Most research in children has been in nausea and vomiting associated with chemotherapy.  Nausea and vomiting is known to be a significant symptom among children needing palliative care, particularly in cancer.  A rational approach in adults has been proposed but never validated in children.

Receptors

The mechanism of the physiological basis of nausea and vomiting is essentially an interaction of neurochemicals with receptors.  Each of the organs primarily involved in nausea and vomiting is associated with a group of receptors.  Most antiemetics work by blocking one or more of the receptors.  No antiemetic blocks all receptors.

Most is known about 6 antiemetic receptors:

D₂ dopamine receptor.  Found in gastrointestinal tract and centrally.  Blocked by Metoclopramide and Haloperidol.

H₁ histamine receptor.  Associated with intracranial and vestibular causes, blocked, along with ACh by Cyclizine.

Acetylcholine (ACh).  Associated with vestibular causes and with vagal nerve neurotransmission. Hyoscine is a pure ACh blocker.

5HT₂ seretonin receptor.  Associated with the bowel wall, blocked, among other things, by Levomepromazine.

5HT₃ receptor.  Associated with bowel wall, blocked by Ondansetron.

5HT₄ receptor.  Associated with bowel wall, blocked by high dose Metoclopramide.

A further class of receptors has been identified, with three subtypes associated with the bowel mucosa.  They are neurokinin receptors NK₁, NK₂ and NK₃.  This further opens up the possibilities for pharmacological intervention using antagonists.  To date, only one neurokinin antagonist has been fully developed.  Aprepitant, a pure NK₁ antagonist, has been studied in adults and appears to be well tolerated with good effect.

Organs

Four organs are particularly involved in nausea and vomiting:  the gastrointestinal tract, the blood stream, the liver and the brain.  In considering a rational approach to managing nausea and vomiting, it is first necessary to decide which of these is or are the main cause(s).

Gastrointestinal:

• Mucosal damage
  • Chemotherapy (D₂, 5HT₃)
  • Radiotherapy (5HT_3,4)
  • Obstruction
• Mechanical
  • Obstruction
  • Reflux

Blood (toxins)

• Medication (D₂)
• Infection (5HT₂)
• Constipation (5HT_3,4)

Liver damage

• Focal deposits (physical effect)
• Diffuse disease (5HT₄)

Brain

• Vestibular
  • Vertigo (ACh)
  • Travel sickness (H₁)
• Raised intracranial pressure
  • Tumour (H₁)
  • Oedema
• Psychological
  • Anticipation
  • Anxiety (Benzodiazepine receptors)

NB.  The motor pattern that constitutes the act of vomiting is generated in a specialised part of the brain, the vomiting centre (also known as the emetic pattern generator) and affected via the vagus nerve (ACh).

Non-Receptor mechanisms

Drug receptor interactions are not the only links in the chain of causality for nausea and vomiting.  It may be possible to modify other factors:

Physical factors

• Raised intracranial pressure (for example, brain tumour and cerebral oedema).
• Liver damage (for example metastatic cancer, particularly where the liver capsule is stretched).
• Gastrointestinal obstruction.
• Reflux

Psychological factors

There is often a close association between anxiety and nausea and vomiting.