Ototoxicity

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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). 

Gapreomycin, Viomycin, and Enviomycin. Capreomycin (Capastat, Lilly), a bacteriostatic, antimycobacterial peptide mixture isolated from Streptomjces capreolus was first reported in 1961 (106—108). This tuberactinomycin family member, shown in Table 4, was introduced into the U.S. market in 1971 where it has remained a usehil but nephrotoxic and ototoxic second-line alternative to first-line tuberculosis therapies. Because capreomycin is somewhat less toxic than viomycin (tuberoactinomycin B [32988-50-4]) C25H42N23O2Q (109,110), capreomycin has now displaced viomycin in the United States and most other markets. The stmcture of viomycin is shown in Figure 2. The related enviomycin (tuberactinomycin N [33103-22-9]), C23H43N23O2Q,... 

A.n log ue Synthesis. Two notable examples, in which analogues have greater therapeutic indexes than the parent dmgs, have been identified in Phase I trials. These are carboplatin (29) and ado2elesin (37) (35). Carboplatin s approval was based on its comparable efficacy to cis-platinum (28) and its more favorable toxicity profile, ie, reduced and delayed episodes of emesis, reduced ototoxicity, etc. On the other hand, ado2elesin, a totally synthetic analogue of natural product CC1065, has demonstrated a similar potency and antitumor activity profile as its natural prototype but is devoid of the delayed death UabiUty associated with the parent dmg in animals (36). 

Ototoxicity, as evidenced by transient or permanent hearing loss, is a serious side effect of ethacrynic acid, and occurs less frequently with furosemide. Bumetanide is claimed to have only 20% of the ototoxic potential of furosemide (43). It has been reported that patients treated with torasemide at high doses for four weeks did not suffer hearing loss (36). 

Airway inflammation is a characteristic clinical feature of asthma. The distinction between the LAR and chronic inflammation becomes more difficult as the disease progresses. Infiltrated leukocytes release ototoxic mediators such as reactive oxygen species (ROS) and cationic (basic) proteins causing epithelial damage and cyfo/cmas that perpetuate the inflammation. Sustained inflammation leads to airway hyperrespon-siveness and airway remodeling. 

Ototoxicity describes a harmful effect on the inner ear, especially the sensory cells in the cochlea and the vestibular organ. Aminoglycosides are an example of drugs with ototoxic side effects. 

Administration of the aminoglycosides with the cephalosporins may increase the risks of nephrotoxicity. When the aminoglycosides are administered with loop diuretics there is an increased risk of ototoxicity (irreversible hearing loss). There is an increased risk of neuromuscular blockage (paralysis of the respiratory muscles) if the aminoglycosides are given shortly after general anesthetics (neuromuscular junction blockers). 

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. 

Which of the following complaints by a patient taking tobramycin would be most indicative the patient is experiencing ototoxicity ... 

Identify nursing assessments that are performed when a drug is potentially nephrotoxic or ototoxic. 

Nephrotoxicity (damage to the kidneys) and ototoxicity (damage to the organs of hearing) may be seen with the administration of this drug. Additional adverse reactions include nausea, chills, fever, urticaria, sudden fall in blood pressure with parenteral administration, and skin rashes. 

When administered with other ototoxic and nephrotoxic dm, additive effects may be seen. 

MONITORING FOR NEPHROTOXICITY AND OTOTOXICITY. It is important for the nurse to monitor for nephrotoxicity. The nurse measures and records intake and output during the time the patient is receiving these dm. Any changes in the intake and output ratio or in the appearance of the urine must be reported immediately because these may indicate nephrotoxicity. 

When performing the ongoing assessment, the nurse observes the patient daily for the appearance of adverse reactions. These observations are especially important when a drug is known to be nephrotoxic or ototoxic. It is important to report any adverse reactions to the primary health care provider. In addition, the nurse carefully monitors vital signs daily or as frequently as every 4 hours when the patient is hospitalized. 

This drug has relatively few adverse reactions. The most common include nausea, vomiting, and diarrhea The more serious adverse reactions, although rare, are nephrotoxicity and ototoxicity. 

When ondansetron is administered with rifampin, blood levels of ondansetron may be reduced, decreasing the antiemetic effect. Dimenhydrinate may mask the signs and symptoms of ototoxicity when administered with ototoxic drugp, such as the aminoglycosides (see Chap. 10), causing irreversible hearing damage. When lithium is administered with prochlorperazine, the risk of extrapyramidal reactions increases (see Chap. 32). 

These dm are contraindicated in patients with known hypersensitivity to the drug or any components of the drug. Because neomycin toxicity can cause nephrotoxicity and ototoxicity, neomycin is used cautiously in patients with extensive bums or trophic ulceration when extensive absorption can occur. 

Stiepton dn was isolated by Waksman in 1944, and its activity against M tuberculosis ensured its use as a primaiy ding in the treatment of tuberculosis. Unfortunately, its ototoxicity and the rapid development of resistance have tended to modify its usefulness, and although it still remains a front-hne dmg against tuberculosis it is usually used in combination with isoniazid and p(4)-aminosalicyhc acid (section 11.5). Streptomycin also shows activity against other types of bacteria,... 

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