Antiemetics - 5-HT3 receptor antagonists

Question 1

Where in the brain is the vomiting centre and chemoreceptor trigger zone located?

1 - hypothalamus
2 - midbrain
3 - pons
4 - medulla oblongata

Answer 1

4 - medulla oblongata

• when stimulated the vomiting centre coordinates the vomiting response

Question 2

The chemoreceptor trigger zone (CTZ) is sensitive to specific stimuli. Which of the following is NOT a receptor located on the CTZ?

1 - 5-HT3 (serotonin)
2 - D2 dopamine
3 - opioid (mu, kappa)
4 - neurokinin-1 (NK1)
5 - GABA

Answer 2

5 - GABA

• these receptors detect emetic agents
• the CTZ then stimulates the vomiting centre

Question 3

Is the chemoreceptor trigger zone (CTZ) located inside or outside the blood brain barrier?

Answer 3

• outside
• important as the CTZ has a high density of 5HT3 receptors able to sense emetic substance that may otherwise not be able to cross the BBB

Question 4

In addition to the vomiting centre and chemoreceptor trigger zone, the 3rd part of the vomiting response is called the vestibular nuclei. Where is this located in the brain?

1 - pons
2 - midbrain
3 - medulla
4 - cerebellum

Answer 4

1 - pons

• receives input from the labyrinth in the inner ear
• this is where motion sickness comes from

Question 5

Which 2 of the following type of receptors are located on the vomiting centre?

1 - 5-HT3 (serotonin)
2 - D2 dopamine
3 - histamine H1 receptors
4 - muscarinic receptors

Answer 5

3 - histamine H1 receptors
4 - muscarinic receptors

Question 6

What type of receptors are located on the vestibular nuclei that are able to receive stimulus from the labyrinth of the inner ear?

1 - 5-HT3 (serotonin)
2 - D2 dopamine
3 - histamine 1 receptors
4 - muscarinic receptors

Answer 6

3 - histamine 1 receptors
4 - muscarinic receptors

Question 7

What is the normal communication pathway between the vomiting centre (VC), chemoreceptor trigger zone (CTZ), and the vestibular nuclei (VN)?

1 - VC to VN to CTZ
2 - CTZ to VN to VC
3 - VN to CTZ to VN or CTZ to VC

Answer 7

3 - VN to CTZ to VN or CTZ to VC

Question 8

Our senses can trigger a vomiting reflex, which is trigger in the higher brain centres. Once stimulated which of the following do they stimulate to initiate vomiting?

1 - vomiting centre (VC)
2 - chemoreceptor trigger zone (CTZ)
3 - vestibular nuclei (VN)?

Answer 8

1 - vomiting centre (VC)

Question 9

Which cells in the stomach are able to detect cytotoxic or other potentially dangerous products?

1 - parietal cells
2 - enterochromaffin like cells
3 - chief cells
4 - mucous cells

Answer 9

2 - enterochromaffin like cells

Question 10

The enterochromaffin like cells of the stomach are able to detect cytotoxic or other potentially dangerous products in the stomach. What neurotransmitter are these cells able to release that ultimately will stimulate the vomiting centre?

1 - 5-HT3 (serotonin)
2 - dopamine
3 - glutamate
4 - GABA

Answer 10

1 - 5-HT3 (serotonin)

• specifically stimulates the vagus nerve

Question 11

During a vomiting response, which of the follow occurs?

1 - lower oesophageal sphincter relaxes
2 - diaphragm and abdominal muscles contract
3 - intra-abdominal pressure increases
4 - autonomic response (tachycardia)
5 - epiglottis closes (reduce aspiration)
6 - all of the above

Answer 11

6 - all of the above

Question 12

The vomiting centre co-ordinates the vomiting response. Which of the following pathways converge and stimulate the vomiting centre to elicit a vomiting response?

1 - vestibular system
2 - vagus nerve
3 - chemoreceptor trigger zone
4 - higher centres (sensory)
5 - all of the above

Answer 12

5 - all of the above

Question 13

Which of the following is the core 5-HT3 (serotonin) receptor antagonists drug we need to know?

1 - Metoclopramide
2 - Chlorpromazine
3 - Ondansetron
4 - Cyclizine

Answer 13

3 - Ondansetron

Question 14

What is the mechanism of action of Ondansetron?

1 - inhibit sensory information from reaching the vestibular nuclei
2 - inhibit 5-HT3 receptors on the vestibular nuclei
3 - inhibit 5-HT3 receptors of the vomiting centre
4 - inhibit 5-HT3 receptors on on chemoreceptor trigger zone

Answer 14

4 - inhibit 5-HT3 receptors on on chemoreceptor trigger zone

• may also act on peripheral 5-HT3 receptors in GIT and vagus nerve

Question 15

Ondansetron is the core 5-HT3 (serotonin) receptor antagonists drug we need to know. This drug is indicated in nausea and vomiting due to a myriad of reasons including cytotoxic drugs, radiation and postoperatively. Why is this drug indicated in nausea and vomiting?

1 - 5-HT3 (serotonin) is the key neurotransmitter released in the GIT
2 - 5-HT3 (serotonin) has a maximal effect on the vagal nerve
3 - 5-HT3 (serotonin) is particularly sensitive to cytotoxic drugs
5 - 5-HT3 (serotonin) is effective at inhibiting the vestibular nuclei

Answer 15

1 - 5-HT3 (serotonin) is the key neurotransmitter released in the GIT

• no interaction with vestibular nuclei, so not effective in motion sickness

Question 16

All of the following are common adverse events of Ondansetron, EXCEPT which one?

1 - constipation
2 - flushing
3 - prolonged QT-interval
4 - headaches

Answer 16

3 - prolonged QT-interval

• can occur but this is rare and generally only on higher doses

Question 17

Which 2 of the following patients should not be prescribed Ondansetron?

1 - pregnant women in 1st trimester
2 - hepatic encephalopathy
3 - already have prolonged QT-interval
4 - CKD

Answer 17

1 - pregnant women in 1st trimester
- teratogen linked with cleft lip and pallate

3 - already have prolonged QT-interval

Question 18

Ondansetron should NOT be prescribed in patients taking the following drug classes, anti-psychotics, quinine and SSRIs. Why is this?

1 - accentuate the the effects of these drugs
2 - these drugs are cytochrome P450 inhibitors so could increase concentration of Ondansetron
3 - these drugs prolong QT-interval

Answer 18

3 - these drugs prolong QT-interval

Question 19

What would a standard dose of Ondansetron be?

1 - 1-2mg/12 hours as required
2 - 4-8mg/8 hours as required
3 - 20-30mg/8 hours as required
4 - 50-60mg/8 hours as required

Answer 19

2 - 4-8mg/8 hours as required

• higher doses given for chemotherapy
• can be given orally, suppository or injected, depending on the patients symptoms

Question 20

A patient is receiving highly emetogenic chemotherapy for metastatic carcinoma. To prevent chemotherapy-induced nausea and vomiting, she is likely to be treated with which of the following?

A. Levodopa
B. Methotrexate
C. Misoprostol
D. Ondansetron
E. Omeprazole

Answer 20

D. Ondansetron

The 5-HT3 receptor antagonists are highly effective at preventing chemotherapy-induced nausea and vomiting, which can be a dose-limiting toxicity of anticancer drugs. The answer is D