Aminoglycosides Flashcards
What are indications?
systemic Used for severe infections especially G-negative aerobes
- sepsis
2.pyelonephritis and complicated UTIs - Intrabdominal infection
- endocarditis
- Otitis externa- neomycin topical
What is the spectrum of activity?
G-NEGATIVE
aerobic
Activity against some staphylocci and mycobacteria
Inactive against strep and anaerobes so are often used as part of combo treatment (e.g with a penicillin and metronidazole)
What is the mechanism of action?
Bind irreversibly to bacterial ribosomes and inhibit protein synthesis.
Bacteriacidal
They enter bacterial cells via an oxygen dependent transport system
Strep and anaerobic bacteria do not have this transport so are resistant
How do bacteria develop resistance?
reduced cell membrane permeability to amino-glycosides
acquisition of enzymes that modify amino-glycosides to prevent them from reaching ribosomes
Hoe do penicillins enhance the spectrum of activity of ahminoglycosides?
As penicillins weaken bacterial cell walls, they may enhance aminoglycoside activity by increasing penetration into bacterial cells.
What are important side effects?
systemic-
nephrotoxicity:
reduced urine output
rising CrCl
ototoxicity:
hearing loss
tinnitus
vertigo
Who should be prescribed with caution?
Systemic-
dose adjustment:
neonates
older people
renal impairment
Avoid:
myasthenia gravis
What are important interactions?
Side effects more likely if
co-prescribed with loop diuretics or glycopeptide antibiotics
Nephrotoxicity more likely if:
co-prescribed with NSAIDs, cephalosporins and other nephrotoxic drugs.
What are examples of amino-glycosides?
Gentamicin, amikacin,neomycin
What is the route of administration for systemic therapy?
Parenterally-
ahminoglycosides are highly polarised and do not cross the lipid membrane
aminoglycosides are infused slowly (e.g. over 30min).
This limits exposure of the ear to high peak concentrations (a potential hazard of impatience during IV injection).
What is dosage?
IV intermittent infusion once daily
Dose calculated by weight and renal function
Dose interval is determined by drug level monitoring
subsequent doses administered when plasma concentrations have fell to safe level
Dose interval normally 24 hours in normal renal function
Longer in renal impairment
What formula is normally used to figure out dosage in obese patients and why?
ideal body weight +0.4 x (actual body weight-ideal body weight)
In obese patients, ‘excess weight’ contains disproportionately more fat than water. Since aminoglycosides distribute only through body water (not fat), only a proportion of the excess weight is included in dosage calculation
Why is dosage calculating so important in amino-glycosides?
It had a narrow therapeutic index meaning little safety margin between effectiveness and the toxic dose.
What are monitoring requirements for safety?
For safety, measure renal function before (to guide dosing) and during (to detect toxicity) parenteral aminoglycoside therapy.
Follow local protocols for plasma drug concentration measurement. Levels may be taken 18–24hours after a dose (trough level), and the next dose administered if this has fallen to a safe level (e.g. gentamicin <1mg/mL).
Alternatively, a mid-interval concentration (6–14hours after the dose) may be compared to a nomogram to determine when the next dose is given.
How long should treatment last?
Treatment duration should be as short as possible to limit toxicity: usually less than 7days, and often just a single dose
