Chemotherapy Flashcards
D-cycloserine
Structural analogue of D-Ala; prevents the synthesis of
pentapeptide by inhibiting L-Ala racemase, D-Ala-D-Ala synthetase and D-Ala-DAla/muramyl tripeptide ligase
Fosfomycin
Inhibits pyruvyl transferase required for the conversion of NAG into NAM. Was recently approved in the USA for treatment of urinary tract infections
Bacitracin
Cyclic polypeptide antibiotic; forms a tight complex with Mg2+ and bactoprenol pyrophosphate; inhibits the dephosphorylation to bactoprenol phosphate (lipid carrier for NAM-NAG unit). It is active against Gram-positive bacteria
Penicillin, Ampicillin, Amoxicillin, and Methicillin
ß-lactam antibiotics; inhibit peptidoglycan-crosslinking transpeptidase enzymes by covalent and irreversible binding as a pseudosubstrate. The combination of the ß-lactam amoxicilin and the ß-lactamase inhibitor clavulanate is used as augmentin
Vancomycin
Glycopeptide antibiotic; binds
to D-Ala-D-Ala termini of the pentapeptide in peptidoglycan, thereby preventing its cross-linking to a neighbouring pentapeptide in another peptidoglycan strand. Vancomycin is effective against Clostridium difficile, and is used intravenously against Gram-positive cocci, such as Enterococcus and Staphylococcus
Isoniazid
Isoniazid is a first-line medication used in the prevention and treatment of tuberculosis. It inhibits the biosynthesis of mycolic acids in the cell envelope of Mycobacterium tuberculosis
Chloramphenicol
Blocks aminoacyl tRNA binding to 50S subunit of ribosome. Very effective broad-spectrum antibiotic but use is restricted because of bone marrow suppression in some cases. Drug is indicated in life-threatening infections such as meningitis.
Tetracycline
Polyketide antibiotic; binds to 16 rRNA in 30S subunit of ribosome and inhibits the movement of aminoacyl-tRNA into the A site. Tetracyclines are effective against a wide range of bacteria, and are first-line drugs against 72 mycoplasma and cholera. Drug toxicity is associated with binding of calcium in bones and teeth.
Erythromycin
14-membered macrolide antibiotic; binds to 23S rRNA in 50S subunit, and blocks the polypeptide exit tunnel. Drug has a similar antibacterial spectrum as penicillin, and is a suitable second-line drug for patients allergic to penicillin.
Fusidic acid
Inhibits elongation factor G, and hence, the movement of the 30S subunit by one codon along the mRNA. Drug has narrow spectrum, and is used against staphylococcal infections
Streptomycin and gentamycin
Aminoglycoside antibiotics; target 30S subunit of ribosome and decrease fidelity of mRNA translation. Streptomycin exhibits nephrotoxicity and ototoxicity. These effects are reduced for gentamycin. Used against Gram-negative rods including Pseudomonas and Proteus. Most streptococci
(Gram-positive) are resistant because gentamycin cannot penetrate the cell. However, penicillin and gentamycin have a synergistic effect against some streptococci.
Ciprofloxacin
Fluoroquinolone antibiotic; inhibits type II DNA topoisomerases (DNA gyrase and topo IV), and hence, inhibits changes in supercoiling required for replication and gene expression. Ciprofloxacin is an FDAapproved drug for killing Bacillus anthracis in anthrax infections. It is particularly useful for Pseudomonas infections where oral therapy is preferred, such as respiratory tract infections in patients with cystic fibrosis.
Rifampin
Binds to β subunit of the DNA-dependent RNA polymerase, and inhibits initiation of RNA synthesis. Is often used to treat infections by Mycobacterium
Daunomycin
Planar polycyclic anthracycline antibiotic; intercalates in dsDNA and causes local unwinding. Used as anticancer agent.
Bleomycin
Metal-chelating glycopeptide antibiotic; generates superoxide and hydroxyl radicals, causing single- and double-strand breaks in DNA.
Mitomycin C
Aziridine-containing antibiotic; alkylates and cross-links DNA, thereby preventing strand separation during DNA replication and transcription. Antibiotics that act as antimetabolites
Sulfamethoxazole
Sulfa drug; p-aminobenzoate analogue that competitively inhibits dihydropteroate synthase in the biosynthesis of tetrahydrofolate (methyl carrier required for synthesis of dTMP).
Trimethoprim
Dihydrofolate reductase in the biosynthesis of tetrahydrofolate
Co-trimoxazole
Combination of sulfamethoxazole and trimethoprim. Cotrimoxazole has been withdrawn as a routine anti-bacterial agent in this country, as result of its being implicated in cases of Stevens-Johnson syndrome – a severe and sometimes fatal allergic reaction. Co-trimoxazole is used in AIDS patients with fungal Pneumocystis carinii infections.
Valinomycin
Cyclic peptide antibiotic that binds K+, and facilitates K+ diffusion across the membrane.
Gramicidin A
Linear polypeptide antibiotic; forms a homodimeric complex that acts as an ion channel in the membrane.
Polymixin
Cationic detergent antibiotic containing cyclic peptide and hydrophobic tail; binds to membrane and alters its ion permeability.
Amphotericin B
Polyene antifungal and antiparasitic drug; forms pores in the membrane by an ergosterol-dependent mechanism. Is currently the drug of choice for most systemic mycoses: active against Cryptococcus, Candida, and Aspergillus.
Fluconazole
Triazole antifungal drug. Fluconazole is often used in the treatment of athlete’s foot and vaginal candidiasis. Inhibits ergosterol synthesis
Miconazole
Imidazole antifungal and antiprotozoal drug. Inhibit ergosterol biosynthesis. antiprotozoal drugs
Melarsen
Arsenic compound; selectively accumulated in Trypanosoma species, inhibits energy metabolism. Used for treatment of human sleeping sickness and other diseases caused by trypanosomes.
Suramin
Introduced in 1920 as a development of Ehrlich’s Trypan Red, and today still remains the drug of choice for human trypanosomiasis. Does not contain toxic metal, hence, its therapeutic index is much higher than that of melarsen. Molecular mechanism still unknown; might act on glycolytic enzymes.
Chloroquine and Mefloquine
Antimalarial 4-aminoquinoline drug; inhibits heme polymerisation in food vacuole of Plasmodium.
Artemisinin
Prodrug of the biologically active metabolite dihydroartemisinin, which is active during the stage when the parasite is located inside red blood cells. Mode of action might be based on the production of oxygen radicals.
Sulfadoxin
Sulfa drug that inhibits dihydropteroate synthase in Plasmodium. Analogue of the antibiotic sulfamethoxazole.
Pyrimethamine
Inhibits dihydrofolate reductase in Plasmodium. Analogue of the antibiotic trimethoprim.
Fansidar
Combination of sulfadoxin and pyrimethamine; analogous to antibacterial co-trimoxazole. Used in the treatment of patients with P.falciparum malaria when chloroquine resistance is suspected and oral treatment is appropriate.
Amantadine
Blocks the function of M2 ion channel protein involved in nucleocapsid uncoating of influenza virus. Is used predominantly in prophylaxis and treatment of infections by Influenza A virus. Not effective against Influenza B virus.
Oseltamivir and Zanamivir
Inhibit neuraminidase (sialidase), a glycoprotein enzyme that plays an essential role in the release of the virion progeny from infected cells, and that assists in the movement of the virus particles through the upper respiratory tract
Aciclovir
Purine analogue; upon activation by viral thymidine kinase, phosphorylated compound inhibits viral DNA polymerase. Is present in Zovirax creams against herpes simplex infections of the skin and mucous membranes.
Ganciclovir
Purine analogue; upon activation by viral thymidine kinase, phosphorylated compound inhibits viral DNA polymerase. Selective against cytomegalovirus.
Cidofovir
Nucleoside phosphonate analogue of cytosine that inhibits DNA polymerase of cytomegalovirus.
Foscarnet
Organic analogue of pyrophosphate that inhibits DNA polymerase of cytomegalovirus and herpes virus.
Nevirapine
Anti-HIV drug; non-nucleoside reverse transcriptase inhibitor
Zidovudine (Azidothymidine, AZT)
Nucleoside reverse transcriptase inhibitor; thymidine analogue.
Saquinivir
Inhibitor of HIV protease; this protease is vital for both viral replication within the cell and release of mature viral particles from an infected cell. The combination of nevirapine, zidovudine and saquinavir is used in HAART therapy (p. 68) during serious manifestations of HIV infections in patients with AIDS.
Interferon
Immunoregulatory cytokine that is synthesised in response to viral infection. Interferons are used as antiviral agents against hepatitis B and C, and AIDS related Kaposi sarcomas.
Melphalan
Belongs to the class of nitrogen mustard alkylating agents, and is used to treat chronic myeloid leukaemia. It is occasionally used against melanoma. Melphalan is a phenylalanine derivative of mechlorethamine.
Cyclophosphamide
Nitrogen mustard alkylating agent, but is a “prodrug”; it is converted in the liver to active forms that have chemotherapeutic activity. The main use of cyclophosphamide is in the treatment of lymphomas, some forms of leukemia and some solid tumours.
Lomustine
Member of the nitrosurea class of agents, which acts by crosslinking DNA to other DNA strands or to protein in such a way that dsDNA cannot be replicated. Lomustine is most commonly used against lymphoma (particularly cutaneous (skin) lymphoma) and melanoma, and tumours in kidney and lung. Lomustine has the special ability to penetrate the blood/brain barrier, and can be used to treat cancers in the brain.
Cisplatin
Platinum-based drug to treat various types of cancers, including sarcomas, some carcinomas (e.g. small cell lung cancer, and ovarian cancer), lymphomas and germ cell tumours.
Doxorubicin
Anthracycline antibiotic that intercalates in DNA. it is structurally closely related to daunomycin. The drug is often administered by local injection.
Daunomycin
Anthracycline antibiotic that intercalates in DNA in a non-covalent manner.
Mitoxantrone
Anthracycline agent used in the treatment of certain types of cancer, mostly metastatic breast cancer, acute myeloid leukemia, and non-Hodgkin’s lymphoma.
Methotrexate
Antimetabolite and antifolate drug. It acts by inhibiting the metabolism of folic acid. Methotrexate replaced the more powerful and toxic antifolate aminopterin
Leucovorin
Adjuvant used in cancer chemotherapy involving the drug methotrexate. It is also used in synergistic combination with the chemotherapy agent 5-fluorouracil
5-Fluorouracil
Belongs to the family of antimetabolites, and is a pyrimidine analogue. It is typically administered with leucovorin. Some of its principal use is in colorectal cancer and pancreatic cancer, in which it has been the established form of chemotherapy for decades (platinum-containing drugs are a recent addition).
Etoposide
Inhibitor of the enzyme topoisomerase II. It is used in the treatment of lung cancer, testicular cancer, lymphoma and non-lymphocyte leukaemia.
Topotecan
Topoisomerase I inhibitor. Is used to treat ovarian cancer and lung cancer.
Vinblastine
Vinca alkaloid and an anti-mitotic drug used to treat Hodgkin’slymphoma, non-small cell lung cancer, breast cancer and testicular cancer.
Taxol
Belongs to the drug category of the taxanes, and is a mitotic inhibitor used to treat patients with lung, ovarian, breast cancer, head and neck cancer, and advanced forms of Kaposi’s sarcoma.
Tamoxifen
Orally-active oestrogen receptor antagonist which is used in the treatment of breast cancer and is currently the world’s largest selling drug for that purpose.
Toremifene
Tamoxifen analogue without estrogen agonist properties.
Goseraline
Decapeptide analogue of gonadotropin-releasing hormone that disrupts endogenous hormonal feedback systems, resulting in the down-regulation of testosterone and estrogen production.
Flutamide
Oral anti-androgen drug primarily used to treat prostate cancer. It competes with testosterone and its powerful metabolite, dihydrotestosterone (DHT) for binding to androgen receptors in the prostate gland. By doing so, it prevents their stimulation of growth of prostate cancer cells.
Prednisone
Synthetic corticosteroid prodrug that is converted by the liver into prednisolone, which is the active agent that inhibits growth of lymphocytes in leukemias.
Rituximab
Anti-CD20 monoclonal antibody.
Trastuzumab
Anti-HER2 monoclonal antibody.
Bevacizumab
Anti-VEGF monoclonal antibody.
Cetuximab
Anti-EGFR monoclonal antibody.
Erlotinib
Small molecule ligand that inhibits EGFR tyrosine kinase.
Imatinib
2-phenylaminopyrimidine derivative that functions as a specific inhibitor of a number of tyrosine kinase enzymes. Is used in treating chronic myeloid leukemia, and gastrointestinal stromal tumours, and is currently marketed as Gleevec(USA) or Glivec (Europe/Australia).
