Pharmacology Exam II

  1. A group of closely related compounds characterized by a macrocyclic lactone ring to which deoxy sugars are attached
  2. Macrolides contain ___-___ carbon atoms
  3. Erythromycin
    • macrolide
    • wider spectrum than PCN
    • used in people with PCN allergy
  4. Erythromycin consists of
    • two sugar moieties attached to a 14-atom lactone ring
    • sugars are desosamine and cladinose
  5. Erythromycin stability
    • poorly water soluble
    • solutions unstable at room temp
    • lose activity rapidly in acidic pH
  6. Reason why erythromycins are usually dispensed as various esters
    to increase solubility
  7. Erythromycin is active against
    • gram-positive organisms
    • gram-negative organisms
    • Mycoplasma
    • haemophilus influenzae somewhat less susceptible
  8. Mechanism of Erythromycin
    • inhibitory or bacteriocidal
    • binds 50s ribosomal subunit
    • blocks the aminoacyl translocation preventing transfer of tRNA at the A site from moving to the P site
  9. Three mechanisms of resistance to macrolides
    • reduced cell membrane permeability or active efflux
    • production of esterases that hydrolize macrolides
    • modification of the ribosomal binding site (ribosomal protection)
  10. Most important resistance mechanisms against macrolides in gram positive organisms
    • efflux
    • methylase production
  11. Cross resistance exists between
    erythromycing and other macrolides
  12. Erythromycin absorption
    • erythromycin is destroyed in stomach acid and needs an enteric coating
    • food interferes with absorption
    • large amounts excreted in bile and feces, 5% in urine
  13. Fairly acid-resistant, better absorbed forms of erythromycin
    • stearates
    • erythromycin ethylsuccinate
  14. Distribution of erythromycin
    widely distributed except CNS
  15. Erythromycin is taken up by
    • polymorphonuclear leukocytes
    • macrophages
  16. Will erythromycin cross the placenta?
  17. Erythromycin t1/2 is increased in patients with____ and is not removed via____.
    • anuria
    • dialysis
  18. Erythromycin dosing must be done for patients with renal failure

    A. True
    B. False
    B. False
  19. Erythromycin is the drug of choice for
    corynebacterial infections
  20. Erythromycin is also used for
    • respiratory infections
    • neonatal/ocular/genital infections
    • community aquired pneumonia
  21. Erythromycin is recommended as prophylaxis against
    • endocarditis during dental procedures
    • largely replaced by clindamycin
  22. ADRs with erythromycin
    • N/V/D
    • anorexia
    • direct stimulation of GI motility
  23. Forms of Erythromycin less likely to have adverse effects
    • stearate
    • succinate salt
  24. Liver and Erythromycin
    • can produce acute cholestatic hepatitis
    • hepatitis recurs when the pt is given e-mycin again
  25. Drug interactions with Erythromycin
    • Erythromycin inhibits CYP3A4
    • statin levels will ^^
    • ergotamine and dihydroergotamnie levels ^^
    • digoxin levels will ^^
  26. Simvastatin + erythromycin
    can cause rhabdomyolysis
  27. clarithromycin
    • derived from erythromycin by addition of 1 methyl group
    • improved acid stability
    • improved oral absorption
  28. Uses of clarithromycin
    • upper RTIs
    • chronic bronchitis
    • pneumonia
    • skin infections
    • legionellosis
    • lyme disease
  29. Mechanism of action for clarithromycin
    • same as erythromycin
    • binds 50s subunit and inhibits translocation of peptides
  30. clarithromycin is metabolized by the _____ to _____.
    • liver
    • active metabolites (14-hydroxy clarithromycin)
  31. 14-hydroxy clarithromycin
    • active metabolite of clarithromycin
    • almost twice as active with a longer half life
  32. Clarithromycin and metabolites are excreted via
    • urinary
    • biliary
  33. Dosage reduction is recommended for patients with creatinine clearance less than ____ who are taking clarithromycin
  34. Clarithromycin compared to erythromycin
    • similar drug interactions
    • cross resistance
    • clarithromycin has a longer half life permiting bid dosing
    • Cl. has lower incidence of GI intolerance
  35. Clarithromycin is more effective than erythromycin against
    certain gram negative bacteria including legionella pneumophila
  36. Clarithromycin has bacteriostatic and bacteriocidal effects against
    • H. Influenzae
    • S. pneumonia
    • N. Gonorrhoeae
  37. Azithromycin
    • zithromax
    • 15 atom lactone macrolide
    • additional methylated nitrogen added into the lactone ring of erythromycin
  38. Mechanism of action for Azithromycin
    • prevents bacterial growth
    • binds 50s subunit of ribosome inhibiting translovation of mRNA
    • nucleic acid synthesis is not affected
  39. Azithromycin activity compared to Clarithromycin and Erythromycin
    same spectrum
  40. Active against M Avium complex and T gondii
  41. More effective against staph and strep
    • erythromycin
    • clarithromycin
  42. more active against H. influenzae
  43. Highly active against chlamydia
  44. Kinetics of Azithromycin
    • low serum concentration
    • absorbed into tissues and released slowly with a half life of 3 days
    • once daily dosing
  45. A single 1 gram dose of azithromycin is as effective as _____ for chlamydial cervictis and urethritis.
    a 7 day course of doxycycline
  46. Azithromycin administration with reguard to meals
    1 hour before or 2 hrs after
  47. Azithromycin CYP interaction
    because it has a 15 membered ring it does not inactivate CYP enzymes
  48. Ketolides
    • semisynthetic 14 membered ring macrolides
    • substitution of a 3-keto group for cladinose
  49. Example of a ketolide
  50. Mechanism of action for telithromycin
    • prevents bacterial protein synthesis
    • binds 50s ribosomal subunit
    • can also inhibit formation of ribosomal complex formed between 50s and 30s
  51. Telithromycin vs. erythromycin
    telithromycin has over 10x higher affinity for the 50s subunit than erythromycin
  52. Many macrolide resistant strains are succeptible to ketolides because
    • poor substrates for efflux pumps
    • bind ribosome with higher affinity
  53. Absorption and excretion of telithromycin
    • 57% oral bioavailability
    • metabolized in the liver
    • eliminated by biliary and urinary routes
  54. Clinical uses for telithromycin
    • Respiratory tract infetions
    • non-tuberculosis mycobacteria
  55. Telithromycin toxicities
    rare cases of hepatitis and liver failure
Card Set
Pharmacology Exam II