Protein synthesis inhibitors - Macrolides

Question 1

Erythromycin

Answer 1

• **Bacteriostatic **
• useful alternative to PCN G for **G+ and some G - **
  
  • **​G+ cocci and bacilli **(mycoplasma, legionella, chlamydia)
  • **inactive against most aerobic G - bacilli **
• MOA = binds L15 protein of 50S and inhibits protein synthesis by inhibiting translocation; premature release of polypetides by preventing exit of the nascent polypeptide chain​
• **PO or parenteral **
• concentrated in liver
• widely distributed (NOT to CNS) (WILL reach fetus)
• **biliary excretion **
• drug interactions due to inhibition of P450
• adverse effects =
  
  • **GI intolerance (direct stimulation of gut motility) **= promotes peristalsis postop
  • **liver toxicity **= estolate salt greatest risk
    
    • acute cholestatic hepatitis (hypersensitivity rxn) (reversible)
    • **reversible hearing loss **(high doses)
    • **QT prolongation w/ ventricular tachycardia **
• resistance
  
  • efflux (remove drug from cell)
  • metabolism (inactivate drug)
  • mutation (alter binding site) = add methyl group

Question 2

Clarithromycin

Answer 2

• Bacteriostatic
• more stable than erythromycin
• useful alternative to PCN G for G+ and some G -
  
  • ​G+ cocci and bacilli (mycoplasma, legionella, chlamydia)
  • **inactive against most aerobic G - bacilli **
• MOA = binds L15 protein of 50S and inhibits protein synthesis by inhibiting translocation; premature release of polypetides by preventing exit of the nascent polypeptide chain​
• PO or parenteral
• liver metabolism - active metabolite (reduce dose in hepatic dz)
• widely distributed (NOT to CNS) (WILL reach fetus)
• renal excretion
• drug interactions due to inhibition of P450
• adverse effects =
  
  • lower frequency of GI intolerance
  • reversible hearing loss (high doses)
  • teratogenic in animals (AVOID pregnancy)
• resistance
  
  • efflux (remove drug from cell)
  • metabolism (inactivate drug)
  • mutation (alter binding site) = add methyl group

Question 3

Azithromycin

Answer 3

• Bacteriostatic
• **useful alternative to PCN G for G+ and some G - **
  
  • **​G+ cocci and bacilli **(mycoplasma, legionella, chlamydia)
  • **inactive against most aerobic G - bacilli **
• MOA = binds L15 protein of 50S and inhibits protein synthesis by inhibiting translocation; premature release of polypetides by preventing exit of the nascent polypeptide chain​
• **penetrates tissues very well **(NO CNS)
  
  • drug slowly released from tissues
  • elimination half life = 3 days
• well tolerated PO
• adverse effects =
  
  • ** DOES NOT INHIBIT P450 **(relatively free of drug-drug interactions)
• **resistance **
  
  • **efflux **(remove drug from cell)
  • **metabolism **(inactivate drug)
  • **mutation **(alter binding site) = add methyl group