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.
• There is variable gram-positive activity.
• 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.

Streptomycin

• The weakest spectrum of activity of the aminoglycosides. It is active against some Staphylococcal species and is active against mycobacteria.
• Reistance to this drug is widespread.
• It's use is limited by its toxicity, especially in cats. It is main toxicity problem is with ototoxicity. If used post-anaesthesia there is a higher risk of the patient experiencing a neuromuscular block.

Neomycin

• More active than Streptomycin but still not very active. Good activity against S.aureus but is poor against other gram-positives. Though it is active against most gram-negatives including Pseudomona.
• This is the most toxic of all aminoglycosides and is mainly nephrotoxic and toxic to the cochlear.

Kanamycin

• Similar potency to Neomycin but is active against mycoplasma and mycobacteria. It isn't effective against Pseudomonas.
• It has a wider therapeutic index than neomycin, but the normal toxicity risks still stand.
• Cross-resistance exists with neomycin.

Gentamicin

• The most broad spectrum of the group. It works well against Pseudomonas and gram-negative rods.
• It is very nephrotoxic and shouldn't be used for more than seven days and it is recommeneded to only give once daily doses.
• Resistance is currently uncommon in veterinary pathogens.

Amikacin

• More active than Kanamycin but not as broad spectrum as Gentamicin.
• Standard concerns about toxicity remain.

Tobramycin

• Similar level activity against pathogens as Gentamicin but with the least toxicity of all aminoglycosides.
• It is currentlt too expensive to use in the veterinary field.

Aminocyclitols

This is a closely related group of drugs that are essentially the same as aminoglycosides.

=Apramycin

• It's full spectrum is not yet known but it is active against S.aureus, many Streptococci, Treponema hyodysenterae and some mycoplasmas.
• There are few reports of toxicity except nephrotoxity in cats.

Spectinomycin

• Poor gram-positive activity but works well against gram-negatives and mycoplasmas.
• Not very toxic but has been known to cause neuromuscular junction blockades.
• It has the highest oral bioavailability out of any of the drugs in this group.