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29 Cards in this Set
- Front
- Back
MOA of Lincosamides, Streptogramins
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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 |
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Advantages of Synergism of quinupristin and dalfopristin
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1) lower doses of each drug
2) decreases resistance 3) decrease MIC |
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Mechanism of Synergistic activity of quinupristin and dalfopristin (Streptogramins)
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binding of one to its target changes the conformation of hte ribosomal subunit to facilitate the binding of the other to its target
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Mechanism of RESISTANCE of Lincosamides and Streptogramins
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1) Binding site alteration (Methylase)
2) MDR efflux pump (proton gradient) 3) Decreased membrane permeability (OMPC>>>OMPF) |
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MOA of Tetracyclines
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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 |
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Steps of Chemical Degradation of Tetracyclines in BASIC soln
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**Lactone formation in C-Ring**
1) C-ring breaks as C6-OH forms lactone with C-11 2) Rearrangement at C11 and C12 |
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Steps of Chemical Degradation of Tetracyclines in Mildly Acidic Soln (pH 3-5)
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1) Epimerization (protons cycle down and double back - change the tertiary amine to R configuration)
2) Dehydration (Double Bond at 6) |
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Steps of Chemical Degradation of Tetracyclines in Strongly Acidic Soln
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1) Dehydration (double bond at 6)
2) Epimerization |
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Resistance to Tetracyclines
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1) TET efflux pump (Major)
2) MDR efflux pump (Minor) 3) Alteration of rRNA binding site (NOT methylase) 4) OMPF<<OMPC |
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MOA of Aminoglycosides
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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 |
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Major Resistance mechanism of Aminoglycosides
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R-plasmid genes that code for enzymes capable of modifying amino or hydroxyl groups at a specific location on the molecule
Inactivate the drug |
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Three enzymes that inactivate aminoglycosides for resistance
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1) Aminoglycoside acetylase enzymes (AAC)
2) Aminoglycoside Nucleotydltransferases (ANT) 3) Aminoglycoside Phosphotransferase (APH) |
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MOA of mupirocin (Bactroban)
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inhibition of bacterial isoleucyl-tRNA synthase
1) prevents incorporation of ILE in growing peptides 2) broad spectrum against COCCI, including MRSA |
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MOA of Sulfonamides
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**PABA Antimetabolites**
combine with dihydropteroate diphosphate to form a false substrate that cannot be converted o dihydrofolic acid (FAH2) by dihydrofolate synthase. BACTERIOSTATIC |
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Metabolic Transformation and Elimination of Sulfonamides
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1) N-acetyl Transferase (NAT)
2) UDP-Glucuronyl transferase (UGT) |
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Mechanism of Resistance for Sulfonamides
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1) Synthesizing more PABA
2) Substitute read-made products from the host (bacteria will use host FAH4) |
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MOA of Trimethoprim
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inhibitor of the enzyme, dihydrofolate reductase
blocks the conversion of dihydrofolate (FAH2) to tetrahydrofolate (FAH4) |
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MOA of nitrofurans and nitroimidazoles
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reduction of aromatic nitro group by bacterial reductases creates chemically reactive radical intermediates that cause damage to bacterial ribosomal proteins and nucleic acids
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Metabolic transformation of Nitroimidazoles
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1) Benzylic hydroxylation
2) Alcohol oxidation 3) Glucuronide Conjugation |
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MOA of Fluoroquinolones
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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 |
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Resistance to Fluoroquinolones
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1) mutations that decrease binding interactions with the drug or alter the binding of ATP (TOP II)
2) mutations that alter TOP IV |
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MOA of Ansamacrolides (Rifampin) and Fidaxomicin
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Inhibit DNA-Dependent RNA Polymerase (DDRP) - Zn metalloenzyme
Inhibits RNA synthesis (nucleic acid synthesis) BACTERICIDAL |
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MOA of nicotinamide analogs (INH and ethionamide)
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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 |
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MOA of Pyrazinamide
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*inhibition of trans-translation*
converted to pyrazinoic acid; pH decreases which interferes with membrane transport and energetics Inhibits correction of mistakes |
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MOA of ethambutol
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*inhibition of arabinogalactan synthesis*
inhibits arabinosyltransferase, stopping synthesis of arabinogalactan, a cell wall glycolipid |
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MOA of Linezolid (Oxazolidinone)
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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 |
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MOA of resistance for Linezolid
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point mutation and modifications of the RNA sequence at the binding site in the 23s fragment of the 5-s ribosomal subunit
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Metabolism & Excretion for Linezolid
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NON-CYP Mediated
1) oxidation of morpholine ring position 2 or 3 with subsequent ring opening 2) Oxidation of resulting aldehyde to COOH |
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MOA of Daptomycin (lipopeptides)
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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
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