Lecture 7- Ototoxicity Flashcards Preview

HESP 632 - Medical Audiology > Lecture 7- Ototoxicity > Flashcards

Flashcards in Lecture 7- Ototoxicity Deck (44)
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How could you define ototoxic?

Any source of non-mechanical damage to the ear, including:
- Several medications
- Many solvents
- Some heavy metals
- Possibly select asphyxiants


What are aminoglycoside antibiotics?

- Among the most commonly used antibiotics worldwide
- Sold OTC in some countries
- Treatment for gram negative infections, including pseudomonas and mycobacterium tuberculosis
- Side effects include ototoxicity and nephrotoxicity


What are some examples of aminoglycoside antibiotics?

- Gentamicin
- Neomycin
- Kanamycin
- Tobramycin
- Amikacin
- Streptomycin


How are aminoglycosides used today?

- Tuberculosis
- Gentamicin used to treat infections in neonates
- Tobramycin used to treat respiratory infections in cystic fibrosis
- Gentamicin used to treat endocarditis
- Neomycin used prior to bowel surgery


How are aminoglycosides ototoxic?

- Amikacin, tobramycin, and gentamicin about equally toxic
- As many as 21% of children with CF have aminoglycoside ototoxicity
- HL caused by death of sensory hair cells


How do aminoglycoside antibiotics cause HL?

- Enter HC through mechano-electrical transduction channels
- Once in HC, may not be readily cleared
- High concentration --> off-target binding of ribosomes and inhibition of protein translation
- Formation of reactive oxygen species in HC
- Apoptopia death of HC


What are audiologic manifestations of aminoglycoside ototoxicity?

Hearing Loss
 Bilateral, HFSN
 Onset of HL is often delayed days or weeks after onset of therapy
• Rapidity of hearing loss is dose-related
• Dependent on renal function
 Most often permanent
• Recovery may occur over a 1-6-month period
• Most likely if ototoxicity occurs early, hearing shift is <25 dB, and corrective measures are taken immediately
• Sx that present weeks after treatment are most likely permanent

 Occurs before the onset of hearing loss
 High pitched ringing
 Immediately following first treatment
 Weeks after d/c (discontinuation)


What are vestibular manifestations of aminoglycoside ototoxicity?

Acute Phase
 Headache may be the first Sx
 Nausea, vomiting, imbalance 1-2 weeks
 Vertigo in upright position
• Sitting, standing
 Inability to perceive termination of movement
 Positive Romberg

Chronic Phase
 Sx of chronic labyrinthitis
• Difficulty with sudden movements
• Imbalance when walking
• Lasts up to 2 months

Compensatory Phase
 Centrally mediated
 12-18 months


What are antineoplastic drugs?

• Platinum Compounds
o Cisplatinum (CDDP)- cumulative cochleotoxicity
 Among the most widely used and effective of the anti-cancer drugs
 Most ototoxic drug in clinical use
o Carboplatin- less cochleotoxicity

• Nitrogen mustard- cochleotoxic

• Vincristine or vinblastine sulfate – rare reports of cochlear toxicity

• Difluoromethylornithine- transient or permanent dose related cochlear toxicity


How does cisplatin kill cancer cells?

o Cisplatin binds DNA and results in a kink in the DNA helix
o Damage to the DNA is recognized as irreversible damage to the cell and the cell proceeds to die


What is cisplatin ototoxicity?

o Typically, bilateral, symmetrical, sensory, permanent

o Appears first in the high frequencies
 Can progress to low frequencies with continued treatment, higher cumulative dose

o HL time course
 Gradual onset, progressive and cumulative, or sudden
 Evidence of progression years after cisplatin is d/c

o Prevalence
 HL in 7-71% in adults
 HL ~60-70% in children
 Tinnitus, with or without HL, ~60%


What is carboplatinum toxicity?

o Less cochleotoxic than Cisplatinum

o Indications are similar to Cisplatinum
 Ovarian cancer data shows response rates similar to Cisplatinum

o Histopathology
 Destruction of IHC demonstrated in animal models


What are loop diuretics?

• Ethacrynic acid, furosemide (Lasix) butametanide
• Drugs that inactivate the sodium-potassium pump at the loop of Henle in the kidney
• Prevent reabsorption of sodium, potassium, chloride, and water – potent diuretics


What are the indications for loop diuretics?

o Heart failure
o Edema
o Hypertension
o Ascites (fluid accumulation in the gut) from liver failure
o Bronchopulmonary dysplasia in neonates


What is loop diuretic ototoxicity?


Hearing loss
 Permanent with ethacrynic acid
 Usually reversible with furosemide
 Flat, SNHL, and reversible hearing loss with use of Lasix

Rare reports of vertigo

Toxicity related to
 Dosing: slow-low is best
 Concomitant aminoglycoside Rx
 Renal function/failure


What are chelating agents?

Deferoxamine (desferal) and desferasirox (exjade, jadenu)
o Chelating agent used to treat iron overload
o Beta thalassemia
o Diamond Blackman anemia
o Sickle cell disease

Deferoxamine alone or in combination: HL in 32%

Desferasirox alone: not ototoxic


What are the indications of ototopic agents?

o Suppurative otitis media
o Otorrhea following myringotomy and tube placement
o Draining mastoid cavities
o Otitis externa


Why do audiologists monitor for ototoxicity?

• Ensure early identification of hearing loss
• Prevent functional hearing loss
o Treatment alternatives
o Smaller or less frequent doses
o Interruption of suspension of treatment
• Care and support of patient and family
o Assist in re/habilitation, as indicated
o Ensure informed decision making
• Evaluate drug safety
o Known efficacious drugs
o Research using new or experimental treatments
o Criteria for clinical trials


What are considerations for ototoxicity monitoring?

• Patient age and medical status – will this change over time?
• Underlying diagnosis – can this affect hearing?
• Purpose of monitoring – are there alternatives?
• How will a change in hearing be defined and reported?


Why are ototoxicity grading scales beneficial?

o Consistency
o Objective
o Approachable numbers to the non-audiologist
o Defined parameters; operational definition
o Rank or grade the degree of hearing loss
o Provide government agencies with data to judge drug safety
o Assess effectiveness of otoprotective interventions
o Assess genetic susceptibility to ototoxicity


What are the ASHA Ototoxicity criteria (Binary yes/no)?

>20 dB decrease in pure-tone threshold at one test frequency OR

>10 dB decrease at two adjacent test frequencies OR

Loss of response at 3 consecutive test frequencies where responses were previously attained

Threshold change confirmed on retest


What are the advantages/disadvantages of the ASHA ototoxicity?

- Provides early detection of ototoxicity

- Does not assign a grade; binary yes/no
- Patient serves as their own control


What are the NCI Common Terminology Criteria for Adverse Events (CTCAE)?

o Grading of adverse events, hearing change, and/or therapeutic needs
o Hearing only graded up to Grade 4
o Graded on a scale of 0-5
 No adverse event

Grade 1: Mild Adverse Event

Grade 2: Moderate Adverse

Grade 3: Severe Adverse Event

Grade 4: Life Threatening Adverse Event

Grade 5: Fatal Adverse Event


What is the Monitoring for FDA Approval of drugs?

Phase 1: safety

Phase 2: efficacy – optimum dose-response

Phase 3: large scale study to detect side effects not identified in first 2 phases

Phase 4: further evaluation on subpopulations such as children, pregnant women and the elderly


What is the Brock Criteria (grading of hearing loss at the end of the trial)?

o Grade 0: Hearing thresholds less than 40 dB HL at all frequencies
o Grade 1: Thresholds 40 dB HL or greater at 8000 Hz
o Grade 2: Thresholds of 40 dB HL or greater at 4000-8000 Hz
o Grade 3: Thresholds of 40 dB HL or greater at 2000-8000 Hz
o Grade 4: Thresholds of 40 dB or greater at 1000-8000 Hz


What is the Boston SIOP grading of hearing loss?

Based on sensorineural hearing thresholds in dB HL (bone conduction or air conduction with a normal tympanogram)

Grade 0: <20 dB HL at all frequencies

Grade 1: >20 dB HL SNHL above 4000 Hz

Grade 2: >20 dB HL SNHL at 4000 Hz and above

Grade 3: >20 dB HL SNHL at 2000 or 3000 Hz and above

Grade 4: >40 dB HL SNHL at 2000 Hz and above


Why are neonates administered aminoglycosides?

o Broad spectrum specificity toward organisms commonly encountered in neonatal sepsis
o Considered clinically essential despite known ototoxicity and nephrotoxicity


Why is rate of HL in NICU higher?

o Etiology largely unknown
o Aminoglycoside use is one common risk factor


What are factors potentiating aminoglycoside ototoxicity?

Concurrent medications
 Glycopeptide antibiotic – vancomycin
 Neuromuscular blocking agents- pancuronium bromine and vecuronium bromide
 Loop diuretics- Lasix

Inflammatory status
 Host-induced inflammatory response to infection or bacterial immunogens
 Systemic inflammation 2o abdominal irradiation

 Mitochondrial DNA variant, A1555G
 ACMG recommends screening for this variant

Noise levels in NICU
 Sustained noise may potentiate ototoxicity of aminoglycosides


What are approaches to monitoring neonates for ototoxicity?

JCIH recommendations regarding ototoxicity
 If aminoglycosides >5 days, diagnostic audiologic follow up by 9 months of age unless there has been a toxic-level (not defined) or there is a known genetic susceptibility to aminoglycosides

How do we typically test for ototoxicity?
 Behavioral pure-tone thresholds in children
 Baseline test followed by monitoring tests

What are we looking for?
 Changes in the high frequencies
 Early detection

No specific screening and monitoring protocol for ototoxicity in neonates