Antiemitics

Question 1

What are the three classes of antiemitic?

Answer 1

D2 receptor antagonists (metoclopramide and domperidone)

H1 receptor antagonists (cyclizine, cinnarizine, promethazine)

Serotonin 5-HT3-receptor antagonists (ondansetron, granisetron)

Question 2

What are the inputs that act on the comitting centre in the medulla?

Answer 2

Chemoreceptor trigger zone (CTZ)

Solitary tract nucleus (which is innervated by the vagus nerve), Vestibular system

Higher neurological centres

Question 3

What are the causes of nausea and vomitting?

Question 4

What are the two mechanisms of action for D2 receptor antagonists?

Answer 4

Inhibits activity of the chemoreceptor trigger zone which senses emetogenic substances in the blood.

Is prokinetic - therefore is useful in the context of opiods and diabetic gastroporesis

Question 5

What are the important adverse effects of D2 receptor antagonists?

Answer 5

Diarrhoea

Metoclopramide can induce extrapyramidal syndromes such as acute dystonic reactions (occulogyric crisis)

Domperidone tends not to cause extrapyramidal symptoms because it does not cross the blood–brain barrier (note that the CTZ is largely outside the blood–brain barrier). Domperidone is associated with an increased risk of QT-interval prolongation and arrhythmias.

Question 6

How long can metoclopromide be prescribed for?

Answer 6

To reduce the risk of extrapyramidal effects, metoclopramide should be prescribed for no more than 5 days

Question 7

Which patients should not be prescribed metoclopramide?

Answer 7

It should be avoided in neonates, ▴children and ▴young adults, who are at increased risk of adverse effects

Question 8

What are the contraindications of domperidone?

Answer 8

Domperidone is contraindicated in patients with ✗cardiac conduction abnormalities and severe ▴hepatic impairment.

Question 9

What bowel problems would contraindicate the use of D2 receptor antagonists?

Answer 9

Both drugs are avoided in ▴intestinal obstruction and ✗perforation their prokinetic effects

Question 10

Which D2 receptor antagonist can be used in parkinsons?

Answer 10

Domperidone because it does not cross the BBB

Question 11

What are the important drug interactions for metoclopramide?

Answer 11

Antipsychotics = worsen EPSE

Parkinsons dopaminergic agents = will cancel out the effects

Question 12

What are the drug interactions for domperidone?

Answer 12

Domperidone should not be prescribed alongside other drugs that prolong the QT interval, such as antipsychotics, quinine and selective serotonin reuptake inhibitors or those which inhibit cytochrome P450 (CYP) inhibitors (e.g. amiodarone, diltiazem, macrolides, fluconazole, protease inhibitors) as these may increase the risk of adverse effects. If in doubt, check the BNF.

Question 13

What antibiotic has good prokinetic properties and may be used in alternation with d2 receptor antagonists?

Answer 13

Despite general recommendations to limit duration of D2-receptor antagonist therapy, patients with gastroparesis may require long-term prokinetic treatment (i.e. greater than 5 days). To minimize exposure to metoclopramide, it should be used at the lowest effective dose (e.g. 5 mg 8-hrly). It may be alternated with erythromycin, which also has prokinetic properties

Question 14

What are the indications of H1 receptor antagonists?

Answer 14

Prophylaxis and treatment of nausea and vomiting, particularly in the context of motion sickness or vertigo. Other drugs in this class are used in the treatment of allergies

Question 15

What type of receptors predomiate the vomiting centres and the vestibular system?

Answer 15

H1 and acetylcholine

Drugs such as cyclizine block both of these receptors

Question 16

What are the adverse reactions of H1 receptor antagonists?

Answer 16

Drowsiness (cyclizine is the least sedating)

Due to their anticholinergic effects they may cause dry throat and mouth.

After IV injection they may cause transient tachycardia, which the patient may notice as palpitations. Along with their central anticholinergic effects (excitation or depression) this may make for a rather unpleasant experience.

Question 17

What are the contraindications for H1 receptor antagonists?

Answer 17

Due to their sedating effect, these drugs should be avoided in patients at risk of ▴hepatic encephalopathy. They should also be avoided in patients susceptible to anticholinergic side effects, such as those with ▴prostatic enlargement (who may develop urinary retention).

Question 18

What are important drug interactions for H1 receptor antagonists?

Answer 18

Sedation may be greater when combined with other sedative drugs (e.g. benzodiazepines, opioids). Anticholinergic effects may be more pronounced in patients taking ipratropium or tiotropium.

Question 19

What is the typical cyclizine prescription?

Answer 19

A typical prescription might be for cyclizine 50 mg 8-hrly as required. It may be given orally, IV or IM; no dosage adjustment is required when switching between routes. The route of administration, and whether it is prescribed on a regular or as-required basis, depends on the clinical situation. For example, the oral route is clearly inappropriate for a patient who is actively vomiting. As IM injections are painful and rapid IV injections are unpleasant (see Adverse effects), we would suggest that slow IV injection is the best choice when oral administration is inappropriate.

Question 20

What are the indications for 5HT3 receptor antagonists?

(ondansetron and granisetron)

Answer 20

Prophylaxis and treatment of nausea and vomiting, particularly in the context of general anaesthesia and chemotherapy.

Question 21

How to 5-HT3 antagonists work to prevent nausea and vomitting?

Answer 21

There is a high density of 5HT3 receptors in the chemoreceptor trigger zone. Therefore 5HT3 receptor antagonists inhibit the activation of the CTZ.

5HT is released by the gut in response to emetogenic stimuli. 5HT then acts on the 5HT3 receptors on the vagus nerve. The solitary tract nucleus is then activated by the vagus nerve that feeds into the vomitting centre in the medulla. Antagonists of 5HT therefore limit this process.

5HT is not involved in the communication between the vestibular system and the vomitting centre, therefore these are not effective for motion sickness.

Question 22

What are the adverse effects of ondansetron

Answer 22

Adverse effects are rare with these medications, although constipation, diarrhoea and headaches can occur.

Question 23

What are the warnings for ondansetron?

Answer 23

There is a small risk that 5-HT3 antagonists may prolong the QT interval, although this is usually evident only at high doses (e.g. >16 mg ondansetron). Nevertheless, they should be avoided in patients with a ▴prolonged QT interval. If there is clinical suspicion, review an ECG before prescribing.

Question 24

What are the important drug interactions by ondansetron?

Answer 24

Avoid 5-HT3 antagonists when patients are taking ▴drugs that prolong the QT interval, such as antipsychotics, quinine and selective serotonin reuptake inhibitors. If in doubt, check the BNF

Question 25

What is the typical starting dose for ondansetron 12hourly?

Answer 25

4-8mg

Question 26

Morning sickness is an unpleasant manifestation of early pregnancy that can be severe enough to require hospitalisation. It can be difficult to treat as drugs administered during the first trimester of pregnancy may cause spontaneous abortion and fetal abnormalities. Although ondansetron is not licensed for morning sickness, a retrospective study of 608,385 women in Denmark found no evidence of adverse fetal outcomes related to taking ondansetron in pregnancy. Ondansetron may therefore be an option for severe morning sickness (e.g. hyperemesis gravidarum) where the benefits outweigh potential risks.