Anti-emetics

Question 1

Describe the physiological control of nausea and vomiting?

Answer 1

Motor output for vomiting originates in the vomiting centre (area postrema): innervated by the nucleus of the tractus solitarius and the chemoreceptor Trigger Zone: communicates with the vomiting centre.

Sensory triggers for vomiting: Cytotoxic drugs, motion sickness, gastrointestinal problems

Question 2

What are the 4 main drug types used?

Answer 2

5-HT3A receptor antagonists
Histamine H1 receptor antagonists
Muscarinic receptor antagonists
Dopamine D2 receptor antagonists

Question 3

Give an example of each type?

Answer 3

Ondansteron - 5-HT3A receptor antagonist
Promethazine - H1 receptor antagonist
Hyoscine (scopolomine) – non-selective muscarinic receptor antagonist
Metoclopramide: Dopamine D2 receptor antagonist &
5-HT3A receptor antagonist

Question 4

Explain how cytotoxic drugs induce vomiting?

Answer 4

Drugs that are toxic to enterochromaffin cells (ECs) cause release of free radicals which causes an excessive 5-HT release
5-HT activates 5-HT3A receptors on:
Nerve fibres to nucleus tractus solaris (NTS)
Nerves fibres to vomiting centre (VC)
Nerve fibres to chemoreceptor trigger zone (CTZ)

Question 5

Explain how treatment for cytotoxic drug-induced vomiting works?

Answer 5

Ondansteron 5-HT3A receptor antagonist so limits activation of CTZ and VC

Question 6

Explain how motion sickness induces vomiting?

Answer 6

Auditory labyrinth activates the Vestibular system (via muscarinic (M) receptors) there is also increased hypothalamic histamine (H) release which activates H1 receptors in CTZ
Vestibular system & hypothalamus activate the VC though M receptors

Question 7

Explain how the treatment of motion sickness induced vomiting works?

Answer 7

Promethazine - H1 receptor antagonist reduces activation of CTZ
Hyoscine (scopolomine) – non-selective muscarinic receptor antagonist reduces activation of hypothalamus and VC

Question 8

Explain how GI problems can induce vomiting?

Answer 8

Reduced stomach contraction is detected and results in release of 5-HT which activates 5-HT3A receptors on:
Nerves fibres to vomiting centre (VC) and CTZ.
Also activation of VC via D2 receptor-mediated action.

Question 9

Explain how treatment for GI problem induced vomiting works?

Answer 9

Metoclopramide is a dopamine D2 receptor antagonist so reduces activation of VC
It’s prokinetic so stimulates gastric emptying
It’s also a 5-HT3A receptor antagonist so inhibits activation of CTZ

Question 10

What are side effects of each of the 4 dug classes?

Answer 10

5-HT3A receptor antagonists: headaches and constipation
Histamine H1 receptor antagonists: drowsiness
Muscarinic receptor antagonists: dry mouth and drowsiness
Dopamine D2 receptor antagonists: galactorrhea and extrapyramidal side effects