Final study guide (quizzes and assignments)

Explain the role of an audiologist in pharmacology

An audiologist must understand the role of distribution in pharmacology to understand how the drug may impact the auditory system. Their role is to minimize auditory and balance damage by understanding the drug’s impact (and ototoxic effects) on the auditory/vestibular system as they interact. At the end of the day we want to provide best appropriate care.

Which branch of pharamcology studies what the body does to a drug, including absorption and excretion?

Pharmacokinetics

What are examples of drugs derived from natural sources?

Morphine, Insulin, Penicillin, Aspirin

What are the types of names that are given to drugs? (3)

Proprietary/Trade nae, chemical name, generic/non-proprietary name

What is one example of replacement therapy?

Injecting L-Dopa for people with Parkinson’s Disease to Trigger Dopamine

What is the definition of affinity

How well a drug is able to bind to the receptor

What are the factors that can influence variability in drug response?

Genetic factors, age, gender, size/surface area, disease state, and body weight

What do you call a drug that has intermediate levels of efficacy, producing a submaximal response even when all receptors are occupied?

Partial agonist

What is the primary characteristic of a drug receptor?

It is a protein that transfers drug binding to a physiological action

What is a type of loop diuretic known to have ototoxic adverse effects?

Furosemide

What’s an example of a chemotherapeutic agent known for ototoxic side effects?

Cisplatin

What’s an example of an aminoglycoside known for ototoxic side effects?

Antibiotics - Gentamicin

What kind of medication is known as a Type B (idiosyncratic) ototoxic agent?

Vancomycin

Which of the following mechanisms contributes to furosemide’s ototoxic effects in the inner ear?

Impairing the function of the stria vascularis, leading to changes in the endocochlear potential and subsequent hair cell damage

Interacting with GABA receptors, disrupting inhibitory neurotransmitters

What is a metabolite?

A small molecule produced during metabolism, including intermediates and products

Name four distinct mechanisms of drug action

Ion channel regulation

Enzyme modulation

Transcription control

Receptor Binding

Name two major types of cellular receptors that drugs frequently target

Ion channel receptors

G-Protein coupled receptors (GPCR)

What kind of drug activates specific transcription factors that reduce inflammation. These factors suppress the expression of inflammatory genes, leading to fewer inflammatory proteins being made. What’s the name of the drug type and an example?

Corticosteroids, like prednisone

What are the essential amino acids?

Histadine, Lysine, Leucine, Isoleucine, Methionine, Phenylalannine, Threonine, Tryptophan, Valine

What is the term that refers to the amount of drug needed to produce a specific effect?

Potency

Define Efficacy

The maximum possible effect a drug can produce under ideal conditions

What’s the formula for Therapeutic Index ?

Toxic/Effective (EX: If the median toxic dose is 80 and the median effective dose is 20, the TI is 4)

How do NSAIDs (nonsteroidal anti-inflammatory drug) like ibuprofen cause ototoxicity

When ibuprofen attaches to the enzyme, cyclooxygenase, it inhibits the enyzme’s catalytic activity in the production of inflammatory prostaglandin, a hormone released to create/cause inflammation.

Prostaglandin is necessary for regular blood flow, so when ibuprofen disrupts the production of prostaglandin, the ototoxic effect can be due to the decreased blood flow within the stria vascularis in the cochlea.

What’s the main significant plasma protein involved in drug binding?

Albumin

How does protein binding impact drug interactions

Protein binding impacts drug interactions when more than 1 drug is introduced in the body. A higher dose of a drug is needed in case the drug binds to Albumin, causing that drug to be ineffective, the leftover unbound drug will maintain effectiveness. However, if another drug with a higher dose enters, it displaces the original bound medication, increasing the bound of drugs that are unbound and now in effect. The release of these drugs into the system, in addition to the interaction with the new unbound drugs, ultimately increases the risk of adverse effects, including ototoxicity.

Which body organ is the major site of drug metabolism?

Liver

What is the primary goal of metabolism

To convert lipophilic drugs into hydrophilic substances in order to be eliminated through the excretion system

True or false, phase 1 reactions in drug metabolism always lead to inactivation of the drug’s activity

False

What enzyles catalyze phase 1 reactions in drug metabolisms, and where is it located?

Cytochrome P450 (CYP), located in endoplasmic reticulum of liver cells.

What is the priamry therapeutic reason for using glucocorticoids in the treatment of inner ear disorders like SSNHL and Meniere’s disease?

They improve microcirculation by reducing inflammation in the inner ear tissues

Based on the provided evidence, what can be concluded about the effectiveness of IT corticosteroids for treating vertigo in Meniere’s disease?

They are less effective than IT gentamicin, though some weak evidence suggests they may provide substantial improvement in the long term

What kind of administration treats the whole body but carries the risk of side effects

Systemic

What’s intratympanic administration

IT delivers high concentration of the drug directly to the target site but has local risks such as a pain and ear drum perforation

Are systemic corticosteroids are a recommended option for the routine management of Meniere’s Disease

According to the AAOHNS guidelines, they are NOT

T or F Intratympanic steroids can be offered as a salvage therapy for patients who don’t fully recover from initial treatment for SSNHL (AAOHNS)

True

Define Type A and Type B adverse drug reactions.

Type A (Intrinsic) adverse drug reactions is defined by the side effects being dose dependent, predictable, having high incidence, and low mortality rates.

Type B (Indiosyncratic) adverse drug reactions are not common but can happen at any time, since they are not dose dependent, they are unpredictable, uncommon (low incidence), and have high mortality rates. 

If the patient is taking

• Furosemide (Lasix) - 40 mg daily

• Lisinopril - 20 mg daily

• Ibuprofen - 800 mg three times daily

• Metoprolol - 25 mg twice daily

and is experiencing dizziness/hearing loss, what kind of adverse drug reaction would it be?

Most likely type A because of the furosemide being dose-dependent, and the lisinopril and metoprolol.

How are the ASHA Standard Threshold Shift categorized

The ASHA STS has three categories to identify the changes. The first category is a 10-dB decrease in threshold at any two adjacent frequencies, the second is a 20-dB decrease in threshold at any ONE test frequency, and the third is a loss of response at any three consecutive test frequencies when it was obtained before.

How are the National Cancer Institute Common Terminology Criteria for Adverse Events NCI CTCAE categorized

 

The NCI CTCAE has four grades to categorize the hearing changes in adults enrolled in a monitoring program for the thresholds of 1000, 2000, 3000, 4000, 6000, and 8000 Hz. Grade 1 is categorized as a threshold shift of 15-25 dB averaged at two adjacent test frequencies in at least one ear.

Grade 2 is categorized as a threshold shift of greater than 25 dB averaged at two adjacent test frequencies in at least one ear.

Grade 3 is categorized as a threshold shift of greater than 25 dB averaged at three consecutive test frequencies in at least one ear.

Grade 4 is categorized as a decrease in hearing to profound bilateral loss, absolute thresholds above 80 dB HL at 2000 Hz and above.

What are Phase 1 Reaction Outcomes

Active metabolites, inactive metabolites, and toxic metabolites

What are Phase II conjugative reactions

The second step of metabolism of xenobiotics, but it can also happen independently. Including conjusgation of xenobiotics with endogenous molecules.

What are three types of endogenous molecules. What does it do to xenobioitcs

Glucuronic acid, sulfate, glutathione and amino acids. Making xenobiotics more hydrophilic to excrete easier

TYPE OF CONJUGATION DEPENDS ON STRUCTURE OF XENOBIOTIC

What is the major route of final drug elimination from the body

Renal excretion (main purpose of hepatbic metabolism

What are three factors affecting renal excretion

Renal blood flow, glomerular filtration rate (GFR), and protein binding.

Where is the glomerulus found and what is it

It is found in the nephron of the kidney, it’s a tiny specialized network of blood vessels playing a crucial role in the process of filtering waste products and excess fluid from the blood to form urine

What does protein binding mean for renal excretion

Drug protein complexes are large so it’s more difficult or unable to pass thru the filtration units of the kidneys.

T or F - renal function declines with increasing age (65+)

True

How are dose regimens needed to be adjusted for patients with impaired renal function

IT needs to be adjusted to accomoate and account for decreased ability to eliminate certain drugs (ex: ototoxic drugs like cisplatin, aspirin, and gentamicin)

What are four pharmacokinetic concepts that we learn about

Clearance, half life, steady state, and washout period

What does drug clearance mean (CL) and what of the four parts of pharmacokinetics take into consideration

PRocess of removing a drug from the blood stream, considering both metabolism and elimination

T or F - clearance is essential to helping determine the appropriate dosing regimen for a drug

True

How can clearance be measured

Rate - millimeter/minutes

What is half-life and what’s it for

The parameter of how much time it takes for the concentration to decrease by 50% in the plasma, to determine how long a drug remains active in the body

What is the half life formula including what phases

ln2xVd (volume of distribution)/clearance - includes distribution, metabolism, and elimination

What factors affect half-life

Drug-drug interactions, metabolic changes, changes in elimination, including impaired renal function

What does steady state mean

The rate of a drug elimination is equal to the rate of drug administration, resulting in consistent drug concentration

Why is reaching steady state crucial for mainitaining therapeutic drug levels in the body

Effectiveness of the drug means the drug has to be at the steady state rate, making the drug’s desired effects sustained without excessive accumulation or subtherapeutic concentrations

What is the washout period

The time we stop using the drug to make sure the body is clean

What is the half life equivalent for the washout period for a drug if the last dose was administered after achieving steady state

5 half lives

If the drug has a 24h half life, and it’s been administered to a patient for the last month and a steady state had been achieved, what’s the washout period estimated to be?

~ 5 days of a washout period

What are vasodilators

Medications designed to relax smooth muscles in blood vessels to increase the vessel diameter and improve blood flow

What’s the primary goal of vasodilators

Enhance perfusion to the cochlea, supporting hair cell function, and overall cochlear helath

What are 2 types of vasodilators used for SSNHL?

Pentoxifylline and Betahistine

What is pentoxifylline

Decrease viscosity to make the flow easier for circulation problems that impact the thickness of red blood cells. mostly for SSNHL

What is betahistine

widely used as a first line of tx for Menieres Disease

Increases blood flow in cochlear microvasculature by acting on H1 and H3 histamine receptors, reducing endolymphatic pressure.

24-48mg per day, widening blood vessels making flow easier.

What are the main side effects of vasodilators

Gastrointestinal issues and headaches

What are the main side effects for betahistine for MD

Upper GI symptoms (nausea and headache)

What are the main side effects for pentoxifylline for SSNHL

GI, nausia, dyspepsia (discomfort in upper abdomen) and diarrhea are reported. Mild headaches and dizziness.

What’s an example of analgesics

NSAIDS and aspirin

What’s an example of antimalarials

Quinine

What’s an example of antineoplastics

Chemotherapy - cisplatin

What are platinum coordination complexes and examples

anti-neoplastic (antitumor) drugs that typically manifest HL and tinnitus

CISPLATIN

CARBOPLATIN

What is cisplatin vs carboplatin

CIS - widely used and most ototoxic drug clinically, permanent hearing loss and tinnitus.

CARBO - less ototoxic

What are other platinum compounds

Oxaliplatin, nedaplatin, ZD0473, BBR3464, and Satraplatin

What is the site and nature of lesion fo rchemotherapy induced ototoxicity

Cochlear, cell death of outher hair cells and spiral ganglion neurons, basal end to apical end

Where else can cisplatin cause damage

Stria vascularis

What are four audiological monitoring protocols for ototoxicity

Patient identification and referral

Baseline testing

Monitoring methods

Testing schedule

How should audiologists get referrals for cancer pts and why is it important

Develop strong working relationships with oncologists

Monitoring is usually limited to patients on platinum based drugs and aminoglycoside antibiotics

What is baseline testing

Absolutely critical to see ototoxicity over time BEFORE treatment starts

What are monitoring methods

High frequency audiometry (HFA) - testing above 8khz

Otoacoustic emissions - dpoaes, changes occur before threshold shifts. most sensitive for children than adults because of good HF

Conventional audiometry - tymps to rule out any middle ear paths

tinnitus monitoring - common symptom of cisplatin, systemically question about the tinnitus

What’s the testing schedule for

To maintain follow up testing before each administration of chemotherpay

Follow up test after completion of all chemotherapy tx because of delayed or progressing HL

Head and neck radiation → monitoring for 1-2 years due to risk of continued loss

What are special considerations for chemotherapy patients

OM - Immunosuppressed and susceptible to OM → interfere with OAE testing and confound HFA results

Noise - Pt is very sensitive to NIHL with cisplatin, avoid exposure as much as possible since noise can exacerbate ototoxicity

Rehab - management, counseling, communication strats, fitting amps

What are Type A drugs examples

Aminoglycosides (gentamicin), loop diuretics, salicylates - aspirin, antimalerials - quinine, cisplatin

What are Type B drugs

NSAIDs (ibuprofen or naproxen), antbiotics - vancomycin or erythromycin), psychotropic meds