Anti-emetics

Question 1

Chemotherapy induced nausea and vomiting pathophysiology

Answer 1

Cisplatin used for lung cancer chemotherapy (chemotherapy induced nausea and vomiting)

• Cisplatin toxic to enterochromaffin cells, leading to free radical release
• Free radicals stimulate excess serotonin release
• Serotonin activates 5-HT receptors on the nerve fibres to nucleus tractus solaris (NTS), nerve fibres to vomiting centre (VC) and nerve fibres to chemoreceptor trigger zone (CTZ)
• leads to vomiting reflex

Question 2

Chemotherapy induced nausea and vomiting treatment

Answer 2

ONDANSTERON
-5-HT3A receptor antagonist to prevent vomiting side effect from chemotherapy
-oral administration and excreted in urine
-side effects include headache, flushing and constipation
GLUCOCORTICOIDS
-combination use to reduce free radical production
AREPEPRITANT
-neurokinin-1 receptor antagonist

Question 3

Mechanistic vomiting triggers

Answer 3

1) Cytotoxic drugs
2) Motion sickness
3) Gastrointestinal problems

Question 4

Motion sickness pathophysiology

Answer 4

• Neural mismatch between signals from auditory labyrinth (inner ear fluid responsible for balance) and vestibular system (via muscarinic receptors)
• increased hypothalamic histamine release leads to Histamine H1 receptor activation in chemoreceptor trigger zone (CTZ)
• vestibular system and hypothalamus also activate vomiting centre (VC) through cholinergic system

Question 5

Motion sickness treatment

Answer 5

PROMETHAZINE
-Histamine H1 receptor antagonist
-acts centrally to block vomiting centre activation
-best used prophylactically
-oral administration
-1-2 hours before action onset
-24 hour action
-side effects include dizziness, tinnitus, fatigue, sedation, excitation (in excess) and convulsions
HYOSCINE (Scopolomine)
-Non-selective muscarinic receptor antagonist
-needs to be given prophylactically (little effect if given after onset)
-oral administration or via transdermal patch
-side effects include drowsniess, dry mouth, cycloplegia, mydriasis and constipation

Question 6

Gastrointestinal

problem pathophysiology

Answer 6

Vomiting due to unknown cause

• Gastroparesis (delayed emptying of the stomach contents due to reduced stomach contraction and often accompanied with abdominal pain, bloating and feeling full quickly etc)
• causes serotonin release, leading to the activation of 5-HT receptors on nerve fibres to vomiting centre (VC) and nerve fibres to chemoreceptor trigger zone (CTZ)

Question 7

Gastrointestinal problems vomiting treatment

Answer 7

METOCLOPRAMIDE
-Dual action as Dopamine D2 receptor antagonist and 5-HT3A receptor antagonist

Dopamine D2 receptor antagonist

• prokinetic, increasing smooth muscle motility and stimulating gastric emptying->accelerates transit of intestinal contents
• inhibits Dopamine D2 receptors in vomiting centre (VC)

5-HT3A receptor antagonist

• inhibition of chemoreceptor trigger zone (CTZ) activation
• side effects include drowsiness, dizziness, anxiety, extrapyramidal reactions (Parkinsonian-like syndrome), hyperprolactinaemia, galactorrhoea and menstruation disorders

Question 8

Anti-emetic drug classes

Answer 8

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

Question 9

Physiological control of nausea/vomiting

Answer 9

• Area postrema (vomiting centre)=innervated by nucleus of tractus solitarius
• Chemoreceptor trigger zone=communicates with vomiting centre