24 - Anti-Emetics

Question 1

Outline how cisplatin can induce nausea and vomiting

Answer 1

Cisplatin = Chemotherapy

Chemotherapy is designed to kill cells, but also is having an effect on ECs

Cisplatin is toxic to enterochromaffin cells (ECs)

ECs apoptose

Causes release of free radicals

Leads to excessive 5-HT release

5-HT activates 5-HT_3A receptors on:

• nerve fibres to nucleus tractus solaris (NTS) around brainstem in medulla oblongata
• nerve fibres to vomiting centre (VC)
• nerve fibres to chemoreceptor trigger zone (CTZ) - outside BBB, sends signals to VC

Vomiting Centre has fibres which go to the stomach and cause contraction of the stomach. This causes expulsion of the stomach’s contents.

Serotonin released by ECs act on the 5-HT_3A receptors

Question 2

Outline how you would treat Chemotherapy Induced Nausea & Vomiting (CINV)

Answer 2

Ondansteron

• selective 5-HT_3A receptor antagonist

Glucocorticoids

• reduced free radical production

Arepepritant

• neurokinin-1 receptor antagonist
• found on the vomiting centre

Question 3

Outline the pathophysiology of motion sickness

Answer 3

Auditory labyrinth

• usually involved in balance
• neural mismatch
• projects to vestibular system (via muscarinic (M) receptors)

Increased hypothalamic histamine (H) release

• activates H₁ (histamine) receptors in CTZ in brainstem

Vestibular system (close to medulla oblongata in brainstem) & hypothalamus may also activate the VC though cholinergic system

Question 4

Outline how you would treat motion sickness

Answer 4

FIRST LINE TREAT IS NOT PHARMACOLOGICAL

WOULD HAVE TO BE LONG-TERM AND VERY BAD

Promethazine

• H₁ receptor antagonist

Hyoscine (Scopolomine)

• non-selective muscarinic receptor antagonist

Question 5

What is the diagnosis for someone with:

• Vomiting, due to unknown cause
• Abdominal pain & bloating
• History of type 2 diabetes

?

Answer 5

GASTROPARESIS - DELAYED EMPTYING OF THE STOMACH

Reduced stomach contraction (not due to serotonin)

Dopamine D₂ receptors:

• direct contact to VC
• VC in the medulla oblongata has D2 receptors

5-HT – activates 5-HT_3A receptors on:

• Nerve fibres to chemoreceptor trigger zone (CTZ)
• Nerves fibres to vomiting centre (VC)

Question 6

How would you treat someone with gastroparesis?

Answer 6

Metoclopramide

Dopamine D₂ receptor antagonist

• Prokinetic– stimulates gastric emptying
• Inhibits D₂ receptors in VC

5-HT_3A receptor antagonist

• Inhibits activation of CTZ