Vertigo, Hearing Loss & N/V-Drugs

Question 1

name 3 major classes of drugs that have ototoxicity

Answer 1

aminoglycosides
cisplatin
loop diuretics

Question 2

name the drug class: causes ototoxicity that is usually not reversible; possible improvement w/ N-acetylcysteine; dose dependent

Answer 2

aminoglycosides

Question 3

which class of drugs produces irreversible ototoxicity?

Answer 3

cytostatic drugs (cisplatin)

Question 4

is the ototoxicity with loop diuretics reversible?

Answer 4

can be irreversible

Question 5

are most of the drugs that cause ototoxicity reversible or irreversible?

Answer 5

reversible

Question 6

which drug class enters into outer hair cell –> cell death by either caspase-dependent or caspase independent mechanisms?

Answer 6

aminoglycoside

Question 7

which drug enters outer hair cells and results in cell death, which appears to be primarily caspase-dependent?

Answer 7

cisplatin

Question 8

how do the loop diuretics cause ototoxicity?

Answer 8

interfering with the production and maintenance of endolymph in the stria vascularis

• upset the fluid balance & this results in edema & loss of function
• the effect is dose-rate dependent (the concentration gradient is an important factor in the penetration of drugs into this area of the body)

Question 9

meclizine, diphenhydramine, & promethazine all work to treat vertigo via which two types of receptors?

Answer 9

H1 & M1 receptors

Question 10

which drug is useful for nausea arising from higher brain centers mediating fear, emotion, anticipation?

Answer 10

diazepam

Question 11

which drug used to treat vertigo has the longest duration of action?

Answer 11

scopolamine

Question 12

diphenhydramine & promethazine are inhibitors of what CYP enzyme?

Answer 12

CYP2D6

Question 13

what are the general adverse effects of the drugs that treat vertigo?

Answer 13

drowsiness, dizziness

Question 14

scopolamine is an antagonist at what receptor?

Answer 14

M1

Question 15

diphenhydramine, meclizine, & promethazine all block which 2 receptors in the treatment of vertigo?

Answer 15

H1 & M1

Question 16

which drug used to treat vertigo has a BBW for use by injection?

Answer 16

promethazine

Question 17

which drug used to treat vertigo has an adverse effect of fatal respiratory depression in <2 y/o?

Answer 17

promethazine

Question 18

all 4 drugs to treat vertigo (diphenhydramine, meclizine, promethazine, & scopolamine) are all inappropriate in what pt population?

Answer 18

geriatric

Question 19

the vomiting process appears to be coordinated by what center in the lateral retcular formation of the mid-brainstem adjacent to both the CTZ in the area postrema at the bottom of the 4th ventricle & the solitary tract nucleus?

Answer 19

central emesis center

Question 20

the lack of a BBB allows the CTZ to monitor blood & CSF constantly for toxins & to relay info to what center to trigger nausea and vomiting?

Answer 20

emesis center

Question 21

other than the CTZ, what are four other inputs to the emesis center?

Answer 21

1. vagus nerve (via solitary tract nucleus)
2. splanchnic afferents via the spinal cord
3. cerebral cortex
4. vestibular apparatus

Question 22

the CTZ has high concentrations of what 3 receptors?

Answer 22

serotonin (5-HT3), Dopamine (D2), Opioids

Question 23

the solitary tract nucleus has what 4 types of receptors?

Answer 23

Enkephalin
histamine
ACh
5-HT3

Question 24

what is the efferent component for the emesis center?

Answer 24

sends efferents to nuclei responsible for respiratory, salivary, vasomotor activity, and striated & smooth muscle involved in act of vomiting

Question 25

what is the only 5HT-3 antagonists that has to be adjusted in hepatic disease?

Answer 25

ondansetron

Question 26

all the 5HT-3 antagonists have what cardiac adverse effect?

Answer 26

QT-prolongation

Question 27

ECG monitoring is recommended in pts taking which two 5HT-3 antagonists?

Answer 27

dolasetron or Ondansetron

Question 28

what are the most common adverse effects of the 5-HT3 antagonists?

Answer 28

headache constipation diarrhea

Question 29

the serotonin antagonists are used for CINV & PONV prophylaxis, often with what other drug class?

Answer 29

corticosteroid

Question 30

which two D2 receptor antagonists are considered general purpose anti-nausea & anti-emetic drugs?

Answer 30

prochlorperazine | Chlorpromazine

Question 31

Prochlorperazine & Chlorpromazine are D2 receptor antagonists and have what two other functions?

Answer 31

1. antihistaminic 2. anticholinergic (used in other forms of Nausea, such as motion sickness)

Question 32

chronic use of D2 receptor antagonists can have what adverse effect?

Answer 32

bone marrow suppression / blood dyscrasias

Question 33

co-administration of D2 receptor antagonists with what other drug class may cause increased CNS adverse effects?

Answer 33

antipsychotics

Question 34

phenothiazines (prochlorperazine, chlorpromazine) are associated with what cardiac adverse effect?

Answer 34

risk of QT prolongation w/ Torsades de pointes

Question 35

what is the MOA for aprepitant?

Answer 35

substance P/NK-1 receptor antagonist - central action (solitary tract) essential - peripheral effects (vagal terminals in GI tract) also contribute

Question 36

Aprepitant is metabolized by what CYP enzyme?

Answer 36

CYP3A4

Question 37

what is the name of the pro-drug substance P / NK-1 receptor antagonist that is activated by extra-hepatic metabolism?

Answer 37

fosaprepitant

Question 38

MOA dronabinol

Answer 38

G-protein coupled decreased neuronal activity in the medullary vomiting center & solitary tract nucleus - oppose 5-HT3 mediated stim of vagal afferents - appetite stim. via CB receptors in lateral hypothalamus (lower doses than for antiemetic action)

Question 39

emesis is most likely from what 6 anti-neoplastic drugs?

Answer 39

``` cisplatin mechlorethamine streptozotocin cyclophosphamide carmustine dacarbazine ```

Question 40

what is the treatment of choice for prophylaxis against acute emesis?

Answer 40

serotonin receptor antagonist + corticosteroid & possibly NK-1 antagonist

Question 41

how do corticosteroids help reduce emesis caused by antineoplastic drugs?

Answer 41

corticosteroids act on steroid receptors in solitary tract nucleus (reduced release o serotonin has been proposed)