high yield antibiotics stuff you need to memorize Flashcards
Antibiotic side effects
all antibiotics-> antibiotic associated diarrhea (C. difficile)
Tetracycline-> discoloration of teeth
Amino glycosides-> auditory damage
Chloramphenicol->aplastic anemia (bone marrow blood cell damage)
Penicillin-> anaphylactic shock
Mechanisms of antibiotic resistance
- horizontal gene transfer
- Spontaneous mutation
Mechanisms:
- Mod/inactivate the antibiotic itself
- mod antibiotic target
- reduce antibiotic concentration (pump out thru efflux pumps, mutations in porins to prevent access)
Beta Lactams
Broad spectrum
Four main classes: Penecillin, Cephalosporins, Carbepenems, Monobactam (all work at different levels of PG synthesis)
Penecillin (all end in cillin)
Cephalosporins (all begin with ceph except cefazolin and cefadroxil)
Carbepenems (all end in penem)
Monobactam (only one- axtreonam)
MOA: bind to penecillin-binding-proteins (aka transpeptidase used to crosslink) inactivating them and disrupting crosslinking of peptidogylcan
Resistance mechanism:
1. B-lactamase- cleaves the enzyme inactivating it (overcome with b-lactamase inhibitors like clavulanic acid, tazobactam, and sulbactam. Slow releasing b-lactamase inhibitors to prevent b-lactamase)
- Reducing Permeability: making it hard for B-lactam to access the PBP
- PBP mutations- prevents B-lactam binding most common in MRSA mecA gene
Vancomyocin
glycopeptide antibiotic not a B lactam
Mechanism of action: binds to D-ala-D-ala at the end of the peptide side chain on peptidoglycan precursors
Only effective in gram positive bugs bc its bulky af and cant get into gram neg om
mechanism of resistance bacteria acquire genes that produce an altered pg structure D-ala-D-lac the genes that encode resistance are on plasmids or transposons (VRSA)
Cycloserine
mechanism: inhibits peptidoglycan crosslinking by acting as a competitive inhibitor of D-ala
Useful in second line anti-TB therapy
Bacitracin
Mechanism: binds to pyrophosphate on the lipid carrier for peptidoglycan precursors and blocks recycling inhibiting pg layer
Group A streptococci are very sensative so useful for diagnostic tests
too toxic for systemic use
Cell envelope antibiotics
Daptomycin: Mechanism- binds and disrupts cytoplasmic membrane, causing rapid membrane depolarization narrow spectrum (useful for gram + and MRSA)
Polymyxins:
Mechanism: bind to LPS in outer membrane of gram - leading to messed up outer and inner membranes
novility allows for use against abx resistant gram - bacteria
Protein synthesis inhibitors
specifically target smaller bacterial ribosome 70 s (30 and 50 s subunit)
30 s inhibitors: aminoglycosides (bacteriacidal), and tetracyclines (bacteriostatic)
30 A T
50 s inhibitors: Chloramphenicol, clindamycin (bactericidal), erythromycin/macrolides (bacteriostatic), linezolid (variable)
50 CCEL
Buy AT 30 CCEL (sell) at 50
Tetracycline
MoA: binds to 30s subunit interfering with the binding of aminoacyl tRNA to the ribosome
resistance: efflux pump and ribosomal mutations
tetra is mostly resistant but doxy and mino are still used
Side effects: teeth discoloration, photosensitivity for children
Tigecycline (new bacteriostatic form)
Aminoglycosides
gentamicin, amikacin, tobramycin, kanamycin etc
MoA: binds to 30 s to cause misreading and release from mRNA
side effects: ototoxic and nephrotoxic
resistance: enzymatic modification of Abx
Macrolides
erthryomycin, azithromycin, clarithromycin etc
MoA: Binds to 50 s to block elongation (macroslides)
often used for people allergic to B-lactams and against gram + bacteria
Resistance: Methylation of rRNA and efflux pumps
Clindamycin
same MoA as macrolides
resistance: methylation of rRNA and and cross resistance with macrolides
useful for MRSA, anaerobes above the diaphragm
Chloramphenicol
blocks elongation thru 50 s, aplastic anemia (gray bababy)
resistance: alters drug
Linezolid
MoA: binds to a unique 50s location to prevent formation of the ribosome
resistance: mutations in ribosomal components
DNA Replication inhibitors
1st generation quinolones- nalidix acid
2nd gen fluoroquinolones-norfloxacin, ciprofloxacin
MoA: bind to bacterial DNA gyrase to inhibit catalytic function- disrupting DNA replication and repair
Resistance: point mutations in bacterial DNA gyrase preventing antibiotic binding
Efflux pumps
Metronidazole
MoA: free radical produced in anaerobic environments leading to toxic metabolites that damage DNA
only useful in ANAEROBIC infections (c diff and pseudomonas colitis)
RNA synthesis inhibitors
Rifamins 4 Rs: RNA polymerase inhibitor, Ramps up microsomal cytochrome, Red/orange body fluids, Rapid resistance if used alone
MOA: binds to B subunit of RNAP to inhibit RNA synthesis,
Resistance: acquisitions of mutations in the B subunit of RNAP that prevent antibiotic from binding
Fidaxomicine: MOA: noncompetitive inhibitor of RNA synthesis by binding bacterial RNAP
uced agains c diff to preserve normal gut flora
Antimetabolate
Trimethoprim+Sulfamethoxazole (TMP/SMX) Bactrim
Metabolic analogs are structurally similar to natural metabolic intermediates and block the normal pathways
FOLATE INHIBITORS
Bacteriostatic
resistance: acquisition o f another gene: dihydrofolate reductase
Examples of transduction
Cholera toxin: core element and repetitive sequence
Has 5 bindning subunits and 1 enzymatic subunit, binding subunit attaches to ganglioside GM1, interacts with adenylate cyclase, converting ATP to cAMP enhancing secretion of water and electrolytes
Shiga Toxin phage: Temperate (has a lytic and lysogenic phase) 5B-1A subunits. B subunit binds to Gb3 glycolipid and modifies ribosome acceptor site blocking protein synthesis. Causes HUS (hemolytic-uremic syndrome)-severe diarrhea and hemorrhaging
