Nausea and vomiting

Question 1

What’s anticipatory nausea and vomiting?

Answer 1

• usually associated with chemotherapy
• N/V occurs before a new chemotherapy cycle in response to conditioned stimuli such as smells, sights and sounds of the treatment room etc
• it is when a person has experienced N/V related to chemo

Pathophysiology: generated by the cerebral cortex through the fear and anxiety related to the memory of previous experience

Question 2

What’s regurgitation?

Answer 2

Regurgitation → backflow of fluid in the body

• usually across partially or wholly failing valve mechanism
• it can happen passively (e.g. when pressure on the stomach is applied)

Question 3

What’s expectoration?

Answer 3

Expectoration → to expel secretions from the lungs (ie coughing up)

• secretions in the back of the throat can trigger a gag reflex and make someone nauseated or to vomit (therefore may be confused with actual vomiting)

Question 4

What’s the vomiting centre?

Type of receptors

Answer 4

Medulla Oblongata

• muscarinic receptors in the medulla oblongata
• when they are stimulated → vomiting reflex

Question 5

What other (4) parts send the signals to the medulla oblongata and stimulate vomiting reflex?

+ their receptors

Answer 5

• vestibular nuclei (cochlear)→ muscarinic and histamine receptors
• chemoreceptor trigger zone → 5HT receptor, Dopamine 2 receptor
• higher brain centres → muscarinic receptors, D2 (triggered by repulsive vomiting)
• peripheral (GI &Viscera) → enterochromaffin cells in the stomach (5HT receptors)

*all these stimulate vomiting reflex

Question 6

What cancers metastasise to the brain?

Answer 6

• breast
• lung
• melanoma

Question 7

Metoclopramide

• class
• receptors it acts on
• SEs

Answer 7

Metoclopramide

Class: Prokinetic agent

Receptors: D2 & 5HT4 & 5HT3

SEs:

• can cause colic
• parkinsonian features
• oculogyric crisis (especially in kids and youth, so don’t prescribe)

Question 8

Domperidone

• class
• receptors it acts on
• contraindication

Answer 8

Domperidone

Class: prokinetic agent

Receptors: D2

Contraindication: not in HF as it is cardiotoxic

Question 9

Haloperidol

• class
• receptors it acts on
• SEs
• contraindications

Answer 9

Haloperidol

Class: butyrophenone

Receptor: D2

Haloperidol is good n nausea and vomiting but also with confusion (as it has a sedating effect)

SEs: extrapyramidal side effects, sedation, prolong QT

Contraindications: cardiac problems (cytotoxic) Parkinson disease and above

Question 10

Cyclizine

• class
• receptors it acts on
• SEs

Answer 10

Cyclizine

Class: antihistamine

Receptors: H1 and muscarinic cholinergic

SEs: constipation, irritation at SC site

Question 11

Levomepromazine

• class
• receptors it acts on
• SEs

Answer 11

Levomepromazine

Class: Phenothiazine

Receptors: H1 & 5HT2 & muscarinic & D2

*used often as it acts on broad-spectrum receptors (as antagonist)

SEs: drowsiness at higher doses, constipation, anti-muscarinic (but all these are milder due to broad spectrum action)

Question 12

Ondansetron

• class
• receptors it acts on
• SEs

Answer 12

Ondansetron

Class: 5HT3 antagonist

Receptors: 5HT3

• It acts on gut specific receptors
• Good for chemotherapy induced nausea

SEs: constipation

Question 13

Lorazepam

class

receptors

indicaiton

Answer 13

Lorazepam

Class: benzodiazepine

Receptor: GABA

Indication: for anxiety/ anticipatory nausea

Question 14

What drug and why do we commonly prescribe with cyclizine SC?

Answer 14

small amount of dexamethasone to minimise injection site irritation

Question 15

Antibiotics commonly cause nausea?

Answer 15

• Flucloxacillin
• Clarithromycin
• Metronidazole (with alcohol)

Question 16

Diet advise in N/V

Answer 16

• eat little and often (rather than large meals)
• carbs are better tolerated (fats and proteins delay gastric emptying)

Question 17

Can we use metoclopramide + cyclizine?

Answer 17

No, as they have antagonistic effects

Question 18

Chemical causes of N/V (3)

Answer 18

• Drugs → e.g. opiates, antibiotics, chemotherapy
• Toxins → e.g. ischaemic bowel, tumour products
• Metabolic → organ failure, electrolyte imbalance, ketoacidosis

Question 19

GI-related causes of N/V (4)

Answer 19

• Pharyngeal irritation → Herpes, Candida, excess of sputum
• Gastric stasis → anticholinergics/ opiates, mechanical resistance (ascites, organomegaly)
• Stretch of GI tract → constipation, mesenteric mets
• other GI irritation → e.g. reflux

Question 20

Cranial causes of N/V

Answer 20

• raised ICP → cerebral primary or mets, intracranial bleeding
• meningism → inflammation, irritation by tumour, cerebral infections

Question 21

Other (2) causes of N/V

Answer 21

• movement associated → vestibular, visceral distortion, motion sickness
• anxiety and anticipatory

Question 22

Common reversible causes of N/V + their management

Answer 22

• severe pain → good pain control
• infection → antibiotics
• cough → treat underlying cause/opioids and antitussives
• hypercalcaemia → rehydration and IV bisphosphonates
• gastric irritation → stop irritant drugs (e.g. NSAIDs, use of PPI/H2 antagonists)
• oropharyngeal candida→ nystatin/ fluconazole and good mouth care
• constipation → laxatives, rectal measures, altering constipating meds
• tense ascites → consider paracentesis
• raised ICP → use corticosteroids
• emetogenic drugs → stop or reduce dose
• anxiety → pharmacological and psychological meanagement

Question 23

Features of vomiting due to gastric stasis

Answer 23

• large volume of vomits
• infrequent vomiting
• relief of symptoms after vomiting
• also: oesophageal reflux, epigastric fullness, early satiety, hiccups

Question 24

Symptoms of N/V due to gastric outflow obstruction

Answer 24

• symptoms similar to gastric stasis e.g. large volume of vomits, relieve after vomiting
• forceful vomiting
• rapid dehydration

Question 25

'***Squashed stomach syndrome'*** - whats that - feature of N/V due to this

Answer 25

***'Squashed stomach syndrome'*** → reduction in the gastric cavity by tumour or external compression Symptoms: * infrequent vomiting * relief after vomits * low volume vomits

Question 26

Symptoms of N/V due to ***oesophageal blockage***

Answer 26

* vomiting soon after eating/ drinking * vomits consist of what has just been swallowed * sensation of food sticking

Question 27

Symptoms of N/V due to **bowel obstruction**

Answer 27

* intermittend nausea (often relieved by vomiting) * worsening nausea * faeculant vomit as obstruction progresses * abdominal pain (may be colicky) * abdominal distention (may be absent if obstruction is high)

Question 28

Symptoms of N/V due to **increased ICP**

Answer 28

* efortless vomiting (often in the morning) * vomiting may be associated with headache and papilloedema \*neurological signs e.g. photophobia may be absent

Question 29

Symptoms of N/V associated with: * motion - associated emesis * chemically induced nausea * anxiety-related nausea

Answer 29

* **motion - associated emesis** → N/V on movement * **chemically induced nausea** → constant nausea, variable vomiting * **anxiety-related nausea** → may be triggered by a previously experienced stimulus; relieved by distraction

Question 30

What types of drinks to have in N/V?

Answer 30

* **cool** rather than hot * **fizzy** rather than still (except when in obstruction) * **citrus flavoured** (possibly are better tolerated)

Question 31

Drugs used in management of N/V due to gastritis, gastric stasis, bowel obstruction (due to peristaltic failure)

Answer 31

**Prokinetic anti-emetics** * metoclopramide * domperidone Alternatives: Ondansetron, cyclizine

Question 32

Drugs used in the management of N/V due to chemicals (drug, toxins metabolic causes)

Answer 32

Anti-emetics acting principally on chemoreceptor trigger zone * *Haloperidol* * *Ondansetron*

Question 33

Drugs used in the management of N/V due to **raised ICP** or **vestibular symptoms**

Answer 33

**Anti-emetic acting peripherally in the vestibular system and vomiting centre** * *Cyclizine* * \*Add dexamethasone due to irritation of the skin in SC route*

Question 34

Which anti-emetic to use when the cause of vomiting is unknown or if the anti-emetics specific for identified cause (e.g. metoclopramide for gastric stasis) failed?

Answer 34

Broad-spectrum anti-emetics ***Levomepromazine***

Question 35

What other anti-emetics we can add to levomepromazine (broad-spectrum) when any other therapy fails?

Answer 35

* **Levomepromazine + 5HT3 antagonist** (e.g. ondansetron) * **Levemepromazine + benzodiazepine** (e.g. lorazepam or midazolam) * **Levomepromazine + dexamethasone** (stop dexamethasone if no benefit after one week)

Question 36

What two anti-emetics can worsen constipation?

Answer 36

* 5HT3 antagonists → ***ondansetron*** * anticholinergics → e.g. ***cyclizine, hyoscine butylbromide/hydrobromide***

Question 37

***Nabilone*** ***-*** MoA - when to use?

Answer 37

***Nabilone*** ## Footnote **MoA**: cannabinoid drug; central actions at the level of the cerebral cortex **Use:** potentially helpful in managing intractable N/V uncontrolled by other drugs

Question 38

***Aprepitant*** ## Footnote - MoA - when to use

Answer 38

***Aprepitant*** ## Footnote **MoA**: Neurokinin-1 (substance P) receptor antagonist **Use**: given 1 hour prior first dose of chemotherapy