Vertigo Tx

Question 1

Irreversibly vestibulotoxic drugs are?

Answer 1

• Aminoglycosides
• Cisplatin
• Ototoxicity caused by loop diuretcs may be reversible

Question 2

Amonoglycosides enter into outer hair cells and result in cell death via ……

Answer 2

Caspase dependent or Caspase independent mechanisms

Question 3

The steps involved in aminoglycoside ototoxicity

Answer 3

• AG enters via mechanoelectrical transducer channels
• Formation of an AG- iron complex
• AG- Iron interacts with electrical donors to form ROS.
• ROS then activate JNK which can translocate to the nucleus and activate teh cell death pathway
• genes from cell death pathway go to mitochondria which causes the release of cyt c. which can trigger apoptosis via caspases

Question 4

Cisplatin results in what type of cell deathw

Answer 4

caspase dependent

Steps basically the same except that once CP enters through the mechano-transducer channels and it can form a monohydrate complex

Question 5

Short term tx of vertigo is accomplished by drugs which act primarily where?

Answer 5

H1 and M1 (Histamine and Muscarinic) receptors on the cerebellum

Question 6

WHich vertigo drugs act via H1 and M1 blockade

Answer 6

• Diphenhydramine
• Meclizine
• Promethazine

Question 7

OF the three H1 and M1 blcokers, which are CYP2D6 inhibitors

Answer 7

Diphenhydramine and Promethazine

Di and Pro

Question 8

All H1 and M1 blockers undergo what type of metabolism

Answer 8

hepatic

Question 9

H1 and M1 blockers cause side-effects that are serious enough to prevent use in

Answer 9

old ppl

Question 10

What are the serotonin antagonists used for?

Answer 10

Anti-emesis. They block serotonin in the stomach and small intestine.

• Called “setrons”

Question 11

Where do the serotonin antagonists work?

Answer 11

In the CTZ (chemotherapeutic Trigger zone- monitors blood and CSF for toxic substances) and the STN (solitary tract nucleus).

Question 12

AE of setrons

Answer 12

Hepatic metabolism (Ondansetron needs a dose adjustment)

All have ppotential for CV issues by action on cardiac cycle

Question 13

What are the two anti-dopaminergics that we need to know?

Answer 13

Chlorpromazine
Prochlorperazine

• These also have a problem with the cardiac cycles
• Risk of QT prolongation and torsades de pointes

Question 14

Aprepitant/ fosaprepitant

Answer 14

Substance P and NK1 antagonists. Used for adjunct chemo, crosses BBB so it acts centrally

• CYP3A4

Question 15

KNOW that corticosteroids like dexamethasone and methyl prednisilone can increase the anti-emetic effect of other drugs and lower the adverse effects. May also have their own anti-emetic effect by lowering prostaglandins

Answer 15

ok

Question 16

Benzodiazepines (Diazepem) and vomitting?

Answer 16

They are used in anticipatory vomitting (prior to chemo) because tehy cause somnolence and amnesia lasting for hours.

Question 17

Dronabino

Answer 17

stimulates cannabinoid receptors. Used in chemo pts when all other possibilities fail

Question 18

What is Scopalamine

Answer 18

anti-cholinergic

• blocks M1 and stimulation of CNVIII that fires cholinergic stimulation to the VC

Used to treat motion sickness

Can cause drowsiness and dry mouth