45b - Vertigo Therapy

Question 1

Which drugs produce notable irreversible ototoxicity?

Answer 1

aminoglycoside antibiotics and cisplatin, also possibly loop diuretics

Question 2

What drugs can cause ototoxicity?

Answer 2

aminoglycosides, erythromycin, minocycline, fluoroquinolones, NSAIDs/salicylates, loop iduretics, cytostatic drugs and antimalarials

Question 3

How do aminoglycosides cause ototoxicty?

Answer 3

drug entry into the outer hair cell results in cell death by either caspase-dependent OR independent mechanisms.
1 AG entry into outer hair cell through mechnoelectrical channels
2 formation of AG-iron complex creacts with arachidonic cid to form ROS
3 ROS can activate JNK
4 JNK translocates to nucleus to activate cell death

Question 4

How does cisplatin cause hair cell death?

Answer 4

through caspase dependent mechanisms.

1. CP enters outer hair cell
2. CP forms mnohydrate complex MHC, MHC activates NOX-3, resulitng in ROS
3. ROS activates JNK which translocates to nucleus
4. nuclesu activates genes in cell death pathway to translocate to mitochondria
5. mitochondria releases cty c and triggers Capsase apoptosis

Question 5

How do loop diuretics cause ototoxicity?

Answer 5

by their natural mechanism of inhibiting Na/K/2Cl co-transporter, which is important in the ears as well as kidneys. Act through the stria medullaris to cause edema and loss of function that is dose-dependent.

Question 6

What are treatments for vertigo?

Answer 6

M1 or H1 antagonists OR diazepam for psychosomatic induced vertigo

Question 7

BBW for promethazine?

Answer 7

BBW for use by injection. Sedation and fatal respiratory depression

Question 8

What are ADE of scopalamine?

Answer 8

xerostomia, drowsiness, oular effects after touching patch.

Question 9

What is longest acting anti-vertigo drug?

Answer 9

scopalamine transdermal patch

Question 10

What is MOA of meclinzine?

Answer 10

H1 and M1 antagonist

Question 11

What is MOA of promethazine?

Answer 11

H1 and M1 antagonist

Question 12

What is MOA diphenhydramine?

Answer 12

H1 and M1 antagonist

Question 13

Which anti-vertigo drug should NOT be used with a cyp2D6 inhibitor?

Answer 13

meclizine because it is predominantly hepatic CYP2D6 metabolized.

Question 14

Which antiemetic needs dose adjustmant in hepatic dysfunction?

Answer 14

ondansetron

Question 15

ADE of D2 receptor antagonists?

Answer 15

chronic use leads to bone marrow suppression and blood dyscrasias,
risk of proonged QT and torsade de pointes
Don’t give with antipsychotics

Question 16

Where do NK1 antagonists act?

Answer 16

in the substantia nigra

Question 17

What is primary interaction concern with N1 antagonists?

Answer 17

they are CYP3A4 inhibitors.

Question 18

What is mechanism of cannabinoid agonists?

Answer 18

G-protein coupled decrease in neuronal activity in medullary vomiting center and solitary tract nucleus.

Question 19

ADE of cannabinoid receptor agonists?

Answer 19

causes high. Caution in pts with history of stustance abuse. Most ommon effect is elation and heightened awareness

Question 20

What is treatment of choice for emesis from antineoplastics?

Answer 20

serotonin receptor antagonist + a corticosteroid and possibly an NK-1 antagonist.

Question 21

What is mechanism of corticosteroids as anti-emetics?

Answer 21

act on steroid receptors in STN to possibly reduce release of serotonin.