Chemotherapy Flashcards
Isoniazid
Limited spectrum antibiotic. First-line drug for prevention/treatment of TB
Inhibits mycolic acid synthesis
D-cycloserine
Antibiotic: structural analogue of D-Ala, prevents D-Ala-D-Ala & therefore pentapeptide inhibiting cell wall cross-linking
Fosfomycin
Antibiotic: inhibits pyruvyl transferase (required to convert NAG to NAM)
Approved in USA to treat UTI
Penicillin, Amoxicillin
Beta-lactam antibiotics irreversibly covalently bind to transpeptidases inhibiting cell wall peptidoglycan cross-linking
Methicillin
Beta-lactamase resistant beta-lactam antibiotic
Vancomycin
Glycopeptide antibiotic binds D-Ala-D-Ala preventing transpeptidase activity & cell wall cross-linkage formation
Effective against C. difficile & IV against Gram +ve cocci
Tetracycline
Broad spectrum polyketide antibiotic: binds 16 rRNA of 30S subunit
Inhibits tRNA entry to A-site & thus protein synthesis
Destroys gut flora (secondary infection) & stains/impairs structure of bone/teeth
Bacteriostatic
Streptomycin
Narrow spectrum aminoglycoside antibiotic: binds 30S subunit & decrease fidelity of translation
Effective against aerobic Gram -ve rods eg Pseudomonas/Proteus (& some Gram +ve bacteria)
Exhibits nephro/ototoxicity (reduced in gentamycin)
Bactericidal
Erythromycin
Macrolide antibiotic: binds 50S subunit & blocks polypeptide exit tunnel
Similar spectrum to penicillin so suitable second-line drug for patients with penicillin allergy
Chloramphenicol
Very effective broad-spectrum antibiotic: binds 50S subunit & blocks peptidyl transferase activity
Uses limited by bone marrow suppression
Used in life-threatening infections (meningitis, typhus)
Fusidic acid
Narrow spectrum antibiotic: inhibits elongation factor G & thus movement of 30S subunit along mRNA
Used in staphylococcal infections (Gram +ve skin/eye infections)
Ciproflaxin
Synthetic, broad spectrum fluoroquinolone antibiotic: inhibits type II topoisomerases
Used in anthrax & Pseudomonas infections where oral therapy preferred (eg respiratory tract infections in cystic fibrosis)
Relatively expensive
Bacteriocidal
Rifampin
Antibiotic: binds beta-subunit of DNA-dependent RNA polymerase blocking initiation of RNA synthesis
Does not inhibit synthesis in progress
Used in TB
Can be bactericidal
Daunomycin
Planar polycyclic anthracycline antibiotic: intercalates in dsDNA and causes local unwinding
Also fragments DNA via ROS formation (gives cardiovascular toxicity)
Used as an anticancer agent
Mitomycin C
Aziridine-containing antibiotic: alkylates and cross-links (at guanines) DNA
Prevents strand separation in DNA replication & transcription
Sulfamethoxazole
Sulfa drug antibiotic: competitive inhibitor of dihydropteroate synthase in tetrafolate biosynthesis
Trimethoprim
Antibiotic: inhibits dihydrofolate reductase in tetrafolate biosynthesis
Co-trimoxazole
Combination drug of sulfamethoxazole & trimethoprim causing rapid bactericidal effects (either on own have slow bactericidal effects)
Use discontinued in UK because implicated in Stevens-Johnson syndrome (severe & potentially fatal allergic reaction)
Still used in AIDS patients with fungal Pneumocystis carinii infections
Valinomycin
Cyclic peptide ionophore antibiotic: binds K+ ion and causes membrane depolarisation by facilitating diffusion across membrane
Compromises homeostasis, growth & cell viability
Amphotericin B
Polyene antifungal: forms pores in membrane dependent on ergosterol
Used in most systemic mycoses
Some Leishmania species have ergosterol in their membranes so active against these (antiprotozoal)
Miconazole
Imidazole antifungal: inhibits ergosterol biosynthesis
Some Leishmania species have ergosterol in their membranes so active against these (antiprotozoal)
Fluconazole
Triazole antifungal: inhibits ergosterol biosynthesis
Used in athlete’s foot & vaginal candidiasis
Chloroquine
Antiprotozoal drug: active against Plasmodium in red blood cell
Inhibits haem polymerisation to haemozoin causing toxic build of haem & generation of ROS
Artemisinin
Antiprotozoal: rapidly acting antimalarial (Plasmodium) thought to act on production of ROS in RBC
Prodrug converted to dihydroartemisinin
Sulfadoxin
Sulfa drug antiprotozoal: inhibits dihydropteroate synthase in Plasmodium inhibiting tetrahydrofolate biosynthesis
Pyrimethamine
Antiprotozoal: inhibits dihydrofolate reductase in Plasmodium inhibiting tetrahydrofolate biosynthesis
Fansidar
Antiprotozoal: combination of sulfadoxin & pyrimethamine especially effective against P. falciparum when chloroquine resistance is suspected
Melarsoprol
Antiprotozoal arsenic compound: prodrug converted to melarsen oxide active against Trypanosomes
Inhibits glycolytic & TCA enzymes inhibiting ATP synthesis
Actively accumulates in Trypanosomes
Suramin
Antiprotozoal: first useful agent against Trypanosomes which doesn’t contain a toxic metal ion
Only effective in early stage of infection
May act on glycolytic enzymes (mechanism unknown)
Zanamivir
Antiviral drug: active against influenza inhibits NA
Oseltamivir
Antiviral drug: active against influenza inhibits NA
Pro-drug broken down by esterases in plasma
Amantidine
Antiviral drug: active against influenza blocks M2 channel (proton channel) involved in the uncoating of the nucleocapsid (requires acidification of virion interior)
Aciclovir
Antiviral drug: active against Herpes simplex & zoster
Purine analogue phosphorylated by viral thymidine kinases then acts as chain terminator and inhibits viral DNA polymerase (30x more potent than host DNA pol)
Niverapine
Antiviral drug: non-nucleoside inhibitor of reverse transcriptase in HIV
AZT
Antiviral drug: nucleoside inhibitor (thymidine analogue) of reverse transcriptase in HIV
Saquinavir
Antiviral drug: HIV protease inhibitor preventing viral replication & release of virions from infected cells
Cyclophosphamide
Nitrogen mustard anticancer drug: alkylates DNA causing crosslinks within or between strands
Prodrug: activated in liver
Mainly used in lymphomas
Lomustine
Nitrosourea anticancer drug: alkylates DNA causing crosslinks with other DNA strands or proteins
Commonly used in lymphoma (especially cutaneous), melanoma & tumours of kidney/lung
Can cross BBB so can be used in cancers in the brain
Use limited due to decreases in WBC/platelets & damage to multiple organs
Cisplatin
Platinum-based anticancer drug: crosslinks DNA and revolutionised treatment of testicular cancer
Bone marrow suppression and renal toxicity limit use
Mitoxantrone
Anthracycline anticancer drug: intercalates within DNA
Used in metastatic breast cancer, acute myeloid leukaemia & non-Hodgkin’s lymphoma
Methotrexate
Antimetabolite anticancer drug: inhibits dihydrofolate reductase preventing tetrahydrofolate synthesis (& thus purine synthesis)
Leucovorin
Adjuvant used in methotrexate chemotherapy used to salvage normal cells from folate depletion
Etoposide
Anticancer drug: type II topoisomerase inhibitor
Used to treat lung & testicular cancer, lymphoma
Topotecan
Anticancer drug: type I topoisomerase inhibitor
Used to treat lung & ovarian cancer
Vinblastine
Vinca alkaloid anticancer drug: antimitotic which binds tubulin dimers causing disassembly of microtubule
Used in Hodgkin’s lymphoma
Taxol
Taxane anticancer drug: antimitotic which binds microtubules and stabilises them
Used in advanced forms of Kaposi’s sarcoma
Tamoxifen
Anticancer drug: oestrogen receptor antagonist used in breast cancer
Anastrozole
Anticancer drug: aromatase inhibitor causing a reduction in oestrogen synthesis
Goseraline
Anticancer drug: analogue of GnRH which is an agonist at its receptor. Sustained agonism shuts down testosterone production
Used in prostatic cancer
Prednisone
Glucocorticoid prodrug converted into prednisolone in the liver
Used in the treatment of acute lymphoblastic leukaemia
Cetuximab
Monoclonal antibody against the epidermal growth factor receptor
Used in colorectal cancer
Erlotinib
Small molecule inhibitor of EGFR (RTK)
Used in lung cancer
Imatinib
Receptor tyrosine kinase inhibitor
Inhibits Bcr-Abl so used in chronic myeloid leukaemia
Clavulanate
Augmentin: inhibits beta-lactamases by forming slowly hydrolysing acyl-enzyme intermediate
Used to recapture use of beta-lactams in resistant strains
Cephalosporin
Beta-lactam antibiotic
