethargy, drowsiness, depression, arterial hypotension, and allergic reactions are possible.
Letrozole (Femara*) is a drug that selectively inhibits aromatase activity. Letrozole is used for breast cancer in postmenopausal women. Side effects: headache, dizziness, dyspepsia, etc.
42.3. CYTOKINES
Cytokines are produced by various cells, primarily cells of the immune system, and appear to be natural components of the body's repair and defense system. A number of cytokines are used in the treatment of malignant neoplasms. The antitumor effect of many cytokines is associated with the activation of cytotoxic T-killers, natural killers and the release of mediators of immune responses (IL-2, IFN-γ, etc.).
In medical practice, the drug IL-2 aldesleukin (Proleukin *) is used for renal carcinoma. In the complex therapy of some tumors, IFN is used -a-2b human recombinant.
42.4. ENZYME PREPARATIONS
A number of tumor cells are unable to synthesize L-asparagine and obtain this amino acid from media and body fluids. The introduction of asparaginase (L-asparaginase *) reduces the flow of L-asparagine into tumor cells. The drug is used in the treatment of acute lymphoblastic leukemia. Side effects include liver dysfunction and allergic reactions.
It is advisable to periodically use the listed drugs for all people after 40 years for prevention 1-2 times a year, after 50 years - 2-3 times a year. Other drugs - as needed.
How to take peptides
Since the restoration of the functional ability of cells occurs gradually and depends on the level of their existing damage, the effect can occur both 1-2 weeks after the start of taking peptides, and 1-2 months later. It is recommended to conduct a course within 1-3 months. It is important to take into account that a three-month intake of natural peptide bioregulators has a prolonged effect, i.e. works in the body for another 2-3 months. The effect obtained lasts for six months, and each subsequent course of administration has a potentiating effect, i.e. amplification effect already obtained.Since each peptide bioregulator has a focus on a specific organ and does not affect other organs and tissues in any way, the simultaneous administration of drugs with different effects is not only not contraindicated, but is often recommended (up to 6-7 drugs at the same time).
Peptides are compatible with any drugs and biological supplements. Against the background of taking peptides, it is advisable to gradually reduce the doses of simultaneously taken drugs, which will positively affect the patient's body.
Short regulatory peptides do not undergo transformation in the gastrointestinal tract, so they can be safely, easily and simply used in encapsulated form by almost everyone.
Peptides in the gastrointestinal tract decompose to di- and tri-peptides. Further breakdown to amino acids occurs in the intestine. This means that peptides can be taken even without a capsule. This is very important when a person for some reason cannot swallow capsules. The same applies to severely weakened people or children, when the dosage needs to be reduced.
Peptide bioregulators can be taken both prophylactically and therapeutically.
Efficiency natural(PC) 2-2.5 times lower than encapsulated. Therefore, their intake for medicinal purposes should be longer (up to six months). Liquid peptide complexes are applied to the inner surface of the forearm in the projection of the course of the veins or on the wrist and rubbed until completely absorbed. After 7-15 minutes, the peptides bind to dendritic cells, which carry out their further transport to the lymph nodes, where the peptides make a "transplant" and are sent with the blood flow to the desired organs and tissues. Although peptides are protein substances, their molecular weight is much smaller than that of proteins, so they easily penetrate the skin. The penetration of peptide preparations is further improved by their lipophilization, that is, the connection with a fatty base, which is why almost all peptide complexes for external use contain fatty acids.
Not so long ago, the world's first series of peptide drugs appeared for sublingual use—
A fundamentally new method of application and the presence of a number of peptides in each of the preparations provide them with the fastest and most effective action. This drug, getting into the sublingual space with a dense network of capillaries, is able to penetrate directly into the bloodstream, bypassing absorption through the mucosa of the digestive tract and metabolic primary deactivation of the liver. Taking into account direct entry into the systemic circulation, the rate of onset of the effect is several times higher than the rate when the drug is taken orally.
Revilab SL line- these are complex synthesized preparations containing 3-4 components of very short chains (2-3 amino acids each). In terms of peptide concentration, this is the average between encapsulated peptides and PC in solution. In terms of speed of action, it occupies a leading position, because. absorbed and hits the target very quickly.
It makes sense to introduce this line of peptides into the course at the initial stage, and then switch to natural peptides.
Another innovative series is a line of multicomponent peptide preparations. The line includes 9 preparations, each of which contains a range of short peptides, as well as antioxidants and building materials for cells. An ideal option for those who do not like to take many drugs, but prefer to get everything in one capsule.
The action of these new generation bioregulators is aimed at slowing down the aging process, maintaining a normal level of metabolic processes, preventing and correcting various conditions; rehabilitation after serious illnesses, injuries and operations.
Peptides in cosmetology
Peptides can be included not only in drugs, but also in other products. For example, Russian scientists have developed excellent cellular cosmetics with natural and synthesized peptides that affect the deep layers of the skin.External aging of the skin depends on many factors: lifestyle, stress, sunlight, mechanical stimuli, climatic fluctuations, dieting hobbies, etc. With age, the skin becomes dehydrated, loses its elasticity, becomes rough, and a network of wrinkles and deep grooves appears on it. We all know that the process of natural aging is natural and irreversible. It is impossible to resist it, but it can be slowed down thanks to the revolutionary ingredients of cosmetology - low molecular weight peptides.
The uniqueness of peptides lies in the fact that they freely pass through the stratum corneum into the dermis to the level of living cells and capillaries. Restoration of the skin goes deep from the inside and, as a result, the skin retains its freshness for a long time. There is no addiction to peptide cosmetics - even if you stop using it, the skin will simply age physiologically.
Cosmetic giants create more and more "miraculous" means. We trustfully buy, use, but a miracle does not happen. We blindly believe the inscriptions on the banks, not suspecting that this is often just a marketing ploy.
For example, most cosmetic companies are in full production and advertising anti-wrinkle creams with collagen as the main ingredient. Meanwhile, scientists have come to the conclusion that collagen molecules are so large that they simply cannot penetrate the skin. They settle on the surface of the epidermis, and then washed off with water. That is, when buying creams with collagen, we are literally throwing money down the drain.
As another popular active ingredient in anti-aging cosmetics, it is used resveratrol. It really is a powerful antioxidant and immunostimulant, but only in the form of microinjections. If you rub it into the skin, a miracle will not happen. It has been experimentally proven that creams with resveratrol practically do not affect the production of collagen.
NPCRIZ (now Peptides), in collaboration with scientists from the St. Petersburg Institute of Bioregulation and Gerontology, has developed a unique peptide series of cellular cosmetics (based on natural peptides) and a series (based on synthesized peptides).
They are based on a group of peptide complexes with different application points that have a powerful and visible rejuvenating effect on the skin. As a result of application, skin cell regeneration, blood circulation and microcirculation are stimulated, as well as the synthesis of collagen-elastin skin skeleton. All this manifests itself in lifting, as well as improving the texture, color and moisture of the skin.
Currently, 16 types of creams have been developed, incl. rejuvenating and for problematic skin (with thymus peptides), for the face against wrinkles and for the body against stretch marks and scars (with bone and cartilage tissue peptides), against spider veins (with vascular peptides), anti-cellulite (with liver peptides), for eyelids from edema and dark circles (with peptides of the pancreas, blood vessels, bone and cartilage tissue and thymus), against varicose veins (with peptides of blood vessels and bone and cartilage tissue), etc. All creams, in addition to peptide complexes, contain other powerful active ingredients. It is important that the creams do not contain chemical components (preservatives, etc.).
The effectiveness of peptides has been proven in numerous experimental and clinical studies. Of course, to look beautiful, some creams are not enough. You need to rejuvenate your body from the inside, using from time to time various complexes of peptide bioregulators and micronutrients.
The line of cosmetic products with peptides, in addition to creams, also includes shampoo, mask and hair balm, decorative cosmetics, tonics, serums for the skin of the face, neck and décolleté, etc.
It should also be borne in mind that the appearance is significantly affected by the sugar consumed.
Through a process called glycation, sugar is destructive to the skin. Excess sugar increases the rate of collagen degradation, leading to wrinkles.
Glycation - the interaction of sugars with proteins, primarily collagen, with the formation of cross-links - is a natural for our body, permanent irreversible process in our body and skin, leading to hardening of connective tissue.
Glycation products - A.G.E particles. (Advanced Glycation Endproducts) - settle in cells, accumulate in our body and lead to many negative effects.
As a result of glycation, the skin loses its tone and becomes dull, it sags and looks old. This is directly related to lifestyle: reduce your intake of sugar and flour (which is good for normal weight) and take care of your skin every day!
To counter glycation, inhibit protein degradation and age-related skin changes, the company has developed an anti-aging drug with a powerful deglycing and antioxidant effect. The action of this product is based on stimulating the deglycation process, which affects the deep processes of skin aging and helps to smooth out wrinkles and increase its elasticity. The drug includes a powerful complex to combat glycation - rosemary extract, carnosine, taurine, astaxanthin and alpha-lipoic acid.
Peptides - a panacea for old age?
According to the creator of peptide drugs V. Khavinson, aging largely depends on lifestyle: “No drugs will save if a person does not have a set of knowledge and the right behavior - this is the observance of biorhythms, proper nutrition, physical education and the intake of certain bioregulators.” As for the genetic predisposition to aging, according to him, we depend on genes by only 25 percent.The scientist claims that peptide complexes have a huge reduction potential. But to elevate them to the rank of panacea, to attribute non-existent properties to peptides (most likely for commercial reasons) is categorically wrong!
Taking care of your health today means giving yourself a chance to live tomorrow. We ourselves must improve our lifestyle - play sports, give up bad habits, eat better. And of course, to the extent possible, use peptide bioregulators that help maintain health and increase life expectancy.
Peptide bioregulators, developed by Russian scientists several decades ago, became available to the general public only in 2010. Gradually, more and more people around the world learn about them. The secret to maintaining the health and youthfulness of many famous politicians, artists, scientists lies in the use of peptides. Here are just a few of them:
UAE Minister of Energy Sheikh Saeed,
President of Belarus Lukashenko,
Former President of Kazakhstan Nazarbayev,
King of Thailand
pilot-cosmonaut G.M. Grechko and his wife L.K. Grechko,
artists: V. Leontiev, E. Stepanenko and E. Petrosyan, L. Izmailov, T. Povaliy, I. Kornelyuk, I. Viner (rhythmic gymnastics coach) and many, many others...
Peptide bioregulators are used by athletes of 2 Russian Olympic teams - in rhythmic gymnastics and rowing. The use of drugs allows us to increase the stress resistance of our gymnasts and contributes to the success of the national team at international championships.
If in youth we can afford to do health prevention periodically, when we want, then with age, unfortunately, we do not have such a luxury. And if you don’t want to be in such a state tomorrow that your loved ones will be exhausted with you and will wait impatiently for your death, if you don’t want to die among strangers, because you don’t remember anything and everything around you seems to be strangers in fact, you should take action from today and take care not so much about themselves as about their loved ones.
The Bible says, "Seek and you will find." Perhaps you have found your own way of healing and rejuvenation.
Everything is in our hands, and only we can take care of ourselves. No one will do this for us!
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Summary of the article:
1) Antitumor ointments,
2) Antitumor plants,
3) Antitumor mushrooms,
4) Anticancer teas,
5) Antitumor tinctures,
6) Antitumor dietary supplements,
7) Antitumor agents of plant origin.
Antitumor ointments
And so very often I advise people who are faced with oncology antitumor ointments based on plant poisons. In this situation, a very good ointment from herb hemlock spotted. This article will also write about this plant as the main antitumor folk remedy in the CIS. In some European countries, this drug is officially used in the treatment of cancer, but so far this is not the case in our country, it is most likely not profitable for pharmaceutical companies to produce a drug that in many cases helps patients. It's not for me to judge them.
Hemlock-based antitumor ointment is used in the treatment of skin cancer, breast cancer and other types of cancer, when the tumor is close to the skin and alkaloids can easily penetrate the skin to the formation.
Second, anticancer folk remedy on the basis of hemlock, you can make an oil that, like an ointment, is used to treat cancer. In order to prepare such oil on hemlock, we need to take dry hemlock, pour it into a glass jar and pour oil over it. Put in a dark place for six months, after which it can be used for treatment.
Anticancer plants
On the territory of Russia and the CIS, many medicinal plants grow that can be used as antitumor plants. These plants include:
Herbs Jungar aconite, collected in Central Asia high in the mountains;
Spotted hemlock, also desirable when collected high in the mountains;
Grass cocklebur;
Grass elecampane;
Grass celandine.
It makes no sense to write a lot of herbs, otherwise you will get even more confused, but these are the main antitumor plants that can be used in the treatment of cancer.
Why is the article focused on collecting herbs high in the mountains? It's no secret that plants that grow in difficult conditions are much stronger and more hardy than plants that grow, say, on the plains. You can also say about people, the same highlanders who live longer. Therefore, the medicinal properties of such antitumor plants are much better. Let's talk about Dzungarian aconite. There are many types of aconite, and the aconite itself is used as a garden plant because of its beauty, but again, it should not be confused with the Dzungarian aconite. Jungar aconite itself is very poisonous, this poison is its medicinal property, therefore, before buying on the Internet, always ask where the raw material comes from and how it was collected. I collect Jungar aconite high in the mountains.
You can also say about grass hemlock spotted. If it is collected high in the mountains, then the healing properties are also better. More about the antitumor folk remedy hemlock tincture can be found in the article below.
Grass celandine, cocklebur is also an antitumor plant and is often used in the treatment of oncology. Articles about them below.
Anticancer mushrooms
There is a so-called fungotherapy, that is, treatment with mushrooms. Yes, in my healing practice I use mushroom tinctures and advise people to drink this or that tincture for treatment. Anticancer fungi include:
Mushroom Amanita;
Birch mushroom (chaga);
Reishi mushroom.
I can say about the fly agaric mushroom that by its action it behaves like Dzhungarian aconite and like hemlock, since these plants and the fungus are united by the presence of poisonous alkaloids, which give these plants and the fungus poisonous properties. I’ll tell you about fly agaric tincture in the topic anticancer tinctures.
antitumor fungus- birch fungus, often used in folk medicine for treatment.
First soften the birch mushroom (chaga) (you can in warm water), then pass it through a blender or meat grinder, pour warm water in a ratio of 1 to 2 and insist for two days. Drink 600 gr. per day, that is, three times a day, 200 ml. Continue like this for 3 months
Preparation of a birch alkaline solution according to the following recipe: we take birch ash and place it in water (1: 5 ash / water ratio) and boil for 10 minutes in a glass or enamel bowl. After that, cool and strain. Method of treatment: dose: 50 g (8 tsp) solution mixed with milk or fruit juice, 3 times a day.
Diet, as with the above appointments, vegetable, dairy (you must use sour milk); eliminate meat from the diet completely (in any form).
anticancer reishi mushroom. The composition of the fungus is quite complex. It contains trace elements: a high level of germanium, coumarins, vitamins, organic acids, polysaccharides. The most important fungal compounds are triterpenes, polysaccharides, ganoderm acids and germanium. It is these compounds that determine the medicinal properties of the fungus.
Medicinal properties of reishi: immunomodulatory, soothing, antiallergic, antispasmodic, lowering blood pressure, antitumor (due to activation of the immune system), expectorant, hypoglycemic, antimicrobial, anti-inflammatory.
Mushroom applications. Make a tincture according to this method: 10 grams of chopped mushroom are infused in 400 ml. vodka for 2 weeks. Take 1 tbsp. l. 2-3 times a day 30 minutes before meals.
Reishi mushroom infusion should be made according to the following recipe: 1 tbsp. l. crushed mushroom per 700 ml. water, simmer for 60 minutes. Strain. Take 200 ml. decoction 3 times a day 30 minutes before meals.
Anticancer teas
To antitumor teas, I include herbal preparations that can be drunk as infusions or as teas.
Here I will write you one of the anticancer teas that you need to drink to prevent cancer. Take 1 tablespoon of pine needles, 1 tablespoon of young sea buckthorn leaves, 1 teaspoon of crushed milk thistle fruit. All herbs pour three cups of boiling water and boil for 18-20 minutes over low heat. Then strain the broth. Take 0.5 cup instead of tea.
Second anticancer tea: Burdock roots - 30 g, Burnet roots - 30 g, Marsh cinquefoil roots - 30 g, Rhizome of evading peony - 30 g, Bedstraw herb - 20 g, Dioecious nettle leaves - 20 g, Common agrimony grass - 20 g. Take one dessert spoon of a well-mixed collection of herbs and pour boiling water over it, leave for 30 minutes. Drink like tea with honey, 2-3 times a day. A month later, the fee is changed.
Antitumor tinctures
I already wrote in a paragraph about antitumor plants, those plants that are used in the treatment of oncology. Antitumor tinctures are made from these plants.
Antitumor tinctures include tinctures:
Tincture of hemlock spotted;
Tincture of aconite Dzungarian;
Tincture of celandine;
Cocklebur tincture;
Fly agaric tincture;
Reishi mushroom tincture;
Chaga tincture,
Basically, poisonous tinctures are used in the treatment of oncology. Why poisonous? As they say: poison is also a medicine, and if it is used in moderation, it has a beneficial effect on the body. The main toxic substance in poisonous tinctures is alkaloids. These are organic nitrogen-containing substances, which in their pure form are poison. Each plant or fungus has its own alkaloid. In hemlock it is coniine, in aconite it is aconitine, in fly agaric it is muscarine. They are different. That is why they say that it is better to drink poisonous tincture up to a maximum of 8 months? The body gets used to the poison, that is, the use of poison in the first month and in the tenth has a different effectiveness. Why is it necessary to drink another poison in between, say, if you take hemlock tincture, then you need to drink aconite during the break, because, so that the body does not lose the immunity reserve that it received from hemlock tincture, another poison, another alkaloid, another effect. You also need to look at which poison is best for the patient. When taking hemlock, there can be zero effect, since the body is like that, well, it does not perceive this poison, then we change it to aconite, if it does not perceive it, then we switch to fly agaric tincture.
Anticancer agents of plant origin
To antitumor agents of plant origin, I refer to agents that are made from natural material. I can refer Flaraxin to such means.
Flaraxin is an anticancer agent of plant origin, which is used in the treatment of oncology.
Other herbal antitumor agents:
Befungin
Vinblastine
Vincristine
Vinorelbine
Docetaxel
Irinotecan
Paclitaxel
Teniposide
Topotecan
Ukraine
etoposide
Summing up this, a large article, you learned that treatment with folk remedies is a complex treatment that is complex. Just taking one tincture is good, but you still need to work with other herbs and tinctures from herbal preparations.
Be healthy!
Other useful articles on the site:
The first antitumor antibiotic - dactinomycin- received in 1963. Subsequently, the screening of microbial waste products led to the discovery of a number of effective chemotherapeutic antitumor drugs that are products of various types of soil fungi or their synthetic derivatives.
In our time, with antitumor antibiotics, anthracycline antibiotics have the greatest practical use, they are among the most effective antitumor agents.
The mechanism of the cytotoxic action of anthracycline antibiotics is mainly due to inhibition of nucleic acid synthesis, impaired secondary DNA helixing, and binding to lipids of cell membranes, which is accompanied by a change in ion transport and cellular functions. This mechanism causes high antimitotic activity with low selectivity of action. Anthracycline antibiotics also have immunosuppressive (myelosuppressive) and antibacterial effects, but are not used as antimicrobial agents.
The pharmacokinetics of anticancer antibiotics is almost not studied, which can be explained by the methodological difficulties in identifying drugs of this group in the biological media of the body.
Pharmacodynamics. The antitumor effect of most antibiotics is mainly due to their ability to form complexes with DNA, which leads to the suppression of its informational (matrix) function, that is, to disruption of RNA synthesis. Thus, they exhibit an antitumor effect, in particular rubomycin hydrochloride, dactinomycin, bleomycin hydrochloride, olivomycin .
Feature of pharmacodynamics bleomycin hydrochloride is its pronounced organotropism relative to lung tissue, it does not affect hematopoiesis. For adriamycin immunosuppressive and cardiotoxic effects are characteristic. The cardiotoxic effect of this drug can be exerted by aglycone, which is formed during the metabolism of the antibiotic.
Almost all antitumor antibiotics also have antimicrobial activity. they can be combined with antitumor agents of other groups, in particular with alkyl ureas and antimetabolites.
Indications. Olivomycin used in the form of sodium salt for testicular tumors, tonsillar tumors, reticulosarcoma with lesions of peripheral nodes, melanoma. This antibiotic is attracting attention due to the effectiveness of its topical application in the form of an ointment for ulcerative cancers and metastases that are not treatable by other methods.
Bleomycin prescribed in cases of squamous cell carcinoma of the oral mucosa, tongue, tonsils, larynx, skin, cervix, as well as lymphogranulomatosis and penile cancer (in combination with vinblastine).
Sufficiently wide range of antitumor activity has adriamycin; breast carcinoma, lung cancer, bladder cancer of the thyroid gland, ovaries, bone and soft tissue sarcoma.
Bruneomycin patients are prescribed lymphogranulomatosis, reticulosarcoma, lymphosarcoma, chronic lymphocytic leukemia.
Side effect nausea, vomiting, anorexia, leukopenia, thrombocytopenia, bleomycin - hair loss, allergic skin rash.
Contraindications: leukopenia, thrombocytopenia, allergic reactions (urticaria, angioedema), severe renal dysfunction, circulatory disorders, active myelosuppression after radiation therapy.
Anticancer agents of plant origin
The active principle of anticancer drugs, which are obtained from plant materials, are alkaloids, which are diverse both in chemical structure and in the mechanism of the antiblastoma effect. One of the first herbal preparations used in oncological practice were kolhamin and birch fungus extract befungin, which is used as a symptomatic agent. Later, vinblastine and vincristine were introduced into medical practice. Antitumor alkaloids are characterized by very high toxicity. they are obtained from various plants: from pink periwinkle ( vinblastine , vincristine), from the bulbs of the luxurious colchicum ( kolhamin), podophyllum of the shield-shaped ( dofilin) and etc.
Pink periwinkle alkaloids - vincristine and vinblastine- were isolated from the plant Catharanthus roseus. A new semi-synthetic derivative of vinblastine is named wine-relbino. These are phase-specific antitumor agents that act predominantly during mitosis. By binding to tubulin, they stop the collection of microtubules.
Pharmacokinetics. The pharmacokinetic parameters of herbal antitumor agents are practically not studied, which, as with antitumor antibiotics, can be explained by the complexity of their identification in biological media.
Pharmacodynamics. The cytostatic effect of alkaloids consists in selective inhibition of transfer RNA and DNA synthesis, which leads to blocking of mitosis at the metaphase stage. Thus, the development of tumor (and normal) tissue is delayed, and it rapidly proliferates.
The cytostatic effect of antitumor alkaloids is the inhibition of leuko-verses, erythropoiesis and thrombocytopoiesis.
Indications: vinblastine , vincristine- hemoblastosis (hematosarcoma, multiple myeloma, acute leukemia, etc.); breast cancer, neuroblastoma, chorionepithelioma, lymphogranulomatosis (alone, and also combined with other antitumor agents) kolhamin: locally in ointments - skin cancer, in combination with Sarcolysin - cancer of the esophagus, highly located cancer of the stomach; podophyllin- papillomatosis of the larynx, papilloma of the bladder.
Side effect dose-limiting side effect of vincristine - neurotoxicity, which is manifested by sensory and autonomic neuropathy. Another side effect of vincristine is ADH hypersecretion syndrome. Inhibition of hematopoiesis is usually not characteristic of this drug. In vinblastine and vinorelbine, on the contrary, the main side effect is bone marrow hypoplasia; they rarely cause neurotoxic effects compared to vincristine.
Contraindications: severe concomitant diseases, including kidneys, liver, when hematopoiesis is suppressed (leukopenia, thrombocytopenia, anemia); kolhaminova ointment - skin cancer IN and stage IV with metastases.
Enzyme preparations with antitumor activity
Asparaginase is the only enzyme used as an anticancer agent. Under its action, extracellular reserves of asparagine are exhausted, which tumor and normal lymphocytes need, since the cells themselves almost do not synthesize asparagine. This position became the basis for the search for agents capable of destroying this enzyme and artificially limiting its supply to tumor cells, and leading to their death. The enzyme has these properties. L-asparaginase .
Pharmacokinetics. After administration, the enzyme circulates in the blood for quite a long time: its half-life is 8-30 hours. L-asparaginase appears in the blood even a few days after withdrawal.
Pharmacodynamics. The enzyme cleaves L-asparagine to aspartic acid and ammonium. Thus, an amino acid deficiency is formed, which inhibits the synthesis of nucleic acids, and, consequently, cell reproduction.
Indications: acute lymphoblastic leukemia, lymphosarcoma.
Side effect L-asparaginase causes allergic reactions, even at the first application, anaphylactic shock is possible. Other side effects are hepatotoxicity, nephrotoxicity, neurotoxicity, pancreatitis. Over time, the content of fibrinogen in the blood may decrease, and a tendency to hemorrhage may appear.
Contraindications: pregnancy, severe diseases of the liver, kidneys, pancreas, central nervous system, severe leuko- and thrombocytopenia.
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