Physiology and Pharmacology of Nausea and Vomiting

Question 1

What three pathways can stimulate nausea and vomiting?

Answer 1

Central pathway
Vestibular pathway
Vagal pathway

Question 2

What stimulates the above three pathways?

Answer 2

Central - sight, smell, pain, memories
Vestibular - motion sickness
Vagal - toxins, heavy metals, alcohol

Question 3

Describe what occurs in the vagal pathway

Answer 3

Toxic materials in the gut lumen stimulate enterochromaffin cells in the mucosa
These stimulated cells depolarise sensory afferent terminals in mucosa
There is an action potential discharge to vagal afferents in the brainstem (chemoreceptor trigger zone (CTZ) and nucleus tractus solitartius (NTS))
Co-ordinated vomiting by the vomiting centre takes place

Question 4

Outline the events that take place in vomiting

Answer 4

Slow wave intestinal activity suspended
Retrograde contractions from ileum to stomach
Breathing suspended (closed glottis)
LOS relaxes, diaphragm contracts and stomach compressed
Gastric contents ejected through open UOS

Question 5

State the effects of vagal efferents in vomiting

Answer 5

Shorted oesophagus
Relaxed stomach
Giant retrograde contraction of small intestine

Question 6

State the effects of somatic motor neurones in vomiting

Answer 6

Anterior abdominal wall muscle contracts

Diaphragm contracts

Question 7

State the effects of autonomic/somatic efferents in vomiting

Answer 7

Increased heart rate
Increased saliva secretion
Pallor and cold sweating
Bladder and anus sphincters constrict

Question 8

Name some consequences of severe vomiting

Answer 8

Dehydration
Hypocholaraemic metabolic alkalosis
Hypokalaemia
Mallory-Weiss tear
Aspiration

Question 9

Give examples of dopamine antagonists, name the receptor they block and where they are administered

Answer 9

Prochlorperazine, droperidol and levomeprazine
D2 receptor in CTZ
Orally, rectally or sublingually

Question 10

Describe the effect of prokinetic drugs and give example

Answer 10

Prokinetic drugs also block the D2 receptor and can increase peristalsis and LOS tone
Examples include metaclopramide and domperidone

Question 11

Give examples of 5HT3 receptor antagonists and their common side effects

Answer 11

Examples include granisetron and palonosetron

The common side effect is a headache

Question 12

Give examples of antihistamines and how they work

Answer 12

Antihistamines include promethazine and cyclizine. They block H1 receptors in vestibular nuclei and the NTS

Question 13

Give examples of anticholinergics, how they work, how they are administered and common side effects

Answer 13

Anticholinergics include hyosine and dicyclomine. They block the muscarinic receptors in the vomiting centre and NTS.
Anticholinergics can be administered orally, IM or transdermally. They may cause blurred vision, urinary retention, dry mouth and sedation

Question 14

Give some classes of adjuvant antiemetics

Answer 14

NK1 receptor antagonists
Corticosteroids
Benzodiazepines
Cannabinoids

Question 15

How is chemotherapy-induced nausea and vomiting cause and what drugs are used to treat it?

Answer 15

CINV is commonly caused by doxorubicin. It is treated with a triple drug regimen involving a 5HT3 receptor antagonist + dexamethasone + apreptiant

Question 16

What drugs are used to treat post-operative nausea and vomiting?

Answer 16

5HT3-receptor antagonists
Dropiderol
Cyclizine
Dexamethasone

Question 17

What drugs are indicated in managing pregnancy associated nausea and vomiting?

Answer 17

Antihistamines (promethazine/cyclizine)