Antiemetics - D2 receptor antagonist

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

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
• stimulates vomiting centre directly
• 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

• this is why D2 antagonist such as Metoclopramide and Chlropromazine are NOT indicated in motion sickness as no effect

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
- neuroendocrinologies 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 (labyrinth in ear)
2 - vagus nerve (from GIT)
3 - chemoreceptor trigger zone
4 - higher centres (sensory)
5 - all of the above

Answer 12

5 - all of the above

Question 13

Which 2 of the following are the core dopamine D2 receptor antagonists drugs we need to know?

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

Answer 13

1 - Metoclopramide
2 - Chlorpromazine

Question 14

What is the mechanism of action of Metoclopramide and Chlorpromazine?

1 - inhibit sensory information from reaching the vestibular nuclei
2 - inhibit D2 dopamine receptors on the vestibular nuclei
3 - inhibit D2 dopamine receptors of the vomiting centre
4 - inhibit D2 dopamine receptors on on chemoreceptor trigger zone (CRZ) and in peripheral tissue (GIT)

Answer 14

4 - inhibit D2 dopamine receptors on on chemoreceptor trigger zone and in peripheral tissue (GIT)

• D2 dopamine receptors are the main receptor on the CRZ

Question 15

Metoclopramide and Chlorpromazine are core dopamine D2 receptor antagonists. These 2 drugs are indicated in all of the following conditions EXCEPT which one?

1 - nausea and vomiting
2 - motion sickness
3 - acute migraine induced nausea and vomiting
4 - delayed chemotherapy induced nausea and vomiting

Answer 15

2 - motion sickness
- no interaction with vestibular nuclei

• especially in reduced gut motility
• used for a variety of reasons, including, cytotoxic drugs, radiation and postoperatively

Question 16

Metoclopramide and Chlorpromazine are core dopamine D2 receptor antagonists are indicated in nausea and vomiting, specifically related to poor gut motility. Why are these drugs good for this?

1 - acts centrally and peripherally increasing gut motility
2 - dopamine D2 receptor has a maximal effect on the vagal nerve
3 - dopamine D2 receptor is particularly sensitive to cytotoxic drugs
5 - dopamine D2 receptor is effective at inhibiting the vestibular nuclei

Answer 16

1 - acts centrally and peripherally increasing gut motility

• metoclopramide especially has prokinetic effects as it is augmented with enteric 5-HT3
• metoclopramide inhibits presynaptic and postsynaptic D2 receptors and antagonism of presynaptic inhibition of muscarinic receptors. Acetylcholine is released promoting relaxation of the stomach and lower oesophageal sphincter, and good in opioid induced constipation
• inhibits gastroduodenal co-ordination

Question 17

All of the following are adverse events of Metoclopramide and Chlorpromazine, but which is most common?

1 - extrapyramidal effects
2 - diarrhoea
3 - prolactin release
4 - galactorrhoea
5 - menstruation dysfunction

Answer 17

2 - diarrhoea

• extrapyramidal effects are similar to first generation antipsychotic drugs

Question 18

Metoclopramide and Chlorpromazine should be avoided in all of the following EXCEPT which one?

1 - paediatrics
2 - perforation
3 - obstruction
4 - parkinsons disease
5 - AF

Answer 18

5 - AF

• SHOULD NOT be prescribed alongside anti-psychotic drugs due to risk of extrapyramidal effects

Question 19

Due to the adverse effects, Metoclopramide and Chlorpromazine should only be used short term, over what period?

1 - 24h
2 - 48h
3 - 5-7 days
4 - 2 weeks

Answer 19

3 - 5-7 days

• symptoms should be absent when completed, but monitor for extrapyramidal effects
• occasionally needed longer term (gastroparesis) so drug holidays are a good idea

Question 20

What are the typical starting doses for these drugs?

1 - 1 mg/8 hours as required
2 - 4 mg/8 hours as required
3 - 10 mg/8 hours as required
4 - 50 mg/8 hours as required

Answer 20

3 - 10 mg/8 hours as required
- given orally typically, but can be given via IV and IM

Question 21

Spasmodic torticollis, also called Cervical dystonia, is a side effect of which antiemetic drug?

A. Aprepitant
B. Cyclizine
C. Metoclopramide
D. Nabilone
E. Ondansetron

Answer 21

C. Metoclopramide

Question 22

A patient is recently diagnosed as having Parkinson disease. Which antiemetic drug is contraindicated in this patient?

A. Aprepitant
B. Cyclizine
C. Metoclopramide
D. Ondansetron
E. Scopolamine

Answer 22

C. Metoclopramide

• D2 receptor antagonist
• Parkinson has degeneration of dopamine neurons.
• giving metoclopramide will block D2 receptors leading to decrease availability of D2 receptors on which dopamine require to act.