Ototoxicity Flashcards
Why are ototoxic monitoring programs important?
1) early identification of hearing loss during treatment process
2) if a change in hearing occurs, can possibly alter treatment in terms of drug, dosage, frequency in order to prevent a functional hearing loss
3) Can assist in habilitation/rehabilitation and also ensure informed decision making during the treatment process
4) To help evaluate drug safety as they can help outline the ototoxicity profile for a new drug
What are the goals of an individual in an ototoxicity monitoring program?
1) hearing preservation
2) counseling b/c more concerned about treating disease they have at cost of hearing loss
**Should be patient-specific
Who is the target population for an ototoxocity monitoring program?
Anybody taking ototoxic medications
Who are considered high-risk patients when it comes to ototoxic medications and hearing loss?
1) people in poor overall health
2) age extremes
3) poor renal function
4) low red blood cell count
Who are the stakeholders of an ototoxicity monitoring program?
1) patients
2) family members
3) physicians
4) Third party payers –> limit alternatives available for the patient
5) Regulatory bodies (such as the FDA)–> may decide if a drug is available for treatment or not
What information is important to provide in an ototoxicity monitoring program?
- Any change in hearing (to patient and oncologist/physician)
- Use terminology that is appropriate for target audience
- Written material to supplement anything said to patient
Why should written materials be provided to patients?
About 50% of what is stated is remembered. Their understanding affects their satisfaction (Nair & Cienkowski, 2010)
What testing should be completed at a baseline ototoxic monitoring exam?
- Case history
- Otoscopy
- Tympanometry
- Pure tone air conduction and bone conduction
- Word recognition
- SRT
- Ultra-high frequency audio at all frequencies in 1/6 octaves between 9000-20,000 Hz
- OAEs
What information should be obtained in the initial case history?
- Hearing history
- Noise and solvent exposure
- Tinnitus
- Vestibular symptoms
- Current medical status
- Goal/purpose of the ototoxicity monitoring (prevent hearing loss in speech frequency region or for counseling purposes?)
Why is it important to ask about tinnitus in a case history?
Tinnitus can be a side effect of medications so important to know if it is present before taking medication
Why is it important to ask about noise exposure history?
Synergistic effects of noise exposure and ototoxic medications (Li & Steyger, 2009)
What is the importance of tympanometry?
To rule out middle ear dysfunction
Why test ultra-high frequencies?
This is the area that is sensitive to any initial changes in hearing (Reavis et al., 2011)
Why test word recognition?
As part of counseling, especially if the goal is to prevent any hearing loss in the frequency region important for speech understanding
Why test otoacoustic emissions?
- To assess the status of the outer hair cells.
- Can be used as an objective measure at follow-up if patient is unable to provide behavioral responses
What tests should be completed at each follow-up?
- Ultra high frequency testing in sensitive region for ototoxicity (SRO)
- DPOAEs
These tests can be completed using portable equipment at the patient’s bedside
What is the sensitive region for ototoxicity (SRO)?
The highest frequency at which the threshold is 100 dB SPL and the 6 adjacent frequencies
Region thought to be where change in hearing is initially most likely to be seen due to basal to apical pattern of OHC damage from drugs (Reavis et al., 2011)
What is classified as a change in hearing?
There are different grading scales to classify hearing.
ASHA grading scale defines a change in hearing as:
1) change of 20 dB or more at 1 frequency
2) change of 10 dB or more at 2 adjacent frequencies
3) No response at 3 adjacent frequencies where there previously was a response
changes should be confirmed on retest in 24 hours in the audiology clinic to control for noise
What is the follow-up schedule for ototoxicity?
It is patient specific and depends on the drug and dosage.
Should be completed following each treatment session and before the next session.
Some medications have been shown to have delayed effects, even after cessation, thus should continue monitoring after stop taking (Wilmington et al., 2011)
What are 2 common categories of ototoxic agents?
1) aminoglycosides
2) antineoplastic drugs
What are aminoglycosides used to treat? (Li & Steyger, 2009)
Gram negative infections bacterial such as tuberculosis and advanced bacterial infections
What are some examples of aminoglycosides?
- Streptomycin
- gentamicin
- Tobramycin
- Kanamicin
- Neomycin
- Amikacin
Which aminoglycosides are primarily vestibulotoxic?
Streptomycin and gentamicin
Which aminoglycosides are primarily cochleotoxic?
Kanamycin, neomycin, amikacin
How do aminoglycosides work to kill the bacteria?
Work to inhibit protein growth.
DNA in the cell nucleus is transcribed to RNA. The RNA leaves the cell nucleus and enters the cytoplasm where the ribosomes translate it into protein. These ribosomes have 2 subunits- 30th and 50th. The aminoglycosides bind to the 30th subunit which prevents the bacteria from making the protein it needs to survive.
What is the mechanism for ototoxicity with aminoglycosides?
Aminoglycosides enter the hair cells through the mechanotransduction (MET) channel.
Once inside hair cell, it is harder to clear from the cell resulting in a higher concentration of the drug reaching the hair cell.
As a result, there is inhibition of protein translation and the formation of ROS occurs in the hair cells. This results in the apoptotic death of hair cells.
Do the effects of aminoglycosides continue even after cessation of the drug?
Yes– up to 4 weeks (Li & Steyger, 2009)
What are the vestibular symptoms/effects of aminoglycosides?
Nystagmus, disequilibrium, oscillopsia
Which of the vestibular symptoms occur if the vestibulotoxicity is severe with aminoglycosides?
Disequilibrium and oscillopsia (Selimoglu, 2007)
What is the hearing loss associated with aminoglycosides?
Variable and possibly delayed onset
Bilateral, high frequency, SNHL
What structures are damaged from aminoglycosides?
Basal to apical pattern of damage (Li & Steyger, 2009)
OHCs–> IHCs–> Supporting Cells
What are the risk factors for ototoxicity with aminoglycosides?
- Pre-existing medical conditions such as those affecting renal function
- age
- prior ototoxicity
- genetic susceptibility
- dosage and duration of drug
- combo of drugs
- pre-existing SNHL
What are some of the different classifications of antineoplastic drugs?
Nitrogen mustards
platinum compounds (including cisplatin and carboplatin)
What is cisplatin used to treat?
Cancer in adults and children
How does cisplatin work?
Binds to DNA and creates a kink in the DNA helix.
This kink is recognized as irreversible damage to the DNA and the cell dies
What is the ototoxicity path for cisplatin? (Dille et al., 2015)
- Directly into the hair cells affecting the OHCs in a basal to apical pattern initially, and then the stria vascularis
- As damage progresses, IHCs and supporting cells also affected
What is the hearing loss associated with cisplatin?
Bilateral, high frequency, SNHL.
May also experience tinnitus as a result of their treatment (Dille et al., 2015)
What is the time course for ototoxicity with cisplatin? (Fausti et al., 1999)
Variable occurring any time after first treatment
True or False: Cisplatin is not nephrotoxic.
FALSE!
It is nephrotoxic, thus should also be monitored by a nephrologist when taking cisplatin
What are some risk factors for ototoxicity with antineoplastic drugs (specifically cisplatin)? (Reavis et al.., 2011)
- Dose, duration, and frequency
- Combination of medications
- Age
- Genetics
- Pre-existing hearing loss
