C.13 Flashcards
Aminoglycosides
Gentamycin,
Neomycin,
Amikacin,
Tobramycin,
Streptomycin,
Netilmycin,
Kanamycin
Aminoglycosides
MOA: Binds to 30S subunit → misreading, functionally uneffective proteins → irreversible cell damage → bactericidal effect (concentration-dependent killing effect).
Additionally interfere with the initiation complex and breaks the polysomes into monosomes.
PAE- 3-6 h.
-First exposure effect → transient resistance after the exposure → administer once daily;
Penetration: brought into the cell in partly active transport, requires O2 → in anaerobic bacteria aminoglycosides are not effective!;
Mechanism of resistance: Inactivating enzymes (adenylation, acetylation, phosphorylation), Impaired entry into cell, Altered binding site;
Pharmacokinetics: Highly polar molecules (→ poor absorption), Bad penetration, bad distribution (no penetration through BBB), Excreted unchanged by kidneys → to avoid toxicity the kidney function is extremely important! - dose reduction in renal impairment;
SEs: Narrow therapeutic index, risk of severe toxicity.
-Nephrotoxicity (→continuous concentration in the proximal tubular cells by active transport → saturable: The duration of the high level is important, and not how high is the level! - usually reversible, combination with other nephrotoxic substances (e.g. vancomycin) - the risk is higher),
-Ototoxicity (→vestibular (vertigo, ataxia, loss of balance) damage. Auditory (tinnitus, high frequency hearing loss) damage), Neuromuscular blockade (→high concentration → avoid RAPID I.V administration),
-Allergy (→rare),
-Teratogenic (→Fetal ototoxicity);
Spectrum: Most important: Gram(-) rods, Gram(+) may be sensitive or resistant
- Sensitive: S.aureus, Coagulase-negative staphylococci, A-streptococci.
-Less sensitive/resistant: B-streptococci, enterococci, others.
-Anaerobe and intracellular bacteria are resistant!;
Clinical use:
-Newer aminoglycosides - important antibiotics for treatment of severe bacterial infections (usually in combination with β-lactams).
-Older aminohlycosides- special indications or topical use only! Once-daily administration schedule. Renal function is important to avoid adverse effects - if necessary: monitoring;
Contra-IND: patients with myasthenia gravis (b/c of the neuromuscular blockade)
Gentamycin & Tobramycin & Netilmicin
Gentamycin → Standard substance.
Tobramycin → More active against pseudomonas.
Netilmicin → Slightly less resistance;
IND: Parentral for: Acute life-threatening infections in combination with β-lactams (cephalosporins), but NOT in the same infusion → inactivity may occur.
Sepsis, pneumonia, endocarditis;
Spectrum: Gram (-) → pseudomonas, enterobacter (w. penicillin/vancomycin), serratia, proteus, acinetobacter, klebsiella infections;
Resistance: May occur (pseudomonas, staphylococci, enterococci);
ROA: Parentral mainly, but topical is also possible;
Dosing regime: 1-3xdaily;
T1/2 :2-3h
Amikacin
spectrum: Broadest spectrum aminoglycoside → the least resistance!;
IND: Reserve antibiotic for those cases when other aminoglycosides are not active;
Dosing regime: 1-3xdaily;
T1/2 :2-3h
Streptomycin
resistance: Limits its usefulness;
IND: Tubercolosis: (second line agent, in combination), rarely plague, tularemia, brucellosis (in combination with tetracyclin);
Dosing regime: 1-3xdaily
Neomycin + kanamycin
IND: topical use on infected surfaces, injected into joints, pleural cavity, tissue spaces, abscess cavities. Pre-bowel surgery:
suppress intestinal flora (GI decontamination);
ROA: Neomycin- Oral, Kanamycin
-topical; Systemic/topical use: Too toxic for systemic use!
Postantibiotic effect (PAE)
refers to the temporary suppression of bacterial growth following transient antibiotic treatment
Why is Neomycin safe to use in liver failure?
If someone has liver failure the liver cannot reduce ammonia.
Bacteria are the number 1 source of ammonia in the body, so we can decontaminate the GI from the normal flora with neomycin and reduce the toll on the liver
