Ototoxicity

Ototoxicity Ototoxicity is especially ear damage the auditory nerve cochlea and the vestibular system and sometimes by a toxin. The drug induced. Ototoxic drugs include antibiotics such as aminoglycosides, loop diuretics: furosemide and platinum-based chemotherapeutic agents such as cisplatin. A number of NSAIDs such as meloxicam were also shown to be ototoxic. These substances can cause deafness senzoneurala, imbalance, or both. They may be reversible or irreversible and permanent and temporary. Any drug with the potential to cause toxic reactions in the inner ear structures, including Cohl, vestibules, and semicircular canals otoliti is considered ototoxic. Drug-induced destruction of this structure of the auditory system and balance lead to deafness, tinnitus and dizziness. Propensity to specific classes of ototoxic drugs has been well established comprising over 100 classes. Ototoxicity doctors came to the attention with the discovery of streptomycin in 1944. Streptomycin was used successfully to treat tuberculosis is still a substantial number of patients treated were found later with cochlear and vestibular dysfunction irreversible. These findings associated with the development of ototoxicity of aminoglycosides leads to medical investigations into the etiology and mechanisms of ototoxicity. Today many pharmacological agents have been shown to have toxic effects on cohleovestibular system. The list includes other aminoglycoside antibiotics, platinum-based antineoplasici agents, salicylates, and diuretics quinina chance. Ototoxicity is typically associated with hearing loss and high frequency senzoroneurala bilateral tinnitus. Deafness may be temporary but it is usually irreversible in most agents. The antibiotic-induced ototoxicity is usually bilateral and symmetrical but may be asymmetrical. Onset is unpredictable and marked deafness may occur after a single dose. In addition to deafness may remain silent until a few weeks or months after therapy. Vestibular lesions are also a notable side effect of aminoglycosides and may occur early with positional nystagmus. If severe vestibular toxicity can lead to imbalance and oscillopsia. Permanent hearing loss or balance disorders caused by ototoxic drugs can alter the communication, social, educational and serious. Therefore the benefits of these drugs must be weighed with potential risks better and alternative medication should be taken into account. Prevention is important because most cases of deafness are irreversible. No therapy is not available to restore hearing. Amplification may be the only treatment.
Ototoxicity from aminoglycosides:
Aminoglycosides are bactericidal antibiotics that bind to the 30S ribosome and inhibit bacterial protein synthesis. They are the only active agents against gram-negative bacilli and staphylococci. Although the ototoxic effects of aminoglycosides are well documented, this class of drugs is still widely used today. Can be used in combination with penicillin in staphylococcal endocarditis, especially the strep and enterococci. One must always be associated with an aminoglycoside betalactam when treating infections with Pseudomonas aeruginosa. Certain groups of patients including those with cystic fibrosis, immune dysfunction and certain infectious diseases are treated with this class of antibiotics. Of all ototoxic drugs, aminoglycosides are most vestibulotoxice though vary greatly in different effects on vestibular and cochlear system. Kanamycin, neomycin, and amikacin are preferentially cohleotoxice Dihydrostreptomycin. Gentamicin affects cochlear and vestibular systems. Streptomycin, tobramycin and netilmicin are vestibulotoxice primary. Pathogenesis: Toxicity of aminoglycosides chic appeal especially his kidney cochlear system, however there is a degree of correlation between the two systems. Cause cochlear toxicity and high frequency hearing loss is secondary to destruction of cells in the organ of Corti, predominantly basal cochlea tower. These substances are eliminated more slowly than in the serum of internal fluids and their latent cause adverse effects. Latent determine the progression or late onset of deafness after treatment. Apoptosis is the main mechanism of cell death and is mediated by mitochondrial-mediated intrinsic cascade. It seems that aminoglycosides interact with metals such as iron and copper and oxygen free radicals formed. Risk factors: Some factors may put patients at the predisposition to ototoxicity. This occurs mostly at high doses, high in the blood or the long duration of therapy. Other risk factors include old age, renal failure, hearing problems background, family history of ototoxicity and those receiving loop diuretics or other ototoxic drugs. A genetic predisposition exists creating an alteration in mitochondrial protein synthesis. Chinese patients shows faster and more severe deafness. Signs and symptoms: Clinical lesions may present as acute cochlear tinnitus. Early hearing loss may exist unrecognized by the patient and initially manifest as an increase in high frequency hearing problems. With the progression of low frequencies for speech are affected and the patient can profoundly deaf devein if the drug is continued. If cesta future is stopped early lesions can be prevented and partial recovery of hearing may be possible. But the loss is irreversible. Vestibular toxicity symptoms typically include imbalance and visual symptoms. This imbalance is exacerbated in the dark or in situations where progress is on shaky ground. Vertigo is unusual. Called oscillopsia visual symptoms appear only when the head moves. Fast movements of the head are associated with transient blurring of vision. Nystagmus may be present as an early sign. Prevention: Prevention of ototoxicity to aminoglycosides include careful monitoring of serum drug levels and renal function and hearing assessment before, during and after therapy. Daily administration decreases the incidence of ototoxicity and should be considered. It will identify high-risk patients and other antibiotics will select for them. Since aminoglycosides in the cochlea remain long after therapy Voe patients should avoid noisy places for 6 months after therapy because they remain succeptibili to noise-induced deafness. Were found promising agents in preventing ototoxicity uni: vitamin E, ginkgo biloba, alpha lipoic acid.
Ototoxicity of macrolide:
Erythromycin is considered a safe drug. And rare cases of ototoxicity are associated with renal disease, hepatic disease, and intravenous doses. The onset is 3 days of treatment. Are particularly affected frequencies that are higher than those talks. The effects are usually reversible. Azithromycin and clarithromycin are macrolides us. New studies show that could have ototoxic effects. Reports are still sporadic.
Vancomycin ototoxicity:
Vancomycin is a glycopeptide antibiotic used because of its effectiveness on methicillin-resistant staphylococcal infections. Are some reports about tinnitus in patients with high serum levels and renal insuficeintei awarded to those with concomitant aminoglycoside therapy. Ototoxicity is reversible. No study shows vancomycin ototoxicity alone in therapeutic doses.
Ototoxicity of loop diuretics:
Loop diuretics have therapeutic effects on Henle's loop. This class of drugs includes several different chemical groups including sulfonamides, phenoxyacetic acid derivatives and heterocyclic compounds. They are used to treat congestive heart failure, kidney failure, cirrhosis and hypertension. The most effective and diuretics and determines folosiet experimental ototoxicity include: torsemida, azosemida, ozolinona, and piretanid indacrinona. Ototoxicity developed etacrinic acid seems to develop more gradually and require more time to deliver than that caused by furosemide or bumetanide. Ototoxicity attributed this group of drugs is usually self-limiting and reversible in adult patients although irreversible deafness has been reported in newborns. Ototoxicity is estimated to occur in 7% of patients. It depends on the dose, infusion rate, history of renal failure and coadministration of other ototoxic agents. Signs and symptoms: Depending on the diuretic patients history of deafness after accusing the administration of the agent. Complain of tinnitus and imbalance, however, these symptoms are rare and can occur without deafness. Some patients may experience permanent hearing loss especially those with kidney failure, high doses or concomitant therapy with aminoglycosides. Prevention: consists of taking the lowest dose possible to achieve the desired effect evitind rapid infusion rate. Risk factors associated with administration of these drugs require investigation, including coadministration of other ototoxic drugs and a history of kidney failure.
Ototoxicity to antineoplastic agents:
Antineoplastic agents often are ototoxicity associated with platinum-based compounds cisplatin and carboplatin less. They are used in gynecological cancers, lung, central nervous system, head and neck and testicular. Antineoplazicele alkilanti nonspecific agents that are inserted into the DNA helix interrupting cell replication. Cisplatin is widely distributed in high concentrations in kidney, liver and prostate. It binds irreversibly to plasma proteins and can be detected up to 6 months after completion of therapy. Carboplatin is not bound to protein and is quickly cleared by the kidneys. Dosage and its effectiveness is limited by side effects. Higher doses produce ototoxicity. Risk factors: The incidence and severity of ototoxicity depends on the dose, infusion rate and number of cycles, and coadministration of other ototoxic renal status. Pediatric population are higher in patients receiving radiotherapy of head and neck. Some studies describe a 61% hearing loss in children with platinum-based chemotherapy. Signs and symptoms: Patients with this type of tinnitus and deafness accuse subjective ototoxicity. Bilateral hearing loss is associated with cisplatin, senzoneurala, irreversible and progressive. High frequency hearing is affected first, but deafness occurs only in a few days or months after the last dose. Severe hearing loss may occur after a single dose. Prevention: The patient should avoid areas with lots of noise for 6 months after treatment. Audiometry will be performed before and after treatment. Recent studies show that tocopherol, a derivative of vitamin E, D methionine, salicylates, chelating iron, N-acetyl cysteine and caspase inhibitors are useful in prevention Calpain.
Ototoxicity from salicylates:
Acetisalicilic acid known as aspirin is used widely for its effects-inflammatory, antipyretic and analgesic. It is a platelet aggregation inhibitor used to treat patients with a history of transient ischemic attack, unstable angina and myocardial infarction. Pathogenesis: Aspirin and quickly enter the cochlea perilimfei parallel with serum levels. High levels senzoneurala produce reversible tinnitus and deafness. The incidence of deafness is 1% and is seen especially in elderly patients, even at low doses. A risk factor is dehydration. Signs and symptoms: Tinnitus is the most common side effect of salicylates. Other adverse effects include deafness, nausea, vomiting, headache, confusion, tachycardia and tahipnea. Mild to moderate hearing loss is bilateral and symmetrical. Recovery requires 24-72 hours after drug cessation.