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

Lecture 7- Ototoxicity Flashcards

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USMLE® Step 1 flashcards
1
Q

How could you define ototoxic?

A

Any source of non-mechanical damage to the ear, including:

  • Several medications
  • Many solvents
  • Some heavy metals
  • Possibly select asphyxiants
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2
Q

What are aminoglycoside antibiotics?

A
  • 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
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3
Q

What are some examples of aminoglycoside antibiotics?

A
  • Gentamicin
  • Neomycin
  • Kanamycin
  • Tobramycin
  • Amikacin
  • Streptomycin
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4
Q

How are aminoglycosides used today?

A
  • 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
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5
Q

How are aminoglycosides ototoxic?

A
  • 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
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6
Q

How do aminoglycoside antibiotics cause HL?

A
  • 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
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7
Q

What are audiologic manifestations of aminoglycoside ototoxicity?

A

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

Tinnitus
	Occurs before the onset of hearing loss 
	High pitched ringing
	Immediately following first treatment
	Weeks after d/c (discontinuation)
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8
Q

What are vestibular manifestations of aminoglycoside ototoxicity?

A 
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

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9
Q

What are antineoplastic drugs?

A

• 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
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10
Q

How does cisplatin kill cancer cells?

A

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

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11
Q

What is cisplatin ototoxicity?

A

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%

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12
Q

What is carboplatinum toxicity?

A

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

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13
Q

What are loop diuretics?

A
  • 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
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14
Q

What are the indications for loop diuretics?

A 
o	Heart failure
o	Edema
o	Hypertension
o	Ascites (fluid accumulation in the gut) from liver failure
o	Bronchopulmonary dysplasia in neonates
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15
Q

What is loop diuretic ototoxicity?

A

Tinnitus

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

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16
Q

What are chelating agents?

A

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

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17
Q

What are the indications of ototopic agents?

A

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

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18
Q

Why do audiologists monitor for ototoxicity?

A

• 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

19
Q

What are considerations for ototoxicity monitoring?

A
  • 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?
20
Q

Why are ototoxicity grading scales beneficial?

A

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

21
Q

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

A

> 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

22
Q

What are the advantages/disadvantages of the ASHA ototoxicity?

A

Advantage
- Provides early detection of ototoxicity

Disadvantage:

  • Does not assign a grade; binary yes/no
  • Patient serves as their own control
23
Q

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

A

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

24
Q

What is the Monitoring for FDA Approval of drugs?

A

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

25
Q

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

A

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

26
Q

What is the Boston SIOP grading of hearing loss?

A

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

27
Q

Why are neonates administered aminoglycosides?

A

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

28
Q

Why is rate of HL in NICU higher?

A

o Etiology largely unknown

o Aminoglycoside use is one common risk factor

29
Q

What are factors potentiating aminoglycoside ototoxicity?

A

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

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

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

30
Q

What are approaches to monitoring neonates for ototoxicity?

A

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

31
Q

What are some challenges in monitoring neonates for ototoxicity?

A

Timing and feasibility of test
 Ototoxicity monitoring protocols recommend baseline test
 80% of NICU admissions receive prophylactic or empiric treatment with aminoglycosides

Focus of test
 NBHS protocols looking for mild to moderate loss in mid frequencies
• Do not test above 4kHz (Oae)
• Broadband click (aABR)
 Ototoxicity monitoring requires higher frequencies
• DPOAE at 10 kHz or above not available on clinical equipment

Serial ABR or OAE
 Labor intensive
 Difficult to interpret in premature infants (<34 weeks)

Noise from medically necessary interventions
 Mechanical ventilation
 Acoustic and electrical artifact

32
Q

What are clinical issues specific to monitoring ototoxicity in neonates?

A

Some neonates spend several months in the NICU
 Screening if often delayed until just prior to d/c
 If HL is identified, may not have intervention by 6 months of age
 May increase risk for neurodevelopmental delays

Increased noise floors interfering with testing –> false positive screening and/or need for rescreening –> unduly stress parents

33
Q

What are recommendations for ototoxicity prevention in neonates?

A

o Minimize use of aminoglycosides
o Monitor level of ambient noise in NICU and take steps to mitigate
o Prenatal testing for genetic risk factors
o Education of parents and NICU staff regarding the risk of progressive or late onset HL and importance of follow-up

34
Q

What are some childhood cancers treated with platinum chemotherapy?

A 
o	Osteosarcoma
o	Germ cell tumors
o	Hepatoblastoma
o	Medulloblastoma
o	Neuroblastoma
o	Pontine glioma
35
Q

What are cisplatin ototoxicity risk factors?

A

Younger age

Effect of dose

Cranial radiation

Use of other ototoxins during treatment

Genetic predisposition

36
Q

What are the impacts of cisplatin ototoxicity in children?

A

o Reduces utility of cisplatin therapy by limiting dose escalation
o Precludes investigation of novel strategies to enhance cisplatin cytotoxicity
o Infants and young children at critical stage of development
 Speech language development
 Literacy
o Older children and adolescents
 Educational achievement
 Social-emotional development
 Quality of life

37
Q

What are the impacts of minimal SNHL in children?

A

Educational performance
 Lower performance as compared to normal hearing peers (grade 3) (CTBS/4)
• Reading vocabulary, language mechanics, word analysis, science, spelling
 Teacher perception (SIFTER)
• 66% difficulty with academics
• 48% reduced attention
• 79% problems with communication
 Retention rates
• Overall 37% as compared to 3% in normal hearing peers

38
Q

What are the most common cancers in adults?

A

o Men: lung, prostate, colorectal

o Women: breast, colorectal, lung

39
Q

What are some cancers treated with platinum-based chemotherapy?

A 
o	Head and neck
o	Lung
o	Colorectal
o	Bladder
o	Germ cell
o	Ovarian
o	Testicular
40
Q

What are the goals of OMP?

A

o Use of standard definition of threshold shift

o Pre-treatment counseling regarding potential ototoxicity

41
Q

What are the advantages and limitations of obtaining extended high frequencies thresholds?

A

Advantages:
o Monitoring above 8000 Hz more sensitive to ototoxic changes than monitoring standard test frequency range
o Intrasubject variability is within standard test-retest criteria

Limitations:
o Requires “add-on” of extended high frequencies to audiometer
o EHF plus standard frequencies make for a long test session

42
Q

What are the service delivery gaps for OMP?

A

Inconsistent referrals
• Self-referral and physician referral after treatment
• Multiple staff shifts and rotating residents made in-service training difficult
• Insufficient lead time prior to treatment
• Solutions:
o Participation in oncology multidisciplinary team clinics
o Referrals from pharmacy

Scheduling limitations

Location and space limitations

Staffing limitations

Logistical Barriers
• Patient schedules and compliance with audiology visits
• Audiology not near the oncology or infectious disease locations
• Other appointments running late
• Number of schedules, booths, and audiologists
• Solutions:
o Dedicated appointment slots/rooms/staff
o Creative scheduling

43
Q

What are the advantages and limitations of ABR monitoring for ototoxicity?

A 
Advantages:
	Reliable, portable, objective
	Greater dB range than OAE
	May capture pre-clinical changes
	Helpful in cases when patient is very ill and/or uncooperative

Limitations
 Lengthy
 Lacks frequency specificity at high stimulus levels
 High frequency stimuli may not be available
 May require sedation

44
Q

What are the advantages and limitations of OAE monitoring for ototoxicity?

A

Advantages:
 Efficient, portable, and reliable objective tool
 May capture pre-clinical changes
 Helpful in cases when patient is very ill and/or uncooperative

Limitations
	Limited ability to assess the higher frequencies
	No widely accepted standard for change
	Limited dB range
	Obscured by ME disease
	Require careful measurement

HESP 632 - Medical Audiology (7 decks)

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