Anti-emetics

Question 1

Summarise the physiological control of nausea/vomiting?

Answer 1

Vomiting centre (area postrema) innervated by nucleus of tractus solitarius

Chemoreceptor trigger zone communicates with vomiting centre

Question 2

What are the main mechanistic triggers of nausea/vomiting?

Answer 2

1. Cytotoxic drugs
2. Motion sickness
3. GI problems

Question 3

What are the main classes of anti-emetic drugs?

Answer 3

1. 5-HT3A receptor antagonists
2. Histamine H1 receptor antagonists
3. Muscarinic receptor antagonists
4. Dopamine D2 receptor antagonists

Question 4

What are 5-HT3A receptor antagonists principally used for clinically? How do they work?

Answer 4

• Chemotherapy-induced N&V

- Block activation of nerve fibres to nucleus tractus solaris, vomiting centre and chemoreceptor trigger zone

Question 5

What are histamine H1 receptor antagonists principally used for clinically? How do they work?

Answer 5

• Motion sickness
• Block hypothalamic histamine release from chemoreceptor trigger zone
• Blocks activation of vomiting cenre

Question 6

What are muscarinic receptor antagonists principally used for clinically? How do they work?

Answer 6

• Motion sickness
• Has little effect once nausea/emesis is established
• In operative pre-medication
• Block activation of vomiting centre by vestibular system and hypothalamus

Question 7

What are dopamine D2 receptor antagonists principally used for clinically? How do they work?

Answer 7

Main ** = gastroparesis induced N&V
Also N&V associated w/:
- uraemia (severe renal failure)
- radiation sickness
- cancer chemotherapy (high doses) e.g. Cisplatin (intractable vomiting)

• *Inhibit D2 receptor in VC
• Prokinetic - stimulates gastric emptying

Question 8

What are some possible side effects of anti-emetics?

Answer 8

• Headaches
• Constipation
• Dry mouth
• Extrapyramidal side-effects

Question 9

What are the side effects of H1 receptor antagonists?

Answer 9

• • Sedation (‘do not drive or operate machinery’)
• Dizziness
• Tinnitus
• Fatigue
• Excitation in excess
• Convulsions (children more susceptible)
• Anti-muscarininc side-effects

Question 10

What are the side effects of 5-HT3A receptor antagonists?

Answer 10

• headache
• sensation of flushing and warmth
• increased large bowel transit time (constipation)

Question 11

What are the side effects of muscarinic receptor antagonists?

Answer 11

Typical anti-muscarinic side-effects:
- drowsiness
- dry mouth
- cycloplegia
 mydriasis
- constipation (not usually at anti-emetic doses)

Question 12

What are the side effects of dopamine D2 receptor antagonists

Answer 12

In CNS:

• drowsiness
• dizziness
• anxiety
• extrapyramidal reactions; children more susceptible than adults (Parkinsonian-like syndrome: rigidity, tremor, motor restlessness)

Endocrine:

• hyperprolactinaemia
• galactorrhoea
• disorders of menstruation

Question 13

How can chemotherapy cause nausea and vomiting?

Answer 13

• Cisplatin is toxic to enterochromaffin cells in stomach lining - causes destruction and release of free radicals and excessive 5-HT (serotonin) release
• Free radicals cause further destruction of EC cells
• 5-HT activates 5-HT3A receptors on:
  1. Nerve fibres to nucleus tractus solaris (NTS)
  2. Nerve fibres from NTS to vomiting centre
  3. Nerve fibres to chemoreceptor trigger zone (CTZ) - communicates w/VC

Question 14

How can motion sickness cause nausea and vomiting?

Answer 14

• Auditory labyrinth - nerual mismatch - vestibular system (via muscarinic receptors)
• Increased hypothalamic histamine release - activates H1 receptors in CTZ
• Vestibular system + hypothalamus may also activate VC thr cholinergic system

Question 15

How can gastroparesis cause nausea and vomiting?

Answer 15

Gastroparesis = delayed emptying of stomach

• Reduced stomach contraction
• 5-HT activates 5-HT3A receptors on:
  1. Nerve fibres to vomiting centre
  2. Nerve fibres to chemoreceptor trigger zone