Antimetabolites Health Dictionary

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Antimetabolites: From 1 Different Sources

A group of drugs used in the treatment of certain forms of malignant disease. Chemically, they closely resemble substances (or METABOLITES) which are essential for the life and growth of CELLS. Antimetabolites are incorporated into new nuclear material in the cell or combine irreversibly with essential cellular enzymes, thus disrupting normal cellular division (see MITOSIS and MEIOSIS) and causing death of the cell. There is now a range of antimetabolites including CYTARABINE, METHOTREXATE, FLUOROURACIL and MERCAPTOPURINE.
Health Source: Medical Dictionary
Author: Health Dictionary

Chemotherapy

The prevention or treatment of disease by chemical substances. The term is generally used in two senses: the use of antibacterial and other drugs to treat infections; and the administration of ANTIMETABOLITES and other drugs to treat cancer. The discovery by Paul Ehrlich in 1910 of the action of Salvarsan in treating syphilis led to the introduction of sulphonamides in 1935, followed by PENICILLIN during World War II, which revolutionised the treatment of common infections. Many ANTIBACTERIAL DRUGS have been developed since then: these include CEPHALOSPORINS, cephamycins, TETRACYCLINES, AMINOGLYCOSIDES, MACROLIDES and CLINDAMYCIN as well as antituberculous drugs such as STREPTOMYCIN and METRONIDAZOLE. Unfortunately, overuse of chemotherapeutic drugs in medicine and in animal husbandry has stimulated widespread resistance among previously susceptible pathogenic microorganisms. Chemotherapy also plays an important role in treating tropical diseases, especially MALARIA, SLEEPING SICKNESS and LEPROSY.

Recently chemotherapy has become increasingly e?ective in the treatment of cancer. Numerous drugs, generally CYTOTOXIC, are available; great care is required in their selection and to minimise side-effects. Certain tumours are highly sensitive to chemotherapy

– especially testicular tumours, LEUKAEMIA, LYMPHOMA and various tumours occurring in childhood (e.g. Wilm’s tumour – see NEPHROBLASTOMA) – and may even be cured.... chemotherapy

Cytotoxic

Cytotoxic means destructive to living cells. Cytotoxic drugs possess anti-cancer properties but also have the potential to damage normal tissue. Their use is twofold: to eliminate a cancer and so prolong life; or to alleviate distressing symptoms, especially in patients whose prospects of a cure are poor. In many cases CHEMOTHERAPY with cytotoxic drugs is combined with surgery, RADIOTHERAPY or both. Chemotherapy may be used initially to reduce the size of the primary TUMOUR (a process called neoadjuvant therapy) before using radiotherapy or surgery to eliminate it. Cytotoxic drugs may also be used as adjuvant treatment to prevent or destroy secondary spread of the primary tumour that has either been removed by surgery or treated with radiotherapy. All chemotherapy causes side-effects: the ONCOLOGIST – a specialist in cancer treatment – has to strike a balance between hoped-for bene?ts and acceptable (for the patient) toxic effects, which include nausea and vomiting, BONE MARROW suppression, ALOPECIA (hair loss) and teratogenic effects (see TERATOGENESIS).

Cytotoxic drugs are used either singly or in combination, when an enhanced response is the aim. Chemotherapy of cancer is a complex process and should be supervised by an oncologist in co-operation with physicians, surgeons, radiotherapists and radiologists as appropriate.

The cytotoxic drugs include:

(1) The alkylating agents which act by damaging DNA, thus interfering with cell reproduction. Cyclophosphamide, ifosfamide, chlorambucil, kelphalan, busulphan, thiotepa and mustine are examples of alkylating agents.

(2) There are a number of cytotoxic antibiotics used in the treatment of cancer – doxorubicin, bleomycin, dactinomycin, mithramycin and amsacrine are examples. They are used primarily in the treatment of acute leukaemia and lymphomas.

(3) Antimetabolites – these drugs combine irreversibly with vital enzyme systems of the cell and hence prevent normal cell division. Methotrexate, cytarabine, ?uorouracil, mercaptopurine and azathioprine are examples.

(4) Another group of cytotoxic drugs are the vinca alkaloids such as vincristine, vinblastine and vindesima.

(5) Platinum compounds such as carboplatin, cisplatin and oxaliplatin are e?ective. All of them are given intravenously, but the latter two tend to have more unpleasant side-effects. Carboplatin and cisplatin are useful in the treatment of solid tumours. Carboplatin, a derivative of cisplatin, is given intravenously in ovarian cancer and in small-cell lung cancer. Better tolerated than cisplatin, the drug causes less nausea and vomiting, nephrotoxicity, neurotoxicity and ototoxicity. Where platinum-containing therapy has failed, intravenous treatment with paclitaxel may be tried. With only a limited success rate, it is relatively toxic and should be carefully supervised; responses, however, are sometimes prolonged.

Also of increasing importance in treating cancer are interferons. These are naturally occurring proteins with complex effects on immunity and cell function. Although toxic, with numerous adverse effects, they have shown some anti-tumour e?ect against certain lymphomas and solid tumours.... cytotoxic

Mercaptopurine

One of the antimetabolite group of drugs (see ANTIMETABOLITES), which includes methotrexate, ?uorouracil and thioguanine. These drugs are incorporated into new nuclear material in the cell or combine irreversibly with vital cellular enzymes, preventing normal cellular metabolism and division. Mercaptopurine is used mainly for the maintenance treatment of acute LEUKAEMIA, though it is increasingly proving valuable in the treatment of CROHN’S DISEASE. As with all CYTOTOXIC drugs, dosage must be carefully controlled; in particular it must be reduced if used concurrently with allopurinol. Side-effects include gastrointestinal upsets (including ulceration), and bone-marrow depression.... mercaptopurine

Antagonist

n. 1. a muscle whose action (contraction) opposes that of another muscle (called the agonist or prime mover). Antagonists relax to allow the agonists to effect movement. 2. a drug or other substance with opposite action to that of another drug or natural body chemical, which it inhibits. Examples are the *antimetabolites. —antagonism n.... antagonist

Antimetabolite

n. any one of a group of drugs that interfere with the normal metabolic processes within cells by combining with the enzymes responsible for them. Some drugs used in the treatment of cancer, e.g. *cytarabine *fluorouracil, *methotrexate, and *mercaptopurine, are antimetabolites that prevent cell growth by interfering with enzyme reactions essential for nucleic acid synthesis. For example, fluorouracil inhibits the enzyme thymidylate synthetase. Side-effects of antimetabolites can include blood cell disorders and digestive disturbances. See also chemotherapy; cytotoxic drug.... antimetabolite

Gemcitabine

n. a *cytotoxic drug that has an established role in the treatment of lung, pancreatic, bladder, and breast cancers. Side-effects are less severe than those of other *antimetabolites.... gemcitabine

Methotrexate

One of the ANTIMETABOLITES used to treat certain forms of malignant disease. Acting to inhibit the ENZYME dihydrofolate reductase, which is essential for purine and pyrimidine synthesis, it is given orally, intravenously, intramuscularly or intrathecally. Methotrexate is used as maintenance therapy for childhood acute lymphoblastic LEUKAEMIA, while other uses include CHORIOCARCINOMA, nonHodgkin’s LYMPHOMA, and various solid tumours. Intrathecally, it is used in the prophylaxis of childhood acute lymphoblastic leukaemia, and as treatment for established meningeal cancer or lymphoma.

Side-effects include suppression of myelocytes in bone marrow, in?ammation of mucous membranes, and, rarely, PNEUMONITIS. It should be avoided whenever signi?cant renal impairment is present, while signi?cant pleural e?usion or ascites is also a contraindication. Blood counts should be carefully monitored whenever intrathecal methotrexate is given. Oral or parenteral folinic acid helps to prevent, or to speed recovery from, myelosuppression or mucositis.

Methotrexate is used in dermatology, where it may be indicated for cases of severe uncontrolled PSORIASIS unresponsive to conventional therapy; it may also be indicated for severe active RHEUMATOID ARTHRITIS. Because of its potentially severe haematological, pulmonary, gastrointestinal, and other toxicities it should be used only by specialists and appropriate renal and liver function tests carried out before and during treatment. It should be avoided in pregnancy, and conception should be avoided for at least six months after stopping, as should breast feeding. Concurrent administration of aspirin or other NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) reduces methotrexate excretion, increasing its toxicity, and should therefore be avoided whenever possible.... methotrexate

Oncology

The management of MALIGNANT disease – a major health problem since successful management requires close liaison between the patient, surgeons, physicians, oncologists, haematologists, paediatricians and other specialists. Diagnosis may involve various investigations and often requires a BIOPSY. Once a diagnosis has been established, treatment may involve surgery, radiotherapy or chemotherapy (or various combinations as required) – see below, and main dictionary entries.

Surgery may be most common, and is often the only treatment, for some gastrointestinal tumours, soft-tissue tumours, gynaecological tumours and advanced cancers of the head and neck.

Radiotherapy uses ionising radiation to kill tumour cells. Radiation is by naturally occurring isotopes (see ISOTOPE) or arti?cially produced X-RAYS. Germ-cell tumours (see SEMINOMA; TERATOMA) and malignant lymphomas (see LYMPHOMA) appear to be particularly sensitive to irradiation, and many head and neck tumours, gynaecological cancers, and localised cancers of the PROSTATE GLAND and URINARY BLADDER are curable with radiotherapy. It is also a valuable means of reducing pain from bone metastases (see METASTASIS). Unpleasant side-effects are common: chie?y lethargy, loss of appetite and dry, itchy skin symptoms.

Chemotherapy is also an important treatment in germ-cell tumours (see above); in some forms of LEUKAEMIA and lymphoma; in ovarian cancer (following surgery – see OVARIES, DISEASES OF); and in small-cell lung cancer (although most patients die within 18 months – see LUNGS, DISEASES OF). It is also used in some breast cancers (see BREASTS, DISEASES OF); advanced myeloma (see MYELOMATOSIS); sarcomas (see under CANCER); and some childhood cancers (such as WILMS’ TUMOUR).

More than 20 substances are in common use, the major classes being ALKYLATING AGENTS (e.g. cyclophosphamide, chlorambucil, busul fan); ANTIMETABOLITES (e.g. methotrexate); VINCA ALKALOIDS (e.g. vincristine, vinblastine); and antitumour ANTIBIOTICS (e.g. actinomycin D). Choice of agent and the appropriate regimen requires expert guidance. Common side-effects include nausea and vomiting, bone-marrow suppression and ALOPECIA, with each substance having its own spectrum of unwanted effects.

Good doctor-patient communication, with the sharing of information and bringing the patient into the decision-making process, is vital even if time-consuming and exhausting.

Equally imortant treatment is PALLIATIVE, for example to ensure e?ective pain or nausea control. Common sources of pain in cancer may involve bone, nerve compression, soft tissue, visceral, myofascial, constipation, muscle spasm, low-back pain, joint pain (e.g. capsulitis) and chronic post-operative pain. Patients may be suffering from more than one pain, all of which should be identi?ed. The aim should be to eliminate pain.

There are three rungs of the analgesic ladder; if one rung fails, the next one should be tried:

(1) non-opioid drugs – for example, aspirin, PARACETAMOL, NON-STEROIDAL ANTIINFLAMMATORY DRUGS (NSAIDS); (2) weak opioids – for example, CODEINE, DIHYDROCODEINE, dextropropoxyphene; (3) strong opioids

– for example, MORPHINE, DIAMORPHINE, buprenorphine. Oral treatment is always preferable, unless prevented by severe vomiting. (See also CANCER; ONCOLOGIST; PAIN; PALLIATIVE CARE.)... oncology

Cytotoxic Drug

any drug that damages or destroys cells: usually refers to those drugs used to treat various types of cancer. There are various classes of cytotoxic drugs, including *alkylating agents (e.g. *chlorambucil, *cyclophosphamide, *melphalan), *antimetabolites (e.g. *fluorouracil, *methotrexate, *mercaptopurine), *anthracycline antibiotics (e.g. *doxorubicin, *daunorubicin, *dactinomycin), *vinca alkaloids, and platinum compounds (e.g. *carboplatin, *cisplatin). Other cytotoxic drugs include *taxanes and *topoisomerase inhibitors, and some *monoclonal antibodies (e.g. *bevacizumab, *trastuzumab) have cytotoxic activity. All these drugs offer successful treatment in some conditions and help reduce symptoms and prolong life in others. Cytotoxic drugs destroy cancer cells by interfering with cell division, but they also affect normal cells, particularly in bone marrow (causing *myelosuppression), hair follicles (causing hair loss), the stomach lining (resulting in severe nausea and vomiting), mouth (causing soreness), and fetal tissue (they should not be taken during the later stages of pregnancy). Dosage must therefore be carefully controlled. See also chemotherapy.... cytotoxic drug

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