Ototoxicity, aminoglycosides and

Lima da Costa D, Erre JP, Pehourq F, Aran JM. Aminoglycoside ototoxicity and the medial efferent system II. Comparison of acnte effects of different antibiotics. Audiology 1998 37(3) 162-73. 

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). 

The aminoglycosides are potentially neurotoxic, nephrotoxic, and ototoxic and are capable of causing permanent damage to tiiese organs and structures. The nurse notifies the primary health care provider immediately when one or more signs and symptoms of tiiese adverse reactions is suspected. 

Hutchin T, Cortopassi G. Proposed molecular and cellular mechanism for aminoglycoside ototoxicity. Antimicrob Agents Chemother 1994 38 2517-2520. 

Vancomycin can cause red-man syndrome consisting of diffuse flushing, presumably mediated by histamine-release. This problem can be prevented by limiting the infusion rate. The most serious adverse reactions are ototoxicity and nephrotoxicity. The toxicity for both organ systems is potentiated by aminoglycosides. Vancomycin will cross the placenta barrier and has the potential to cause fetal ototoxicity. 

Answer Ototoxicity and nephrotoxicity are common adverse effects of aminoglycoside therapy, particularly when administered orally. You immediately arrange to check renal function and fortunately discover that renal function is not significantly impaired in this patient. You inform the patient that the hearing loss is probably permanent and that he should carefully check with pharmacists and physicians in the future to be certain that any prescriptions drugs that he might receive do not further aggravate this condition. 

Ototoxicity and nephrotoxicity are the major concerns during administration of streptomycin and other aminoglycosides. The toxic effects are dose related and increase with age and underlying renal insufficiency. All aminoglycosides require dose adjustment in renal failure patients. Ototoxicity is severe when aminoglycosides are combined with other potentially ototoxic agents. 

Like other aminoglycosides, tobramycin is ototoxic and nephrotoxic. Nephrotoxicity of tobramycin may be slightly less than that of gentamicin, but the difference is clinically inconsequential. 

Streptomycin is ototoxic and nephrotoxic. Vertigo and hearing loss are the most common adverse effects and may be permanent. Toxicity is dose-related, and the risk is increased in the elderly. As with all aminoglycosides, the dose must be adjusted according to renal function (see Chapter 45). Toxicity can be reduced by limiting therapy to no more than 6 months whenever possible. 

Paromomycin sulfate is an aminoglycoside antibiotic that until recently was used in parasitology only for oral therapy of intestinal parasitic infections (see previous text). It has recently been developed for the treatment of visceral leishmaniasis. A phase 3 trial in India showed excellent efficacy for this disease, with a daily intramuscular dosage of 11 mg/kg for 21 days yielding a 95% cure rate, and noninferiority compared with amphotericin. The drug was registered for the treatment of visceral leishmaniasis in India in 2006. In initial studies, paromomycin was well tolerated, with common mild injection pain, uncommon ototoxicity and reversible liver enzyme elevations, and no nephrotoxicity. Paromomycin is much less expensive than liposomal amphotericin or miltefosine, the other promising new therapies for visceral leishmaniasis. 

It is important to monitor peak and trough plasma levels (see p. 20) of gentamicin, tobramycin, netilmicin, and amikacin to avoid concentrations that cause dose-related toxicities (Figure 31.7). [Note Peak levels are defined as those obtained 1/2 to 1 hour after infusion. Trough levels are obtained immediately before the next dose.] Patient factors, such as old age, previous exposure to aminoglycosides, gender, and liver disease, tend to predispose patients to adverse reactions. The elderly are particularly susceptible to nephrotoxicity and ototoxicity. 

LOOP DIURETICS AMINOGLYCOSIDES t risk of ototoxicity and possible deafness as a result of concomitant use of furosemide and gentamicin Both furosemide and gentamicin are associated with ototoxicity this risk is t if they are used together If used concurrently patients should be monitored for any hearing impairment... 

In a quantitative assessment of vestibular hair cells and Scarpa s ganglion cells in 17 temporal bones from 10 individuals with aminoglycoside ototoxicity, streptomycin caused a significant loss of both type I and type II hair cells in all five vestibular sense organs (19). The vestibular ototoxic effects of kanamycin appeared to be similar to those of streptomycin, whereas neomycin did not cause loss of vestibular hair cells. There was no significant loss of Scarpa s ganglion cells. 

A second pathogenic mutation that could predispose to aminoglycoside ototoxicity has been identified in an Italian family, of whom five members became deaf after aminoglycoside exposure (62). In the mitochondrial 12S ribosomal RNA gene, the deletion of nucleotide 961 thymidine was associated with a varying number of inserted cytosines. Transient evoked otoacoustic emission has been suggested as a sensitive measure for the early effects of aminoglycosides on the peripheral auditory system and may be useful as a tool for the prevention of permanent ototoxicity (66). 

In rats, ototoxicity caused by gentamicin or tobramycin was amehorated by melatonin, which did not interfere with the antibiotic action of the aminoglycosides (70). The free radical scavenging agent alpha-lipoic acid has previously been shown to protect against the cochlear adverse effects of systemically administered aminoglycoside antibiotics, and in a recent animal study it also prevented cochlear toxicity after the administration of neomycin 5% directly to the round window membrane over 7 days (71). 

---