Ototoxicity, of aminoglycosides

Loop diuretics (especially as i.v. boluses) potentiate ototoxicity of aminoglycosides and nephrotoxicity of some cephalosporins. NSAIDs tend to cause sodium retention which counteracts the effect of diuretics the mechanism may involve inhibition of renal prostaglandin formation. Diuretic treatment of a patient taking lithium can precipitate toxicity from this drug (the increased sodium loss is accompanied by reduced lithium excretion). Reference is made above to drug treatments which, when combined with diuretics, may lead to hyper-kalaemia, hypokalaemia, hyponatraemia, or glucose intolerance. 

Deafness occurred after 5 days treatment with dantrolene 25 mg/day in a patient who was also taking long-term baclofen and diazepam (8). This may have been coincidental, but the authors suggested that dantrolene may have caused the effect by interfering with the release of calcium from the sarcoplasmic reticulum. It is therefore interesting that one hypothesis that explains the ototoxicity of aminoglycoside antibiotics involves disturbance of calcium ion binding and phosphorylation processes (SED-11, 549). 

It is still controversial whether vancomycin can cause ototoxicity when given alone. However, vancomycin can augment the ototoxicity of aminoglycosides (30). Tinnitus and dizziness have been noted, resolving on withdrawal (31). Hearing loss can be transient or permanent. If vancomycin is combined with aminoglycosides, toxicity may be additive (32). 

Studies of the comparative nephro- and ototoxicity of aminoglycoside antibiotics generate assurance that in the effective clinical dose range of 1-3 mg/kg and with peak serum levels not above 12 ig/ml7t, gentamicin does possess a favorable margin of safety in man. 

Gentamicin is an aminoglycoside. All aminoglycosides tend to be nephrotoxic and ototoxic. The dose must be reduced and serum concentrations must be monitored in patients with impaired renal function. Concomitant administration of aminoglycosides and other nephrotoxic drugs, such as certain diuretics, ciclosporin, teicoplanin and vancomycin should be avoided. 

A major clinical distinction between the effects on the inner ear and the kidney is the fact that the renal effects are reversible while the effects on the inner ear are irreversible, leading to permanent loss of balance or auditory function. Furthermore, renal insults can more easily be monitored and thereby largely prevented, while monitoring of impending auditory or vestibular damage is not always possible. Ototoxic side effects frequently develop after cessation of aminoglycoside treatment, sometimes delayed by weeks. This review will therefore focus on the ototoxic side effects as a major unresolved issue in aminoglycoside toxicity. 

Uses Edema, HTN, CHF, h atic cirrhosis Action Loop diuretic -1- reabsorption of Na Cr in ascending loop of Henle distal tubule Dose 5-20 mg/d PO or IV 200 mg/d max Caution [B, ] Contra Sulfonylurea sensitivity Disp Tabs, inj SE Orthostatic -1- BP, HA, dizziness, photosens, electrolyte imbalance, blurred vision, renal impair Notes 20 mg torsemide = 40 mg furosemide Interactions t Risk of ototox W/ aminoglycosides, cisplatin t effects W/ thiazides t effects OF anticoagulants, antih5rpCTtensives, Li, salicylates X effects IT/barbiturates, carbamaz ine, cholestyramine, NSAIDs, phenytoin, phenobarbital, probenecid, dandehon EMS t Effects of anticoagulants monitor for S/Sxs tinnitus, monitor ECG for hypokalemia (flattened T waves) OD May cause HA, hypotension, hypovolemia, and hypokalemia give IV fluids symptomatic and supportive... 

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. 

PLATINUM COMPOUNDS AMINOGLYCOSIDES, CAPREOMYCIN, COLISTIN, STREPTOMYCIN, VANCOMYCIN t risk of renal toxicity and renal failure and of ototoxicity. The ototoxicity tends to occur when cisplatin is administered early during the course of aminoglycoside therapy Additive renal toxicity Monitor renal function prior to and during therapy, and ensure an intake of at least 2 L of fluid daily. Monitor serum potassium and magnesium and correct any deficiencies. Most side-effects of aminoglycosides are dose-related, and it is necessary to t interval between doses and 1 dose of aminoglycoside if there is impaired renal function... 

Bums. Infection may be reduced by application of silver sulphadiazine cream. Substantial absorption can occur from any raw surface and use of aminoglycoside, e.g. neomycin, preparations can cause ototoxicity. 

The main adverse reactions of aminoglycosides consist of kidney damage (often presenting as non-ohguric renal insufficiency) and ototoxicity, including vestibular and/ or cochlear dysfunction. Neuromuscular transmission can be inhibited. Hypersensitivity reactions are most frequent after topical use, which should be avoided. Anaphylactic reactions can occur. Tumor-inducing effects have not been reported. 

Ototoxicity is a major adverse effect of aminoglycoside antibiotics (13). They all affect both vestibular and cochlear function, but different members of the family have different relative effects (Table 1). 

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