Vertigo, Hearing Loss, N/V

Question 1

What are otoxic and vestibulotoxic drugs

Answer 1

Amionglycosides - dose dependent, usually irreversible
Erythromycin
Minocycline
Fluoroquinolones
NSAIDs/salicylates - dose dependent
Loop Diuretics - dose dependent, can be irreversible
Cytostatic drugs - dose dependent, Irreversible
Antimalarials

Question 2

What is the mechanism that aminoglycosides and cisplatin cause damage?

Answer 2

• both end up inducing ROS to activate JNK to increase transcription of cell death proteins that act on the mitochondria to activate caspases – apoptosis

Question 3

What is the mechanism that loop diuretics cause damage?

Answer 3

• block the same channels in inner ear that disrupt fluid balance created by stria vascularis and cause edema of inner ear
• dose dependent

Question 4

What is short term treatment of Vertigo and their MOA

Answer 4

1. meclizine hydrochloride - blocks H1 and M1
2. Diphenhydramine - blocks H1 and M1
3. Scopolamine transdermal patch - blocks M1
4. Promethazine hydrochloride - blocks H1 and M1
5. Diazepam - useful for psychosomatic vertigo

Question 5

What are the CYP2D6 inhibitors

Answer 5

diphenhydramine and promethazine

Question 6

Which should not be given to geriatric patients?

Answer 6

meclizine, diphenhydramine, scopolamine, promethazine b/c all have drowisness and dizziness as side effects

Question 7

Promethazine ADE

Answer 7

• BBW for injection use

- fatal respiratory depression in < 2 yo

Question 8

ADE of scolopamine

Answer 8

xerostomia, ocular effects after touching patch and rubbing eyes

Question 9

DDX for N/V

Answer 9

• EtOH, NSAIDs, oral antibiotics, vestibular disorder, labyrinithitis, Meniere’s dz, motion sickness, migraine, anticipatory vomiting

Question 10

vomiting process?

Answer 10

1. pre-ejection
2. Retching
3. Ejection
   - accompanied by multiple autonomic phenomena including salivation, shivering, and vasomotor changes

Question 11

Vomiting coordinated by what?

Answer 11

• Central emesis center in lateral reticular formation of mid-brainstem next to both CTZ in area postrema and bottom of 4th ventricle and solitary tract nucleus

Question 12

What works at solitary tract nucleus for emesis?

Answer 12

enkephalin, histamine, Ach, serotonin - vagal and sympathetic afferents as well as CN 5 and 9 afferents

Question 13

What are the most potent antiemetics?

Answer 13

Serotonin Antagonists - setrons

• works at CTZ and solitary tract nucleus
• all undergo hepatic metabolism (only ondansetron needs adjustement)

Question 14

What receptors are on CTZ

Answer 14

Serotonin, D2, M2

Question 15

ADE of setrons

Answer 15

QT prolonation

- headache, constipation, diarrhea

Question 16

What are the D2 receptor antagonists that work at CTZ?

Answer 16

Prochlorperazine, chlorpromazine - also possess antihistamine and anticholinergic activities

Question 17

ADE of prochlorperazine and chlorpromazine

Answer 17

• chronic use –> bone marrow suppression
• QT prolongation, and Torsades de pointes
• Coadminstration w/ antipsyhcotics may increase CNS adverse effects

Question 18

What are the SubP/NK1 receptor antagonists that work at Solitary tract nucleus

Answer 18

Aprepitant and Fosaprepitant

- extensive hepaptic metabolism (CYp3A4 inhibitor)

Question 19

ADE of aprepitant and fosaprepitant

Answer 19

• Headache, constipation, diarrhea

- numerous potential interactions w/ CYP

Question 20

What are the cannabinoid receptor agonist that work in medullary vomiting center and STN?

Answer 20

Dronabinol, THC –> also enhance appetite via effects in lateral hypothalamus

Question 21

Dronabinol details

Answer 21

• Schedule III drug - slow and gradual onset

- produces high - elation and heightened awareness

Question 22

Which antineoplastics have high likelihood of emesis

Answer 22

Cisplatin, mechlorthamine, streptozotocin, cyclophsophamide

Question 23

What is the treatment of choice for prophylaxis against acute emesis

Answer 23

Serotonin receptor antagonists + corticosteroid + NK1 antagonist

Question 24

MOA of steroids for anti-emesis

Answer 24

act on steroid receptors in STN - might be due to decrease in 5HT