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 […]

Asteraceae: Drug Interactions, Contraindications, And Precautions

Patient survey data from Canada, the U.S., and Australia show that one in five patients use prescription drugs concurrently with CAM. The inherent polypharmaceutical nature of complementary and alternative medicine increases the risk of adverse events if these complementary and alternative medicine either have pharmacological activity or interfere with drug metabolism. Since confirmed interactions are sporadic and based largely on case reports, advice to avoid certain drug-CAM combinations is based on known pharmacological and in vitro properties. Known Hypersensitivity to Asteraceae Cross-reactive sesquiterpene lactones are present in many, if not all, Asteraceae. Patients with known CAD from one plant may develop similar type IV reactions following contact with others. Affected patients are often advised to avoid contact with all Asteraceae, yet this advice is based on limited knowledge of cross-reactivity between relatively few members of this large family. Some authorities recommend avoiding Asteraceae-derived complementary and alternative medicine if, for example, the patient is known to have IgE-mediated inhalant allergy to ragweed. While a reasonable approach, this ignores a number of important facts: (1) 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 […]

Echinacea (E. angustifolia, E. purpurea, and E. pallida)

Echinacea: Medical Uses Echinacea is used for the common cold, infections, and low immune status. It is given with antibiotics and chemotherapy and acts as an anti-inflammatory. Historical Uses Native Americans and Eclectic physicians used echinacea as a natural anti-infective for colds and flu. Native Americans first introduced echinacea to the colonists. Growth There are nine species of echinacea. This perennial will grow in most herb gardens in the northeast. The beautiful flower of E. purpurea, commonly called “purple cone-flower,” may grow up to 6 feet tall. E. angustifolia has narrow leaves and is much shorter, at about 2 feet. It has pink flowers. E. pallida grows to about 3 feet and is much paler. All three species have been cultivated in the U.S. and Europe. E. angustifolia is listed as an at-risk endangered herb. Parts Used • Aerial (above-ground) parts • Whole plant and root Major Chemical Compounds • Alkylamides • Caffeic acid derivatives • Cichoric acid • Polysaccharides • Glycoproteins Not all active chemical compounds are found in each species of echinacea. Mechanism of Action Alkylamides, which cause a tingling sensation on the tongue, produce anti-inflammatory Read more […]

DIHYDROFOLATE REDUCTASE INHIBITORS

DIHYDROFOLATE REDUCTASE INHIBITORS have as a target the enzyme dihydrofolate reductase, and are known as folate antagonists. These include anticancer agents (‘antimetabolites’) such as methotrexate, antibacterial AGENTS such as trimethoprim, and the ANTIPROTOZOALS pyrimethamine and proguanil (which are used to treat malaria). Folate is required for synthesis of purine nucleotides, which in turn are essential for DNA synthesis and cell division. In mammals it is necessary to convert body folates, through two separate enzyme-catalysed reduction stages, to tetrahydrofolate (FH4). The first stage involves the enzyme dihydropteroate reductase, which catalyses the conversion of beta-aminobenzoic acid to folate (and this stage can be inhibited by sulphonamides). The second stage is conversion of folate to tetrahydrofolate by the enzyme dihydrofolate reductase. Methotrexate, trimethoprim, pyrimethamine and proguanil inhibit this latter conversion and lead to depletion of folic acid. Methotrexate is used as an oral anticancer agent, but resistance may develop in tumour cells, and there are a number of unwanted side-effects. It has a high affinity for the mammalian form of dihydrofolate reductase and cannot be used as an antibacterial Read more […]

Herb-Drug Interactions: Kudzu

Pueraria montana (Lour.) Merr. (Fabaceae) Synonym(s) and related species Ge Gen. Pueraria hirsuta (Thunb.) C. Schneider, Pueraria lobata (Willd.) Ohwi, Pueraria lobata (Willd.) Ohwi var. thomsonii (Benth.) Maesen, Pueraria thunbergiana (Sieb. & Zucc.) Benth., Dolichos lobatus Willd. Other species used include Pueraria mirifica Airy Shaw & Suvatabandhu (Thai kudzu, Kwao Kreu Kao) and Pueraria phaseoloides (Roxb.) Benth. (Puero, Tropical kudzu). Constituents The major isoflavone constituent of the root of Pueraria lobata is puerarin, which is the 8-C-glucoside of daidzein, but there are many others, such as puerarin hydroxy- and methoxy- derivatives and their glycosides, daidzein and its O-glycoside daidzin, biochanin A, genistein and formononetin derivatives. Pterocarpans are also present, including medicarpin glycinol and tuberosin. The flowers contain the phytoestrogens kakkalide and tectoridin. Pueraria mirifica root contains similar constituents to Pueraria lobata, the major difference being lower amounts of daidzein. Much of the research carried out on kudzu has been on the effects of isolated puerarin. Use and indications Kudzu contains isoflavones and is used as a phytoestrogen for Read more […]

Herb-Drug Interactions: Echinacea

Echinacea species (Asteraceae) Synonym(s) and related species Black sampson, Brauneria, Coneflower, Purple coneflower, Rudbeckia. Echinacea angustifolia (DC) Heller, Echinacea pallida (Nutt.) Britt, Echinacea purpurea (L.) Moensch. Other names that have been used include Brauneria pallida (Nutt.) Britton, Echinacea intermedia Lindl., Rudbeckia hispida Hoffm, Rudbeckia pallida Nutt. Rudbeckia purpurea L. and Rudbeckia serotina (Nutt) Sweet. Pharmacopoeias Echinacea angustifolia: Powder and Powdered extract (US Ph 32); Root (British Pharmacopoeia 2009). Echinacea pallida: Powder and Powdered extract (US Ph 32); Root (British Pharmacopoeia 2009). Echinacea purpurea: Aerial Parts (US Ph 32); Herb (British Ph 2009); Powder and Powdered extract (US Ph 32); Root (British Ph 2009, The United States Ph 32). Constituents The constituents of the various species are slightly different and this leads to confusion as to the potential for drug interactions. (a) Echinacea angustifolia The root contains alkamides, mainly 2-monoene isobutyl-amides, and similar caffeic acid esters and glycosides to Echinacea purpurea, including the major component, echinacoside, and cynarin. Alkylketones, and the saturated pyrrolizidine Read more […]