Anti-nausea And Anti-emetic Drugs (Segars)

Question 1

List important receptors in nausea and vomiting:

Answer 1

5-HT3 
NK1 (neurokinin)
H1
D2
M1
Cannabinoid 

All should be antagonized with the exception of cannabinoids for anti-nausea/vomiting

Question 2

Dolasetron, granisetron, ondansetron, and palonosetron are what type of drugs?

Answer 2

5-HT3 antagonists

Question 3

Aprepitant, fosaprepitant, netupitant, and rolapitant are what type of drugs?

Answer 3

NK1 antagonists

Question 4

Chlorpromazine, perphenazine, prochlorperazine are these types of drug:

Answer 4

D2 antagonists: Phenothiazines

Question 5

Scopolamine is this type of drug

Answer 5

M1 antagonist

Question 6

Dronabinol and nabilone are this type of drug

Answer 6

Cannabinoid agonist

Question 7

Diphenhydramine, dimenhydrinate, hydroxyzine, promethazine, meclizine, and cyclizine are these types of drug:

Answer 7

H1 antagonists

Question 8

What is the MOA of the “-setron’s”?

Answer 8

Block 5-HT3 receptors at vagal nerve terminals and block signal transmission to chemoreceptor trigger zone

Also block 5-HT3 receptors activation after 5-HT3 release from intestinal enterochromaffin cells

Question 9

What is the most worrisome adverse effect of 5-HT3 antagonists?

Answer 9

Dose-dependent QT prolongation and torsades

Extreme caution required when using with other QT-prolonging agents (antiarrhythmics) –> Dolasetron very high risk so longer recommended by the FDA for prophylaxis of CINV

Question 10

What are interactions with use of 5-HT3 antagonists?

Answer 10

Mainly via CYP450 system
QT prolonging agents
Antiarrhythmics

Question 11

What is the MOA of the “-pitants”?

Answer 11

Blockade of NK1 (substance P) receptors in chemoreceptor trigger zone/vomiting center

Peripheral blockade of NK1 receptors located on vagal terminals in gut an additional hypothesis

These are moderate antiemetic agents

Question 12

This H1 receptor antagonist is the initial drug of choice for n/v of pregnancy

Answer 12

Doxylamine with B6 (pyridoxine)

Question 13

What is the MOA of H1 receptor antagonists?

Answer 13

Block H1 receptors in the vomiting center and vestibular system

THESE AGENTS EXHIBIT VARYING LEVELS OF CENTRAL ANTI-CHOLINGERGIC PROPERTIES AT THE LEVEL OF THE CHEMORECEPTOR TRIGGER ZONE

Question 14

List the classic anti-cholinergic effects of H1 receptor antagonists:

Answer 14

Drowsiness (CNS depression)
Dry mouth
Constipation
Urinary retention
Blurred vision
Decrease BP

Question 15

Where do D2 receptor antagonists work?

Answer 15

In the CTZ

Metoclopramide also stimulates Ach actions in GI, enhancing GI motility and increases lower esophageal sphincter tone

Question 16

What are adverse effects of Dopamine receptor antagonists (the slide with the star)?

Answer 16

Classic anti-cholingeric effects:
Drowsiness
Dry mouth
Constipation
Urinary retention 
Blurred vision
Hypotension (arrhythmias are possible. Usually with larger doses)
Extrapyramidal side effects (dyskinesias)

Question 17

This anti-emetic is a transdermal patch most commonly utilized for motion sickness and is a M receptor antagonist

Answer 17

Scopolamine

Question 18

What are adverse effects of scopolamine (slide with the star)?

Answer 18

Classic anti-cholinergic effects:
Drowsiness
Dry mouth
Constipation
Urinary retention
Blurred vision

Question 19

These drugs are strong anti-emetic agents reserved for chemo-induced n/v and are scheduled drugs

Answer 19

Cannabinoids

Dronabinol (C-3)

Nabilone (C-2)

Question 20

What are therapeutic uses of cannabinoids?

Answer 20

Chemo-induced N/V

D/t FDA schedule, commonly reserved for tx-resistant clinical scenarios

Question 21

What is the 3-drug regimen (high-emetogenic regimen) for Chemo-induced N/V?

Answer 21

1) 5-HT3 receptor antagonist
2) NK1 receptor antagonist
3) Corticosteroid (dexamethasone)

Question 22

What is the 2 drug regimen (moderate-emetogenic regimen) for chemo-induced N/V?

Answer 22

1) 5-HT3 receptor antagonist (Palonosetron)

2) corticosteroid (dexamethasone)

Question 23

What is the 1 drug regimen (low-emetogenic regimen) for chemo-induced N/V?

Answer 23

Corticosteroid (dexamethasone)

Question 24

What drug for motion sickness?

Answer 24

Scopolamine (patch) or Dimenhydrinate (oral)

Question 25

What drug(s) for vertigo?

Answer 25

Meclizine or cyclizine

Question 26

What drug for diabetic gastroparesis?

Answer 26

Metoclopramide

Question 27

What drugs for pregnancy induced n/v?

Answer 27

Stepped-therapy:

1) 5-HT3 antagonist or histamine antagonist
2) dopamine antagonist
3) steroid or different dopamine antagonist