Aminoglycosides Flashcards
What is the chemical structure of aminoglycosides?
Two or three sugars attached through glycosidic linkages to an aminocyclitol
What are the admixture incompatibilities?
Admixture with penicillins can cause precipitation (insoluble salt complex) and inactivation of both drugs
What aminoglycosides are most susceptible to admixture incompatibilities?
- Gentamicin
- Tobramycin
- Amikacin
What beta-lactam antibiotics are the most problematic in admixture incompatibilities?
- Ticarcillan, Carbenicillin–no longer available
- Piperacillin/tazobactam
How do you avoid admixture incompatibilities?
If giving two drugs, then administer into different tissue compartments (one drug on each arm)
What is the MOA?
Inhibition of protein synthesis
* Binds to the bacterial 30S ribosomal unit which:
* Interferes with initiation of protein synthesis
* Blocks 30S-50S ribosomal complex from forming at the start codon of 16S mRNA
* Blocks further translation of the message
* Causes misreading of mRNA which leads to
* Production of nonfunctional proteins
* Incompletely synthesized protein
What is the SOA of aminoglycosides?
Serious systemic infections due to gram-negative bacilli (rods) that can grow aerobically
* Strict aerobes
* Facultative aerobes
* Ex: Pseudomonas, enterobacterales
What is aminoglycosides less susceptible to?
- Aerobic gram-positive cocci (synergism with beta-lactams for Enterococci)
- Aerobic gram-negative cocci
What are aminoglycosides resistant to?
- Anaerobes
- Stentrophomonas
- Burkholderia
What are aminoglycosides pharmacodynamic properties?
- Bactericidal
- Rate and extent of killing is concentration dependent
Post antibiotic effect
- Residual bactericidal activity persist after serum concentration has fallen below the MIC
What are the special patient populations with altered PK?
- Burn patients
- Critically ill
- Obesity
- CF
- Ascites
- Overhydration
- Dialysis
What are the pharmacokinetics?
- Very poor oral bioavailability due to high polar cations
- Wide to extracellular fluid (ECF)
- Highly polar nature excludes many cells
- Negligible protein binding
What is the elimination of aminoglycosides?
- Almost entirely via glomerular filtration as unchanged drug
- Do NOT require metabolism
- Elimination rate increases in proportion with CrCl
- Half-life: 2-3 hrs in patients with normal renal function (anephric patients: half-life is 20-40x that of those with normal renal function)
- Regimen MUST be adjusted with impaired renal function (to avoid nephrotoxicity)
- Pharmacokinetic/Therapeutic Drug Monitoring (TDM) is required
Nephrotoxicity
- Toxicity due to accumulation and retention in the proximal renal tubular cells
- Consequence = reduced excretion and additional risk of other toxicities
What are the two types of ototoxicity?
- Cochlear
- Vestibular
What are the risks of getting cochlear ototoxicity?
- Genetic predisposition
- Preexisting hearing problems
- Loop diuretics co-admin
Vestibular ototoxicity
- Manifest as vertigo or ataxia
- Most common with streptomycin
What are the risk factor of ototoxicity?
- Frequent or very high doses
- Very high blood levels of the drug
- Long duration of therapy ( > 3 days)
- Older age
Neuromuscular toxicity
- Rare
- Prolongs neuromuscular blocker effect (typically with higher doses)
- Can worsen weakness in disorders affecting neuromuscular transmission (ex: myasthenia gravis)
What are some contraindications?
- Pregnancy
- Hypersensitivity
When should aminoglycosides be used in caution in?
- Vertigo
- Tinnitus
- Hearing loss
- Renal disease
- Neuromuscular disease
What are some drug interactions?
- Vancomycin (nephrotoxicity)
- Loop diuretics (nephrotoxicity, ototoxicity)
- Polypeptide antibiotics (nephrotoxicity, neuromuscular toxicity)
Which aminoglycosides are used to treat Pseudomonas?
- Tobramycin preferred for urinary tract
- Amikacin for urinary infections
