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

Disodium folinate – active substance, antidote to antagonists folic acid, used to treat poisoning by certain medicines, for example, methotrexate.

pharmachologic effect

Folic acid is extremely important substance regulating the processes significant amount biochemical processes, which have an important metabolic role. In particular, it participates in biosynthesis 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 organs digestive system, uterine cancer and some other ailments.

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

At intravenous administration, under the influence of certain 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 corresponding pool and sent to meet the current needs of the body.

In the process of converting disodium folinate, other metabolites are synthesized that do not have pronounced biochemical activity, which are excreted through 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

Drugs are prescribed 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 oncological diseases.

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

Contraindications for use

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

Anemic conditions based on cyanocobalamin deficiency;
Pregnancy and lactation.

In addition, the drug is contraindicated for individual intolerance.

Application and dosage

The drugs are available in the form of solutions and must be administered intravenously by bolus 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.

Typically 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 quite in 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

Prescription of drugs should be carried out as soon as possible after the diagnosis of poisoning with folic acid antagonists. With prolonged toxic effects of methotrexate, the effectiveness of the drugs is significantly reduced.

In patients receiving antiepileptic treatment, the frequency of seizures may increase. This is due to a decrease in concentration anticonvulsants in blood. If necessary, the attending physician should update the dosage of the relevant medications.

Administration of the drug should be combined with hydration of the patient. Typically, it is recommended to administer three liters of fluid per day, which should help eliminate acidification of 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 containing disodium folinate. Treatment of methotrexate poisoning, as mentioned earlier, should be carried out as early as possible. Only in this case toxic effects will be minimally expressed and in most cases, it will be possible to avoid severe consequences intoxication.

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Folate antagonists

Methotrexate(Methotrexate) – an 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 and thymidylate and, accordingly, DNA synthesis and cell division are disrupted. Methotrexate has antitumor, immunosuppressive and anti-inflammatory properties.

Methotrexate is prescribed orally, intravenously and intramuscularly for cancer Bladder, chorionepithelioma of the uterus, 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, it is prescribed calcium folinate(Calcium folinate; leucovorin calcium; citrovorum factor; folinic acid; Ν-5-formyltetrahydrofolate) is an antidote for folic acid antagonists, which in the presence of methotrexate can be converted into coenzymes without converting dihydrofolic acid into tetrahydrofolate. Since normal cells, unlike tumor cells, are able to concentrate folinic acid, the purpose of calcium folinate is to prevent the death of non-tumor cells from toxic effect methotrexate; prevents the inhibitory effect on the bone marrow. Against the background of calcium folinate, it is possible to increase the dose of methotrexate. Calcium folinate is used intramuscularly or intravenously.

Purine analogues

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

Thioguanine(Tioguanine) – purine antimetabolite; its structure and mechanism of action are similar to mercaptopurine. Has a selective effect on bone marrow cells. Prescribed orally for acute leukemia, erythremia.

Side effect mercaptopurine and thioguanine – bone marrow suppression.

Fludarabine(Fludarabine) inhibits DNA polymerase and disrupts DNA synthesis. Inhibits RNA polymerase and disrupts protein synthesis. Administered intravenously for chronic lymphocytic leukemia.

Pyrimidine analogues

Fluorouracil(Ftoruracil; 5-fluorouracil) is converted into 5-fluorodeoxyuridine monophosphate in tumor cells, 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 is converted 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 tumor tissue under the influence of thymidine phosphorylase is converted into 5-fluorouracil, the activity of which in the tumor is 4 times higher than in healthy tissues. Prescribed orally for breast and colon cancer.

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

Antagonists of both biosynthesis and utilization of folic acid are known. About the history of the discovery of antibacterial sulfonamides - typical representatives antagonists of its biosynthesis, already mentioned in section. 2.1 and 6.3.1.

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

The enzyme mistakes streptocide for 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 is slightly ionized at physiological values pH. The primary amino groups of both substances are weakly basic (pKa 2.5 and 2.6, respectively) and are non-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 flat; in both, the primary amino group is in the para position relative to the electron-withdrawing group. Thus, the listed facts indicate a high degree of similarity between two molecules and, therefore, the possibility of manifestation biological activity analogue molecule. The indicated sizes of the substances under discussion change little during ionization.

para-Amiobenzoic acid (PAB)

After introducing streptocide (9.2) into clinical practice Attempts have been made to modify its molecule in order to create more active analogues. It was found that the most suitable for this purpose are those sulfonamides 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 sulfonamides, fully ionized at pH 7, and therefore most similar to PAB, 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. 100 times lower than streptocide. This is consistent with the greater ease of ionization of sulfazine (pKa = 6.5), 75% of which is converted into an anion at pH 7. In all of these N-substituted sulfonamides, the R radical associated with the nitrogen atom is moved out of the plane of the rest of the molecule and, therefore, it 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 from food. In the same time pathogenic bacteria cannot absorb exogenous dihydrofolic acid and are therefore vulnerable to the action of sulfonamides, which inhibit its synthesis.

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

Currently, antibacterial sulfonamides are usually used as uroantiseptics, for example, for diseases caused by E. coli and Proteus mirabilis. They are also prescribed for nocardiosis of the lungs or feet, eye trachoma, lymphogranuloma venereum, and herpetic dermatitis. Their importance for prevention is great streptococcal infections in patients predisposed to them, as well as to prevent relapses of rheumatic inflammation.

Antibacterial sulfonamides can be divided into two main classes: (a) quickly eliminated from the body and (b) circulating in the bloodstream for a long time. The most commonly used compounds of class (a): 1) sulfazine, M"-(pyrimidin-2-yl) sulfonamide (9.9), is in fact the standard compound with which all others are compared (its scope of application is expanded by its ability to penetrate into therapeutic concentrations in cerebrospinal fluid); 2) sulfafurazole (9.10)-N"-(3,4-dimethylisoxazol-5-yl)sulfanilamide drug wide range action, characterized by a higher concentration in 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 synergism with trimethoprim (section 9.6); 4) sulfacytin (9.12) and 5) sulfamethizole (9.13) are most preferred as uroantiseptics due to their short half-life in the bloodstream and the lack of specific accumulation.

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

yl) sulfanilamide; 2) sulfamethoxydiazine, N"-(5-methoxypyrimidin-2-yl) sulfanilamide; 3) sulfametopyrazine, N"-(3-Methoxypyrazin-2-yl) sulfanilamide (9.15); 4) sulfadimethoxine, 1M"-(3,6-dimethoxypyrimidin-4-yl) sulfonamide; 5) sulfadoxine, N"-(5,6-dimethoxypyrimidin-4-yl) sulfonamide - one of the least toxic sulfonamides, widely used together with a diaminopyrimidine to achieve sequential blocking (section 9.6). Besides, in special cases used: silver sulfazine (externally 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 sulfonamide drugs are discussed in Sect. 10.5.

There are many known analogues of PABs 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 drugs 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 into 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 influence of PAB. In addition, para-aminobenzolarsonic acid - atoxyl (6.2) has a typical sulfonamide effect. Although in general arsenic acids are not antibacterial drugs, atoxyl is an exception, since it is quite close to PAB both in 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 an N-group, only those that will easily disintegrate in the body and release the primary amino group can be introduced. It is obvious that azo groups or azomethine groups, unlike acylamino or alkylamino groups, are cleaved in this way, for example, in sulfahrizoidine (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 importance of the distance between the amino and electronegative group for the manifestation of antagonistic properties can be illustrated by the example of 4-amino-4"-sulfonamidodiphenyl (9.18), which does not possess these properties.

Mafenide (4-aminomethylbenzenesulfonamide) (9.19), according to structural formula resembling streptocide, is a highly basic substance with specific activity By
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 commonly used drugs containing sulfonamide groups are not classified as antibacterial agents, because during their creation 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).

Antagonists of both biosynthesis and utilization of folic acid are known. The history of the discovery of antibacterial sulfonamides, typical representatives of antagonists of its biosynthesis, has already been discussed in section. 2.1 and 6.3.1.

The enzyme mistakes streptocide for 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 poorly ionized at physiological pH values. The primary amino groups of both substances are weakly 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 flat; in both, the primary amino group is in the para position relative to the electron-withdrawing group. Thus, the listed facts indicate a high degree of similarity between the two molecules and, therefore, the possibility of the analogue molecule exhibiting biological activity. The indicated sizes of the substances under discussion change little during 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 the most suitable for this purpose are those sulfonamides in which the R radical in molecule (9.8) is a heterocyclic 7-ring. Bell and Roblin (1942) showed that this increases the degree of acid ionization and that sulfonamides, fully ionized at pH 7, and therefore most similar to PAB, 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. 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 anion at pH 7. In all of these N-substituted sulfonamides, the R radical associated with the nitrogen atom is moved out of the plane of the rest of the molecule and, therefore, it 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 from 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, for diseases caused by E. coli and Proteus mirabilis. They are also prescribed for nocardiosis of the lungs or feet, eye trachoma, lymphogranuloma venereum, and herpetic dermatitis. Their importance is great for the prevention of streptococcal infections in patients predisposed to them, as well as for the prevention of relapses of rheumatic inflammation.

Antibacterial sulfonamides can be divided into two main classes: (a) quickly eliminated from the body and (b) circulating in the bloodstream for a long time. The most commonly used compounds of class (a): 1) sulfazine, N"-(pyrimidin-2-yl) sulfonamide (9.9), is actually the standard compound with which all others are compared (the scope of its application is expanded by its ability to penetrate into therapeutic concentrations into the cerebrospinal fluid); 2) sulfafurazole (9.10)-N"-(3,4-dimethylisoxazol-5-yl) sulfanilamide drug with a broad spectrum of action, characterized by a higher concentration in 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 most preferred as uroantiseptics due to their short half-life in the bloodstream and the lack of specific accumulation ability.

Streptocide (anion) (R=H)

in formula (9.8):

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

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

Factors that determine the distribution of sulfonamide drugs are discussed in Sect. 10.5.

Mafenide (4-aminomethylbenzenesulfonamide) (9.19), whose structural formula resembles streptocide, is a highly basic substance with specific activity in

against 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 sulfonamide groups are not antibacterial agents, since during their creation 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, and acute lymphoblastic leukemia. In relatively low doses, methotrexate is used for rheumatoid arthritis as an anti-inflammatory and immunosuppressive agent.

Side effects of methotrexate:

– ulcerative stomatitis;

– gastritis;

– diarrhea;

– bone marrow suppression (leukopenia, thrombocytopenia);

– nephrotoxicity.

To reduce the side effects of methotrexate, it is prescribed calcium folinate(Calcium folinate; leucovorin calcium; citrovorum factor; folinic acid; Ν-5-formyltetrahydrofolate) is an antidote for folic acid antagonists, which in the presence of methotrexate can be converted into coenzymes without converting dihydrofolic acid into tetrahydrofolate. Since normal cells, unlike tumor cells, are able to concentrate folinic acid, the purpose 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, it is possible to increase the dose of methotrexate. Calcium folinate is used intramuscularly or intravenously.

Purine analogues

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

Fludarabine(Fludarabine) inhibits DNA polymerase and disrupts DNA synthesis. Inhibits RNA polymerase and disrupts protein synthesis. Administered intravenously for chronic lymphocytic leukemia.

Pyrimidine analogues

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

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 cancer lung, bladder cancer. .

Altretamine(Altretamin; hexalene) is a drug whose metabolites form covalent bonds with DNA. Prescribed orally for ovarian cancer.

Substances plant origin and their synthetic derivatives

Substances of plant origin include:

1) Vinca rosea alkaloids– vinblastine, vincristine, vinorelbine;

2) Podophyllum thyroid alkaloids– podophyllotoxin, etoposide, teniposide;

3) taxanes(obtained from the products of processing yew needles) – paclitaxel, docetaxel;

4) camptotheceps (alkaloid derivatives of Campotheca acuminata)– 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 functions of microtubules in tumor cells and thus prevent cell division.

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

Side effects: myelosuppression, paresthesia.

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

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

Side effects: peripheral neuropathies (impaired functions of microtubules in peripheral nerve fibers).

Alkaloids of podophyll thyroid

Podophyll thyroid alkaloids and their derivatives inhibit topisomerase-II (DNA gyrase) and thus interfere with DNA replication and mitosis.

Podophyllotoxin(Podophyllotoxin) is a podophyll alkaloid. Used for external genital warts. The drug solution 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 lung and bladder cancer; lymphogranulomatosis, acute leukemia.

Taxanes

Paclitaxel(Paclitaxel; taxol) is obtained from the bark of the Pacific yew tree (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, and Kaposi's sarcoma in patients with AIDS.

Side effect: neutropenia.

Docetaxel(Docetaxel; taxotere) is a semi-synthetic derivative of a compound obtained from the needles of the European yew. The structure and action are 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.

Camptothecines

Camptothecin is an alkaloid from the Campotheca acuminata tree; inhibitor of topisomerase-1 (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. Administered intravenously for cancer of the stomach, pancreas, colon and rectum.

Side effects of captothecins:

– bone marrow suppression;