Pharm 24 - Anti-emetics

Question 1

Name 3 things that can induce vomiting

Answer 1

1. Chemotherapy (e.g. cisplatin for lung cancer)
2. Motion sickness
3. Gastroparesis

(Pregnancy also)

Question 2

Explain how chemotherapy (e.g. cisplatin) can cause vomiting

Answer 2

1. Cisplatin is toxic to enterochromaffin cells —> causes free radical release
2. Free radicals cause excess 5-HT release in stomach (and destroys EC cells)
3. Binds to 5-HT3a receptors (Excitatory) on nerve fibres to Nucleus tractus solitarius (NTS), vomiting centre (VC) and Chemoreceptor trigger zone (CTZ)

Question 3

What is the treatment for chemotherapy induced vomiting

Answer 3

1. Ondansetron - 5-HT3A receptor antagonist
2. GCs - reduce free radical production
3. Aprepitant - neurokinin-1 receptor antagonist (substance P binds NK-1 receptors)

Question 4

What causes motion sickness-induced nausea and vomiting?

Answer 4

1. Neural mismatch between auditory labyrinth + vestibular system of CNS
2. Causes increased histamine release from hypothalamus - activates H1 receptors in CTZ. VC may also be activated by cholinergic system.

(Vestibular system communicates with VC too)

Question 5

The vestibular system of CNS is mediated by which receptor?

Answer 5

Muscarinic

Question 6

What is the treatment for motion sickness induced nausea and vomiting

Answer 6

1. Promethazine - H1 receptor antagonist

2. Hyoscine - non-selective muscarinic receptor antagonist (most effective)

Question 7

What causes gastroparesis induced vomiting?

Answer 7

Delayed emptying of stomach —> stomach can’t contract properly —> increased stomach contents —-> triggers vomiting

Question 8

What is gastroparesis induced vomiting associated with?

Answer 8

Abdominal pain, bloating, T2DM

Question 9

In gastroparesis induced vomiting, 5-HT activates 5-HT3A receptors on ….?

Answer 9

1. Nerve fibres to VC (Area postrema)
2. Nerve fibres to CTZ
   (3. Not involved in gastroparesis but also nerve fibres to NTS)

Question 10

Metoclopramide is the treatment for nausea and vomiting. It acts via 3 mechanisms of action, which are

Answer 10

1. D2 receptor antagonist —> inhibits D2 receptors in VC
2. Prokinetic - stimulates gastric emptying/contraction directly
3. 5-HT3a receptor antagonist –> inhibits CTZ activation

Question 11

What are the 4 classes of antiemetics

Answer 11

1. 5-HT3a receptor antagonists
2. H1 receptor antagonists
3. Muscarinic receptor antagonists
4. D2 receptor antagonists

Question 12

What is the main clinical use of 5-HT3a receptor antagonists?

Answer 12

Chemotherapy induced nausea and vomiting

Question 13

What is the main clinical use for H1 receptor antagonists

Answer 13

Motion sickness

Question 14

What is the main clinical use for muscarinic receptor antagonists?

Answer 14

Motion sickness

Question 15

What is the main clinical use for D2 receptor antagonists

Answer 15

Gastroparesis induced nausea and vomiting

Question 16

What are the principal side effects of muscarinic receptor antagonists

Answer 16

Dry mouth, drowsiness, constipation

Question 17

What are the principal side effects of histamine receptor antagonists

Answer 17

Drowsiness

Question 18

What are the principal side effects of D2 receptor antagonists

Answer 18

Extra-pyramidal SEs (maybe headaches as well)

Question 19

What are the principal side effects of 5-HT3a receptor antagonists

Answer 19

Headaches and constipation