Pharmacology 30 - Anti-Emetics

Question 1

How does chemotherapy cause nausea and vomiting?

Answer 1

• Chemotherapy (cisplatin) is toxic to enterochromaffin cells (ECs) – release of free radicals
• Free radicals cause excessive 5-HT release
• 5-HT activates 5-HT3A receptors on nerve fibres to chemoreceptor trigger zone (CTZ)
• CTZ activates nerves fibres to vomiting centre (VC)
• VC (area postrema) causes nausea

Question 2

How is chemotherapy induced nausea and vomiting (CINV) treated?

Answer 2

Triple therapy…
- Ondansetron (5-HT3a receptor antagonist - all end in setron, effective in early stage nausea and vomiting)

For later stage chemotherapy induced nausea and vomiting

• Glucocorticoids (reduce free radical production - antiinflammatory agents)
• Arepepritant (neurokinin-1 receptor antagonist, receptors present in the vomiting centre activated by substance B)

Question 3

Describe the pathophysiology of motion sickness

Answer 3

• Auditory labyrinth - neural mismatch (between what you are seeing and where you are moving) activates histamine receptors on vestibular nuclei
• Vestibular nuclei activate muscarinic receptors on CTZ
  CTZ activates VC, which causes nausea

Question 4

How is motion sickness treated?

Answer 4

• Promethazine - H1 (histamine) receptor antagonist OTC

- Hyoscine (scopolomine) – non-selective muscarinic receptor antagonist

Question 5

Describe pathophysiology of gastroparesis

Answer 5

• Delayed emptying of the stomach
• Reduced stomach contraction
• Excessive 5-HT release activates 5-HT3A receptors on chemoreceptor trigger zone
• CTZ activates nerves fibres to vomiting centre (VC)
• VC causes nausea
• Dopamine D2 receptors on the chemoreceptor trigger zone can also stimulate nausea when activated

Question 6

How is nausea and vomiting caused by gastroparesis treated?

Answer 6

Metoclopramide

• Dopamine D2 receptor antagonist
• Prokinetic – stimulates gastric emptying
• Inhibits D2 receptors in VC
• 5-HT3A receptor antagonist
• Inhibits activation of CTZ

Question 7

List main mechanistic triggers of nausea and vomiting

Answer 7

• Cytotoxic drugs
• Motion sickness
• GI problems
• Pregnancy
• Other higher functions

Question 8

List the main classes of anti-emetic drugs

Answer 8

• 5-HT3a receptor antagonists (ondansetron)
• Histamine H1 receptor antagonists (promethazine)
• Muscarinic receptor antagonists (hyoscine)
• Dopamine D2 receptor antagonists (metoclopramide)

Question 9

List side effects of 5-HT3A receptor antagonists

Answer 9

• Headaches

- Constipation

Question 10

List side effects of histamine H1 receptor antagonists

Answer 10

Drowsiness

Question 11

List side effects of muscarinic receptor antagonists

Answer 11

• Dry mouth

- Drowsiness

Question 12

List side effects of dopamine D2 receptor antagonists

Answer 12

• Galactorrhoea

- Extrapyramidal side-effects