Specific Medicinal Uses of Cannabis: Use as an Antiemetic

Many agents used in cancer chemotherapy produce severe nausea and vomiting in most patients. Symptoms can last for hours or days and have a major impact on patient nutrition and electrolyte status, body weight and physical and mental resilience to both the disease and its treatment. The current choice of available anti-emetics is limited and most are only partially effective, which may lead patients to refuse therapy all together, or for clinicians to use chemotherapeutic regimens which are less than optimum. For these reasons, the search for more effective antiemetics continues. Cannabis In the late 1960s and early 1970s, patients receiving various cancer chemotherapy regimes (including mustine, vincristine, prednisone and procarbazine) noted that smoking cannabis from illicit sources, before and during chemotherapy, reduced the incidence of nausea and vomiting to a variable degree. Only since the isolation of THC have formal clinical trials on the safety and efficacy of cannabis derivatives been conducted. As far as crude cannabis is concerned, we have only anecdotal evidence that inhaling its smoke is effective in a variable percentage of patients who vomit, despite supposedly adequate doses of standard antiemetics. There Read more […]

Taxol (Paclitaxel) and Cancer Chemotherapy

Taxol is an antineoplastic agent. This compound, first isolated from the bark of the Western yew tree in 1971, exhibits unique pharmacological actions as an inhibitor of mitosis, differing from the vinca alkaloids and colchicine derivatives in that it promotes rather than inhibits microtubule formation. Following its introduction into clinical trial, the drug was approved for treatment of cisplatin-refractory ovarian cancer in 1992 and has promising activity against cancers of the breast, lung, esophagus, and head and neck. Malignant neoplastic diseases may be treated by various approaches: surgery, radiation therapy, immunotherapy, or chemotherapy, or a combination of these. The extent of a malignant disease (staging) should be ascertained in order to plan an effective therapeutic intervention. Plants have antineoplastic activities. A significant portion of the product derived from plants serve either as protective agents against various pathogens (e.g., insects, fungi, or bacteria) or growth regulatory molecules (e.g., hormonelike substances that stimulate or inhibit cell division and morphogenesis). Chemical Groups Of Natural Products With Anticancer Properties Cancer Chemotherapy Before discussing the specific Read more […]

Alkylating Agents

The alkylating agents exert their antineoplastic actions by generating highly reactive carbonium ion intermediates that form a covalent linkage with various nucleophilic components on both proteins and DNA. The 7 position of the purine base guanine is particularly susceptible to alkylation, resulting in miscoding, depurination, or ring cleavage. Bifunctional alkylating agents are able to cross-link either two nucleic acid molecules or one protein and one nucleic acid molecule. Although these agents are very active from a therapeutic perspective, they are also notorious for their tendency to cause carcinogenesis and mutagenesis. Alkylating agents that have a nonspecific effect on the cell-cycle phase are the most cytotoxic to rapidly proliferating tissues. Nitrogen Mustards The activity of nitrogen mustards depends on the presence of a bis-(2-chloroethyl) grouping: CH2—CH2C1 | N | CH2—CH2C1 This is present in mechlorethamine (Mustargen), which is used in patients with Hodgkin’s disease and other lymphomas, usually in combination with other drugs, such as in MOPP therapy (mechlorethamine, Oncovin [vincristine], procarbazine, andprednisone). It may cause bone marrow depression. Chlorambucil Chlorambucil Read more […]

Antimetabolites

Antimetabolites are structural analogues of naturally occurring compounds and function as fraudulent substances for vital biochemical reactions. Folic Acid Analogues Methotrexate (Amethopterin) is a folic acid antagonist that binds to dihydrofolate reductase, thus interfering with the synthesis of the active cofactor tetrahydrofolic acid, which is necessary for the synthesis of thymidylate, purine nucleotides, and the amino acids serine and methionine. Methotrexate is used for the following types of cancer: • Acute lymphoid leukemia: During the initial phase, vincristine and prednisone are used. Methotrexate and mercaptopurine are used for maintenance therapy. In addition, methotrexate is given intrathecally, with or without radiotherapy, to prevent meningeal leukemia. • Diffuse histiocytic lymphoma: Cyclophosphamide, vincristine, methotrexate, and cytarabine (COMA). • Mycosis fungoides: Methotrexate. • Squamous cell, large-cell anaplastic, and adenocarcinoma: Doxorubicin and cyclophosphamide, or methotrexate. • Head and neck squamous cell: Qi-platinum and bleomycin, or methotrexate. • Choriocarcinoma: Methotrexate. Tumor cells acquire resistance to methotrexate as the result of several Read more […]

Taxol and Cancer Chemotherapy: Natural Products

Vinca Alkaloids The vinca alkaloids (vinblastine, vincristine, and vindesine), which bind to tubulin, block mitosis with metaphase arrest. Vinca alkaloids are used for the following types of cancer: • Acute lymphoid leukemia: In the induction phase, vincristine is used with prednisone. • Acute myelomonocytic or monocytic leukemia: Cytarabine, vineristine, and prednisone. • Hodgkin’s disease: Mechlorethamine, Oncovin (vincristine), procarbazine, and prednisone (MOPP). • Nodular lymphoma: Cyclophosphamide, Oncovin (vincristine), and prednisone (CVP). • Diffuse histiocytic lymphoma: Cyclophosphamide, Adriamycin (doxorubicin), vincristine, and prednisone (CHOP); bleomycin, Adriamycin (doxorubicin), cyclophosphamide, Oncovin (vincristine), and prednisone (BACOP); or cyclophosphamide, Oncovin (vincristine), methotrexate, and cytarabine (COMA). • Wilms’ tumor: Dactinomycin and vincristine. • Ewing’s sarcoma: Cyclophosphamide, dactinomycin, or vincristine. • Embryonal rhabdomyosarcoma: Cyclophosphamide, dactinomycin, or vincristine. • Bronchogenic carcinoma: Doxorubicin, cyclophosphamide, and vincristine. The chief toxicity associated with vinblastine use is bone marrow depression. Read more […]

GLUCOCORTICOIDS

GLUCOCORTICOIDS are members of the corticosteroid family, with actions similar to the steroid hormones secreted by the adrenal cortex. There are two main types of corticosteroids: glucocorticoids and MINERALOCORTICOIDS. Glucocorticoids that are important physiologically include hydrocortisone (cortisol), corticosterone and cortisone. These are essential for utilization of carbohydrate, fat and protein in the body, and in the normal response to stress. Naturally occurring and synthetic glucocorticoids have a powerful antiinflammatory effect. In contrast, the mineralocorticoids (e.g. aldosterone) are necessary for the regulation of the salt and water balance of the body. Corticosteroids can be used in hormone replacement therapy. For instance, the glucocorticoid hydrocortisone and the mineralocorticoid fludrocortisone can be given to patients for replacement therapy where there is a deficiency, or in Addison’s disease, or following adrenalectomy or hypopituitarism. The glucocorticoids are potent antiinflammatory and antiallergic agents, frequently used to treat inflammatory and/or allergic reactions of the skin, airways and elsewhere. Absorption of a high dose of corticosteroid over a period of time may also cause undesirable Read more […]

Cervical Dysplasia: Discussion Of Botanicals

Blood Root The blood-red color of the sap from the roots of blood root led to its traditional use as a blood purifier. It was used as an emmenagogue, in the treatment of respiratory conditions, as a strong emetic, and for the treatment of fungal infections and ulcers. By the eighteenth century, blood root was used topically to treat indolent chancres and tumors as an ingredient in the popular “black salve,” an escharotic treatment that was used topically for the treatment of tumors. Extracts of sanguinarine, an alkaloid from the herb, have been shown to possess anti-inflammatory, antimicrobial, antioxidant, antiviral, antiproliferative, and apoptotic activities, and are under active research for the treatment of cancer. Sanguinarine, an alkaloid compound fund in blood root, is a potent inhibitor of NF-kappa B activation.’ Sanguinarine is an ingredient in dental hygiene products, for example, toothpaste, used for its antiplaque activity and in the treatment of gingivitis. There is controversy over the safety of its use in dental products, with contradictory research over whether it may cause malignant cell change and lead to the development of leukoplakia. Most studies have concluded that the extract is safe for dental Read more […]

Herb-Drug Interactions: St John’s wort

Hypericum perforatum L. (Clusiaceae) Synonym(s) and related species Hypericum, Millepertuis. Hypericum noeanum Boiss., Hypericum veronense Schrank. Pharmacopoeias St John’s Wort (British Ph 2009, European Ph 2008, US Ph 32); St John’s Wort Dry Extract, Quantified (British Ph 2009, European Ph, 6th ed., 2008 and Supplements 6.1, 6.2, 6.3 and 6.4). Constituents The main groups of active constituents of St John’s wort are thought to be the anthraquinones, including hypericin, isohypericin, pseudohypericin, protohypericin, protopseudohypericin and cyclopseudohypericin, and the prenylated phloroglucinols, including hyperforin and adhyperforin. Flavonoids, which include kaempferol, quercetin, luteolin, hyperoside, isoquercitrin, quercitrin and rutin; biflavonoids, which include biapigenin and amentoflavone, and catechins are also present. Other polyphenolic constituents include caffeic and chlorogenic acids, and a volatile oil containing methyl-2-octane. Most St John’s wort products are standardised at least for their hypericin content (British Pharmacopoeia 2009), even though hyperforin is known to be a more relevant therapeutic constituent, and some preparations are now standardised for both (The United Read more […]

ANTICANCER AGENTS

ANTICANCER AGENTS are commonly referred to as antineoplastic agents, however, by strict definition, antineoplastic agents are used to treat a neoplasm’ (meaning a ‘new growth’). Neoplasms that have only the characteristic of localized growth are classified as benign. Neoplasms with the additional characteristic of invasiveness, and/or the capacity to metastasise, are classified as malignant. The term cancer’ is usually applied only to the latter group. Similarly, the word tumour (meaning literally ‘a local swelling’) tends to be used in association with cancer, and antineoplastic agent’ is commonly interchangeable with ‘anticancer’. There are a number of approaches to the chemotherapy of cancer, and most can be regarded as complementary or additional to radiotherapy and surgery. Direct approaches to cancer mostly use cytotoxic agents: these work by interfering with cell replication or production, so preventing the growth of new cancerous tissue. Inevitably, this means that normal cell production is also affected, causing serious side-effects. There are many cytotoxic agents with diverse modes of action, but these can be divided into groups on the basis of their mechanisms of action. Alkylating agents and related Read more […]