Antiemetic drugs

Question 1

Give 5 main uses of antiemetic drugs.

Answer 1

1) Motion sickness
2) Postoperative vomiting
3) Drug induced vomiting
4) Cytotoxic drug induced vomiting
5) Pregnancy induced vomiting

Question 2

1) Name the P drug that is an antihistamine which can also act as an antiemetic.
2) What type of drug is the P drug hyoscine?
3) Name 2 antiemetic P drugs which are dopamine receptor antagonists.

Answer 2

1) Cyclizine.
2) Antimuscarinic.
3) Metoclopramide and Prochlorperazine

Question 3

1) Which P drug is anantiemetic is a 5-HT3 receptor antagonist?
2) What class of drug is the P drug aprepitant?
3) Name a P drug which is a cannabinoid and also works as an antiemetic.
4) Name a P drug which is a corticosteroid and also an antiemetic.

Answer 3

1) Ondansetron
2) Neurokinin-1 receptor antagonist.
3) Nabilone
4) Dexamethasone.

Question 4

Give the main common clinical indication for the use of D2 receptor antagonists.

Answer 4

Prophylaxis and treatment of nausea and vomiting in a wide range of conditions, but particularly in the context of reduced gut motility.

Question 5

Give 4 stimuli which can trigger nausea and vomiting.

Answer 5

1) Gut irritation
2) Drugs
3) Motion and vestibular disorders
4) Higher stimuli (sights, smells, emotions)

Question 6

Name 4 inputs to the vomiting centre in the medulla

Answer 6

1) Chemoreceptor trigger zone
2) Solitary tract nucleus
3) Vestibular system
4) Higher neurological centres

Question 7

1) What is the solitary tract nucleus innervated by?
2) What is the main receptor in the Chemoreceptor trigger zone?
3) What is the chemoreceptor trigger zone responsible for?

Answer 7

1) The vagus nerve
2) D2 receptor.
3) The chemoreceptor trigger zone is responsible for sensing emetogenic substances in the blood (e.g. drugs).

Question 8

1) What is the function of Dopamine in the gut?
2) What type of effect do drugs that block D2 receptors have?
3) Name 2 antiemetics which are D2 receptor antagonists.

Answer 8

1) It promotes relaxation of the stomach and lower oesophageal sphincter and inhibits gastroduodenal coordination.
2) They have a prokinetic effect.
3) Metoclopramide and Domperidone.

Question 9

1) What does the prokinetic effect of D2 receptor antagonists promote?
2) Why are D2 receptor antagonists effective in nausea and vomiting?
3) What is the most common side effect of D2 blocking antiemetics?

Answer 9

1) The prokinetic effect promotes gastric emptying which contributes to the antiemetic effect of D2 receptor antagonists.
2) Due to CTZ stimulation (e.g. due to drugs) and reduced gut motility (due to opioids or diabetic gastroparesis).
3) Diarrhoea.

Question 10

1) Why does Domperidone still work as an antiemetic even though it doesn’t cross the blood brain barrier?
2) Who should D2 receptor antagonists not be used in?
3) In who are D2 receptor antagonists contraindicated in?

Answer 10

1) Because the chemoreceptor trigger zone is largely outside the blood-brain barrier.
2) Children and young adults because extrapyramidal side effects are more common.
3) Patients with GI obstruction and/ or perforation due to the prokinetic effects.

Question 11

1) What is the starting dose for both Metoclopramide and Domperidone?
2) How can Metoclopramide and Domperidone be administered?
3) Aside from for nausea and vomiting, what else can Metoclopramide be used for?

Answer 11

1) 10mg, up to 3 times daily.
2) Metoclopramide can be administered PO/IM/IV and Domperidone can be administered PO/ rectally.
3) Metoclopramide can also be used for GORD due to its effects on the lower oesophageal sphincter and gastric emptying.

Question 12

1) What might a typical prescription of Cyclizine be?
2) How can cyclizine be administered?
3) What is the suggested route of administration for cyclizine?
4) What is an alternative and effective treatment to cyclizine for motion sickness?

Answer 12

1) 50mg 8-hourly as required.
2) PO, IV or IM (no dosage adjustment required when switching between routes).
3) PO and if not slow IV injection (as IM injections are painful and rapid IV injections are unpleasant).
4) Hyoscine hydrobromide.

Question 13

1) Name 3 antiemetics which are H1 receptor antagonists.
2) What is the main common clinical indication for the use of H1 receptor antagonists?
3) Where do H1 and muscarinic (ACh) receptors predominate?

Answer 13

1) Cyclizine, Cinnarizine, Promethazine.
2) Prophylaxis and treatment of nausea and vomiting, particularly in the context of motion sickness and vertigo.
3) In the vomiting centre and in its communication with the vestibular system.

Question 14

1) Which receptors do cyclizine and similar drugs block?
2) When are H1 receptor antagonists particularly useful and why?
3) What is the most common adverse effect of H1 receptor antagonists?

Answer 14

1) Both H1 and muscarinic receptors.
2) When there is nausea and vomiting associated with motion or vertigo (they are useful for a wide range of conditions).
3) Drowsiness.

Question 15

1) Why is cyclizine the more preferred drug in the H1 receptor antagonist class?
2) What side effects may H1 receptor antagonists cause due to their anticholinergic effects?

Answer 15

1) Because it is the least sedating drug in the H1 receptor antagonist class.
2) A dry throat and/or mouth.

Question 16

1) When might the dry throat and mouth side effects of H1 antagonists be beneficial?
2) What side effect might H1 antagonists cause after IV injection?
3) In who should H1 antagonists be avoided due to their sedating effect?

Answer 16

1) In patients with copious mucosal secretions.
2) Palpitatons caused by transient tachycardia.
3) They should be avoided in patients at risk of hepatic encephalopathy due to their sedating effect.

Question 17

1) Aside from those with hepatic encephalopathy, who else shouldn’t be given H1 antagonists?
2) When might the sedative effects of H1 antagonists be greater?
3) When might the anticholinergic effects of H1 antagonists be more pronounced?

Answer 17

1) Should be avoided in patients susceptible to anticholinergic side effects, such as those with prostatic hypertrophy (who may develop urinary retention).
2) When they are combined with other sedative drugs (e.g. BDZs or opioids).
3) In patients taking ipratropium or tiotropium.

Question 18

1) What is the main common clinical indication for the use of 5-HT3 receptor antagonists?
2) Name 2 5-HT3 receptor antagonists.

Answer 18

1) Prophylaxis and treatment of nausea and vomiting, particularly in the context of general anaesthesia and chemotherapy.
2) Ondansetron and Granisetron.

Question 19

1) Where is a high density of 5-HT3 receptors found?
1a) What are the 5-HT3 receptors here responsible for?
2) What is the relationship between serotonin and the gut?

Answer 19

1) In the CTZ.
1a) Sensing emetogenic substances in the blood (e.g. drugs).
2) Serotonin is the key neurotransmitter released by the gut in response to emetogenic stimuli.

Question 20

1) What happens when 5-HT3 receptors are acted upon in the gut?
2) In which cases are 5-HT3 receptor antagonists useful?
3) What are 5-HT3 antagonists not effective in?
4) What is serotonin not involved in?

Answer 20

1) Serotonin acts on 5-HT3 receptors, stimulating the vagus nerve which activates the vomiting centre via the solitary nucleus.
2) They are effective against N+V due to CTZ stimulation (e.g. drugs) and visceral stimuli (gut infection/ radiotherapy).
3) They are not effective in motion sickness.
4) It is not involved in communication between the vestibular system and the vomiting centre.

Question 21

1) 5-HT3 antagonists should be avoided in patients taking which drugs?
2) What is a typical starting dose for Ondansetron?
3) What are higher doses of ondansetron typically reserved for?
4) What are the routes of administration available for Ondansetron?

Answer 21

1) Drugs that can prolong the QT interval (e.g. antipsychotics, quinine and SSRIs).
2) 4-8mg 12 hourly (PO/IV)
3) Chemotherapy induced nausea and vomiting.
4) PO/ IV/ IM/ rectal.

Question 22

1) If oral/ rectal routes of administration are not possible, what route of administration would be preferred?
2) When Ondansetron is used to prevent nausea, how long before symptoms are anticipated should oral doses be taken?
2a) How about intravenous doses?

Answer 22

1) The IV route would be preferable as IM injections are painful.
2) An hour before symptoms are anticipated.
2a) Intravenous doses can be given immediately before the treatment or procedure.

Question 23

1) Name 3 adverse effects of 5-HT3 receptor antagonists.
2) Describe an effect that 5-HT3 antagonists can have on the heart.
2a) Therefore, in whom should 5-HT3 antagonists be avoided?

Answer 23

1) Constipation, diarrhoea and headaches (although, adverse effects are rare with 5-HT3 antagonists).
2) There is a small risk that they may prolong the QT interval (however this is only usually evident at high doses - E.G. >16mg).
3) In patients with a prolonged QT interval (if in doubt, review an ECG before prescribing).