Aminoglycosides Flashcards
MoA
Irreversibly bind to bacterial ribosomes.
Active against gram negative aerobe (pseudomonas aeruginosa)
Broad spectrum
Bactericidal
Uses
Severe sepsis
Pyelonephritis
Complicated UTI
Endocarditis
Administration
Parenteral injection
Not absorbed by gut
Different types of aminoglycosides
Gentamicin - choice; active against pseudomonas aerguinoa
Tobramycin - via inhaler for pseudomonal infection in cystic fibrosis
Streptomycin - active against mycobacteria; reserved for TB
Neomycin - parenterally toxic; use in bowel sterilisation
Amikacin - gentamicin resistant gram negative bacilli
Gentamicin
Choice drug in UK
Active against pseudomonas aeruginosa
Blind therapy in serious infection in combination with pencillin/metronidazole
Gentamicin - therapeutic index
Narrow T.I
Monitor Cp
MUST monitor Cp in:
- parenteral aminoglycosides
- elderly
- obesity
- cystic fibrosis
- high doses
- RENAL impairment
ONCE daily regimen
Avoid in:
- Renal impairment (<20 ml/min)
- HACEK or Gram+ endocarditis
- Burns covering >20% of body
Consult local guidelines for serum monitoring.
Multiple dose regimens
Monitor after 3 or 4 doses AND after a dose change.
Renal impairment = more frequent + earlier monitoring
Post-dose (peak) level after 1 hour is too HIGH
Reduce dose to 5-10mg/ml (3-5 mg/ml for endocarditis)
Pre-dose (trough) level before next dose is too HIGH
Increase interval <2mg/ml (<1mg/ml for endocarditis)
Renal impairment
Increase interval
Severe renal impairment
<30 ml/min
Reduce dose
Pregnancy
Can give - AVOID unless essential
Monitor Cp
Side effects
Dose related - do not exceed 7 days
Common in elderly and renal failure (renally cleared)
Nephorotoxicity
Aminoglycosides are excreted by kidneys
Assess renal function before treatment
Correct any dehydration
Signs:
- Low urine output/CrCl
- High serum creatinine/urea
Interactions - increased risk of nephrotoxicity
Ciclosporin
Tacrolimus
Vancomycin
AVOID concomitant nephrotoxic drugs (DAMN)
Reversible ototoxicity
Monitor auditory and vestibular function before treatment
Counsel pt to report:
- Hearing loss
- Tinnitus
- Vertigo
Interactions - increased risk of ototoxicity
Loop diuretics
- If giving concomitant ototoxic loop diuretics, separate by as long a period as possible
Cisplatin
AVOID concomitant ototoxic drugs
Other Side effects
Peripheral neuropathy
Impaired neuromuscular transmission
- C/I in myasthenia gravis
Electrolytes:
HYPO K, Ca + Mg
MHRA: Potential histamine related adverse drug effects
Some batches may contain histamine residue from manufacturing process.
Monitor for signs of histamine-related reactions.
Caution in concomitant drugs known to cause histamine release, in children + severe renal impairment
MHRA: increased risk of deafness in patients with mitochondrial mutations
Increased risk of deafness in patients with mitochondrial mutations (particularly the m.1555A>G mutation), including cases where the patient’s aminoglycoside serum levels were within the recommended range.
