Antibacterial Agents III - Inhibitors of protein synthesis Flashcards
Macrolides: mechanism of action
- Binds to the 50S subunit and inhibits protein synthesis
- Not actively transported, enters bact by passive diffusion
- bacteriostatic
Macrolides: pharmacokinetics:
well absorbed orally (erythro and azithro also in IV)
- erythro - admin with enteric coating- absorption depends on salt form
- Clarithro - can be taken without regard to meals
- Azithro = taken on empty stomach
-Distributed widely, except brain and CSF; reaches the fetus
- E - metab in liver (avoid with liver disease)
- C = metab to active compound, renal elim
- A = not metab
- Excreted in breast mild
Macrolides: spectrum of activity and major clinical uses
- outpt tx of URI and LRI
- atypical organisms
all = g+c, g-c, g-b, mycoplasma pneumoniae A = Chlamydia E = g+b C = H. influenzae
Macrolides: Side effects and significant drug interactions
- GI Disturbances: due to direct stimulation of gut motility by erythromycin, less with azithromycin and clarithromycin.
- Hepatotoxicity
- Prolongs QT interval
- Drug Interactions: Erythromycin metabolites and clarithromycin can inhibit cytochrome P450 enzymes [NOT azithromycin]
Tetracyclines: mechanism of action
- bacteriostatic
- binds to 30S ribosomal subunit and inhibits protein synthesis
- selective toxicity - host cells have active efflux mechanism that prevents intraellular accumulation of drugs and lacks an active transport for moving drug into cell
Tetracyclines: absorption and distribution
- oral absorption from the stomach and SI (best given on an empty stomach)
- doxycycline highest bioavailability
- Absorption is impaired by milk products, Al+++, Ca++, Mg++, and Fe++ salts
- penetration into most tissues/fluids is excellent, including placental / fetal circulation -Concentrated in liver, secreted into bile (use with caution in impaired liver function)
Tetracyclines: Spectrum of activity and Major clinical uses
Broad spectrum agent but overuse has led to widespread resistance for many organisms.
g+c, g-c, g-b, g+b, anaerobes, atypical, spirochetes
-S. aureus [MRSA!] (Doxy)
-chlamydia (Doxy)
-m. pneumoniae (Doxy)
Tetracyclines: side effects and significant DDIs
- temp bone growth dep
- teeth discoloration
- Avoid use during latter half of pregnancy and in children** under 8 years old
- GI disturbance
- Photosensitivity
- Yeast overgrowth
-Antacids/Fe supplements (dec bioavailability)
Clindamycin: mechanism of action
binds to 50S and inhibits protein synthesis
- preventing translocation of peptidyl tRNA and peptide bond formation
- bacteriostatic
Clindamycin: pharmacokinetics
• Absorption: 90% of oral dose absorbed, not affected by presence of food.
• Distribution: Penetrates most tissues well, especially bone, but not well into CSF.
• Metabolism / Excretion: Metabolized by liver, then primarily biliary excretion, no dosage adjustment required in renal failure;
–excreted in breast milk.
Clindamycin: spectrum of activity and major clinical uses
Treatment of severe anaerobic infections
- anaerobes (c. perfringens and B. fragilis)
- -wounds which penetrate the abd
- -gas gangrene - G+ (if severe allergies to PCN and cephalosporin)
- TSS (GAS and S. aureus)
- MSSA and MRSA
Clindamycin: Side effects and significant DDIs
• Pseudomembranous colitis. Toxigenic Clostridium difficile selected out during treatment (superinfection, 0.1-10%).
Common: N/D, skin rashes
-Probably no worse than some broader spectrum agents (amoxicillin-ampicillin, 2nd/3rd generation cephalosporins, fluoroquinolones).
Tetracyclines: metabolism/excretion
- enterohepatic recirculation
- Most excreted into urine, important exceptions are doxycycline and minocycline (thus, doxycycline is choice for patients with underlying renal disease) and breast milk
- tetracycline: short acting
- doxy: longer acting
