Pharm Block 2 (macrolides/ Ketolides)

  1. What are the macrolides/ Ketolides?
    Name them.
    • - They are protein synthesis inhibitors
    • Erythromycin
    • Telithromycin
    • Azithromycin
    • Clarithromycin
  2. What is some of the Pharmacology of The Macrolides?

    Note: What can prolong their efficacy?
    • -Concentrates in respiratory secretions (So, can be used to treat URT infections, pharyngitis, sinusitis, pneumonia)
    • -Azithromycin is concentrated in *phagocytic cells and other tissues
    • -Hepatic metabolism and excretion, some urinary extretion (Azithromycin)

    * Efficacy can be prolonged by their concentrations in secretions.
  3. What is the Mechanism of action of the macrolides?
    • -Bind to 50 S subunit of bacterial ribosome
    • -Prevents ribosomal translocation down m-RNA
    • -Generally Bacteriostatic
  4. What is bacteriostatic mean?
    preventing bacteria from growing and multiplying but possibly not killing them
  5. What are some mechanisms of Resistance to Macrolides?
    • -Plasmid mediated alteration (by a methylase
    • encoded by the erm beta gene) of receptor on ribosome – high level resistance {eg Strep pneumo}

    • -Production of inactivating enzymes
    • -Decrease in permeability of bacterial organism into the antimicrobial agent.
    • -Increased efflux (mediated by mefA gene) - low level resistance
  6. What are the Levels of Pneumococcal resistance of the Macrolides and others?
    • Penicillin V - 15%
    • Erythromycin - 35% (not a good one)
    • Augmentin - 8% (good)
    • Cefpodoxime - 20%
    • Azythromycin - 35% (not a good one)
  7. Why are macrolides good for pneumococcal infections?

    What is the drug of choice for otitus media?
    -becaue they concentrat in the Respiratory secretions

    - Augmentin- due to resistance pneumococi
  8. What is the spectrum of Macrolides?
    • Sensitive gram positive organisms; not enterococcus
    • Some anaerobes
    • Salmonella (Typhoid fever)*
    • Legionnaire’s disease *
    • Mycoplasma *
    • Chlamydia
    • Bordetella pertussis *
    • Campylobacter *
    • Atypical Mycobacteria *
  9. What is the Drug of Choice for:
    Salmonella Typhoid fever infection?
    Bordetella Pertussis (Whooping Cough)?
    Atypical TB?
    • Azythromycin
    • Clarithromycin or Erythromycin
    • Clarithromycin
    • Clarithromycin
  10. What are the Clinical Uses for the Macrolides?
    When are they Contraindicated? except which?
    Penicillin substitute for respiratory bacterial infections

    Atypical pneumonia; Whooping cough (Clarithromycin)

    MAI (Seen in AIDS) (Clarithromycin)

    Resistant Salmonella (Azythromycin)

    Contraindicated in pregnancy (except Azithromycin)
  11. What is the Clinical use and the Spectrum of Telithromycin?
    Where is it metabolized?
    • Metabolized in the liver – half by CYP 450
    • and half by CYP 349

    PCN resistant pneumococci, H. flu, M. catarrhalis, and atypicals: B. pertussis, mycoplasma, legionella, chlamydia
  12. What is the Toxcitity of Telithromycin?
    • Blurred Vision
    • GI disturbances
    • Prolonged QT Interval
    • Exacerbation of Myasthenia gravis
    • Multiple drug interactions
  13. What other drug is similar to microlides due to some cross resistance?
    • - Clindamycin----- a Protein Synthesis Inhibitor
    • -A Lincosamide Antibiotic - static
    • -Good oral absorption (90%) and tissue
    • penetration (not cns,eye)
    • - Resistance is usually due to bacterial increased efflux
  14. Clindamycin – Spectrum and Toxicity
    • -Excellent drug for gram positive infections (including Staph aureus (even MRSA!!!!)
    • -Excellent activity against anaerobes

    • Lincosamides like Clindamycin destroy the
    • normal intestinal flora, which allows C. difficile to grow & secrete its toxin, causing a bloody
    • diarrhea
    • -DOC to treat C. difficile overgrowth is Metronidazole then Vancomycin
  15. What is Synercid?
    How is it metabolized?
    -A Streptogramin combination (quinupristin/dalfopristin 30:70)

    -Metabolized and excreted by the liver. Only for IV use T1/2 1 to 3 hours
  16. What is Synercid's Mechanism of action/ resistance?
    Mechanism of Action

    -Binds to 50 S subunit (unique sites)

    • -Prevents ribosome from translocating down the mRNA and prevents protein synthesis at the elongation step
    • -Bacteriocidal- Actually kills bacteria

    Mechanism of Resistance

    • -Mediated by usual three mechanisms
    • -Resistance develops quite rapidly
  17. What is the Spectrum of Synercid?
    What is its toxicity?
    • -Staph aureus and epidermidis
    • -Strep pyogenes and aglacia
    • -Some enterococci
    • -Only treats Gram + Organisms

    • Toxicity $$
    • Precludes widespread use: drug interactions,
    • phlebitis 40%, jaundice 30%, arthralgia
    • and myalgia 20%
  18. What is Linzolid?
    What is it used to treat?

    Where is it metabolized? better penetration where?
    • -An Oxazolidione
    • Available in oral and intravenous formulations
    • Used to treat Vancomycin resistant microorganisms

    • -Metabolized in liver; excreted by kidney
    • -Better penetration into lung (pneumonia) than Vancomycin
  19. What is Linzolids Mechanism of Action/Resistance?
    • Mechanism of Action
    • -Binds to 50 S subunit (unique site)
    • -Inhibits initiation complex and translocation of tRNA
    • -Generally Bacteriostatic

    • Mechanismof Resistance
    • -Decreased affinity of antimicrobial agent to bacterial target site
  20. What is Linzolides Spectrum and Toxicity?
    -All aerobic gram positive organisms especially resistant staph, strep and enterococci

    • Toxicity
    • -Thrombocytopenia and neutropenia (reversable
    • bone marrow suppression)
    • -weak MAO inhibitor
  21. What are some Antimicrobials to avoid in pregnancy?
    (SAFE Moms Take Really Good Care)

    • Sulfonamides – Kernicterus
    • Aminoglycosides – Ototoxicity
    • Fluoroquinolones – Cartilage damage
    • Erythromycin – Acute cholestatic hepatitis in mom &
    • Clarithromycin – embryotoxic
    • Metronidazole – mutagenasis
    • Tetracyclines – discolored teeth,
    • inhibition of bone growth
    • Ribavirin (antiviral) – teratogenic
    • Griseofulvin (antifungal) – teratogenic
    • Chloramphenicol – “grey baby”
  22. Mechanisms of Protein Synthesis Inhibition.

    Which drugs use Formation of initiation complex?
    Which drugs use Amino Acid incorporation?
    Which drugs use Formation of peptide bond?
    Which drugs use Translocation?
    -Aminoglycosides (30 S) and Linezolide (50 S)

    -Tetracyclines (30 S) and Dalfopristin/Quinupristin (50 S)

    • -Chloramphenicol (50 S)
    • -Macrolides (50 S) and Clindamycin (50 S)
  23. What are the DOC for?
    Meningitis of New born?
    Meningitis of Neonate?
    • -erythromycin or azithromycin (bascially pick a macrolide as the ans choice)
    • -cefotaxime
    • -ceftriaxone
    • -cefotetan
    • -ceftazidime
    • -Penicillin G
  24. What is the DOC for:
    Whooping cough?
    Legionella/Poniac fever?
    Salmonella Typhi?
    Liver abscesses or Cholecystitis?
    • -TMP/Sulfa drugs (next would be ciproflox)
    • -macrolides
    • -erythromycin
    • -Azithromycin; ciproflox; ceftriaxone
    • -ceftriaxone (for later stages);
    • -Cefotaxime
Card Set
Pharm Block 2 (macrolides/ Ketolides)
Pharm Block 2 (macrolides/ Ketolides)