13. Aminoglycosides Flashcards
List the aminoglycoside.
- Streptomycin
- Paromomycin
- Kanamycin
- Neomycin
- Gentamicin
- Tobramycin
- Amikacin
- Netilmicin
- Spectinomycin
What is MOA of Aminoglycosides?
- They irreversibly binds 30s → mRNA misreading → bactericidal effect.
- They are concentration dependent and have long post antibiotic effect.
- They pass outer cell wall via passive diffusion (porin channels) but use active mechanism through inner cell wall which is oxygen dependent → no anaerobe effect
- Co-admin with cell wall synthesis inhibitors (B-lactams, vancomycin) enhances effect by ↑ wall penetration.
List the more resistant aminoglycosides to enzymatic degradation.
These are alternatives for genta-/tobramycin-resistant infections.
- Amikacin: broadest spectrum, but most expensive, resistant to inactivation by many acetylases, 2nd line anti-TBC and also good for Pseudomonas, High ototoxicity, lower nephro
- Netilmicin
- Spectinomycin - structurally-related to aminoglycosides; indicated in penicillin-resistant Gonorrhea infections (but can try cephalosporins first)
What spectrum does aminoglycosides cover?
- Mainly Gram - aerobes (no effect against anaerobes or IC pathogens)
- All Gram - enterics (KES, Proteus, Pseudomonas, Acinetobacter)
- Many zoonotics (streptomycin for Francisella, Yersinia and Brucellosis)
- Some effect on Gram + aerobes (Staph, Strep, Enterococci), but weaker… only given in combo with cell wall inhibitors.
What are the resistance mechanism against Aminoglycosides?
- Fewer porin channels - ↓ permeability
- Degradation - by acetylation enzymes, esp. by Enterococcus; most common resistance mechanism; amikacin + netilmicin are least susceptible to acetylation
How are the kinetic parameters like for Aminoglycosides?
- Not absorbed orally due to hydrophilicity; only given via parenteral admin
- No CNS entry unless given intrathecally (rare, cephalosporins are better for meningitis)
- No IC entry or adipose penetration
- Only enters into hydrophilic spaces (peritoneum, pleura, EC space) → must calculate dosage based on body weight + increases in relative EC space (edema, ascites, pregnancy, newborns) or decreases in relative EC space (obesity; ex: consider only 40% of their weight over 80 kg… so a 120 kg obese man is dosed like a 96 kg person)
What are the side effects of Aminoglycosides?
-
High toxicity → usually only in life threatening diseases + in combo (rarely may be used as monotherapy).
- Ototoxicity - vestibular effects → dizziness, ↓ equilibrium; cochlear effects → high frequency first, lower later. Starts from beginning of treatment and is irreversible. Can cause deafness in newborns.
- Nephrotoxicity - starts later into treatment (~ 5 days). Reversible at first; irreversible only later. (Worse in renal insufficiency or with loop diuretics / other nephrotoxins). (Via acute tubular necrosis → brown casts seen on urinalysis + ↑ creatinine).
- Muscle Relaxant Effect - curare-like NMJ blockade; may cause respiratory failure; contraindicated in myasthenia gravis !
List the most commonly used aminoglycosides.
Most commonly used for resistant UTI as monotherapy (E. coli, KES group) or in combo for Staph/Strep life-threatening endocarditis, osteomyelitis; or Pseudomonas.
- Gentamicin
- Tobramycin
List the most toxic compounds out of the Aminoglycosides.
- Kanamycin: 2nd line anti-TBC
- Neomycin: given before colorectal surgery to eliminate GI bacteria or as hepatoprotective to destroy ammonia-producing flora → ↓ hepatic encephalopathy risk
What are the indications for Streptomycin?
For Brucellosis, Tularemia or Yersinia in combo with doxycycline.
What are the indications for Paromomycin?
For luminal effect on parasites (E. histolytica etc.)
What are the indications of Gentamicin?
Gentamicin is used for:
- Staph: combine oxacillin and gentamicin
- Enterococcal endocarditis: combine ampicillin and gentamicin
- Pseudomonas: combine piperacillin and gentamicin.
What are the indications of Tobramycin?
Tobramycin has similar uses to gentamicin; especially Pseudomonas.
