BIOL 2460 Chapter 14 (ONLY the drrúgs)

Inhibitors of cell wall synthesis

Penicillins,

cephalosporins,

vancomycim,

monobacta,

carbapenems,

bacitracin

Inhibitors of protein synthesis

Aminoglycosides,

tetracyclines,

Chloramphenicol,

Macrolides,

lincosamides,

oxazolidinones

Inhibitors of cell wall synthesis

Penicillins,

cephalosporins,

vancomycim,

monobacta,

carbapenems,

bacitracin

Inhibitors of protein synthesis

Aminoglycosides,

tetracyclines,

Chloramphenicol,

Macrolides,

lincosamides,

oxazolidinones

Inhibitors of membrane Function

Polymyxins,

daptomycin

Inhibitors of nucleic acid synthesis

Rifamycin,

metronidazole,

fluoroquinolones

Inhibitors of metabolic pathways

antimetabolites,

sulfonamides,

trimethoprim,

isoniazid

inhibits ATP synthase

diarylquinolines

Antifungal drugs that disrupt sterol synthesis and membrane integrity

Imidazoles,

triazoles,

allylamines,

polyenes

Antifungal drugs with different MOAs

Flucytosine,

echinocandins,

polyoxins&nikkomycins,

griseofulvin,

atovaquone

Antiprotozoan Drugs that Inhibit metabolic pathways and DNA synthesis

Atovaquone,

proguanil,

metronidazole,

pentamidine

Antiprotozoan drugs with other MOAs

Atremisinin

Quinolines

Antihelminthic Drugs

Niclosamide,

Praziquantel,

Mebendazole,

Ivermectin

Antiviral Drugs

Acyclovir,

amantadine,

rimantadine,

oseltamivir

β-lactams

Presence of lactam ring; similar to peptidoglycan subunit; Blocks cross-linking of peptide chains in new peptidoglycan

Penicillins

derivatives from fungi;

mostly against G+, some G-

Cephalosporins

similar to penicillins;

resistance to β-lactamases

Carbapenems

Broad spectrum against G+/G-

Monobactams

narrow spectrum,

G- only

Vancomycin

Binds to end of peptide chain to block subunits from adding to peptidoglycan backbone;

G+ only

Bacitracin

Derived from B. subtilis;

blocks transport of peptidoglycan precursors

Aminoglycosides

Bind to 30S subunit of ribosome and impair "proofreading" ability;

Streptomycin, gentamicin, neomycin

Tetracyclines

Bind to 30S;

blocks association of tRNA with ribosome

Macrolides

Bind to 50S subunit & inhibit peptide bond formation in specific combos of amino acids;

Broad spectrum; -static

Lincosamides

Bind to 50S subunit & inhibit peptide bond formation in specific combos of amino acids; narrow spectrum;

-static; particularly active against streptococcal and staphylococcal infections

Chloramphenicol

Bind to 50S subunit & inhibit peptide bond formation in specific combos of amino acids; broad spectrum;

-static; rarely used now because of serious side effects

Oxazolidinones

Bind to the 50S ribosomal subunit and interferes with association of 30S and other factors; broad spectrum; -static; (Ex. Linezolid)

Polymyxins

Lipophilic & interact w/ LPS to disrupt outer & inner membrane of Gram (-); target host membranes

Daptomycin

Cyclic lipopeptide that inserts and disrupts Gram (+) membrane

Metronidazole (Antibacterial)

Interferes w/ DNA replication;not very selective in toxicity (targets anaerobic bacteria AND protozoa); broad spectrum; -cidal

Rifampin

blocks RNA polymerase activity; can treat semi-dormant M. tuberculosis; BUT can be antagonistic & hepatotoxic; Narrow spectrum (mainly G+, some G-); -cidal

Fluoroquniolones

Inhibit DNA gyrase enzyme; selective toxicity but many side effects; Broad spectrum; -cidal

Antimetabolites

Competitive inhibitors of enzymes to stop certain pathways

Sulfonamides

Sulfa drugs; halts folic acid synthesis and production of pyrimidines & purines; Often used in combo with Trimethoprim; Broad spectrum; -static alone

Trimethoprim

Inhibits later stage of folic acid synthesis; Sulfamethoxazale & Trimethoprim are commonly used in combination to boost effect (-cidal)

Isoniazid

Specific toxicity for mycobacteria to block synthesis of mycolic acid

Diarylquinolines

Inhibits mycobacterial growth; exact mechanisms is unknown but evidence shows interference with ATP synthase and reducing available ATP

Imidazoles

Disrupt ergosterol biosynthesis; Commonly used in medical and agriculture; Treat infections caused by dermatophytes: ringworm, tinea pedis (athlete's foot), tinea cruris (jock itch)

Triazoles

Inhibit ergosterol biosynthesis; Administered orally or intravenously; Systemic yeast infections: oral thrush, cryptococcal meningitis

Allylamines

Inhibit earlier step in ergosterol biosynthesis; Treat dermatophytic skin infections: athlete's foot, ringworm, jock itch; Terbinafine (Lamisil)

Polyenes

Bind to ergosterol and create pores in the membrane

Flucytosine

interferes with DNA replication and protein synthesis

Echinocandins

Inhibit β(1-3) glucan synthesis; "penicillin for fungi"

Polyoxins & nikkomycins

inhibit chitin synthesis

Griseofulvin

Interferes with microtubules involved in spindle formation during mitosis

Atovaquone (Antifungal)

Antimetabolite for fungal and protozoal mitochondrial cytochrome function

Atovaquone

Inhibits electron transport; Malaria, babesiosis, toxoplasmosis

Proguanil

Inhibits folic acid synthesis

Metronidazole (Antiprotozoan)

Inhibits DNA synthesis; Dysentery, Giardia, trichomoniasis

Pentamidine

Cleaves DNA within kinetoplasts; binds tRNA; African sleeping sickness, leishmaniasis

Atremisinin

unclear, but likely damages target cells by ROS; antimalarial

Quinolines

interferes with heme detoxification; Malaria, dysentery

Mebendazole

Inhibition of microtubule formation; Broad range

Ivermectin

Blocks neuronal transmission in invertebrates causing starvation, paralysis, and death; Round worms and parasitic insects

Niclosamide

Inhibit ATP formation under anaerobic conditions; Intestinal tape worms

Praziquantel

Induce influx of Ca into the worm; paralysis; Tapeworms, liver flukes, schistosomiasis (blood flukes)

Acyclovir

Inhibits nucleic acid synthesis; viral enzyme activation and affinity for viral DNA polymerase

Amantadine & Rimantadine

Treatment of influenza A; binds to transmembrane protein; Blocking escape from endosome prevents RNA release into host cells

Oseltamivir

Tamiflu