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Aminoglycosides: Mechanism, Uses, and Toxicity
Introduction
Aminoglycosides are a class of antibiotics primarily used to treat serious infections caused by Gram-negative bacteria, such as Pseudomonas aeruginosa and Escherichia coli. These drugs are bactericidal and are typically reserved for life-threatening infections due to their potential toxicity.
Examples
- Gentamicin
- Tobramycin
- Amikacin
- Streptomycin
- Neomycin
- Kanamycin
Mechanism of Action
Aminoglycosides inhibit bacterial protein synthesis by binding to the 30S ribosomal subunit, causing misreading of the mRNA and production of faulty proteins. This disrupts the function of the bacterial cell and ultimately leads to cell death. They also disrupt the bacterial cell membrane, contributing to their bactericidal effect.
Mechanism of Resistance
- Enzymatic Inactivation: Bacteria produce enzymes that modify and inactivate the drug.
- Alteration of Target Site: Mutation of the 30S ribosomal subunit reduces drug binding.
- Reduced Drug Uptake: Changes in membrane permeability or active efflux pumps decrease drug uptake.
- Anaerobic Conditions: Lack of oxygen reduces drug uptake, making anaerobic bacteria less susceptible.
Therapeutic Uses
- Sepsis and bacteremia
- Respiratory tract infections (e.g., pneumonia)
- Urinary tract infections
- Intra-abdominal infections (e.g., peritonitis)
- Endocarditis (usually in combination with other antibiotics)
- Tuberculosis (e.g., streptomycin)
- Ophthalmic infections (neomycin)
Adverse Effects
- Ototoxicity: Hearing loss and balance issues, which may be irreversible.
- Nephrotoxicity: Kidney damage, often reversible upon discontinuation of the drug.
- Neuromuscular Blockade: Muscle weakness and respiratory paralysis.
- Hypersensitivity: Rash, fever, and allergic reactions.
Contraindications
- Pregnancy: Especially in the first trimester due to the risk of fetal harm.
- Renal Impairment: Requires dosage adjustment to avoid nephrotoxicity.
- Pre-existing Hearing Loss: Can worsen hearing loss or cause deafness.
- Myasthenia Gravis: Should be avoided due to the risk of neuromuscular blockade.
