Aciclovir
Antiviral Purine analogue (guanine)
Prodrug - only monophosphorylated by
viral thymidine kinase in infected cells
Cellular enzymes convert to acyclovir-TP
Preferentially interacts with viral DNA
polymerase (30 x)
Competitive substrate, and is incorporated in viral DNA, causing termination of DNA replication (no 3’OH)
Resistance in Herpes virus due to change in specificity of viral thymidine kinase
Amantadine
Antiviral for Influenza A
Early - Acts on M2 proton channel involved in nucleocaspid uncoating
High affinity binding site at low pH where it blocks proton conduction
Late - interfere with hemagglutinin processing
Acidification of interior of virion is required for hemagglutinin-mediated membrane fusion and release into cytosol
Amoxicillin
B-lactam Antibiotic
Blocks cell wall peptidoglycan-crosslinking transpeptidase by covalent and irreversible binding as a pseudo-substrate
Forms a slowly hydrolysing covalent acyl enzyme intermediate
Amphotericin B
Polyene antibiotic - antifungal and antiparasitic
Low degree of selective toxicity and low therapeutic index, little selectivity and quite toxic
Target ergosterol in fungal (and leishmania protozoa) cell membranes, forming pores
Artemisinin
Antimalarial
Prodrug of dihydroartemisinin
Generates highly reactive organic free radicals
Short but rapid action
Also prevent development of oocyst in mosquito
Bacitracin
Cyclic peptide antibiotic
Forms a very tight complex with Mg2+ and bactoprenol pyrophosphate, inhibits dephosphorylation to bactoprenol phosphate so inhibits regeneration of the lipid carrier (for NAM-NAG unit), and hence, the biosynthesis of PG
It is active against Gram-positive bacteria.
Bevacizumab
A humanised monoclonal antibody that binds and inhibits the human VEGF
Anti-angiogenic - can interfere with wound healing
anti-VEGF
Cephalosporin
B-lactam antibiotic with B-lactam and thiazolidine ring
B-lactamases result in hydrolytic ring opening and deactivation
Rotating use of antibiotics improves efficacy and reduces emergence of resistance
Chloramphenicol
Bacteriostatic broad spectrum antibiotic
Interfere with protein biosynthesis
Target 50S ribosomal subunit
Blocks amino-acyl tRNA interaction with A site of peptidyl transferase centre
Resistance by inactivating acetyltransferases
Can cause bone marrow suppression
Chloroquine
Antimalarial
Accumulates inside food vacuole
(Plasmodium use hemaglobin as N source. Toxic heme polymerised to non-toxic hemozoin in food vacuole. )
Inhibit heme polymerization reaction in plasmodium
Drug resistance by exclusion of drug from site of action
Efflux by CRT (chloroquine resistance transporter)
Ciprofloxacin
Synthetic fluoroquinolone antibiotic
Activity against gram +ve and -ve bacteria
inhibits type II DNA topoisomerases (DNA gyrase and topo IV)
Inhibits changes in supercoiling in replication and gene expression
Used against Bacillus anthracis in anthrax and Pseudomonas infections - oral therapy preferred
Cisplatin
Anti-cancer
Platinum compound that binds directly to DNA to prevent replication and expression
Only active in cis form
Cross-linking agent in DNA
React at N7 of guanine and adenine
Intrastrand cross-link of 2 neighbouring guanines pGpG
Major bending of duplex to major groove
Inhibit DNA polymerase and DNA replication
Resistance - cells have higher levels of DNA repair enzymes
Used IV
Renal toxicity and bone marrow suppression
Clavulanate
Suicide substrate for lactamase
Forms a slowly hydrolysing acyl enzyme intermediate
Augmentin
Amoxicillin + Clavulanate
B-lactam antibiotic + B-lactamase inhibitor
Co-trimoxazole
Antibiotic acting as anti-metabolite
Trimethoprim + sulfamethoxazole
Both block a step in biosynthesis of folic acid
Work together synergistically
Cyclophosphamide
Anti-cancer
Nitrogen mustard - covalently link alkyl group to chemical moieties in nucleic acids and proteins
Broad application in cancer chemotherapy
Absorbed well orally and do not accumulate in a particular tissue
Metabolised by cytochrome P450 in liver to active phosphoramide mustard
Doxorubicin
Anti-cancer
Anthracycline, bind non-covalently to DNA
Prevent replication and expression
Generate free radicals due to hydroxyquinone moiety –> DNA cleavage and lipid peroxidation
Inhibitor of type 2 topoisomerase
Antibiotic - intercalates into DNA (local injection)
Erlotinib
Orally active
Small molecule ligand that inhibits EGFR tyrosine kinase
(Lung cancer)
Erythromycin
14-membered Macrolide antibiotic
Targets 23S rRNA in 50S ribosomal subunit
Bind 23S rRNA at entrance to polypeptide export tunnel
Allow 6-8 oligopeptidyl tRNA build up before terminating
Competitive with lincosamide antibiotics
Can be bacteriostatic or bactericidal
Resistance - inactivation by enzymatic hydrolysis
Second choice for penicillin allergies
Gram +ve
Short elimination half life
Etoposide
Inhibitor of human type 2 topoisomerase
Resistance can be due to modified topoisomerases
Cancer
Fansidar
A combination of sulfadoxin and pyrimethamine
Against Plasmodium falciparum malaria
Used when chloroquine resistance is suspected and oral treatment is
appropriate
Fluconazole
Antifungal synthetic triazole
Inhibits enzymes in ergosterol biosynthesis
Affects membrane permeability and activity of membrane associated enzymes
Resistance due to active azole efflux and alterations in activity and amount of enzymes
Athletes foot and vaginal cadidiasis
Flutamide
Oral anti-androgen
Prostate cancer
Competes with testosterone and powerful metabolite, dihydrotestosterone
Prevents stimulation of growth of prostate cancer cells
Fosfomycin
Inhibits cell wall biosynthesis
Inhibits pyruvyl transferase (transfers PEP to UDP-NAG in production of UDP-NAM-tripeptide)
Fusidic acid
Affects protein synthesis
Binds and inhibits elongation factor G, preventing movement of 30S subunit along mRNA, blocking translocation
Narrow spectrum, for staphylococcal infections
Goseraline
Decapeptide analogue of GnRH that binds tightly and disrupts endogenous hormonal feedback, causing down-regulation of
testosterone and estrogen production
Biochemical castration
Imatinib
Specific inhibitor of a number of tyrosine kinase enzymes (c-kit , which is over-expressed in gastro-intestinal stromal tumours GISTs)
Inhibits BCR-ACL protein kinase activity, active in CML
Isoniazid
Prevention and treatment of M Tuberculosis
Inhibits biosynthesis of Mycolic acid in cell envelope
Leucovorin
Adjuvant in canver chemotherapy involving methotrexate
Used in combination with 5-fluorouracil
Salvage normal tissues from folate depletion
Readily converted to reduced folic acid derivatives
Does not require action of dihydrofolate reductase, so function as vitamin unaffected by inhibition of these enzymes
Methicillin
ß-lactam antibiotic
Inhibit peptidoglycan-crosslinking transpeptidase enzymes by covalent and irreversible binding as a pseudosubstrate
Resistance with mecA gene, and fem which adds pentaglycyl crossbridge to PG, making it a better MecA substrate
Methotrexate
Antimetabolite and antifolate
Inhibits folic acid metabolism
Folic acid antagonist
Inhibits dihydrofolate reductase
Similar to trimethoprim (bacterial) and pyrimethamine (protazoal)
Competes with folic acid for active transport into mammalian cells
Toxicity to normal tissues, so used with Leucovorin
Resistance based on enhanced expression of DHFR or reduced uptake from mutations in folate carrier
Miconazole
Antifungal synthetic imidazole
Inhibits enzymes in ergosterol biosynthesis
Also active against Leishmania, due to ergosterol membrane
Mitomycin C
Aziridine containing antibiotic that alkylates and cross-links DNA
Cross-linking of 2 G bases, preventing separation of strands
Selectively inhibits DNA synthesis in bacteria and tumour cells
Activated by reduction of the quinone group
Mitoxantrone
Anthracycline
Anti-cancer
Modified structure so lack quinone type free radical generation
Resistance by drug efflux by transporters
Nevirapine
Anti-HIV
Non nucleoside reverse transcriptase inhibitor
Used in HAART therapy
Bind and denature catalytic site of enzyme
Penicillin
Bactericidal
B-lactam antibiotic
Selective toxicity and large therapeutic index
Inhibit PG cross-linking transpeptidases by forming a slowly hydrolysing covalent acyl enzyme intermediate
Contains B-lactam and thiazolidine ring
Resistance by B-lactamases and penicillin-binding proteins
Prednisone
Synthetic corticosteroid prodrug, converted by liver to prednisolone
Inhibits growth of lymphocytes in leukemias
Pyrimethamine
Inhibits dihydrofolate reductase in plasmodium falciparum
Anti-protazoa
Rifampin
Bactericidal, inhibit RNA synthesis
Binds B-subunit of DNA dependent RNA polymerase (tight but non-covalent)
Directly blocks elongating RNA chain - prevents initiation of RNA synthesis
Synthesis in progress at time of exposure is unaffected
Intrinsic resistance by fungi, because drug does not readily enter envelope, so concentration is low
Used to treat mycobacterium infections
Saquinavir
Inhibit HIV protease, essential for viral replication and release of virus particles
Used in HAART therapy
Streptomycin
Aminoglycoside, affects protein synthesis, acts on 30S subunit
Binds the 30S subunit near the A
site for aminoacyl-tRNA binding
Cause disruption in decoding and translational accuracy, decrease in the fidelity of translation
Nephrotoxicity and ototoxicity
Gram negative rods
Sulfadoxin
Sulfa drug, competitively inhibits dihydropteroate synthase in plasmodium
Sulfamethoxazole
Antimetabolite antibiotic
A sulfa drug; p-aminobenzoate analogue
Competitively inhibits dihydropteroate synthase in the biosynthesis of tetrahydrofolate
(methyl carrier required for synthesis of dTMP).
Suramin
Used for human trypanosomiasis
Does not contain toxic metal, so high therapeutic index
inhibits glycerol-3-phosphate oxidase and NAD+-dependent glycerol-3-phosphate dehydrogenase
Interferes with the reoxidation of NADH, and inhibits ATP synthesis
Tamoxifen
Orally-active oestrogen receptor antagonist used in the treatment of breast cancer
Signal transduction inhibitor
Attenuates transcription of estrogen responsive genes involved in breast cancer
Exerts estrogen agonist effects in other tissues such as bone and uterus
Taxol
Causes assembly of microtubules from tubulin dimers
Causes stabilization of ordinary cytoplasmic microtubules and the formation of abnormal bundles of microtubules
Taxane, mitotic inhibitor
Tetracycline
Bacteriostatic antibiotic
Polyketide antibiotic; binds to 16 rRNA in 30S subunit of ribosome and inhibits the movement of aminoacyl-tRNA into the A site
Effective against a wide range of bacteria, and are first-line drugs against mycoplasma and cholera
Drug toxicity associated with binding of calcium in bones and teeth.
Resistance - specific tetracycline efflux transporters
Topotecan
Inhibit human type 1 topoisomerase
Ovarian and lung cancer
Trastuzumab
A humanised monoclonal antibody against the human epidermal growth factor receptor 2 (HER2) in breast cancer
IV once a week
Can cause cardiac dysfunction
Trimethoprim
Antimetabolite antibiotic
Inhibits dihydrofolate reductase in folic acid biosynthesis (tetrahydrofolate)
Valinomycin
Antibiotic acting on cytoplasmic membrane
Ionophoretic capacity
Electroneutral, but carries single +ve charge of K+
A cyclic peptide antibiotic that binds K+, and facilitates K+ diffusion across the membrane
Vancomycin
Glycopeptide antibiotic
Binds pentapeptidyl tails in PG repeating unit terminating in D-Ala-D-Ala
Prevents transpeptidation
Effective against Clostridium Difficile and used IV for Gram +ve cocci
Vinblastine
Vinca alkaloid
Antimitotic drug
Anti-cancer
Zanamivir
Inhibits neuraminidase, a glycoprotein enzyme, of Influenza A and maybe B
Enhance viral aggregation and inhibit release from the host cells
Zidovudine AZT
Nucleoside reverse transcriptase inhibitor
Thymidine analogue
Used in HAART treatment