Pharmacology of Aminoglycosides

Aminoglycosides are among the most widely used antibacterial drugs. They have, through the introduction of Streptomycin, been around since the 1940s. Though bacterial resistance continues to increase, they remain an important antibacterial class.

Aminoglycosides are used to treat a wide variety of bacterial infections – most effective against aerobic, Gram-negative infections (including Pseudomonas aeruginosa). They are generally ineffective against Streptococci and anaerobic bacteria.

Aminoglycosides are frequently used to treat serious infections such as:

  • Intra-abdominal infections
  • Septicemia
  • Complicated urinary tract infections
  • Hospital-acquired respiratory tract infections

Examples of commonly prescribed aminoglycosides include:

  • Gentamicin
  • Tobramycin
  • Amikacin
  • Netilmicin

Let’s take a few minutes to learn more about aminoglycosides pharmacology; how they work to exert their therapeutic effect.

Mechanism of action

Aminoglycosides are protein synthesis inhibitors.

Aminoglycosides enter bacterial cells through oxygen-dependent transport system. This transport system is not present in anaerobic or Streptococci bacteria – meaning they have intrinsic resistance to these medicines.

However, aerobic Gram-negative bacteria do have this transport system. When aminoglycosides enter vulnerable bacterial cells, they irreversibly bind to the bacterial ribosome – inhibiting protein synthesis.

More specifically, aminoglycosides bind to the 30S ribosomal subunit, a binding that has a bactericidal effect. At the 30S unit, aminoglycosides disrupt mRNA translation.

Side effects

Aminoglycosides are associated with their own range of potential side effects.

  • Nausea, vomiting
  • Nephrotoxicity
  • Ototoxicity

Nephrotoxicity and ototoxicity are often reversible, though not always. Nephrotoxicity has led to death and, in other cases, hearing loss is permanent. That’s because aminoglycosides trigger apoptosis in renal tubular epithelial cells and in cochlear cells. Patients often experience ototoxicity only in the post-infection period.

Factors that increase the risk of nephrotoxicity include:

  • Older patients
  • Renal impairment
  • Hepatic impairment
  • In pregnancy
  • Reduced thyroid function
  • Low sodium levels

Approximately 1 in 10 patients receiving aminoglycoside therapy will experience ototoxicity in some form. Similar factors – such as age, hepatic and renal impairment, high doses for prolonged periods, and in patients taking diuretics (for example – furosemide) – increase this risk.

Clinical considerations

When we talk about the clinical pharmacology of aminoglycosides, we need to think about the following factors:

  • Nephrotoxicity is accompanied by reduced urine production, elevated serum creatinine levels and rising urea levels. Nephrotoxicity risk increases if the patient is also taking cephalosporins, ciclosporin or platinum chemotherapy.
  • Ototoxicity often presents in the post-infection phase. Affected persons may experience tinnitus, hearing loss and vertigo. In some cases, ototoxicity is irreversible.
  • As aminoglycosides are eliminated via the renal route, certain populations – such as neonates, the elderly and patients with existing renal damage – are at an increased risk of nephrotoxicity and ototoxicity.
  • Aminoglycosides should be avoided in patients with myasthenia gravis – they exacerbate muscle weakness by interfering with neuromuscular transmission.
  • The risk of ototoxicity is elevated if aminoglycosides are administered alongside loop diuretics (such as furosemide).
  • The risk of both ototoxicity and nephrotoxicity increases when aminoglycosides are administered alongside vancomycin, another antibacterial drug.
  • Some drugs, such as penicillins, work by disrupting the cell wall – meaning that penicillins may encourage aminoglycoside uptake by vulnerable bacterial cells.
  • Aminoglycosides are not absorbed from the gut. They are, then, administered via the intravenous or intramuscular route. Many, such as gentamicin, are administered via IV infusion in severe infection. Dose is dependent upon weight and the patient’s renal function. Therapeutic drug monitoring (TDM) is essential. Tobramycin can be administered via the nebulized route, too.

Aminoglycosides have been around since the 1940s, with the introduction of streptomycin – a drug effective in the treatment of tuberculosis. Though resistance is on the increase, these drugs remain an important drug class in the treatment of serious bacterial infections.

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