Antibiotics Like Whoa

Front 1

Polymixins

Back 1

polymixin B: selective activity against gram negative enteric rods (especially Pseudomonas); has a positively charged polypeptide that binds to neg. LPS in OM, then to CM phospholipids and causes membrane leakage

Front 2

Streptomycin

Back 2

inhibitor of protein synthesis; used in treatment of TB; its discovery extended range to many gram-negative organisms; its positively charged at phy. pH and some metabolic activity is needed for streptomycin to enter; under anaerobic or acidic conditions (urine) action is inhibited; bacteriocidal

Front 3

action of streptomycin

Back 3

action is on 30S ribosomal subunit; few molecules: misreading; higher con: formation of the initiation complex is bad

Front 4

gentamicin

Back 4

inhibit 30S ribosomal function; bacteriocidal; aminoglycoside

Front 5

aminoglycosides

Back 5

gentamicin...all inhibit 30S subunit and are bacteriocidal; interact with more than one ribosomal subunit (resistance harder to get); have toxic effects, damaging 8th cranial nerve or renal function; require aerobic conditions to be effective

Front 6

Tetracyclines

Back 6

tetracycline and doxycycline

Front 7

tetracyclines (cont)

Back 7

widely used; block binding of aminoacyl-RNA of 30S ribosomal subunit; bacteriostatic; well absorbed orally; broad spectrum (mycoplasma, rickettsia, and chlamydia); do NOT give in pregnancy and children under 8 get mottled enamel (broad spectrum may be a problem: destroy natural flora in GI tract)

Front 8

Tigecycline

Back 8

potent tetracycline derivative; contains chemical side chain that makes it refractory to a common mechanism of tetracycline resistance that involves an efflux pump;

Front 9

Erythromycin

Back 9

inhibitors of 50S ribosomal function; macrolide; blocks chain elongation; bacteriostatic; very widely used; activity similar to penicillin but includes mycoplasma and chlamydia

Front 10

Azithromycin

Back 10

new oral drugs related to erythromycin but with higher activity and slightly broader spectrum; give high and sustained tissue concentrations

Front 11

Chloramphenicol

Back 11

blocks polypeptide chain elongation; bacteriostatic; although in H. influenza cessation of growth leads to -cidal effect; can induce aplastic anemia; not widely used

Front 12

use of Chloramphenicol

Back 12

useful against some anaerobes, particularly bowel anaerobes such as B. fragilis; can cause aplastic anemia and therefore not widely used, only restricted to infections in which it is vital for therapy

Front 13

Clindamycin

Back 13

derivative of lincomycin; activity against gram positive and moderate activity against anaerobes; bacteriostatic; inhibits peptidyl transfer

Front 14

oxazolidinones

Back 14

bacteriostatic; highly active against gram positive bacteria; potential treatment for VREF and also MRSA, VRSA and other multiply resistant bacteria; probably work by inhibiting tRNA translocation; interacs with 16S RNA and the 23S rRNA of the 30S and 50S ribosomal subunits

Front 15

Linezolid

Back 15

prototype of oxazolidinone; oral and IV routes; no need for dose adjustments iwth renal impairment;

Front 16

Sreptogramins

Back 16

new class; binds to 50S subunit; bacteriostatic

Front 17

Synergin

Back 17

dalfopristin and quinupristin; clinical prototype of sreptogramins; potential for treating MRSA, VREF, and other multiply resistant bacteria

Front 18

Mupirocin

Back 18

antibiotic that binds a specific tRNA synthetase (isoleucyl-tRNA synthetase); bacteriostatic at low concentrations but bacteriocidal at high concentrations; useful to treat MRSA (nasal carrier state)

Front 19

Quinolones

Back 19

inhibitors of DNA replication; inhibits enzyme DNA gyrase; bacteriocidal; most common ones are fluoroquinolones, ciprofloxacin, and moxifloxacin

Front 20

quinolones (action against)

Back 20

active vs. gram negative enteric bacilli; some gram positive cocci and P. aeruginosa; used for variety of infections...UTI, respiratory, and even anaerobic

Front 21

Ciprofloxacin

Back 21

therapeutic treatment of anthrax, and even as a prophylactic when exposure to B. anthracis is a potential risk...

Front 22

Nitroimidazoles

Back 22

metronidazole; anaerobic drug; activated form of drug binds DNA and fragments it; useful against anaerobic bacteria; bacteriocidal; used for certain protozoal infections (trichomoniasis and amebiasis); action requires anaerobic conditions

Front 23

Rifampin

Back 23

inhibitor of RNA synthesis; broad spectrum; bacteriocidal; inhibits transcription by binding to the B subunit of bacterial RNA polymerase, inhibiting specific binding to DNA...often used in combo with other antibiotics (sinse resistance develops fast)

Front 24

Rifampin used in combo with what?

Back 24

isoniazid or pyrazinamide; major therapies against TB

Front 25

Where is Rifampin secreted?

Back 25

saliva; makes it very useful as a prophylactic against infectious bacteria that enter via the nasopharyngeal route; notable for preventing spread of N. menigitidis

Front 26

Ethambutol

Back 26

important anti-TB; bacteriostatic against tubercle bacilli

Front 27

Pyrazinamide

Back 27

important anti-TB; mech unknown; bacteriocidal drug that requires activity of the Mycobacteria amidase to become activated

Front 28

Erythromycin inactivation

Back 28

by erythromycin esterase hydrolyzes lactone ring;

Front 29

altered membrane permeability...outer membrane

Back 29

OM porins decreased expression; B-lactams, nalidixic acid, chloramphenicol

Front 30

altered membrane permeability...inner membrane

Back 30

inner membrane trasporters altered...aminoglycosides, rare since usually deleterious regarding PMF...

Front 31

alter S12 of 30S subunit

Back 31

streptomycin resistance; these mutations are the most common mech. for Em resistance and Sm resistance; don't occur so much for gentamicin, tobramycin, amikacin...all of which have multiple ribosomal targets

Front 32

alteration of cell wall precursor targets

Back 32

impt. for vancomycin and teichoplanin resistance; inducible genes that encodes an enzyme related to D-ala-D-ligases;

Front 33

Alteration of target enzymes

Back 33

altered PBPs - lower affinity of change in amount; methicillin resistance is associated with altered affinity to PBP's; also common in pen. resistance in Neisseria, H. influenzae, and P. aeruginosa

Front 34

Polyene compounds

Back 34

antifungal; amphotericin B and nystatin; bind to sterols in cell membranes; affinity is better towards ergosterol; poorly absorbed from GI tract

Front 35

amphotericin B

Back 35

antifungal; affect membrane permeability; used systemically, but toxic; fungicidal

Front 36

Nystatin

Back 36

antifungal; affects membrane permeability; too toxic for systemic use; used topically and for oral fungal infections using the "swish and swallow" technique; not absorbed in GI tract and therefore does not lead to toxicity; fungistatic

Front 37

Azoles

Back 37

systemic antifungal agents; inhibitors of cell membrane synthesis; useful for treatment of oral candidiasis (thrush)...impt. in AIDS patients

Front 38

Fluconazole and Ketoconazole

Back 38

azoles; can be given orally, but hepatotoxicity occurs in a smallll amount of patients; major activity is inhibition of ergosterol synthesis, principally by inhibition of cytochrome P450 14a demethylase; fungistatic

Front 39

Caspofungin

Back 39

an echinocandin; inhibitor or cell wall synthesis; inhibitors of glucan synthesis; fungicidal

Front 40

Flucytosine

Back 40

antimetabolite against fungus; replaces uracil with 5-flurouracil in fungal RNA; also inhibits thymidylate synthetase via 5-fluorodeoxy-uridine monophosphate; interferes with fungal DNA synthesis; can be either fungicidal or static, depending on fungal isolate

Front 41

fungal resistance

Back 41

NO acquired resistance mechanisms that inactivate the drugs have thus far been discovered...normal efflux pumps that have increased levels of expression represent a common mech. as does alteration in targets of the drugs