Nausea & Vomiting

Question 1

What is nausea?

Answer 1

Feeling of wanting to vomit accompanied by gastric dilation and upper intestinal contractions propelling the intestinal contents by reverse peristalsis into the stomach.

Question 2

What is retching?

Answer 2

Involuntary contractions of diaphragm and abdominal muscles leading to the cardiac portion of the stomach being forced into the thorax.

Question 3

What is vomiting?

Answer 3

Rapids inspiration followed by reflex closure of the glottis & elevation of the soft palate to prevent vomit entering lungs and nasal cavity.
- Contractions of diaphragm and abdominal muscle compress the stomach and expel gastric contents into oesophagus and mouth through relaxed lower and upper oesophageal sphincters.

Question 4

What are the causes of N & V?

Answer 4

therapeutic agents
pregnancy
CNS - motion sickness
alimentary canal - alcohol
metabolic disorders

Question 5

Describe chemo induced N & V

Answer 5

Acute post treatment - occurs within 24 hours after treatment and may last 120 hours.
- Late response from poorly controlled nausea and vomiting associated with pervious chemo.
- Occurs during following treatment cycle when prophylaxis and/or resue has failed in pervious cycle.

Question 6

What are the effects of N & V?

Answer 6

• Physical: drugs, toxins, chemo, gag reflex
• Psychological: smell, sight
• Emotional: fear, anxiety, panic

Question 7

What are the emesis trigger zones?

Answer 7

CNS
Vestibular nuclei
Vomiting center
Chemoreceptor tigger zone (CTZ)
GI system

Question 8

What ligand is the H1-R attached to and what is its role?

Answer 8

Histamine - neurotransmitter

Question 9

What ligand is the muscarinic receptor attached to and what is its role?

Answer 9

Acetyl choline - is a major neurotransmitter found in synapses neuromuscular junction.

Question 10

What ligand is the 5-HT3-R attached to and what is its role?

Answer 10

Serotonin - monoamine neurotransmitter found in the found the CNS and GI tract.

Question 11

What ligand is the D2 receptor attached to and what is its role?

Answer 11

Dopamine - catecholamine found in the brain which serves as a neurotransmitter for pleasure and pain

Question 12

What ligand is the Neurokinin-1-R attached to and what is its role?

Answer 12

Substance P - Neurotransmitter involved in inflammation, pain and vomiting

Question 13

What ligand is the Mu-R attached to and what is its role?

Answer 13

Opioids - neurotransmitter involved in pain/mood - activated by endorphins and opioids.

Question 14

Describe the chemoreceptor trigger zone (CTZ)

Answer 14

• Outside BBB - accessible to emetogenic stimuli in blood/CBF
• CTZ sense increased blood levels of potentially toxic substances, which initiates nausea and triggers vomit reflex

Question 15

Describe vestibular nuclei

Answer 15

Sense motion
- motion sickness: car/sea sickness, meniere’s disease
- H1 & M1-R mediate stimulus of vestibular apparatus
- Alcohol can trigger stimulation

Question 16

Describe the GI and N

Answer 16

GI is a primary source of toxin absorption
- Stimulation of gut chemoreceptors and stretch-R triggers N & V via vagal nerve afferents and afferent fibres associated with SNS.
- Enterochromaffin cells in GIT respond to chemo by releasing serotonin
- Stomach irritation/ distention can trigger

Question 17

Describe the Cerebal cortex and emesis

Answer 17

• Modulates taste, sight, smell, memory, emotion/ anxiety
• Cortical effects stimulate/suppress N & V

Question 18

What drugs are associated with high incidence of N & V?

Answer 18

• levodopa
• opioid analgesics

Question 19

What is the emesis reflex?

Answer 19

• Afferent impulses from the chemoreceptor trigger zone stimulate the vomiting centre - initiating emesis
• The vomiting centre consists of an intertwined neural network in the nucleus tractus soitartius that controls patterns of motor activity.

Question 20

List the antiemetics used for treatment.

Answer 20

• H1-R antagonists - cinnarizine
• Muscarinic antagonists - hyoscine
• 5-HT3-R antagonists - ondansetron
• D2-R antagonists - metoclopromide HCL, domperidone
• Neurokinin-1- antagonist - aprepitant, fosaprepitant
• Adjuvant antirmetics e.g. dexamethasone, benzodiazepines

Question 21

Antihistamines

Answer 21

• H1RA that prevents/ treat vomiting
• weakly effective
  SE: dizziness, sedation, dry mouth
  EX: Cinnarizine - 20 hour half life, Promethazine - pregnancy 7-14 hour half life

Question 22

Anticholinergics

Answer 22

Muscarinic antagonist
- Does not cross BBB - not sedative
- Poorly absorbed and not very effective
Hyoscine hydro-bromide: motion sickness, nausea, post operative vomiting - short duration
Hyoscine butyl-bromide: relaxes GI SM

Question 23

Dopamine antagonists

Answer 23

Block CTZ
- Effectively treat severe N/V associated with cancer, radiation, therapy, cytotoxic drugs, opioids, anaesthetic.
- In children severe dystonic (movement) reactions can occur
Examples; prochlorperazine, trifluoperazine

Question 24

D2 antagonists

Answer 24

Domperidone - Acts at the CTZ and does not cross BBB and less likely to cause central effects than metaclopromide not indicated in under 12s.

Metaclopromide HCL- Acts on gastric SM stimulating gastric emptying. Antagonises 5HT3-R being phased out by more effective 5HT3-As

Question 25

5HT3-RAs

Answer 25

The antiemetic action is restricted to emesis caused by vagal stimulation.
- Emetic stimuli - motion sickness are poorly controlled
- No effect on GI motility but may slow colonic transit
Explain - ondansetron

Question 26

NK1-RAs

Answer 26

I.V. substance P causes vomiting
- aprepitant- highly selective NK1-RA that crosses the BBB and occupies brain NK1-R
- fosaprepitant IV is converted to aprepitant in 30mins after infusion