Aminoglycosides

WIKIDRUGS ANTIBIOTICS

This is a large group of antibiotics that are made up of a sugar group and an amino group. As this is a large and diverse group we shall firstly discuss general characteristics and then one by one go through each drug to show and explain their differences.

General Group Characteristics

Mechanism of Action

The drug must first enter the bacterial cell which it does via a oxygen-dependent active transport system. Thus it is unable to work against any anaerobic species. Once inside the cell it disrupts protein synthesis by acting directly on the ribosome. Unlike the other antibiotics that act at the level of protein synthesis these drugs are bactericidal and are concentration dependent killers. They will act synergistically with any antibiotic that disrupts cell wall synthesis, ie any of the beta-lactams.

Spectrum of Activity

• They are active mainly against gram-negative species, including some of the hardier species.
• They are inactive against anaerobes, this is because their action is dependent on oxygen-dependent active transport systems.
• They tend not to work well in purulent material.
• If the local tissue environment is acidic the efficacy of the drug will be reduced.

Pharmacokinetic Considerations

Aminoglycosides are very hydrophilic molecules and weak bases and so aren't very well absorbed in the gastrointestinal tract. They distribute poorly and are confined to mainly extracellular fluid. Elimination is performed by the kidneys and the drugs are excreted unchanged in the urine and so have very short half-lives. They also bind to renal tissue and so shouldn't be used in patients with renal failure.

Side Effects and Contraindications

• They tend to be nephrotoxic and shouldn't be used if any renal pathology is suspected. To try and avoid this problem give one large single dose daily rather than splitting the dose up as accumulation of the drug will be increased in the kidney.
• Ototoxicity is a problem with the Vestibulocochlear Nerve (Cranial Nerve VIII) affected.
• They can create non-depolarising neuromuscular junction blocks leading to acute paralysis and cardiovascular collapse if given intravenously.