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AUDE 6120 - Pharmacology and Ototoxicity > Ototoxic and Vestibulotoxic Drugs > Flashcards

Ototoxic and Vestibulotoxic Drugs Flashcards

1
Q

What are unintended consequences of drugs?

A

Side effects
Adverse effects
Toxic effects

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2
Q

What are the unintended consequences a function of?

A

Mechanism of drug action
Drug dosage
Characteristics and health of the patient (genetics, age, cardiac, liver, and kidney disease)

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3
Q

What is the reason that patients are given the lowest possible dose when taking a medication for the first time?

A

Drug toxicity
Only done when possible

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4
Q

How many people do adverse drug effects due to dosing errors affect?

A

About 7 million people annually
Costs around 21 billion annually
Critical for patients, doctors, and hospitals to minimize errors in prescribing and drug dosing

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5
Q

What are idiosyncratic drug reactions?

A

Unpredictable, unusual/unexpected adverse effects not explained by the pharmacologic properties of the drug that occur in some patients, not observed in animal/human clinical trials
Genetic or other patient variables that cause these reactions
Most IDRs are mediated through the immune system and are not dose dependent (can occur with one or fewer doses)

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6
Q

Can idiosyncratic toxicity cause permanent organ damage and death?

A

Yes
Can prompt drug withdrawal from use
Susceptible patients cannot be identified prior to the adverse effect occurring

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7
Q

What is ototoxicity?

A

Damage to the inner ear, targeting cochlear and vestibular structures and sensory function, due to exposure to certain pharmaceuticals, chemicals, and/or ionizing radiation

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8
Q

What are nonmedical agents that can damage the inner ear and are considered ototoxic?

A

Noise exposure
Chemical toxins and many solvents
Some heavy metals such as lead and mercury
Radiation

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9
Q

Is the hearing loss present from ototoxicity always SNHL?

A

Yes
The SNHL may be progressive, reversible, or irreversible
It can be unilateral or bilateral

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10
Q

What is neurotoxicity?

A

It is the alteration of hearing or balance by drugs and chemicals acting at the level of brainstem or central connections of the cochlear and vestibular nuclei
Distinct from ototoxicity

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11
Q

What are the risk factors for ototoxicity?

A

Dosage (the higher the dose and more prolonged the administration, the greater the risk)
Hepatic function (over 30 drug classes are metabolized in the liver, liver disease can decrease drug metabolism causing ototoxicity)
Renal function (most drugs are filtered through the body by way of the kidneys, chances of ototoxicity increase with impaired renal function)
Polypharmacology (greater risk of drug interaction)
Age (very young and old are most susceptible)
Pre-existing SNHL

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12
Q

What does the BLB allow through?

A

Only ions, amino acids, sugars, and other necessary compounds through
Genetic disorders, autoimmune reactions, and some microbes can breakdown the cellular integrity of the BLB resulting in loss of endocochlear potentials and SNHL
Ototoxins, however, appear to be able to cross an intact blood-labyrinth barrier by some yet unknown mechanism

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13
Q

Will ototoxic drugs cause disruption in the stria vascularis?

A

Yes

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14
Q

Do different classes of drugs act on different parts of the cochlear microstructure?

A

Probably, can act on different areas
Results in ototoxicity

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15
Q

Where is the earliest cochlear lesion in OHC destruction?

A

At the basal end
Can be caused by ototoxicity, NIHL, presbycusis, etc.

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16
Q

Will the damage progress from just the basal end (high frequencies)?

A

Yes
As dosage and/or duration increases
IHC can be destroyed and the damage spreads toward the apex, resulting in SNHL at mid and low frequencies

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17
Q

What follows the destruction of IHCs?

A

Degeneration of afferent nerve endings
VIII N tuning curves get shallow with destruction of the high frequency tip and only low frequency tail may be left
Speech perception is then adversely affected

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18
Q

What are the audiologic signs and symptoms of ototoxicity?

A

Tinnitus (change in frequency, intensity, or character of existing tinnitus; acute tinnitus can precede or supersede SNHL; can be intermittent and then become constant; may go away after drug discontinuation)
Aural fullness (patient can report being plugged up)
Recruitment
Abnormal/absent OAEs
Abnormal/absent acoustic reflexes (reflex decay and tone decay are typically negative (normal))
Poor speech perception (WRS scores decreased disproportionately
Some are being treated for life-threatening conditions

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19
Q

What are the vestibular signs and symptoms of ototoxicity?

A

Rarely is true vertigo reported
Typically, light-headedness or dizziness is reported
Unsteadiness or gait abnormalities
Ataxia also is reported
Abnormal ocular tracking on vestibular tests
Nystagmus (rapid involuntary eye movements)

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20
Q

What is it hard to distinguish ototoxicity and vestibulotoxicity from when you only have a pure tone audiogram?

A

Presbycusis
Ototrauma (very loud noise, sudden onset with short duration
Noise induced hearing loss
Sudden onset SNHL that is not caused by medication
Vestibular symptoms are typically rare in any of the above conditions but are more common with drug toxicity and some cases of sudden SNHL

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21
Q

Will the noise notch go away with age (presbycusis)?

A

Yes

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22
Q

What are the target organisms for antibiotics?

A

Bacteria
Affect both gram-positive and gram-negative bacteria

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23
Q

What is gram-positive bacteria?

A

Bacteria that stain dark blue or violet by Gram staining because of high amounts of peptidoglycan in cell wall

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24
Q

What is gram-negative bacteria?

A

Bacteria cannot retain the crystal violet stain because they typically lack the outer membrane found in gram-positive bacteria
Instead they take up the counterstain (e.g., safranin or fuchsine) and appear red or pink

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25
Q

What is antibiotic antagonism?

A

One antibiotic can cancel out desired effects of the other
For e.g., if tetracycline and penicillin are given together, penicillin will not be effective

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26
Q

What is antibiotic synergism?

A

Using more than one antibiotic increases the spectrum of kill and produces a desired effect of greater magnitude
For e.g., enterococci bacteria may not be completely eradicated by penicillin alone
But streptomycin given with penicillin, will kill the enteroccoci bacteria completely

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27
Q

Are aminoglycosides the most studies class of antibiotics for ototoxicity/vestibulotoxicity?

A

Yes
They are also some of the most toxic for the auditory and vestibular system

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28
Q

What are aminoglycosides isolated from?

A

Bacteria called streptomyces genus

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29
Q

What is bactericidal action?

A

Used to treat infections caused by aerobic gram-negative bacteria that can cause serious and life-threatening infections, for e.g., endocarditis, septicemia, and kidney infections
All the above conditions in turn can increase the risk of ototoxicity

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30
Q

What is the bioavailability of most aminoglycosides?

A

Poor following oral administration because they are poorly absorbed by the gut

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31
Q

Do aminoglycosides have low protein binding?

A

Yes
They are, therefore, commonly administered IM or IV for systemic effects
Raising the risk of serous adverse effects in a few doses
Some aminoglycosides can be administered orally or as eye drops (even ear drops)

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32
Q

What are the aminoglycosides commonly available in the US?

A

Amikacin, gentamicin, kanamycin, neomycin, streptomycin, and tobramycin

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33
Q

What are the three toxicity reactions of aminoglycosides?

A

Nephrotoxicity (tubular cell injury because of drug accumulation, which may be reversible; contributes to ototoxicity because renal toxicity causes the drug to accumulate and stay longer in the body)
Neuromuscular blockade (rare; non-depolarizing type of neuromuscular blockade that can lead to respiratory paralysis)
Ototoxicity/vestibulotoxicity

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34
Q

Are most babies admitted to the NICU given antibiotics to prevent bacterial infections and neonatal sepsis?

A

Yes

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35
Q

Why is it difficult to get exact incidence numbers for aminoglycoside ototoxicity?

A

Definition of “hearing loss” differs across studies
Hearing evaluation at conventional frequencies (at < 8000 Hz) does not allow for detection of early ototoxicity

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36
Q

What are the generally accepted incidences of the affects of aminoglycosides?

A

Cochleotoxicity of most commonly seen in children and adults is reported at about 2 to 20% (Lord, 2019)
Vestibulotoxicity is reported at about 15%
Nephrotoxicty is reported at about 20 to 30%, which can potentiate the ototoxicity/vestibulotoxicity

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37
Q

What hair cells are lost first in the vestibular system?

A

Type 1
Causing disturbances in vestibular function

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38
Q

Does the primary site of lesion depend on the drug?

A

Yes
Streptomycin and gentamicin are more vestibulotoxic
Amikacin and neomycin are more ototoxic
All aminoglycosides can damage one or both end organs

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39
Q

Are ototoxicity and vestibulotoxicity with aminoglycosides dose dependent?

A

Yes, unless it’s genetic ototoxicity (genetic predisposition)

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40
Q

Do ototoxicity and vestibulotoxicity generally develop after chronic administration of aminoglycosides?

A

Yes
In a 6-to-8-day treatment regimen, hearing loss may not be noticeable

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41
Q

Can adverse effects become apparent after repeated administration?

A

Yes
Especially parental administration or weeks after initial treatment followed by progression of hearing loss after the drug is discontinued

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42
Q

How long is ototoxic monitoring necessary?

A

Several weeks and months after the drug is discontinued

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43
Q

How does this aminoglycoside damage occur?

A

Several theories are proposed but a definitive mechanism is yet unknown
Cationic charge of the aminoglycosides interacts with anionic charge of membranes of hair cells, which allows for drug transport into the cells
Aminoglycosides form complexes with iron and other metals, which forms free radicals through redox reactions that damage hair cells

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44
Q

Following entry into the inner hair cells, what effects can aminoglycosides have?

A

The drug increases intracellular calcium and generates toxic levels of reactive oxygen species (ROS)
These physiological changes result in cell death through apoptosis and necrosis (non-programmed cell death)
Which mechanism of hair cell death is initiated depends on the type of aminoglycoside and dosage regimen

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45
Q

Does gentamicin show a high concentration in the stria vascularis?

A

Yes
It passes into the marginal cells that line the lumen of the scala media passively diffusing through to the endolymph
It disrupts the ion channels disturbing the delicate homeostatic balance of the inner ear

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46
Q

Is the loss of hair cells most sever at the cochlear basal turn moving towards the apex?

A

Yes
Outer hair cells are affected first
Inner hair cells and rest of the organ of corti can be damaged in more severe cases

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47
Q

What are the other structures that are damaged by aminoglycosides?

A

Stria vascularis, spiral ligament, reissner’s membrane

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48
Q

What type of damage is secondary to hair cell loss for aminoglycoside toxicity?

A

Nerve fiber damage

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49
Q

Can aminoglycosides result in both acute physiological and permanent functional effects?

A

Yes
Hearing loss can sometimes be reversible following discontinuation of drug

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50
Q

What is the single most important factor limiting use of aminoglycosides?

A

Ototoxicity
Both systemic and topical application can cause ototoxicity

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51
Q

Where does ototoxicity hearing loss begin?

A

Higher frequencies
Greater than or equal to 16,000 Hz
By the time hearing loss is measured at 8000 Hz and below, the damage had already occurred
Speech discrimination is already affected
Why OAEs and high frequency audiometry are important for monitoring

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52
Q

Can ototoxicity hearing loss be unilateral or bilateral?

A

Yes
Can be temporary or permanent
May be sudden or progress to complete deafness

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53
Q

Can vestibular toxicity occur without injury to the auditory system?

A

Yes
Prevalence of aminoglycoside induced vestibulotoxicity appears to be greater than cochleotoxicity

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54
Q

Can vestibular injuries be compensated?

A

Yes
By visual and proprioception senses

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55
Q

In what people is vestibular toxicity more likely to occur in?

A

Previous history of balance problems and kidney dysfunction

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56
Q

Can vestibular damage be temporary or permanent?

A

Yes
~ 75% of those who receive chronic treatment with aminoglycosides have permanent vestibular dysfunction

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57
Q

If it is bilateral peripheral vestibular damage or central vestibular damage, is there central compensation?

A

No
Only if it is unilateral peripheral

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58
Q

What are the long-term symptoms that a person could experience from aminoglycoside vestibulotoxicity?

A

Vertigo
Disequilibrium
Oscillopsia or bouncing vision (damage to the vestibulo-ocular-reflex)
Risk of falling

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59
Q

Should monitoring of vestibulotoxicity be independent from auditory monitoring?

A

Yes
It should occur for patients of all ages, before, during, and after aminoglycoside therapy

60
Q

What is the genetic predisposition for aminoglycosides?

A

A point mutation in the mitochondrial DNA (mtDNA) where a guanine (G) has been substituted for adenine (A)
SNP
This mutation makes individuals highly susceptible to aminoglycoside ototoxicity
Only the cochlea is affected resulting in severe to profound permanent SNHL (not dose-dependent; a single injection may lead to profound deafness)
Genetic susceptibility is greater in the Chinese and Japanese

61
Q

What is ototoxicity/vestibulotoxicity associated with?

A

Total daily dose (reduced dosage or once-daily may reduce toxicity)
Duration of treatment (longer the duration, the greater the risk)
Previous treatment with aminoglycosides (increases risk)
Kidney disease (also toxic to kidneys, which delays clearance from body; chronic exposure allows the drug to remain in the ear fluids longer)

62
Q

If ototoxicity/vestibulotoxicity is detected during treatment, should the antibiotic be discontinued?

A

Yes

63
Q

Can all aminoglycosides cross the placental barrier?

A

Yes, and can cause a miscarriage

64
Q

What are some problems that are associated with babies born to pregnant mothers treated with aminoglycosides?

A

Nephrotoxicity
Irreversible congenital deafness
Central nervous system involvement
Respiratory system depression
Flaccidity (poor muscle tone)

65
Q

When used in conjunction with other nephrotoxic or ototoxic drugs, can aminoglycosides (gentamicin) increase the incidence of kidney damage and SNHL?

A

Yes
Most common interaction is reported with loop diuretics, for example with furosemide (Lasix)
Typically when both dugs are administered IV

66
Q

What can happen with aminoglycosides are given in conjunction with neuromuscular blocking agents?

A

Can happen during surgery
Aminoglycosides can lead to skeletal muscle weakness and respiratory depression following surgery

67
Q

Is vancomycin an aminoglycoside?

A

No
It belongs to the glycopeptide antibiotic class of drugs
It works against gram-positive bacteria
Remains the standard for treatment of systemic infection caused by meticillin-resistant staphylococcus aureus (MRSA) and gut infections

68
Q

What can happen with aminoglycosides are used in conjunction with vancomycin?

A

Synergistic effect
On its own, vancomycin has a slight risk of ototoxicity
But the combination of vancomycin and aminoglycosides increases the risk for ototoxicity

69
Q

Is the suffix mycin or micin based on therapeutic or chemical classification?

A

No
It indicates these compounds are synthesized by different strains of Actinomycetes, a specific group of bacteria found in the soil

70
Q

What are the two prominent mycins that bear no resemblance to aminoglycosides?

A

Erythromycin (macrolide) and Vancomycin (glycopeptide)

71
Q

Is erythromycin ototoxic?

A

Slightly
Shows greater risk with higher doses

72
Q

What is erythromycin?

A

Broad spectrum antibiotic (working against both gram positive and gram negative)

73
Q

What is penicillin produced by?

A

Penicillium chrysogenum, a fungus

74
Q

What is the bactericidal action of penicillin?

A

Blocks bacterial cell wall synthesis
Originally had a narrow spectrum action (not both gram positive and negative)

75
Q

Is second generation penicillin broad spectrum?

A

Yes
Includes Ampicillin, Amoxicillin, Amoxicillin with Clavulanic Acid (Augmentin)

76
Q

What is one of the most commonly prescribed drugs in the US for otitis media?

A

Amoxicillin

77
Q

When is augmentin used for?

A

Also used for otitis media if patient develops resistance or no benefits from amoxicillin
More powerful

78
Q

Is penicillin considered to be ototoxic/vestibulotoxic?

A

No

79
Q

What are macrolide antibiotics?

A

Bacteriostatic
Erythromycin, clindamycin, azithromycin (contained in Z-pak - Zinthromax), & clarithromycin

80
Q

What are some indications for macrolides?

A

Otitis media (azithromycin, clarithromycin)
Respiratory tract infections including
Strep throat, tonsillitis, pharyngitis
Sexually transmitted diseases
Useful when patients are allergic to penicillin

81
Q

Are macrolides associated with ototoxicity?

A

Yes
Associated with reversible SNHL
Some case reports of irreversible SNHL
Generally only occurs at very high doses and with IV administration of the drug (low oral dose is okay)
May also effect central auditory pathways

82
Q

What factors increase the risk of ototoxicity for macrolides?

A

Renal failure and liver impairment
Receiving an organ transplant
Age and female gender
Concurrent use of macrolides with other ototoxic drugs
Prolonged, high-dose macrolide treatment

83
Q

What is the purpose of chemotherapeutic agents?

A

To stop cancer cells from proliferating, invading, metastasizing, and killing hosts

84
Q

Are many organisms resistant to macrolide antibiotics?

A

Yes
Which limits its use in medicine

85
Q

What responds well to chemotherapy?

A

Small, rapidly dividing cells
Solid tumors do not respond well because of the slower growth and division of the cells

86
Q

Are normal cells that rapidly divide also subjected to the effects of chemo?

A

Yes
Results in dose-limiting toxicities (challenge is to give an adequate dose to kill the cancer cells without killing too many healthy cells)

87
Q

Do tumor cells mutate?

A

Yes
It allows them to metastasize
Original tumors may respond well to chemotherapy, but metastatic lesions may be less responsive, poor prognosis
Because as they mutate, their response to chemotherapy may change (e.g., altered cell receptors)

88
Q

How are solid tumors treated if not with chemo?

A

Radiation and/or surgery

89
Q

What does cisplatin have a high efficacy for?

A

Germ cell tumors
Ovarian & testicular tumors (including metastatic lesions)
Bladder cancer
Gynecological
Lung tumors
Tumors of head/neck region and brain tumors
Many childhood tumors including neuroblastoma

90
Q

What are some risk factors of ototoxicity for cisplatin?

A

High IV bolus (single dose over a short time) administration – like loading dose
High cumulative dose
Poor renal function
Young and advanced ages
Co-administration of high doses of vinca alkaloids (another cancer med, also ototoxic)
Prior cranial radiation therapy

91
Q

When does the hearing loss that is associated with cisplatin ototoxicity take place?

A

Can be gradual, progressive, cumulative, or present suddenly

92
Q

What frequencies does the cisplatin ototoxic loss take place?

A

Earliest at frequencies at or above 8000 Hz
Loss is typically in high frequencies (greater or equal to 4000 to 8000 Hz)
Hearing loss usually bilateral but maybe asymmetrical
Some degree of reversibility but generally permanent, especially if the hearing loss is profound

93
Q

Is high frequency tinnitus reported in cisplatin patients?

A

Yes, 2 to 36%

94
Q

Is neurotoxicity and vestibulotoxicity also reported?

A

Yes

95
Q

What is carboplatin?

A

Second generation analog of cisplatin
Clinically introduced because of decreased nephrotoxicity as compared to Cisplatin
Unfortunately, it is not any less ototoxic than cisplatin
More vestibulotoxic

96
Q

Does carboplatin have bone marrow toxicity?

A

Yes
It is dose limiting
Toxicity can be overcome by treatment with stem cell rescue

97
Q

What is the mechanism of toxicity for carboplatin?

A

Probably reactive oxygen and nitrogen species
Toxicity risk increases with previous cisplatin or aminoglycoside administration

98
Q

What are the indications for carboplatin?

A

Many of the same as cisplatin

99
Q

What are the mechanisms of ototoxicity for platinum compounds (cisplatin and carboplatin)?

A

Multifactorial
Damage caused by free radical generation and inhibition of anti-oxidation processes
Permanent hearing loss is probably caused by loss of OHCs in the basal turn initially resulting in earlier high frequency SNHL
Damage later spreads to rest of the cochlea
Degeneration of the stria vascularis also occurs
Hair cells and spiral ganglion neurons are the most susceptible to apoptosis

100
Q

How many pediatric patients does cisplatin cause hearing loss in?

A

At least 60% of patients
Platinum initially impairs higher frequencies and progresses to lower frequencies with increasing cumulative dose

101
Q

What regulates platinum toxicities?

A

Genes involves in drug transport, metabolism, and DNA repair

102
Q

Is route of administration and optimal timing relative to platinum therapy are critical issues to address ototoxicity?

A

Yes

103
Q

How can otoprotection be achieved from platinum based drugs?

A

By acting on several of these pathways and generally involves antioxidant agents

104
Q

What is vinca alkaloids derived from?

A

Periwinkle plant
Now manufactured synthetically

105
Q

What are vinca alkaloids?

A

Anti-tumor drugs
Includes vincristine, vinblastine, vinorelbine
Used in combination chemotherapy, often with Cisplatin
Works by blocking mitosis, cell-cycle specific action
Administered IV

106
Q

How are vinca alkaloids metabolized?

A

Metabolized in the liver and primary excretion is through the fecal route

107
Q

Are vinca alkaloids ototoxic?

A

Yes, at higher doses
Primarily affects hair calls
It can be difficult to determine ototoxicity as almost always used in combination with other chemotherapeutic drugs

108
Q

Can vinca alkaloids be neurotoxic?

A

Yes
Can cause numbness, pain, and dizziness

109
Q

What are the indications for use of vinca alkaloids?

A

Leukemia, lymphoma, breast & testicular cancer, in neuroblastoma combination therapy, and Kaposi’s sarcoma

110
Q

Is folate metabolism fundamental to both cancerous and normal cells?

A

Yes
Natural form of B9
Folate depletion and its resultant reduction of DNA synthesis is toxic to both malignant and normal cells
Inhibition of folic acid metabolism has been used as a mechanism for successful elimination of rapidly dividing cells, i.e., tumor cells

111
Q

What is methotrexate?

A

In the folate analog metabolic inhibitors class of drugs
Used to treat severe cancers of the blood, bone, lung, breast, head and neck, rheumatoid arthritis, psoriasis, and Cogan’s syndrome
It is often given in conjunction with Vinblastine & Cisplatin

112
Q

Are folate analog metabolic inhibitors ototoxic?

A

Yes, highly
Especially in children and when given with other cancer drugs
Also nephrotoxic and neurotoxic
Teratogenic and abortifacient (used in ectopic pregnancy)
Recommended to wait 3 to 6 months after taking methotrexate to get pregnant

113
Q

What do diuretics do?

A

Push fluids out of the system
Preventing the reabsorption of sodium (salt) in the body
Which excretes water decreasing blood volume & pressure

114
Q

What are the primary therapeutic indications for diuretics?

A

Hypertension, to reduce edema in patients with congestive heart failure, liver (cirrhosis), or kidney disease

115
Q

Are there many families of diuretics?

A

Yes
Thiazides, potassium-sparing, and loop diuretics
Only loop diuretics are believed to be ototoxic and include ethacrynic acid, furosemide (Lasix), bumetanide, and torsemide (ethacrynic acid and furosemide are most ototoxic)
Loop diuretics prevent reabsorption of Na+, K++, and CL- from the thick ascending limb of the loop of Henle and, therefore, increase fluid excretion from the kidneys
The thick ascending limb is impermeable to water

116
Q

What is the mechanism of ototoxicity for loop diuretics?

A

Dose-related, reversible depression of endocochlear potential and intra-labryrinth electrolyte changes
Reduction in magnitude of the cochlear microphonics (CM), summating potentials (SPs) and eighth nerve compound action potentials (CAPs)
Recovery of cochlear potentials occurs gradually
Reversible hearing loss if loop diuretics are used alone

117
Q

When is the most significant ototoxicity of loop diuretics seen?

A

When given in high IV doses especially in conjunction with aminoglycosides (because of enhanced entry of aminoglycosides into cochlear fluid and tissues)
Can result in rapid onset, flat, typically irreversible SNHL with roaring tinnitus)

118
Q

Can loop diuretics also cause dizziness and vertigo?

A

Yes

119
Q

What does NSAIDs stand for?

A

Salicylates and Nonsteroidal Anti-inflammatory Drugs

120
Q

What are salicylates?

A

A group that includes aspirin
First NSAID discovered

121
Q

What are the therapeutic effects of salicylates?

A

Relief of mild to moderate pain
Reduction in inflammation (blocks synthesis of prostaglandins to reduce all of the signs of inflammation)
Reduction of fever (acts on hypothalamus-heat-regulating center-to reduce fever)
Prevention of stroke (prophylaxis with daily low dose) - prevents platelets from clumping together; thrombus prevention

122
Q

Are salicylates absorbed rapidly?

A

Yes
And are distributed to the cochlea via the arteries and accumulate in perilymph
show reversible biochemical and/or metabolic changes in cochlea with no permanent morphologic abnormality

123
Q

What is the first sign of salicylate ototoxicity?

A

Tinnitus
High-pitched in the frequency of 6000 to 9000 Hz
Becomes louder with continued treatment and abates when treatment ends

124
Q

Are salicylates associated with reversible SNHL?

A

Yes
Mild to moderate symmetric high frequency SNHL
Rarely, permanent cases of ototoxicity have been reported
Hearing typically recovers within 72 hours after treatment is discontinued

125
Q

What is the dosage of salicylates that are associated with ototoxicity?

A

Greater than or equal to 12 regular strength (325 mg)
Taken for several days

126
Q

How many non-aspirin NSAIDs are on the market?

A

About 20
ibuprofen (Advil, Motrin)
indomethacin (Indocin)
ketoprofen (Orudis KT)
Cox-2 inhibitors (Celebrex)
naproxen sodium (Aleve, Anaprox, Naprosyn, Pamprin)

127
Q

What are the therapeutic effects of non-aspirin NSAIDs?

A

Similar to aspirin
Anti-inflammatory, analgesic, and antipyretic effects
All are nephrotoxic and also can affect the GI causing ulcers
Reversible tinnitus and hearing loss (rarely causes significant or permanent SNHL; reversible dizziness reported)

128
Q

What is acetaminophen (tylenol)?

A

Useful for treating mild pain and fever but it is not an anti-inflammatory agent
Mechanism of action is different from an NSAID

129
Q

Is acetaminophen ototoxic?

A

No reported temporary or permanent ototoxic or vestibulotoxic effects
Acetaminophen is hepatotoxic if taken in greater than recommended dosage
Overuse or abuse of multi-ingredient substance like Vicodin, however, can cause rapidly progressive profound permanent SNHL (combination of acetaminophen and hydrocodone)

130
Q

What is quinine?

A

Made from cinchona bark
An antipyretic, primarily used for the treatment of malaria
Off-label use for benign nocturnal night cramps although not approved by FDA for that use
Present in tonic water (could be a source of ototoxicity in high amounts)

131
Q

Is quinine temporarily ototoxic and vestibulotoxic?

A

Yes
Reversible bilateral high frequency SNHL with a characteristic 4000 Hz notch (can be confused with NIHL)
High pitched tonal tinnitus
Dizziness/vertigo

132
Q

Acute toxicity of quinine (cinchonism) is characterized by?

A

Tinnitus, hearing loss, dizziness, headache, nausea, and vision changes

133
Q

Are psychiatric drugs ototoxic?

A

Yes
Ototoxic as well as vestibulotoxic
Tricyclic and other antidepressants generally more ototoxic
Patients complain of tinnitus and hearing loss

134
Q

Are alcohol and caffeine ototoxic?

A

Reversible ototoxic and vestibulotoxic effects
Can cause tinnitus and, rarely, vertigo, and SNHL
Both can affect results of vestibular tests

135
Q

Are cigarettes and other tobacco products ototoxic?

A

It can be
Smoking can have multisystemic effects including increased risk of pulmonary and cardiovascular disease, and strokes
Smoking produces high levels of nicotine and carbon dioxide in the body causing vasospasm & thrombotic occlusions in the microvasculature
Cochlear = hearing loss; Extremities = Raynaud’s disease

136
Q

Are industrial solvents and heavy metals ototoxic?

A

In industrial settings these can be the culprits for SNHL and not just the noise exposure
More vestibulotoxic than ototoxic
Prolonged exposure can lead to neurological problems

137
Q

Is lead ototoxic?

A

Lead is a neurotoxin and disrupts the BBB, allowing other neurotoxins to reach the CNS
Ubiquitous in the environment (used in plumbing, paint, and gasoline)Exposure is of particular concern for fetus and kids <7yrs
Its half life is short in tissues but is ~ 20 years in bone
Substantial exposure in childhood = elevated levels for decades

138
Q

Are blood thinners ototoxic?

A

No, but they can impact the management of the audiology patient
Small nicks can lead to severe bleeding
Especially important when making impressions, particularly deep canal impressions, and for cerumen management

139
Q

Is clearance from a physician or written consent from patients informing them of the risks of the procedure important when treating patients with bleeding disorders, diabetes, or are currently taking blood thinners?

A

Yes
It is important to take a medical/drug profile history prior to audiologic testing and making ear impressions

140
Q

Are there many vestibulotoxins present in the workplace and in paralogical treatments?

A

Yes
We need to be aware of them

141
Q

What are chemicals and solvents that have known vestibulotoxicity?

A

Toluene
Styrene
Xylene
Trichloroethylene
Ethyl benzene

142
Q

Does vestibilar toxicity result in a more complicated deficit than peripheral-based conditions?

A

Yes
Bilateral vestibular dysfunction is more common as systematic nature of toxins does not allow for central compensation

143
Q

Do individuals with vestibulotoxicity become visually surface dependent?

A

Yes
They keep their balance with use of vison and sense of touch making it almost impossible to regain normal equilibrium function
Their condition can be further complicated by comorbidities, such as glaucoma and peripheral neuropathy that can affect vision or sense of touch

144
Q

What is the treatment for drug-induce toxicities?

A

Reducing or eliminating exposure to the toxic drug
Administration of substances that antagonize the drug mechanism or alter its metabolism
Providing supportive measures (IV fluids in cases of renal toxicity to maintain adequate renal blood flow)

145
Q

What are the common symptoms of vestibulotoxicity?

A

Dizziness/vertigo, nystagmus, and oscillopsia

AUDE 6120 - Pharmacology and Ototoxicity (8 decks)

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