Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key

image

Play button

image

Play button

image

Progress

1/103

Click to flip

103 Cards in this Set

  • Front
  • Back
Examples: Beta-lactams
Penicillins (can combine with aminoglycosides in fermenting bacteria)
Cephalosporins
Carbapenems
Monolactams
Structure: Beta-lactams
beta-lactam 3 carbon cyclic amide
Target: Beta-lactams
Cell wall synthesis: Penicillin binding proteins
Mechanism: Beta-lactams
BLOCK TRANSPEPTIDATION
Mimic D-Ala-D-Ala dipeptide
Form Covalente Adduct on Serine in penicillin binding protein binding site
Resistance: Beta-lactams
beta-lactamases cleave lactam ring (can inhibit with beta-lactamase inhibitor)
carrbapenemases
mutation in PBP gene-->decrease drug affinity
alter intake into gram - outer membrane
porins or efflux pump
Examples: Glycopeptides (Cell Wall)
Vancomycin
Teichoplanin
Structure: Glycopeptides
Seven aa peptide. Needs oxidation and glycosylation to complete synthesis
Target: Glycopeptides
D-Ala-D-Ala dipeptide
Mechanism: Glycopeptides
Binds D-Ala-D-Ala terminus of newly linked peptidoglycan (post transglyco, pre transpep)
--> Inhibits wall SYNTHESIS
Resistance: Glycopeptides
Non-protein cell wall component target (no mutational resistance)
(1)change in cell wall composition: D-Ala-D-Ala D-Ala-D-Lac
(make precursors, link it on) --> loss of recognition (Vancomycin Resistant Enterococci – VRE)
Source: Glycopeptides
Bacteria. Synthesized by Non-Ribosomal-Peptide-Synthase (NRPS), w/out ribosome
Combinations: Glycopeptides
Do: combine with beta-lactams (common pathway)
Structure: Bacitracin (Cell Wall)
Thiazalone ring
Target: Bacitracin
topical against Gram + organisms
Mechanism: Bacitracin
Binds to lipid carrier, inhibits LIPID DEPHOSPHORYLATION
Source: Bacitracin
Soil bacteria via NRPS
Target: Cycloserine
"second line" anti-TB
Mechanism: Cycloserine
Competitive agonist of Alanine racemase and D-Alanine ligase
--> Inhibits wall SYNTHESIS
Source: Cycloserine
bacteria
Structure: Phosphonomycin
epoxide ring
Target: Phosphonomycin
UTIs
Mechanism: Phosphonomycin
Reacts with cysteins thiol in active site of Enolpyuruvate tranferase, Blocks NAG-->NAM CONVERSION
Source: Phosphonomycin
Bacteria
Examples: Mycolic Acid Synthesis Inhibitors
Isoniazid
Ethambutol
Ethionamide
Target/Mechanism: Mycolic Acid Synthesis Inhibitors
Inhibit mycolic acid synthesis, an integral cell wall component of mycobacterium TB
Target: Lipopeptides (Membrane)
cell membrane of GRAM + ONLY
Mechanism: Lipopeptides
Attach to cell membrane of gram + (IN PRESENCE OF Ca++), form pore-->DEPOLARIZATION -->death/lysis
Resistance: Lipopeptides
mutations affecting overall membrane charge
(altered uptake not relevant b/c target is extracellular)
Source: Lipopeptides
bactera
Examples: Aminoglycosides (translation inhibitor)
--mycins (from streptomyces) ex) streptomycin & tobramycin

--micins (from micromonospora) ex) gentamicin
Structure: Aminoglycosides
ring with NH2 groups linked with glycosidic bonds
Target: Aminoglycosides
binds with 16S rRNA of 30S Ribosomal subunit at A-site
Mechanism: Aminoglycosides
binds 16S rRNA at A-site (different sequence than eukaryotes)
-->misread codons
-->decrease efficiency of A--->P transition of nascent peptide
-->bactericidal
Resistance: Aminoglycosides
(1) Ezymatic inactivation Transferases: AAC (acetyl), ANT (Adenyl) and APH (phosphor) catalyze transfer of group onto side chain groups
(2) Altered Target Mutations in 16S rRNA molecule/rpsL gene
(3) decrease net negative charge of membrane
Fermenting bac don’t import.
Efflux by MeXY pump (pseudomonas)
Source: Aminoglycosides
bacteria (streptomyces/micromonospora)
Example: Tetracyclines (inhibit translation)
doxycycline
What is special about glycyclines of tetracycline family?
improved stability & binding affinity-->can overcome Ribosomal Protection Proteins
Structure: Tetracyclines
Naphthacene core modified to increase stability
lipophilic-->can diffuse through membrane
Target: Tetracyclines
30S Ribosomal subunit
Mechanism: Tetracyclines
-->Reversible interaction with 30S subunit, block association of aa-tRNA to A-site
--> Also bind 70S subunit in mitochondria for ANTI-PARASITIC effect
-->Bacteriostatic
Resistance: Tetracyclines
(1) Inactivation: tetX gene (Bacteriodes) encode NADPH-dependant tetracycline oxioreductase
(2) Altered Target: RPP (Ribosomal Protection Proteins) – GTPase, related to EFs. Bind and induce conformational change to dislodge tetracycline (prevented by glycyclines)
(3) Altered Uptake: Efflux pumps
Structure: Chloramphenicol (translation inhibitor)
nitrated benzene attached to chlorinated hydroxypropamine
Target: Chloramphenicol
50S Ribosomal Subunit, interacts with 23S rRNA
--> Aplastic anemia side effect (not common in US)
Mechanism: Chloramphenicol
-->Binds two specific adenine residues on 23S rRNA
-->Inhibits transpeptidation
-->Bacteriostatic (mostly), bacteriocidal (for some)
Resistance: Chloramphenicol
(1) Inactivation: Chloramphenicol AcetylTransferase (transferase), acetylates hydroxyl groups
(2) Altered Target: Rare mutations in 23S rRNA; Enxymatic methylation of key adenine NTs
(3) Altered Uptake: gram- Porin mutations affect ease of entry, exportation by efflux
Source: Chloramphenicol
isolated from bacteria, now synthesized
Examples: Macrolides & Ketolides (translation inhibition)
Erythromycin
Azythromycin (semi-synthetic)
Clarithromycin (semi-synthetic)
Target: Macrolides & Ketolides
interact with 23S rRNA of 50S ribosomal subunit

ketolide can overcome MLSB phenotype
Mechanism: Macrolides & Ketolides
-->bind 23s rRNA of 50S near peptidyl transfer site
-->blocks nascent peptide from exit tunnel = dissociation of peptidyl-acyl tRNA
-->Interfere with formation of 50S subunit
-->Bacteriostatic (low conc), lethal at higher
Resistance: Macrolides & Ketolides
(1) Inactivation: Phosphotraferases (mph A,B,C genes) or plasmid-encoded esterases (hydrolysis of lactone ring)
(2)Altered Target: Key site mutations in 23S rRNA, Methylases that target key adenine NTs (MLSB)
Source: Macrolides & Ketolides
Macrolides: bacteria or synthetic derivation
Ketolides: semisynthetic erythromycin derivatives
Examples: Lincosamides (translation inhibitor)
Lincomycin
Clindamycin (chlorinated)
Target: Lincosamides
50S ribosomal subunit
Mechanism: Lincosamides
bind 23S rRNA near peptidyl transfer site (same as macrolides)
mechanism same as macrolides - block dissociation of peptidyl-acyl tRNA
interfere with formation of 50S subunit
Resistance: Lincosamides
Staph strains have enzyme that can nucleotidylate hydroxyl group
Source: Lincosamides
bacteria (streptomyces)
Combinations: Lincosamides
Don’t: combine erythromycin (macrolide erm-inducer) with clindamycin (erm positive but not constitutively)-->MLSB phenotype
Structure: Streptogramins (translation inhibitor)
SgA and SgB
Target: Streptogramins
50S Ribosomal Subunit (2 components bind in close proximity to different sites on 23S rRNA)
Mechanism: Streptogramins
-->A binds near the peptidyltranferase domain: Inhibits (transpeptidation - like chloramphenicol)
-->B-component interferes w/ exiting peptide (like macrolide) – dissociation
-->Synergistic binding effect, irreversible, bactericidal
Resistance: Streptogramins
(1) Inactivation: Vgb lyase, attacks C-O bond in B ring
(2) Altered target: methylation of Key adenine reduces affinity (MLSb Phenotype)
(3) Altered Uptake: gram+ express efflux pumps, export linconsamides and streptogramin A
MsrABC family members efflux macrolides and SgB
Source: Streptogramins
Bacteria (streptomyces) via NRPS
Example: Oxazolidinones (translation inhibitor)
Linezolid
Target: Oxazolidinones
50S ribosomal subunit
Mechanism: Oxazolidinones
Bind at interface with 30S subunit, prevent formation of Pro 70S ribosome-->bacteriostatic
Resistance: Oxazolidinones
Altered target: Only known is 23S rRNA mutation, or staph Cfr methyltransferase
Source: Oxazolidinones
organically synthesized
Examples: Fusidanes (translation inhibitor)
Fusidic Acid
Structure: Fusidanes
steroid-like, similar to cephalosporin
Mechanism: Fusidanes
Binds ribosomal bound EF-G::GDP post hydrolysis, prevents dissociation and blocks elongation (no transition of de-aa-ed tRNA from P to E site)
Resistance: Fusidanes
(2) Altered target: mutations in fusA (encodes EF-G), decrease affinity
(3) Altered Uptake: Mutations, decrease permeability of membranes
(4) UNKNOWN mechanism: FusB gene in PLASMID, cytosolic protein confers resistance
Source: Fusidanes
fungi (Fusidium coccineum)
Examples: Quinolones (Nucleic Acid Synthesis Inhibitor)
Nalidixic acid
Fluroquinolone
Structure: Quinolones
dual ring
fluroquinolones have F ion which drastically improves potency
Target: Quinolones
Type II topoisomerases (gyrase & topoisomerase IV)
Mechanism: Quinolones
Bind DNA-Topoisomerase Complex, block ligation of double strand breaks
-->induce DNA-damage response: triggers bacteriophage lysis and toxin release (cholera and shiga)
Resistance: Quinolones
(1) Inactivation: plasmid qnr gene protects (no clinical resistance, but allows mutation and resistance); altered AAC enzyme can acetylate-->low level resistance facilitates mutation development
(2) Altered target :mutations in gyrase (gram-) and topoisomerase IV (gram+), only mutations in one of two loci is required
(3) Altered Uptake: Efflux pumps (MexAB & AcrAB), also plasmid encoded pumps rarely
Source: Quinolones
Nalidixic acid is byproduct of chloroquine production
Structure: Rifamycins (Transription inhibitor)
Ansa structure
Target: Rifamycin
beta subunit of RNA polymerase (RpoB) deep within DNA:RNA channel
Structure: Rifamycins (Transription inhibitor)
Ansa structure
Structure: Rifamycins (Transription inhibitor)
Ansa structure
Target: Rifamycin
beta subunit of RNA polymerase (RpoB) deep within DNA:RNA channel
Mechanism: Rifamycin
Steric blockage of elongation-->abort transcription
Structure: Rifamycins (Transription inhibitor)
Ansa structure
Structure: Rifamycins (Transription inhibitor)
Ansa structure
Resistance: Rifamycin
Altered Target: Point mutations in the rpoB core region-->precludes binding+inhibition
Mechanism: Rifamycin
Steric blockage of elongation-->abort transcription
Target: Rifamycin
beta subunit of RNA polymerase (RpoB) deep within DNA:RNA channel
Target: Rifamycin
beta subunit of RNA polymerase (RpoB) deep within DNA:RNA channel
Target: Rifamycin
beta subunit of RNA polymerase (RpoB) deep within DNA:RNA channel
Source: Rifamycin
bacteria
Mechanism: Rifamycin
Steric blockage of elongation-->abort transcription
Resistance: Rifamycin
Altered Target: Point mutations in the rpoB core region-->precludes binding+inhibition
Mechanism: Rifamycin
Steric blockage of elongation-->abort transcription
Mechanism: Rifamycin
Steric blockage of elongation-->abort transcription
Resistance: Rifamycin
Altered Target: Point mutations in the rpoB core region-->precludes binding+inhibition
Source: Rifamycin
bacteria
Resistance: Rifamycin
Altered Target: Point mutations in the rpoB core region-->precludes binding+inhibition
Source: Rifamycin
bacteria
Resistance: Rifamycin
Altered Target: Point mutations in the rpoB core region-->precludes binding+inhibition
Source: Rifamycin
bacteria
Source: Rifamycin
bacteria