Women's problems, or why the doctor asks to eat more. Drug intoxication - treatment with drugs with disodium folinate

Disodium folinate - active substance, an antidote of antagonists folic acid used to treat poisoning with certain medicines such as methotrexate.

pharmachologic effect

Folic acid is extremely important substance, which regulates the flow processes significant amount biochemical processes that play an important metabolic role. In particular, it is involved in biosynthetic reactions purine bases, pyrimidine nucleotides and other biologically active components, without which it is impossible to imagine normal work the vast majority of living organisms.

Folic acid antagonists often form the basis of the therapeutic effect on the patient in the presence of diseases such as acute leukemia, malignant neoplasms bodies digestive system, uterine cancer and some other ailments.

Disodium folinate, being a derivative of folic acid, is able to reduce the impact on the body of antagonists of this substance, contributing to the restoration of nucleic acid synthesis reactions, filling the deficiency of this biologically active component, suppressing the toxic effect of certain medicinal compounds.

At intravenous administration, under the influence of individual enzymes, disodium folinate is transformed into 5-methyltetrahydrofolic acid, which is an active metabolite.

In further reactions, 5-methyltetrahydrofolic acid is transformed to folic acid, which is included in the appropriate pool and directed to meet the actual needs of the body.

In the process of converting disodium folinate, other metabolites are also synthesized that do not have a pronounced biochemical activity, which are excreted using the organs of the excretory system.

Disodium folinate quickly penetrates most tissue barriers. The presence of this substance is determined in breast milk, amniotic and hematoencephalic fluid. This circumstance imposes serious restrictions on the use of drugs containing this component.

The medicinal substance is not prone to cumulation (accumulation). Because of this, cases of overdose of disodium folinate have not been recorded. In addition, there is no data on the presence of toxic effects on the patient's body.

Indications for use

The appointment of drugs is carried out in the following cases:

Treatment of body intoxication with methotrexate, pyrimethamine and other folic acid antagonists;
Prevention of intoxication of the body with folic acid antagonists;
As part complex treatment individual cancers.

The use of preparations containing disodium folinate is possible only after a comprehensive examination of the patient. The use of such funds should be carried out only with the participation of an experienced specialist.

Contraindications for use

Appointment of pharmaceuticals is unacceptable in the presence of the following conditions:

Anemia conditions based on cyanocobalamin deficiency;
Pregnancy and lactation.

In addition, the remedy is contraindicated when individual intolerance.

Application and dosage

The drugs are available in the form of solutions and must be administered intravenously by stream or infusion. The dosage should be calculated based on the indications for use and the severity of the patient's condition. As a rule, special tables should be used for this, taking into account the content of methotrexate in the patient's blood plasma.

Usually the recommended dose is from 100 to 500 milligrams of the drug per 1 square meter. skin. In extremely severe cases, the dosage can be up to 15 grams. The duration of treatment is determined by the doctor.

Side effects

Due to the lack of toxicity, disodium folinate preparations have almost no side effects. In pretty rare cases possible development allergic reactions as skin rash, anaphylactic manifestations and so on.

Occur even less frequently dyspeptic disorders in the form of diarrhea, nausea, vomiting, bloating, rumbling in the abdomen and diffuse soreness.

special instructions

Prescribing should be done as soon as possible after the diagnosis of folic acid antagonist poisoning has been made. With prolonged toxic effects of methotrexate, the effectiveness of drugs is significantly reduced.

In patients receiving antiepileptic treatment, an increase in the frequency of seizures is possible. This is due to a decrease in the concentration anticonvulsants in blood. If necessary, the attending physician should update the dosage of the respective medicinal products.

The administration of the drug should be combined with the hydration of the patient. It is usually recommended to administer three liters of fluid per day, which should help eliminate acidification of the urine and speed up the elimination of folic acid antagonists.

Preparations containing disodium folinate

This substance is found in the following pharmacological agents: Folinic acid, .

Conclusion

We talked about how and how drug intoxication is treated - treatment with drugs with disodium folinate. Treatment of methotrexate poisoning, as mentioned earlier, should be carried out as early as possible. Only in this case toxic effect will be minimally expressed and in most cases, it will be possible to avoid severe consequences intoxication.

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folic acid antagonists

Methotrexate(Methotrexate) - analogue of folic acid; irreversibly inhibits dihydrofolate reductase and thus disrupts the conversion of dihydrofolic acid to tetrahydrofolic acid. In this regard, the formation of purine bases, thymidylate and, accordingly, DNA synthesis and cell division are disrupted. Methotrexate has antitumor, immunosuppressive and anti-inflammatory properties.

Assign methotrexate orally, intravenously and intramuscularly for cancer Bladder, uterine chorionepithelioma, acute lymphoblastic leukemia. In relatively low doses, methotrexate is used for rheumatoid arthritis as an anti-inflammatory and immunosuppressive agent.

Side effects methotrexate:

– ulcerative stomatitis;

- gastritis;

- diarrhea;

- oppression bone marrow(leukopenia, thrombocytopenia);

- nephrotoxicity.

To reduce the side effects of methotrexate, prescribe calcium folinate(Calcium folinate; leucovorin calcium; citrovorum factor; folinic acid; Ν-5-formyltetrahydrofolate) is a folic acid antagonist antidote that can be converted to coenzymes in the presence of methotrexate without converting dihydrofolic acid to tetrahydrofolate. Since normal cells, unlike tumor cells, are able to concentrate folinic acid, the administration of calcium folinate is to prevent the death of non-tumor cells from toxic action methotrexate; prevents the inhibitory effect on the bone marrow. Against the background of calcium folinate, an increase in the dose of methotrexate is possible. Apply calcium folinate intramuscularly or intravenously.

Purine analogs

Mercaptopurine(Mercaptopurine; 6-mercaptopurine) is a thioanalogue of hypoxanthine, which is a precursor of adenine and guanine. Competes with hypoxanthine and guanine for hypoxadeninguanine phosphoribosyltransferase and thus disrupts nucleotide synthesis. The drug is administered orally with acute leukemia, chronic myeloid leukemia, chorionepithelioma of the uterus.

thioguanine(Tioguanine) – purine antimetabolite; similar in structure and mechanism of action to mercaptopurine. It has a selective effect on bone marrow cells. Assign inside for acute leukemia, erythremia.

Side effect mercaptopurine and thioguanine - bone marrow suppression.

fludarabine(Fludarabine) inhibits DNA polymerase and impairs DNA synthesis. Inhibits RNA polymerase and disrupts protein synthesis. It is administered intravenously in chronic lymphocytic leukemia.

Pyrimidine analogs

Fluorouracil(Ftoruracil; 5-fluorouracil) in tumor cells is converted to 5-fluorodeoxyuridine monophosphate, which inhibits thymidylate synthetase and thus disrupts DNA synthesis. Fluorouracil is administered intravenously for cancer of the esophagus, stomach, pancreas, colon and rectum, and cervix.

Side effects: bone marrow suppression, ulceration of the oral mucosa and gastrointestinal tract.

Tegafur(Tegafur; ftorafur) - prodrug; in the body it turns into 5-fluorouracil, which inhibits thymidylate synthetase and uracil synthetase involved in the synthesis of nucleic acids. The drug is prescribed orally for cancer of the stomach, colon and rectum.

Capecitabine(Capecitabine) in the tumor tissue under the influence of thymidine phosphorylase turns into 5-fluorouracil, whose activity in the tumor is 4 times higher than in healthy tissues. Assign inside for cancer of the breast and colon.

Cytarabine(Cytarabine) - cytosine arabinoside. Inhibits DNA polymerase. It has a pronounced effect on leukocytes (phosphorylation of cytarabine occurs most intensively in myeloblasts, lymphoblasts and lymphocytes). It is administered intravenously for acute leukemia, lymphogranulomatosis.

Known antagonists and biosynthesis, and utilization of folic acid. On the history of the discovery of antibacterial sulfonamides- typical representatives antagonists of its biosynthesis, already mentioned in Sec. 2.1 and 6.3.1.

In 1940, Woods showed that the antibacterial action of streptocide is determined by its competition with the natural metabolite, para-aminobenzoic acid (PAB) (9.7). Subsequently, it was found that this process is carried out at the site of the enzyme dihydrofolate synthetase, which uses PAB to build the dihydrofolic acid molecule (2.14) .

The enzyme mistakenly takes streptocide as its normal substrate due to the great similarity of their electronic and spatial structure. PAB has pKa=4.9 and is not

an amphoteric bipolar ion like glycine; apparently biologically active form- its anion (9.7). Streptocide - noticeably more weak acid(pKa=10.3) and therefore low ionized at physiological values pH. The primary amino groups of both substances are low-basic (pKa 2.5 and 2.6, respectively) and are neo-ionized at physiological active values pH. The sizes of the PAB anion (2.12) and the non-ionized streptocide molecule (2.13) are almost the same. Both molecules are planar, in both the primary amino group is in paraposition with respect to the electron-withdrawing group. Thus, the above facts indicate a high degree of similarity of two molecules and, consequently, the possibility of manifestation biological activity analogue molecule. The indicated sizes of the substances under discussion change little upon ionization.

para-amiobenzoic acid (PAB)

After the introduction of streptocide (9.2) in clinical practice attempts have been made to modify its molecule in order to create more active analogues. It was found that those sulfonamides are most suitable for this, in which the radical R in the molecule (9.8) is a heterocyclic ring. Bell and Roblin (1942) showed that this increases the degree of acid ionization and that the sulfonamides, which are fully ionized at pH 7, and therefore most similar to PABs, are the most potent antibacterial agents (section 10.5). Sulfonamides that are not capable of acid ionization can also have an antibacterial effect (for example, diphenylsulfone, sulgin), but it is always much weaker than that of easily ionized sulfonamides. So the minimum inhibitory concentration of sulfazine in relation to E. coli is 1.02 µmol / l, which is approximately 1.5 times. 100 times lower than streptocide. This is consistent with the greater ease of ionization of sulfazine (pKa = 6.5), 75% of which is converted to the anion at pH 7. cannot serve as an obstacle to its adsorption on the receptor normally occupied by the PAB anion (9.7).

Selectivity antibacterial action sulfonamides is due to the fact that mammals are unable to synthesize dihydrofolic acid and receive it with food. In the same time pathogenic bacteria cannot absorb exogenous dihydrofolic acid and, therefore, are vulnerable to the action of sulfonamides, which inhibit its synthesis.

Sulfapyridine, the first sulfonamide with a heterocyclic substituent, was soon superseded by sulfathiazole, which in turn was replaced by the three more selective sulfopyrimidines shown in Table 1. 2.5 (vol. 1). These oral preparations have become widely used in the treatment a large number bacterial infections.

Currently, antibacterial sulfonamides are commonly used as uroantiseptics, for example, in diseases caused by E. coli and Proteus mirabilis. They are also prescribed for nocardiosis of the lungs or feet, eye trachoma, venereal lymphogranulomas, herpetic dermatitis. Great importance for prevention streptococcal infections in patients predisposed to them, as well as to prevent recurrence of rheumatic inflammations.

Antibacterial sulfonamides can be divided into two main classes: (a) rapidly excreted from the body and (b) long-term circulating in the bloodstream. The most commonly used compounds of class (a): 1) sulfazine, N"-(pyrimidin-2-yl)sulfanilamide (9.9), is in fact the reference compound against which all others are compared (its scope is extended by its ability to penetrate into therapeutic concentrations in cerebrospinal fluid); 2) sulfafurazole (9.10)-N "- (3,4-dimethylisoxazol-5-yl) sulfanilamide drug a wide range action, characterized by a higher concentration in the urine compared to sulfadiazine; 3) sulfamethoxazole (9.11), which has a fairly long half-life for this class, is one of the best drugs due to its synergy with trimethoprim (section 9.6); 4) sulfacytin (9.12) and 5) sulfamethizole (9.13) are the most preferred uroantiseptics because of their short circulating half-life and lack of specific accumulation.

Sulfonamides of class (a), as well as their acetyl derivatives, into which they are always at least partially converted, must be rapidly eliminated from the body and, accordingly, have a high solubility in the urine. The use of drugs that do not meet these requirements can pose a threat to the life of patients. So, in the 40s, many deaths were recorded due to blockade of the kidneys caused by taking sulfathiazole. Problems of this kind do not arise with class (b) sulfonamides, that is, with those high concentration which remain in the blood for so long that a single dose is often sufficient to achieve the effect. The main disadvantage of these drugs is the duration of the adverse reactions sometimes up to several days. The most dangerous adverse reactions to these drugs are Stevens-Jones syndrome and multiple erythremias, which, although rare, can be fatal. The most widely used the following drugs of this class: 1) sulfapyridazine (9.14) -N "- (6-methoxypyridazine-3-

yl) sulfanilamide; 2) sulfamethoxydiazine, N"-(5-methoxypyrimidin-2-yl) sulfanilamide; 3) sulfamethopyrazine, N"-(3-Methoxypyrazin-2-yl) sulfanilamide (9.15); 4) sulfadimethoxine, 1M "-(3,6-dimethoxypyrimidin-4-yl) sulfanilamide; 5) sulfadoxine, N"-(5,6-dimethoxypyrimidin-4-yl) sulfanilamide - one of the least toxic sulfanilamides, widely used together with diaminopyrimidine to achieve consistent blocking (section 9.6). Besides, in special occasions use: silver sulfazine (topically for severe burns), sodium sulfacetamide (9.16) ( eye infections), sulfapyridine ( herpetic dermatitis), sulfazalazine (colitis) and phthalylsulfathiazole (before operations to suppress intestinal flora).

Factors that determine the distribution of sulfa drugs are discussed in Sec. 10.5.

There are many PAB analogues that are not sulfonamides. Of these, the most widely used is diaphenylsulfone (9.17), the main drug for the treatment of leprosy. Some of the preparations of this type do not contain a sulfur atom, but have the necessary spatial and electronic similarity to PAB. For example, the introduction of a chlorine atom at position 2 or 3 of PAB results in the formation of an active PAB antagonist. Diaminobenzyl (2.15) is several times more active antibacterial drug than streptocide, but its effect is reversible under the action of PAB. In addition, para-aminobenzolarsonic acid - atoxyl (6.2) has a typical sulfanilamide action. Although arsenic acids are generally not antibacterial drugs, atoxyl is an exception, since it is quite close to PAB in both geometric and electronic parameters and can be its competitor.

o=s=o

Deaphenylsulfone

In order for a substance to interact with dihydrofolate synthetase instead of PAB, two conditions are necessary. The first and very essential substance must contain a primary aromatic amino group. In the para-position, instead of the N-group, only those can be introduced that will easily decompose in the body and release the primary amino group. Obviously, azo groups or azomethine groups, in contrast to acylamino or alkylamino groups, are cleaved in this way, for example, in sulfachrhizoidine (3.30). The second condition is that the molecule must contain a negatively charged group located in the para position to the amino group and at the same distance as in PAB. The significance of the distance between the amino and electronegative groups for the manifestation of antagonistic properties can be illustrated by the example of 4-amino-4"-sulfonamidodiphenyl (9.18), which does not have these properties.

Mafenide (4-aminomethylbenzenesulfonamide) (9.19) after structural formula resembling streptocide, is a highly basic substance with specific activity on
towards Clostridia (causing gas gangrene). The drug is not a PAB antagonist and does not appear to play any role in folic acid metabolism.

Many of the commonly used drugs containing sulfonamide groups are not antibacterial agents, because when they were created, they did not strive for an analogy with PAB; some of them are diuretics (section 9.4.7), others are antidiabetic agents (section 12.4).

Known antagonists and biosynthesis, and utilization of folic acid. The history of the discovery of antibacterial sulfonamides, typical representatives of antagonists of its biosynthesis, has already been discussed in Sec. 2.1 and 6.3.1.

The enzyme mistakenly takes streptocide as its normal substrate due to the great similarity of their electronic and spatial structure. PAB has pK a = 4.9 and is not an amphoteric bipolar ion like glycine; apparently the biologically active form is its anion (9.7). Streptocide is a noticeably weaker acid (pK a = 10.3) and therefore is slightly ionized at physiological pH values. The primary amino groups of both substances are slightly basic (pKa 2.5 and 2.6, respectively) and neoionized at physiologically active pH values. The sizes of the PAB anion (2.12) and the non-ionized streptocide molecule (2.13) are almost the same. Both molecules are planar, in both the primary amino group is in paraposition with respect to the electron-withdrawing group. Thus, the above facts indicate a high degree of similarity between the two molecules and, consequently, the possibility of biological activity of the analogue molecule. The indicated sizes of the substances under discussion change little upon ionization.

After the introduction of streptocide (9.2) into clinical practice, attempts were made to modify its molecule in order to create more active analogues. It was found that those sulfonamides are most suitable for this, in which the radical R in the molecule (9.8) is a heterocyclic ring. Bell and Roblin (1942) showed that this increases the degree of acid ionization and that the sulfonamides, which are fully ionized at pH 7, and therefore most similar to PABs, are the most potent antibacterial agents (section 10.5). Sulfonamides that are not capable of acid ionization can also have an antibacterial effect (for example, diphenylsulfone, sulgin), but it is always much weaker than that of easily ionized sulfonamides. So the minimum inhibitory concentration of sulfazine in relation to E. coli is 1.02 µmol / l, which is approximately 1.5 times. 100 times lower than streptocide. This is consistent with the greater ease of ionization of sulfazine (pKa = 6.5), 75% of which is converted to the anion at pH 7. cannot serve as an obstacle to its adsorption on the receptor normally occupied by the PAB anion (9.7).

The selectivity of the antibacterial action of sulfonamides is due to the fact that mammals are unable to synthesize dihydrofolic acid and receive it with food. At the same time, pathogenic bacteria cannot absorb exogenous dihydrofolic acid and, therefore, are vulnerable to the action of sulfonamides, which inhibit its synthesis.

Currently, antibacterial sulfonamides are commonly used as uroantiseptics, for example, in diseases caused by E. coli and Proteus mirabilis. They are also prescribed for nocardiosis of the lungs or feet, eye trachoma, venereal lymphogranulomas, herpetic dermatitis. They are of great importance for the prevention of streptococcal infections in patients predisposed to them, as well as for the prevention of recurrence of rheumatic inflammations.

Antibacterial sulfonamides can be divided into two main classes: (a) rapidly excreted from the body and (b) long-term circulating in the bloodstream. The most used compounds of class (a): 1) sulfazine, N"-(pyrimidin-2-yl)sulfanilamide (9.9), is in fact the reference compound against which all others are compared (its scope is extended by its ability to penetrate into therapeutic concentrations in the cerebrospinal fluid); 2) sulfafurasol (9.10)-N "- (3,4-dimethylisoxazol-5-yl) broad-spectrum sulfanilamide drug, characterized by a higher concentration in the urine compared to sulfadiazine; 3) sulfamethoxazole (9.11), which has a rather long half-life for this class, is one of the best drugs due to its synergy with trimethoprim (Sect.

9.6); 4) sulfacytin (9.12) and 5) sulfamethizole (9.13) are the most preferred uroantiseptics because of their short circulating half-life and lack of specific accumulation.

Streptocide (anion) (R=H)

in formula (9.8):

Sulfonamides of class (a), as well as their acetyl derivatives, into which they are always at least partially converted, must be rapidly eliminated from the body and, accordingly, have a high solubility in the urine. The use of drugs that do not meet these requirements can pose a threat to the life of patients. So, in the 40s, many deaths were recorded due to blockade of the kidneys caused by taking sulfathiazole. Problems of this kind do not arise with class (b) sulfonamides, that is, with those whose high concentration in the blood persists for so long that a single dose is often sufficient to achieve the effect. The main disadvantage of these drugs is the duration of the adverse reactions they cause, sometimes up to several days. The most dangerous adverse reactions to these drugs are Stevens-Jones syndrome and multiple erythremias, which, although rare, can be fatal. The following drugs of this class are most widely used: 1) sulfapyridazine (9.14) - N "- (6-methoxypyridazin-3-yl) sulfanilamide; 2) sulf a methoxy diazine, N" - (5-methoxypyrimidin-2-yl ) sulfanilamide; 3) sulfamethopyrazine, N "- (3-Me- thoxypyrazin-2-yl) sulfanilamide (9.15); 4) sulfadimetok

syn, N "- (3,6-dimethoxypyrimidin-4-yl) sulfanilamide; 5) sulfadoxine, N" - (5,6-dimethoxypyrimidin-4-yl) sulfanilamide - one of the least toxic sulfanilamides, widely used in conjunction with diaminopyrimidine to achieve consistent blocking (section 9.6). In addition, in special cases, silver sulfazine (topically for severe burns), sodium sulfacetamide (9.16) (eye infections), sulfapyridine (herpetic dermatitis), sulfazalazine (colitis) and phthalylsulfathiazole (before operations to suppress intestinal flora) are used in special cases.

Factors that determine the distribution of sulfa drugs are discussed in Sec. 10.5.

Mafenide (4-aminomethylbenzenesulfonamide) (9.19), structurally reminiscent of streptocide, is a highly basic substance with specific activity at

in relation to Clostridia (causing gas gangrene). The drug is not a PAB antagonist and does not appear to play any role in folic acid metabolism.

Many of the widely used drugs containing sulfanilamide groups do not belong to antibacterial agents, since when they were created they did not strive for analogy with PAB; some of them are diuretics (section 9.4.7), others are antidiabetic agents (section 12.4).

Methotrexate is prescribed orally, intravenously and intramuscularly for bladder cancer, uterine chorionepithelioma, acute lymphoblastic leukemia. In relatively low doses, methotrexate is used in rheumatoid arthritis as an anti-inflammatory and immunosuppressive agent.

Side effects of methotrexate:

- ulcerative stomatitis;

- gastritis;

- diarrhea;

- bone marrow depression (leukopenia, thrombocytopenia);

- nephrotoxicity.

To reduce the side effects of methotrexate, prescribe calcium folinate(Calcium folinate; leucovorin calcium; citrovorum factor; folinic acid; Ν-5-formyltetrahydrofolate) is a folic acid antagonist antidote that can be converted to coenzymes in the presence of methotrexate without converting dihydrofolic acid to tetrahydrofolate. Since normal cells, unlike tumor cells, are able to concentrate folinic acid, the appointment of calcium folinate is to prevent the death of non-tumor cells from the toxic effects of methotrexate; prevents the inhibitory effect on the bone marrow. Against the background of calcium folinate, an increase in the dose of methotrexate is possible. Apply calcium folinate intramuscularly or intravenously.

Purine analogs

Mercaptopurine(Mercaptopurine; 6-mercaptopurine) is a thioanalogue of hypoxanthine, which is a precursor of adenine and guanine. Competes with hypoxanthine and guanine for hypoxadeninguanine phosphoribosyltransferase and thus disrupts nucleotide synthesis. The drug is prescribed orally for acute leukemia, chronic myeloid leukemia, uterine chorionepithelioma.

A side effect of mercaptopurine and thioguanine is bone marrow suppression.

Pyrimidine analogs

Side effects: bone marrow suppression, ulceration of the oral mucosa and gastrointestinal tract.

A side effect is bone marrow suppression.

Gemcitabine(Gemcitabine) is an analogue of cytarabine. Gemcitabine metabolites are incorporated into DNA and disrupt its synthesis. The drug is administered intravenously for pancreatic cancer (drug of choice), not small cell carcinoma lung, bladder cancer. .

Altretamine(Altretamin; hexalen) is a drug whose metabolites form covalent bonds with DNA. Assign inside for ovarian cancer.

Substances plant origin and their synthetic derivatives

Herbal ingredients include:

1) alkaloids of vinca rosea- vinblastine, vincristine, vinorelbine;

2) podophyllum thyroid alkaloids- podophyllotoxin, etoposide, teniposide;

3) taxanes(obtained from yew needle processing products) - paclitaxel, docetaxel;

4) camptothecyps (derivatives of Campotheca acuminata alkaloids)- topotecan, irinotecan.

Vinca rosea alkaloids

Vinca rosea alkaloids(Vinca alkaloids) - vinblastine, vincristine, vinorelbine - prevent the polymerization of tubulin and promote its depolymerization; in this regard, they disrupt the formation and function of microtubules in tumor cells and thus prevent cell division.

Vinblastine(Vinblastine; rosevin) is administered intravenously for lymphomas, testicular cancer, and also for lymphogranulomatosis, chronic leukemia, cancer of the lung, kidney, bladder, ovary, chorionepithelioma of the uterus, Kaposi's sarcoma.

Side effects: myelosuppression, paresthesia.

Vinorelbine(Vinorelbine; navelbine) is a semi-synthetic derivative of vinblastine. It is administered intravenously for non-small cell lung cancer, breast cancer.

Vincristine(Vincristine) is administered intravenously for cancer of the lung, bladder, ovary, chorionepithelioma of the uterus, acute leukemia, lymphomas.

Side effects: peripheral neuropathy (impaired function of microtubules in peripheral nerve fibers).

Alkaloids of podophyllum thyroid

Thyroid podophyll alkaloids and their derivatives inhibit topisomerase-II (DNA gyrase) and thus prevent DNA replication and mitosis.

podophyllotoxin(Podophyllotoxin) is a podophyllum alkaloid. Used for external genital warts. The solution of the drug is applied to condylomas.

etoposide(Etoposide) is a semi-synthetic derivative of podophyllotoxin. The drug is administered intravenously for cancer of the lung, stomach, ovary, testicle; lymphogranulomatosis.

Side effect:

- bone marrow suppression;

- alopecia;

- allergic reactions.

Teniposide(Teniposide) is a derivative of podophyllotoxin. Administered intravenously for cancer of the lung, bladder; lymphogranulomatosis, acute leukemia.

Taxanes

Paclitaxel(Paclitaxel; taxol) is derived from the bark of the Pacific yew (Taxus baccata). Stimulates the assembly of defective microtubules from tubulin dimers, prevents tubulin depolymerization (stabilizes the structure of microtubules) and thus prevents mitosis.

Paclitaxel is administered intravenously for non-small cell lung cancer, ovarian cancer, breast cancer, Kaposi's sarcoma in AIDS patients.

Side effect - neutropenia.

Docetaxel(Docetaxel; taxotere) is a semi-synthetic derivative of a compound obtained from the needles of the European yew. About the structure and action is similar to paclitaxel.

Docetaxel is administered intravenously for breast cancer, non-small cell lung cancer, and ovarian cancer.

Side effects:

- bone marrow suppression;

– neurotoxicity;

- hypersensitivity reactions.

Camptothecins

Camptothecin is an alkaloid from the Campotheca acuminata tree; topisomerase-1 inhibitor (an enzyme involved in DNA supercoiling).

Topotecan(Topotecan) is a semi-synthetic analogue of camptothecin. The drug is administered intravenously for small cell lung cancer and ovarian cancer.

Irinotecan(Irinotecan; campto) is a semi-synthetic derivative of camptothecin. It is administered intravenously for cancer of the stomach, pancreas, colon and rectum.

Side effects of captothecins:

- bone marrow suppression;