simple anti-emetics

Question 1

What is the pathophysiology for chemotherapy induced nausea and vomiting (CINV)?

Answer 1

Cisplatin(used in lung cancer treatment) is toxic to enterochromaffin cells in the small intestine and appendix

Question 2

How does toxic effect does cisplatin have enterochromaffin cells in CINV?

Answer 2

Causes increased release of free radicals - 5HT

Question 3

How does increased release of 5HT cause nausea and vomiting in case of CINV?

Answer 3

activates 5HT3aR on nerve fibres innervating the chemoreceptor trigger zone (CTZ)
The CTZ then activates nerve fibres to vomiting centre causing nausea

Question 4

Through which receptors does the CTZ activate vomiting centre?

Answer 4

Muscuranic receptors 1-5

Question 5

What is treatment plan for CINV?

Answer 5

Ondansetron - 5HT3aR antagonist
Glucocorticoids to reduce free radical production
Aprepitant - neurokinin 1 receptor antagonist, a receptor primarily expressed in the VC activated by substance P.

Question 6

What is the pathophysiology in motion sickness?

Answer 6

Neural mismatch in the labyrinth which activates histamine receptors on vestibular nuclei.
Vestibular nuclei activate muscuranic receptors on the CTZ and CTZ activates VC

Question 7

What is the treatment for motion sickness?

Answer 7

Promethazine - h1 receptor antagonist

Hyoscine (non-selective muscranic receptor antagonist)

Question 8

What would be the cause of vomiting due to unknown cause, abdo pain, T2DM presentation?

Answer 8

Gastroparesis

Question 9

What is gastroparesis?

Answer 9

Delayed emptying of the stomach and reduced stomach contraction.

Question 10

How does gastroparesis ultimately lead to VC stimulation?

Answer 10

5HT production binds to CTZ 5HT3aR and then this activates VC

Question 11

What other receptor can be targeted in gastroparesis that is present on CTZ?

Answer 11

D2 receptor

Question 12

What is treatment for gastroparesis pathophysiology NV?

Answer 12

Metoclopramide is a d2 receptor antagonist which is prokinetic i.e. stimulates gastric emptying and inhibits d2 receptors on CTZ
It’s also a 5HT3aR antagonist which inhibits activation of CTZ

Question 13

Describe the receptor pathway in CINV

Answer 13

5HT3aR activation on CTZ

Non-specific muscuranic receptor activation on VC

Question 14

Describe the receptor pathway in motion sickness

Answer 14

H1 receptor activation on vestibular nuclei by neural mismatch in labyrinth
Muscuranic receptor activation on CTZ by vestibular nuclei
Muscuranic receptor activation on VC also

Question 15

Describe the receptor pathway in gastroparesis

Answer 15

5ht3aR on CTZ then activation of muscuranic on VC same as CINV, however dopamine antagonists are utilised against d2 on CTZ due to prokinetic effects on stomach and the effects of dopamin on CTZ

Question 16

What are the 4 classes of drugs used to treat nausea and vomiting?

Answer 16

5ht3aR antagonists - ondansetron
D2 receptor antagonists - metoclopramide
Muscuranic receptor antagonists - hyoscine
H1R antagonists - promethazine

Question 17

What are the side effect profiles of each drug type?

Answer 17

5HT3aR anta - headache, constipation, involved in GI tract
H1R anta - drowsy which is beneficial
Musc R anta - drowsiness and dry mouth
D2 anta - EPS and galactorrhoea

Question 18

What are the triggers for nausea and vomiting?

Answer 18

Mechanistatic triggers - cytotoxic drugs, motion sickness, GI problems, pregnancy, other high functions.