Aminoglycosides instilled

The principal arninoglycoside toxicides are neuromuscular paralysis, ototoxicity, and nephrotoxicity. Neuromuscular paralysis is a relatively rare complication resulting from high aminoglycoside concentrations at the neuromuscular junctions following, for example, rapid bolus intravenous injection or peritoneal instillation, rather than the normal intravenous infusion. The mechanism apparentiy involves an inhibition of both the presynaptic release of acetylcholine and the acetylcholine postsynaptic receptors (51). 

Schreier et al. [85] examined the effects of liposome encapsulation on the pharmacokinetics in sheep of amikacin, a water-soluble aminoglycoside. The dmg was formulated in 200 nm liposomes and administered by means of intratracheal instillation. The liposome formulations were soy PC/phosphatidyl glycerol (PG) (7 3 molar ratio) and soy PC/PG/CH (4 3 3). They found that both liposome formulations reduced plasma Cmax and prolonged the plasma half-life of the amikacin compared with the dmg administered as a solution, once again indicating that liposomes were controlling dmg delivery in the lungs. The inclusion of cholesterol in liposomes more than tripled the plasma half-life for the dmg compared with the liposomes without cholesterol. Cholesterol reduces the fluidity and permeability of liposomes in their liquid crystalline phase. 

Antimicrobials. Aminoglycosides (neomycin, streptomycin, gentamicin), polypeptides (colistimethate sodium, polymyxin B) and perhaps the quinolones (e.g. ciprofloxacin) may cause postoperative breathing difficulty if they are instilled into the peritoneal or pleural cavities. It appears that the antibiotics both interfere with the release of acetylcholine and also have a competitive curarelike effect on the acetylcholine receptor. 

Subconjunctival injection of tobramycin has caused macular infarction (SEDA-20, 238). This potentially devastating consequence suggests that care must be exercised when contemplating instillation of aminoglycosides directly into the eye. 

Tobramycin, a water-soluble aminoglycoside has been found to exhibit pulmonary targeting when encapsulated in liposomes [87-90]. Poyner et al. instilled 720 nm EPC/PA/CH (29.7 3.3 33) tobramycin liposomes into the lungs of rats... 

The aminoglycosides are highly polar and, thus, poorly absorbed from the gastrointestinal (GI) tract. Instillation of these drugs into body cavities with serosal surfaces may result in rapid absorption and unexpected toxicity (e.g., neuromuscular blockade). Toxic levels also may result from sustained topical application to large wounds, bums, or cutaneous ulcers, particularly with renal insufficiency. Long-term oral or rectal administration of aminoglycosides may result in accumulation to toxic concentrations in patients with renal impairment. 

Acute neuromuscular blockade and apnea have been attributed to the aminoglycosides patients with myasthenia gravis are particularly susceptible. In humans, neuromuscular blockade generally has occurred after intrapleural or intraperitoneal instillation of large doses of an aminoglycoside, but the reaction can follow intravenous, intramuscular, and even oral administration. Neuromuscular blockade may be reversed with calcium gluconate infusion. 

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