Protein Synthesis Inhibitors (Aminoglycosides)

Which drugs belong to the aminoglycoside class in this lecture?

Amikacin, Gentamicin, Neomycin, Streptomycin, and Tobramycin.

What routes are listed for amikacin?

IV (Intravenous).

What routes are listed for gentamicin?

IV and Ophthalmic.

What routes and uses are listed for neomycin?

Topical for eye/ear/skin, and oral for gut decontamination.

What routes are listed for streptomycin?

IV (Intravenous).

What routes are listed for tobramycin?

IV, Ophthalmic, and Inhaled.

What is the mechanism of action of aminoglycosides?

They bind to the 30S ribosomal subunit, halting bacterial protein synthesis.

Are aminoglycosides bactericidal or bacteriostatic?

Bactericidal.

What type of killing do aminoglycosides exhibit?

Concentration-dependent killing.

What is the antibacterial spectrum of aminoglycosides?

Gram-negative organisms only, including Pseudomonas.

Which aminoglycosides in the lecture have activity against Mycobacterium tuberculosis?

Amikacin and Streptomycin.

Which aminoglycoside did the professor emphasize as being included in tuberculosis guidelines?

Streptomycin.

How are aminoglycosides absorbed and administered for systemic treatment?

They have poor oral absorption and are given IV or IM.

Why can oral neomycin be used for gut decontamination?

It is not significantly absorbed and works topically within the gut.

When may neomycin be used for gut decontamination?

Before GI surgery when there is a risk of GI spillage.

What is the major use of inhaled tobramycin?

Inhaled via nebulizer in cystic fibrosis to suppress recurrent lung infections.

How well do aminoglycosides penetrate the central nervous system?

Poorly.

How are aminoglycosides eliminated?

By the kidneys.

What dosing change is needed with renal insufficiency?

The aminoglycoside dose must be adjusted.

Where did the professor say aminoglycosides are generally encountered?

On the inpatient side, not in outpatient practice.

Why are serum aminoglycoside concentrations monitored?

Dosing is based on drug levels and pharmacokinetics.

Which serum aminoglycoside levels are monitored?

Peaks and troughs.

What does the peak represent in concentration-dependent killing?

The concentration must reach a high peak to kill the organism.

What culture result indicates an aminoglycoside should work against the organism?

A result reported as sensitive.

What are the aminoglycoside resistance mechanisms listed in the lecture?

Inactivating enzymes, altered ribosomal binding, and altered drug uptake.

What are the two major toxicities of aminoglycosides?

Nephrotoxicity and ototoxicity.

What renal injury can aminoglycosides cause?

Acute tubular necrosis in the proximal tubule cells.

What factors increase the risk of aminoglycoside nephrotoxicity?

Prolonged therapy, elderly age, renal insufficiency, recent use, dehydration, other nephrotoxins.

Why does recent aminoglycoside use increase renal toxicity risk?

The drug accumulates in the renal tubule over time.

Why is hydration important during aminoglycoside therapy?

Volume depletion increases renal risk; hydration helps protect the kidneys.

Why is combining vancomycin with an aminoglycoside concerning?

Both drugs are nephrotoxic, increasing the risk of kidney damage.

What should you remember when serum creatinine begins to rise during aminoglycoside therapy?

Serum creatinine lags behind damage; the injury likely occurred 1-2 days earlier.

What should be done when serum creatinine begins creeping up during aminoglycoside therapy?

Change the therapy or adjust the dosing.

What forms of ototoxicity can aminoglycosides cause?

Vestibular toxicity and auditory toxicity.

Is aminoglycoside ototoxicity reversible?

No, it can be permanent.

What can vestibular toxicity cause clinically?

Loss of balance and unsteadiness, increasing the risk of falls.

Why should aminoglycosides generally be avoided in patients who are blind unless absolutely necessary?

Blind patients rely heavily on vestibular function; damage would severely impair mobility.

What tests did the professor mention for monitoring aminoglycoside ototoxicity?

Romberg test for vestibular function and formal hearing tests.

Why should aminoglycosides be used cautiously in myasthenia gravis?

They can disrupt neuromuscular transmission and worsen the condition.

Why do aminoglycosides act synergistically with beta-lactams?

Beta-lactams disrupt the cell wall, allowing aminoglycosides to enter the cell.

What infections are listed as clinical uses for aminoglycosides?

Febrile neutropenia, intra-abdominal infections, complicated UTIs, septicemia, and endocarditis.

What are the professor's main aminoglycoside take-home points?

Gram-negative coverage, bactericidal, peak/trough monitoring, nephrotoxicity, and irreversible ototoxicity.