Ototoxic deafness

The following reactions are less frequent Cochlear ototoxicity (deafness) exfoliative... 

Ofofox/c/fy. Tinnitus, reversible and irreversible hearing impairment, deafness, and vertigo with a sense of fullness in the ears have been reported. Deafness is usually reversible and of short duration (1 to 24 hours) however, irreversible hearing impairment has occurred. Usually, ototoxicity is associated with rapid injection, with severe renal impairment, with doses several times the usual dose, and with concurrent use with other ototoxic drugs. 

Nephrotoxicity/Ototoxicity Because of reported cases of deafness and potential nephrotoxic effects, closely observe patients. Refer to the Warning Box in the Aminoglycosides, Parenteral monograph concerning aminoglycoside toxicity. Pregnancy. 

Ototoxicity has been reported during therapy with all loop diuretics. This effect seems to be dose related and is most common in patients with renal insufficiency. Deafness is usually reversed when these drugs are discontinued, but irreversible hearing loss has been reported after administration of ethacrynic acid, and this has led to a marked decrease in its use. 

The major adverse effect associated with vancomycin therapy is ototoxicity, which may result in tinnitus, high-tone hearing loss, and deafness in extreme instances. More commonly, the intravenous infusion of vancomycin can result in chills, fever, and a maculopapular skin rash often involving the head and upper thorax (red man syndrome). Red man syndrome is associated with increased levels of serum histamine. Vancomycin is rarely nephrotoxic when used alone. Teicoplanin rarely causes red man syndrome or nephrotoxicity. 

Ototoxicity—manifested as deafness, vertigo, or tinnitus—may occur, especially in patients with severe renal impairment and those taking other ototoxic drugs. Blood dyscrasias and acute hypotensive episodes have been reported. 

The aminoglycosides decrease the fidelity of translation by binding to the 30S subunit of the ribosome. This permits the formation of the peptide initiation complex but prohibits any subsequent addition of amino acids to the peptide. This effect is due to the inhibition of polymerization as well as to the failure of tRNA and mRNA codon recognition. Aminoglycosides are ototoxic (i.e., may produce partial deafness), damaging the auditory nerve. Kanamycin is less toxic. Since aminoglycosides are concentrated in the kidney, they may occasionally cause kidney damage. 

All members of the neomycin group have significant nephrotoxicity and ototoxicity. Auditory function is affected more than vestibular function. Deafness has occurred, especially in adults with impaired renal function and prolonged elevation of drug levels. 

Capreomycin is nephrotoxic and ototoxic. Tinnitus, deafness, and vestibular disturbances occur. The injection causes significant local pain, and sterile abscesses may occur. 

Neomycin is particularly ototoxic and nephrotoxic when given parenterally. As with gentamicin and kanamycin, the nephrotoxicity may be reversible but the ototoxicity is usually irreversible and deafness may occur following oral administration, instillation into cavities, or topical use. It may block neuromuscular action and respiratory depression has been reported. Local treatments may cause hypersensitivity, rashes, pruritus, and anaphylaxis. Neomycin is not geno-toxic. 

Streptomycin is given intramuscularly. It exerts its effects only on extracellular tubercle bacilli. When combined with other drugs, it delays the emergence of streptomycin-resistant mutants. It is ototoxic and may cause deafness. 

Capreomycin is nephrotoxic and ototoxic. Tinnitus, deafness, and vestibular disturbances occur. 

Ototoxicity Ototoxicity (vestibular and cochlear) is directly related to high peak plasma levels and duration of treatment. Deafness may be irreversible and has been known to affect fetuses in utero. Patients simultaneously receiving another ototoxic drug such as the loop diuretics furosemide, bumetanide, ethacrynic acid (see p. 227) or cisplatin (see p. 396), are particulary at risk. Vertigo and loss of balance may also occur because these drugs affect the vestibular apparatus. 

Ototoxicity Transient deafness has been associated with erythromycin, especially at high dosages. 

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... 

There are some serious drawbacks to the use of cis-platin in anticancer therapy. Severe toxicity problems occur, such as failure of the kidneys and bone marrow (nephrotoxicity and hematoxicity), nausea, intractable vomiting (emesis), peripheral neuropathy, deafness (ototoxicity), and seizures. These toxic side effects of cisplatin limit the dose that can be administered to patients typical doses are 100 mg day for up to five consecutive days. The nephrotoxicity can be reduced by hydration and diuresis. 5-HT3-receptor blockers control nausea and emesis. Much effort has been devoted to the development of chemopro-tective agents, which alleviate the side effects on normal tissues without compromising antitumor activity - mainly sulfur-containing agents such as sodium dithiocarbamate (Naddtc), 2-mercaptoethanesulphonate (mesna), and amifos-tine (WR-2721). Amifostine has recently been approved for coadministration with cisplatin, which reduces nephro- and neurotoxicity. ... 

The use of intravenous vancomycin in prolonged therapy, in concomitant or sequential use with other ototoxic or nephrotoxic drugs, or in patients with impaired renal function has caused permanent deafness and... 

In an Italian family of whom five family members became deaf after aminoglycoside exposure, the nucleotide 961 thymidine deletion associated with a varying number of inserted cytosines in the mitochondrial 12S ribosomal RNA gene was identified as a second pathogenic mutation that could predispose to aminoglycoside ototoxicity (62). Molecular analysis excluded the A1555G mutation in this family. 

Serious adverse effects of aminobisphosphonates were reported in otospongiosis. Of two patients with stapedial otosclerosis and sensorineural hearing loss one developed total bilateral deafness and the other retained minimal auditory function in the low frequencies (25). It was recommended that sensorineural deafness in selected patients with otosclerosis should be treated with sodium fluoride, and that patients with Paget s disease treated with aminobisphosphonates should be closely monitored and the drug discontinued immediately if hearing deteriorates. Elsewhere, ototoxicity has been reported (SEDA-20, 440). 

Ototoxicity has been mentioned occasionally over the years tinnitus and deafness can occur in relation to high doses symptoms described after injection of chloroquine phosphate include a case of cochlear vestibular dysfunction in a child (16). However, there is insufficient evidence to attribute ototoxicity to chloroquine in humans, except as a rare individualized phenomenon. In guinea pigs given chloroquine 25 mg/kg/day intraperitoneaUy, one of the first signs of intoxication was ototoxicity (SEDA-11, 586). 

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). 

Furosemide increases the ototoxic risks of aminoglycoside antibiotics (30,31) by reducing their clearance by about 35% (32) permanent deafness has resulted from the use of this combination. 

Ototoxicity manifested as deafness, vertigo, tinnitus (ringing/roaring in ears) may occur especially in those with severe renal impairment. 

Ototoxicity (2% incidence) from hair cell damage includes deafness and vestibular dysfunction, which are not readily reversible. Toxicity may be enhanced by loop diuretics. 

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