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HESP632 Final > Ototoxicity > Flashcards

Ototoxicity Flashcards

1
Q

What is the textbook definition of ototoxicity?

A
  • Any source of non-mechanical, non-disease damage to the ear
  • Includes: medications, solvents, heavy metals, possibly asphyxiants
  • Most often used in content of clinical, medication-induced hearing loss or vestibular dysfunction
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2
Q

What is the operational definition of ototoxicity?

A
  • Based on grading scales

- Beneficial for: consistency, objectivity, approachable numbers to non-audiologists

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3
Q

What are some benefits to using grading scales?

A
  • Defined parameters, operational definition
  • Rank or grade the degree of hearing loss
  • Provide government agencies with data to judge drug safety
  • Assess effectiveness or oto-protective interventions
  • Assess genetic susceptibility to ototoxicity
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4
Q

Describe the ASHA Ototoxicity Grading Scale.

A

-Binary: yes/no ototoxicity:
20 dB+ decrease in pure-tone threshold at 1 test frequency
OR
10 dB+ decrease at 2 adjacent test frequencies
OR
Loss of response at 3 consecutive test frequencies where responses were previously attained
-Threshold change confirmed on retest

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5
Q

Describe the NCI ototoxicity grading scale.

A

-Grading of adverse events, hearing change, and/or therapeutic needs
-Graded on a scale of 0-5:
Grade 0 = no adverse event
Grade 1 = mild adverse event
Grade 2 = moderate adverse event
Grade 3 = severe adverse event
Grade 4 = life-threatening adverse event
Grade 5 = fatal adverse event
-Grading is different for adults vs. pediatrics

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6
Q

Describe the monitoring for FDA approval of new drugs.

A
  • Phase 1: safety
  • Phase 2: efficacy, optimum dose-response
  • Phase 3: large scale study to detect side effects not identified ini first 2 phases
  • Phase 4: further evaluation on subpopulations such as children, pregnant women, and the elderly
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7
Q

Describe Brock criteria for monitoring ototoxicity.

A

-Grading of hearing loss at the end of trial:
Grade 0 = thresholds <40 dB at all frequencies
Grade 1 = thresholds 40 dB+ at 8 kHz
Grade 2 = thresholds 40 dB+ 4-8 kHz
Grade 3 = thresholds 40 dB+ 2-8 kHz
Grade 4 = thresholds 40 dB+ 1-8 kHz

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8
Q

Describe Boston SIOP grading scale for ototoxicity.

A

-Grading of hearing loss
Grade 0 = hearing threshold up to 20 dB at all frequencies
Grade 1 = thresholds > 20 dB above 4 kHz
Grade 2 = thresholds > 20 dB at 4 kHz+
Grade 3 = thresholds > 20 dB at 2 or 3 kHz+
Grade 4 = thresholds > 40 dB at 2 kHz+

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9
Q

How can ototoxicity be defined?

A
  • Textbook definition
  • Operational (i.e. grading scales)
  • Functional (i.e. WR decline)
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10
Q

What medications have been linked to ototoxicity?

A
  • Aminoglycoside antibiotics
  • Antineoplastic drugs
  • Loop diuretics
  • Chelating agents
  • Anti-inflammatory drugs
  • Ototopic agents
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11
Q

What are aminoglycoside antibiotics?

A
  • EX: gentamicin, neomycin, streptomycin
  • First discovered by Albert Schatz in Selman Waksman’s lab in 1944 (ototoxicity was first noted by Feldman & Hinshaw in 1945)
  • Among the most commonly used antibiotics worldwide (i.e. TB, CF, serious infections)
  • Side effects include ototoxicity and nephrotoxicity
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12
Q

What are audiological manifestations of aminoglycoside antibiotic ototoxicity?

A

1) HL
- Bilateral, HF SNHL
- Onset is often delayed days or weeks after onset of therapy
- Most often permanent

2) Tinnitus
- Immediately following first treatment
- Typically occurs before HL

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13
Q

What are vestibular manifestations of aminoglycoside antibiotic ototoxicity?

A

1) Acute
- Headaches
- Nausea, vomitting, imbalance
- Vertigo

2) Chronic
- Difficulty with sudden movements
- Imbalance when walking

3) Compensatory
- Centrally mediated

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14
Q

What are antineoplastic drugs?

A
  • Platinum compounds:
    1) Cisplatin
  • Kills cancer cells by binding DNA, resulting in kinked helix (cannot bind so cell dies)
  • Ototoxicity is typically bilateral, symmetrical, sensory, permanent, HF
  • Onset: gradual, progressive, cumulative, or sudden
  • Evidence of progression after cisplatin is d/c

2) Carboplatinum
- Less cochleotoxic than cisplatin
- Indications are similar to cisplatin

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15
Q

What are loop diuretics?

A
  • Drugs that inactivate the Na-K pump at the loop of Henle in the kidney
  • Prevent reabsorption of Na, K, chloride, and water (potent diuretics)
  • Indications: heart failure, edema, hypertension, ascites from liver failure
  • Ototoxicity: tinnitus, flat SNHL, rare reports of vertigo
  • Toxicity related to:dosing, concomitant aminoglycoside Rx, renal function/failure
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16
Q

What are chelating agents?

A

-Used to treat iron overload, sickle cell disease, etc.

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17
Q

What are anti-inflammatory drugs?

A

1) Salicylates (ASA)
- Mild to moderate SNHL
- Reduced OAEs due to decreased cochlear blood flow
- Recovery in 24-72 hours after cessation of drugs

2) Quinine
- Indications: antimalarial, nocturnal leg cramps
- Bilateral, symmetrical SNHL
- Reduced WR
- HF tinnitus
- Typically reversible

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18
Q

What are ototopic agents?

A

EX: solvents, antiseptics, antibiotics

  • Indications: suppurative OM, otorrhea following myringotomy and tubes, draining mastoid cavities, OE
  • Low incidence of ototoxicity
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19
Q

What is the audiologist’s role in ototoxicity monitoring?

A
  • Monitor for ototoxicity
  • Establishing goals of a monitoring program
  • Participation in therapeutic decision making
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20
Q

Why do we monitor for ototoxicity?

A
  • Ensure early identification of hearing loss
  • Prevent functional hearing loss (i.e. treatment alternatives, smaller/less frequent doses, d/c treatment)
  • Care and support of patient and family
  • Evaluate drug safety
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21
Q

What are some considerations for ototoxicity monitoring?

A
  • Patient age and medical status
  • Underlying diagnosis
  • Purpose of monitoring
  • How will a change in hearing be defined and reported?
  • What is at stake?
22
Q

What are some age-related considerations in ototoxicity monitoring for neonates?

A
  • NICU admissions receive prophylactic or empiric treatment with gentamicin
  • Broad spectrum specificity toward organisms commonly encountered in neonatal sepsis
  • Considered clinically essential despite known ototoxicity and nephrotoxicity
  • Higher incidence of HL in NICU babies is of unknown etiology (but aminoglycoside use is a common risk factor)
23
Q

What are some factors potentiating aminoglycoside ototoxicity in neonates?

A
  • Concurrent medications (i.e. loop diuretics)
  • Inflammatory status
  • Genetics
  • Noise levels in the NICU
24
Q

What does JCIH recommend for neonates taking aminoglycosides for 5 days+?

A
  • Diagnostic follow-up by 9 months of age

- No specific screening/monitoring protocol for ototoxicity in neonates

25
Q

What are challenges to monitoring neonates for ototoxicity?

A
  • Timing and feasibility of test (baseline often cannot be completed before drug administration)
  • Focus of test (i.e. NBS looks for mild-mod HL in MFs but ototoxicity monitoring requires HFs)
  • Serial ABR or OAE is labor-intensive, difficult to interpret in premies
  • Noise from medically-necessary interventions
26
Q

What are recommendations for ototoxicity prevention in neonates?

A
  • Minimize use of aminoglycosides
  • Monitor level of ambient noise in NICU and take steps to mitigate
  • Prenatal testing for genetic risk factors
  • Education of parents and NICu staff regarding the risk of progressive or late-onset HL and importance of follow-up
27
Q

Describe age-related considerations in ototoxicity monitoring in pediatrics.

A

-Childhood cancers are most often treatment with platinum (cisplatin) chemotherapy

28
Q

What are cisplatin ototoxicity risk factors in pediatrics?

A
  • Younger age
  • Dose
  • Cranial radiation
  • Concomitant use of other ototoxins during treatment (i.e. aminoglycosides, loop diuretics)
  • Genetic predisposition
29
Q

How is cranial radiation a risk factor for cisplatin ototoxicity in pediatrics?

A
  • Increased risk of HL as radiation dose increases
  • HL might not appear until 18 months+ after tx completion
  • May develop transient or permanent CHL
  • Combination of cisplatin and radiation therapy potentiates the ototoxic effect of cisplatin
30
Q

Describe the impact of cisplatin ototoxicity in pediatrics.

A
  • Reduces utility of cisplatin therapy by limiting dose escalation
  • Precludes investigation of novel strategies to enhance cisplatin cytotoxicity
  • Infants and young children at critical stage of development
  • Older children and adolescents: educational achievement, social-emotional development, QOL
31
Q

Describe the suggested pediatric monitoring protocol: 5;0+.

A
  • Evaluate at baseline, during therapy, and end of therapy/school re-entry
  • AC 0.5-8 kHz (BC when indicated)
  • EHF
  • Otoscopy
  • Immittance
  • DPOAE
  • Suprathreshold speech recognition
  • Question about tinnitus
32
Q

Describe the suggested pediatric monitoring protocol: 0;8-4;11.

A
  • Evaluate at baseline, during therapy, and end of therapy/school re-entry
  • AC 0.5-8 kHz (BC when indicated)
  • Otoscopy
  • Immittance
  • DPOAE
  • Suprathreshold speech recognition (when possible)
33
Q

Describe the suggested pediatric monitoring protocol: infant or unresponsive patient.

A
  • Evaluate at baseline, during therapy, and end of therapy/school re-entry
  • Tone evoked ABR/ASSR (>4 kHz if possible)
  • Otoscopy
  • Immittance
  • DPOAE
  • Behavioral audiometry as soon as patient is able
34
Q

Describe SIOP Minimal Test Battery for ototoxicity monitoring in pediatrics.

A
  • Sequence for testing: used only when complete evaluation is not possible
  • Purpose: direct testing to critical components for grading hearing loss
  • Improve consistency of data in multi-center studies
  • Allow grading when only 2-3 frequencies can be measured
  • Children tested with minimal battery will require complete evaluation as soon as child is able
35
Q

What adult cancers are usually treated with platinum-based chemotherapy?

A
  • Head and neck
  • Lung
  • Colorectal
  • Bladder
  • Germ cell
  • Ovaria
  • Testicular
36
Q

What are the general goals for adult ototoxicity monitoring programs?

A
  • Use of standard definition of threshold shift
  • Pre-treatment counseling regarding potential ototoxicity
  • Baseline evaluation before (or early in) treatment
  • Monitoring evaluations at sufficient intervals to document hearing loss progress or fluctuation
  • Post-treatment evaluation followed by longer term monitoring
37
Q

When should adult OMPs start?

A
  • Cisplatin: no later than 24 hours after initial treatment and retest prior to each subsequent dose
  • Aminoglycoside: no later than 72 hours after initial administration and monitor at least weekly during treatment
38
Q

When should post-treatment evaluation for adult OMP occur?

A
  • Immediately post-treatment

- Follow-up at 3 and 6 months post-treatment

39
Q

What are baseline, monitoring test components for adult OMP?

A
  • Otoscopy
  • Tympanometry
  • AC 250-8000 Hz
  • BC
  • EHF
  • OAE
  • Speech audiometry
40
Q

What are additional adult OMP components?

A
  • OAEs (focus on HF)
  • Lack of guideline for testing/interpretation
  • Standard clinical protocol?
41
Q

What are some advantages/limitations of EHFs?

A
  • Advantages: monitoring above 8 kHz more sensitive to ototoxic changes, intra-subject variability is within standard test-retest criteria
  • Limitations: requires “add-on” of extended high frequencies to audiometer, increases test time
42
Q

What are some OMP service gaps?

A
  • Inconsistent referrals
  • Scheduling limitations
  • Location and space limitations
  • Staffing limitations
43
Q

Describe OMP service gap: inconsistent referrals.

A
  • 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:
  • Participation in oncology multidisciplinary team clinics
  • Referrals from pharmacy
44
Q

Describe OMP service gap: logistical barriers.

A
  • Patient schedules and compliance with audiology visits
  • Audiology not near the oncology or infectious disease locations
  • Other appointments running late
  • Number of schedulers, booths, and audiologists
  • Solutions:
  • Dedicated appointment slots/rooms/staff
  • Creative scheduling
45
Q

What are some advantages to ABR monitoring for ototoxicity?

A
  • Reliable, portable, objective
  • Greater dB than OAEs
  • May capture pre-clinical changes
  • Helpful in cases when patient is very ill and/or uncooperative
46
Q

What are some limitations to ABR monitoring for ototoxicity?

A
  • Lengthy
  • Lacks frequency specificity at high stimulus levels
  • High frequency stimuli may not be available
  • May require sedation
  • Sensitivity and specificity for detecting ototoxic changes unknown
47
Q

What are some advantages to OAE monitoring for ototoxicity?

A
  • Efficient, portable, and reliable objective tool
  • May capture pre-clinical changes
  • Helpful in cases when patient is very ill and/or uncooperative
48
Q

What are some limitations to OAE monitoring for ototoxicity?

A
  • Limited ability to assess the higher frequencies
  • No widely accepted standard for change
  • Limited dB range
  • Obscured by ME disease
  • Require careful measurement
  • Sensitivity and specificity for detecting ototoxic changes unknown
49
Q

What are requirements of otoprotective drugs?

A
  • Effective
  • Safe for human administration
  • Clinically feasible
  • No interference with primary drug
50
Q

Where are we with regard to otoprotective agents?

A
  • Currently, no drug is FDA approved to prevent or treat ototoxic hearing loss in humans
  • In/approaching clinical trials for:
  • Protection for cisplatin-induced ototoxicity, noised-induced HL, aminoglycoside-induced ototoxicity

HESP632 Final (7 decks)

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