1. 80s ribosomes

    40s and 60s subunits

    bound to the ER
    Eukaryotic Ribosomes
  2. 70s ribosomes

    30s and 50s subunits

    NOT bound to the ER
    Bacterial Ribosomes
  3. True or false, a high concentrations inhibitors of protein synthesis are capable of inhibiting protein synthesis in mammalian cells
  4. How do these antibiotics enter gram negative cells? (2 ways)
    1- passive diffusion

    2- energy-dependent active transport
  5. Selectivity against bacterial cells at the clinical dose is attributed to what 2 things?
    1- lack of 70s ribosomes in mammalian cells

    2- lack of bacterial active transport systems in mammalian cells
  6. Which 3 drugs have a site of action at the 30s ribosomal subunit?
    • 1- aminoglycosides
    • 2- tetracyclines
    • 3- glycylcyclines (tigecycline)
  7. Which 3 drugs are bactericidal?
    • 1- aminoglycosides
    • 2- streptogramins (quinupristin/dalfoprisitin)
    • 3- ketolides (telithromycin)
  8. Broad spectrum
    Not absorbed in the GI-tract
    Cause nephrotoxicity, ototoxicity, and neuromuscular blockade
    Serum concentrations are higher in the renal cortex than serum levels
    Cross the placenta
  9. Of all the aminoglycoside _______ is the least susceptible to enzymatic activation and is reserved for serious infections
  10. What are the 3 mechanisms of microbial resistance to the aminoglycosides?
    • 1- ribosomal alteration (target modification)
    • 2- Production of inactivating enzymes
    • 3- Inhbition of active trasport (downregulation)
  11. The microbes resist aminoglycosides by inactivating enzymes by what 3 mechanisims?
    • 1- acetylation
    • 2- phosphorylation
    • 3- adenylation
  12. Broad-spectrim
    Distributed in the CSF
    High concentrations will increase BUN levels
    Causes chelation when administered with Ca, Mg, Al, Fe
    Contradicted in pregnancy and children <13
  13. Tetracyclines have a _____ affinity for calcified tissues because they _______ calcium

  14. The exent of teeth discoloration is directly proportional to......
    .....the dose and duration of therapy
  15. Which tetracycline is the MOST phototoxic (because of C-7 chlorine)?
  16. What are the 5 mechanisms of resistance to tetracyclines?
    • 1- ribsomal alteration
    • 2- ribosomal protection
    • 3- energy-dependent active efflux
    • 4- decreased antibiotic influx
    • 5- enzymatic activation
  17. What is the MOA for tetracyline?
    It binds to the 30s ribosome and blocks the binding of amino-acyl tRNA to the A-site
  18. What is the MOA for Aminoglycosides (3 total)?
    • 1- blocks the initiation of protein synthesis
    • 2- blocks translation and elicits premature termination
    • 3- incorporation of incorrect AA
  19. What is the only glycylcycline on the market?
  20. Broad-spectrum for IV infusion
    Structurally related to tetracyclines
    Contradicted in pregnancy and children <18
    Glycylcyclines (Tigecycline)
  21. True or false, Tigecycline has cross-resistance with other antibiotics.
  22. What is the glycylcycline MOA?
    It binds to the 30s ribosome and blocks the binding of amino-acyl tRNA to the A-site
  23. Tigecycline may be useful in treating bacterial infections caused by strains that are resistant to ________
  24. Tigecycline _______ warfarin clearance.
    _________ time should be monitored with co-adminsitration.

  25. What are the 5 macrolides?
    • 1- erythromycin
    • 2- azithromycin
    • 3- clarithromycin
    • 4- dirithromycin
    • 5- troleandomycin
  26. Intermediate spectrum
    Do NOT cross the BBB
  27. Which 3 macrolides are inhibitors of cyt P450 enzymes in the liver?
    • 1- erythromycin
    • 2- clarithromycin
    • 3- trolenadomycin
  28. True or false, clarithromycin is not contraindicated in pregnancy.
    False, it should NOT be used in pregnancy
  29. What is the MOA for macrolides (2 total)?
    • 1- Inhibit translocation from the A site to the P-site
    • 2- Interfere with trans-peptidation
  30. What are the 2 lincosamides on the market?
    • 1- Lincomycin
    • 2- Clindamycin
  31. Narrow spectrum
    Colitis (GI irritation)
  32. Clindamycin is more _______ than lincomycin; which means that lincomycin causes _____ GI upset

  33. True or false, lincosamides and macrolides do not share the same binding site.
    False, they DO share the same binding site and will have cross-resistance
  34. What is the MOA for the lincosamides (2 total)?
    • 1- Inhibit translocation from the A site to the P site
    • 2- Interfere with trans-peptidation
  35. What is the only streptogramin on the market?
    Quinupristin (30%)+ Dalfopristin (70%)
  36. True or false, Quinupristin is also known as streptogramin A
    • False!
    • Dalfopristin= streptogramin A
    • Quinupristin= streptogramin B
  37. Bactericidal
    Treats VREF, Staph aureus, Strep pyogens
    Inhibits CYP3A4 isozyme
  38. True or false, streptogramins inhibit CYP3A4 isozyme which will decrease the effect and toxicity of other drugs
    False, it will INCREASE the effect and toxicity of other drugs
  39. What are the 2 resistance mechanisms to quinupristin?
    • 1- ribosomal alteration (target modification)
    • 2- Production of lactonases (inactivate quinupristin)
  40. What are the 2 resistance mechanisms to dalfopristin?
    • 1- production of acetyltransferases (inactivate dalfopristin)
    • 2-production of ATP binding efflux proteins
  41. Is there cross-resistance with strepogramins--more specifically quinupristin, with macrolides, lincosamides?
    Yes, they all share the same binding site
  42. What happens if dalfopristin binds and quinupristin doesn't?
    The effect will be static instead of cidal
  43. What is the MOA for dalfopristin (2)?
    It binds to a site nearby resulting in a conformational change in the 50s ribosome enhancing the binding of quinupristin

    It interferes with polypeptide chain formation
  44. What is the only Ketolide on the market?
  45. Intermediate spectrum (treats mild/moderate community aquired pnemonia)
    Structurally related to macrolides but more specifically to erythromycin
    Ketolides (Telithromycin)
  46. _______ are semi-synthetic 14 membered ring lactones
    Ketolides (telithromycin)
  47. Ketolides have a _______ affinty for binding than macrolides
  48. What is the MOA for ketolides (1)?
    2 binding sites on the 50s!

    One is shared with the macrolides (erythromycin), licosamdides, and streptogramins
  49. True or false, efflux pumps that work for macrolides do not work for ketolides
    True, ketolides are poor substrates for the active efflux pump
  50. True or false, methylases alter both binding sites for telithromycin
    False, it only alters the shared binding site
  51. Telithromycin will _______ the effect or anticoagulants, digoxin, any other drug metabolized by ______ isozyme.

    CYP3A4 (statin, benzos)
  52. Telithromycin is a(n) ________ of CYP3A4 isozyme
  53. True or false, you can use of CYP3A4 inducers and inhibitors with telithromycin.
    False, plasma levels will be altered
  54. Hepatoxicity leading to hepatitis and jaundice
    Prolonged QT leading to fainting and increased risk for ventricular arrhythmias
    Visual disturbances including blurred vision
    Transient loss of conciousness
    Ketolides (telithromycin)
  55. Broad spectrum
    Allosteric inhibitors are macrolides and lincosamides
    Contraindicated in infants and newborns because of gray baby syndrome
  56. What is the MOA for Chloramphenicol?
    It binds on the 50s ribsosome near the site of action of macrolides and lincosamides--which will interfere with the binding of chloramphenicol

    Inhibits the trans-peptidation step
  57. What toxicities are caused by Chloramphenicol?
    • -Dose-related bone marrow depression
    • -immunosuppresion
    • -aplastic anemia
    • -inhibition of Vitamin K
    • -alcohol intolerance
  58. Bacteriostatic
    Poor activity against Gram negative aerobic or anaerobic bacteria
    Contradicted in patients taking MAOIs
    Treats VREF, MRSA, Step, nosocomial pneumonia, and bacteremia
    Oxazolidinones (Linezolid)
  59. What are the toxicities associated with Oxazolidinones (Linezolid)? (2)
    • -PMC (pseudomembraneous colitis)
    • - thrombocytopenia (myelosuppresion)
  60. What is the MOA for Oxzaolidinones (Linezolid)?
    Binds to the P-site of the 50s inhibiting the initiation step in protein synthesis by inhibiting the ribosome assembly step and the formation of the fMet-tRNA complex
  61. How can bacteria resist Linezolid?
    Via target modification due to a mutation of the ribosomal binding site
  62. Bacteriostatic (will be cidal at high concentrations)
    Treats MRSA and impetigo
    Pleuromutilins (Retapamilin)
  63. What are the resistance mechanisms to Pleuromutilins (Retapamilin)? (2)
    • 1- Ribosomal alteration (target modification)
    • 2- active efflux
  64. What is the MOA for Pleuromutilins (Retapamilin)?
    Binds to the 50s subunit inhibiting peptidyl transfer, blocking the P-site interactions, preventing normal formation of active 50s ribosomal subunits
  65. Which 2 subclasses are the inhibitors of bacterial nucleic acid synthesis?
    • 1- Rifamycin
    • 2- Fluroquinolones
  66. Which 3 drugs are classified as Rifamycins?
    • 1- Rifampin
    • 2- Rifabutin
    • 3- Rifapentine
  67. Bactericidal
    Intermediate spectrum
    Treat mycobacterial infections (TB)
    Highly conjugated and colored orange-red
  68. What are the toxicities associated with Rifamycins? (2)
    • 1- discoloration in excretion
    • 2- hepatotoxicity
  69. Rifamycins are ______ of cyt P450 enzymes in the liver but _____ is less potent than the other 2 drugs _______ and _______
    • 1- inducers
    • 2- rifabutin
    • 3- rifampin
    • 4- rifapentine
  70. What is the MOA for Rifamycins?
    Inhibit RNA syntehsis in bacteria ONLY by inhibiting bacterial DNA-dependent RNA polymerase

    They DO NOT inhibit the mammalian enzyme (highly selective)
  71. True or false there is cross resistance to Rifamycin and other drug classes.
    False, there is only cross-resistance between the Rifamycins themselves
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