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29 Cards in this Set

  • Front
  • Back
MOA of Lincosamides, Streptogramins
Bind domains II and IV on the 23s fragment of the 50s ribosomal subunit of the bacterial 70s ribosome

Inhibit action of enzyme peptidyl transferase = translation interrupted
Advantages of Synergism of quinupristin and dalfopristin
1) lower doses of each drug
2) decreases resistance
3) decrease MIC
Mechanism of Synergistic activity of quinupristin and dalfopristin (Streptogramins)
binding of one to its target changes the conformation of hte ribosomal subunit to facilitate the binding of the other to its target
Mechanism of RESISTANCE of Lincosamides and Streptogramins
1) Binding site alteration (Methylase)
2) MDR efflux pump (proton gradient)
3) Decreased membrane permeability (OMPC>>>OMPF)
MOA of Tetracyclines
interact with the 30s ribosomal subunit at a target such that access of aminoacyl-tRNA at the A-site is blocked

Release of complete polypeptides is blocked

Broad Spectrum and bacteriostatic
Steps of Chemical Degradation of Tetracyclines in BASIC soln
**Lactone formation in C-Ring**

1) C-ring breaks as C6-OH forms lactone with C-11
2) Rearrangement at C11 and C12
Steps of Chemical Degradation of Tetracyclines in Mildly Acidic Soln (pH 3-5)
1) Epimerization (protons cycle down and double back - change the tertiary amine to R configuration)
2) Dehydration (Double Bond at 6)
Steps of Chemical Degradation of Tetracyclines in Strongly Acidic Soln
1) Dehydration (double bond at 6)
2) Epimerization
Resistance to Tetracyclines
1) TET efflux pump (Major)
2) MDR efflux pump (Minor)
3) Alteration of rRNA binding site (NOT methylase)
4) OMPF<<OMPC
MOA of Aminoglycosides
bind to the 30s ribosomal subunit with following results:

1) high drug conc - form initiation complex at "P-site" is prevented
2) low drug conc - recognition of mRNA codons is lost = genetic code is misread - mutations in protein synthesis

BACTERICIDAL
Major Resistance mechanism of Aminoglycosides
R-plasmid genes that code for enzymes capable of modifying amino or hydroxyl groups at a specific location on the molecule

Inactivate the drug
Three enzymes that inactivate aminoglycosides for resistance
1) Aminoglycoside acetylase enzymes (AAC)
2) Aminoglycoside Nucleotydltransferases (ANT)
3) Aminoglycoside Phosphotransferase (APH)
MOA of mupirocin (Bactroban)
inhibition of bacterial isoleucyl-tRNA synthase
1) prevents incorporation of ILE in growing peptides
2) broad spectrum against COCCI, including MRSA
MOA of Sulfonamides
**PABA Antimetabolites**

combine with dihydropteroate diphosphate to form a false substrate that cannot be converted o dihydrofolic acid (FAH2) by dihydrofolate synthase.

BACTERIOSTATIC
Metabolic Transformation and Elimination of Sulfonamides
1) N-acetyl Transferase (NAT)
2) UDP-Glucuronyl transferase (UGT)
Mechanism of Resistance for Sulfonamides
1) Synthesizing more PABA
2) Substitute read-made products from the host (bacteria will use host FAH4)
MOA of Trimethoprim
inhibitor of the enzyme, dihydrofolate reductase

blocks the conversion of dihydrofolate (FAH2) to tetrahydrofolate (FAH4)
MOA of nitrofurans and nitroimidazoles
reduction of aromatic nitro group by bacterial reductases creates chemically reactive radical intermediates that cause damage to bacterial ribosomal proteins and nucleic acids
Metabolic transformation of Nitroimidazoles
1) Benzylic hydroxylation
2) Alcohol oxidation
3) Glucuronide Conjugation
MOA of Fluoroquinolones
Inhibits Topoisomerase II and IV

TOP II: introduces negative super-coils into DNA by breaking and re-sealing both strands of the DNA

TOP IV: breaks and re-seals DNA to facilitate the process of catenation & decatenation
Resistance to Fluoroquinolones
1) mutations that decrease binding interactions with the drug or alter the binding of ATP (TOP II)

2) mutations that alter TOP IV
MOA of Ansamacrolides (Rifampin) and Fidaxomicin
Inhibit DNA-Dependent RNA Polymerase (DDRP) - Zn metalloenzyme

Inhibits RNA synthesis (nucleic acid synthesis)

BACTERICIDAL
MOA of nicotinamide analogs (INH and ethionamide)
Inhibit mycolic acid synthesis and incorporation

1) one deactivates a crucial enzyme (katG) in the organism by acylation and,
2) both drugs acylate NADH, poisoning the cofactor of the enzyme Inh A
MOA of Pyrazinamide
*inhibition of trans-translation*

converted to pyrazinoic acid; pH decreases which interferes with membrane transport and energetics

Inhibits correction of mistakes
MOA of ethambutol
*inhibition of arabinogalactan synthesis*

inhibits arabinosyltransferase, stopping synthesis of arabinogalactan, a cell wall glycolipid
MOA of Linezolid (Oxazolidinone)
inhibits protein synthesis by binding a site on 23s fragment of 50s ribosomal subunit and preventing the formation of the initiation complex

different site than macrolides
MOA of resistance for Linezolid
point mutation and modifications of the RNA sequence at the binding site in the 23s fragment of the 5-s ribosomal subunit
Metabolism & Excretion for Linezolid
NON-CYP Mediated

1) oxidation of morpholine ring position 2 or 3 with subsequent ring opening
2) Oxidation of resulting aldehyde to COOH
MOA of Daptomycin (lipopeptides)
calcium-dependent binding and oligomerization in the cytoplasmic membrane with formation of a pore and rapid loss of potassium ions, followed by loss of nucleic acid synthesis and cell death