Cancer Care - N&V prescribing

Question 1

Which stimuli trigger the vomiting center? What receptors are found in the vomiting center?

Answer 1

Stimuli: excitatory stimulus from CTZ, vestibular system and autonomic afferents from the gut viscera and from higher centres within the brain

Receptors present

• H1
• ACh (m)
• 5-HT2

Question 2

What stimuli trigger the chemoreceptors trigger zone? What receptors are present there?

Answer 2

-Stimuli: drugs, toxins and metabolites

Receptors

• Nk1
• D2 (dopamine)
• 5-HT3

Question 3

What stimuli trigger the cerebral cortex? What receptors are present?

Answer 3

Stimuli:

• Anxiety (multiple receptors in cortex)
• Raised ICP (meningeal mechanoreceptors and ACh m and H1)

Question 4

What stimuli target the VIII nucleus? What receptors are present

Answer 4

Stimuli: mechanical gut and serosal distortion and raised ICP - ACh (m) and H1

Question 5

Git and serosal surfaces: What type of receptor do drugs and radiotherapy trigger?

Answer 5

-5-HT3

Question 6

Haloperidol: mechanism of action and uses

Answer 6

• Mainly act on D2 receptors in CTZ, is effective against biochemical/metabolic causes of nausea.
• Good for opioid induced nausea and vomiting
• Example of biochemical nausea: hypercalcemia, renal impairment, hepatic impairment, tumour toxins, sepsis
• Good for persistent, severe nausea unrelieved by vomiting, aggravated by sight/smell of food, drowsiness/confusion

Question 7

Metoclopramide: mechanism of action and uses

Answer 7

• Acts on D2 and 5HT3 receptors in CTZ - pro kinetic to block dopamine D2 receptors in gut and improve gastric emptying.
• Good for chemical nausea (2nd line after haloperidol) and delayed gastric emptying
• Causes of gastric stasis: pyloric tumour/nodes, as cites, hepatomegaly, opioids, Anticholinergics, autonomic neuropathy.

Question 8

Which two anti-emetics should you never prescribe together?

Answer 8

-Do not give prokinetics (eg metoclopramide) with an anti-muscarinic (cyclising, hyoscine) because antimuscaric drugs competitively block the action of prokinetics

Question 9

Give an important side effect of metoclopramide. How do you stop this reaction? Which drug is less likely to cause this reaction?

Answer 9

• Can induce acute dystonic reactions: facial and skeletal muscle spasms and oculogyric crises.
• Generally within a few days of starting treatment and stop within 24h of stopping drug
• Injection of procyclidine (5-10mg IV or IM) will aboard dystonic attack
• Domperidone doesn’t cross BBB as easily so is less likely to cause acute dystonic reaction

Question 10

What is the mechanism of action of domperidone?

Answer 10

• D2 receptor antagonist and 5 HT3 receptor antagonist

- Used as 2nd line for nausea caused by gastric stasis

Question 11

What is the mechanism of action of cyclizine, what is its use?

Answer 11

-Active H1 antagonist and ACh m receptor antagonist
Uses:
-for movement related/vestibular disturbnce nausea and vomiting
-Bowel obstruction
-Raised ICP

Question 12

What is the target of ondansetron? When is it useful? Name an important side effect

Answer 12

-5 HT3 receptor antagonist - good against serotonin release post radiotherapy or post-operatively

Question 13

What anti-emetic would you give for a chemical cause of nausea?

Answer 13

• Haloperidol (1st line)

- Metoclopramide

Question 14

How would you treat CNS mets induced nausea (raised ICP, nausea worse in morning, projectile vomiting)

Answer 14

• Cyclizine

- Dexamethasone: reduced peritumoural oedema

Question 15

How would you treat gastric stasis induced nausea

Answer 15

• Metoclopramide

- Domperidone

Question 16

How would you treat nausea from an abdominal/pelvic tumour

Answer 16

-Cyclizine: blocks H1 receptors and AChm receptors frosts in vomiting center that receive inputs from viscera

Question 17

How would you treat nausea from functional bowel obstruction (regurgitation, forceful vomiting of undigested foot, faeculant vomits)

Answer 17

• Cyclizine 1st line: acts centrally on vomiting centre and also inhibitors vagar afferents from distended bowel behind the obstruction. It isn’t prokinetic so will not make the obstruction worse
• Dexamethasone
• NG tube
• Do not proscribe a prokinetic for bowel obstruction

Question 18

How would you treat nausea caused by psychological factors (anxiety, feat, anticipation)

Answer 18

• Non drug methods

- Benzodiazepines

Question 19

How would you treat nausea caused by constipation?

Answer 19

• Prokinetic: metoclopramide and domperidone

- Laxatines