Antiemetics

Question 1

Difference between vomiting & regurgitation

Answer 1

Vomiting - involuntary forceful expulsion of gastric contents through mouth

Regurgitation - effortless bringing up of things that have not yet reached stomach or passive overflow stomach contents

Question 2

What’s the sequence of steps that triggers vomiting?

Answer 2

Vomiting centre in medulla signals to vomit -> 
Nausea, salivation, sweating -> 
Retrograde peristalsis -> 
deep inspiration -> 
closure of glottis (if not choke)-> 
Abdo muscles contract -> 
LOS relaxes

Question 3

What triggers the vomiting centre/ chemoreceptor trigger zone? Where is it?

Answer 3

• sensory afferents via midbrain
• vestibular nuclei (motion sickness, vertigo)
• visceral afferents from gut (mainly through vagus N)
• direct triggers (drugs/ hormones/ toxins in blood as blood side of BBB)

In medulla on floor of 4th ventricle, blood side of BBB

Question 4

How do muscarinic receptor antagonists work? Give an example. Side effects

Answer 4

Competitive blockade of muscarinic Ach receptors in vestibular nuclei + chemoreceptor trigger zone

E.g. Hyoscine hydrobromide

Uses: can’t take tablets - patch, motion sickness, bowel obstruction, good for agitation (sedation), good for diarrhoea (constipation)

Side effects (receptors all over body, part of parasympathetic NS): sedation, memory Problems, glaucoma, dry mouth & constipation

Question 5

How do H1 receptor antagonists (anti-histamines) work? Give examples. Uses and side effects.

Answer 5

Centrally - acts on vestibular nuclei, inhibits histaminergic signals from vestibular system to CTZ in medulla

E.g. cyclizine, levomepromazine, diphenhydramide

Uses: motion sickness - long plane journeys, promethazine - morning sickness

Cyclizine - not suitable for little old ladies or children <6yrs

Side effects: sedation, excitation, antimuscarinic - dry mouth, constipation, urinary retention, cardiac toxicity (long QT interval)

Question 6

How is serotonin used in the gut?

Answer 6

95% serotonin in the body is located in the gut produced by enterochromaffin cells

PS stimulation -> serotonin excites enteric neurones -> Sm contraction increases motility (except in stomach), increases gut secretions, regulates appetite

Question 7

How do 5HT3 receptor antagonists work? Give examples. Uses and side effects.

Answer 7

5HT = serotonin

Peripherally - reduces GI motility/ secretions

Centrally - inhibits CTZ

E.g. Ondansetron - common.
granesitron/ palonosetron - niche/ palliative/ oncology

Uses: good for almost everyone (often 1st line)

Side effects (uncommon): constipation, headache, elevated liver enzymes, long QT syndrome, extra pyramidal effects (dystopia, Parkinsonism)

Question 8

How does metoclopramide work? Uses and side effects.

Answer 8

D2 receptor anatagonist

Metoclopramide increases Ach at muscarinic receptors in gut -> promotes gastric emptying, increases tone LOS closes, increases tone/ amplitude gastric contractions, decreases tone pylorus opens, increases peristalsis

Uses: GORD, Ileus (normal gut movement lost e.g. post op, infection)

Side effects: galactorrhoea via prolactin release, extra pyramidal effects (dystopia, Parkinsonism)

Question 9

How does domperidone work? Uses and side effects

Answer 9

D2 receptor antagonist

Similar mechanism to metoclopramide, not used much anymore due to cardiac side effects

Uses: improving lactation breastfeeding mothers

Side effects: sudden cardiac death (long QT and VT), galactorrhoea (increases prolactin)

Question 10

D2 (dopamine) receptors antagonists acting on the CTZ, how do they work? Give examples, uses and Side effects

Answer 10

The ‘zines’ act on CTZ, May also block H1 muscarinic receptors

E.g. prochlorperazine, chlorpromazine, haloperidol

Uses: motion sickness, vertigo,
Prochlorperazine in pregnancy, haloperidol (CTZ) chemotherapy & palliation

Side effects: extra pyramidal effects (dystonia, parkinsonism), sedation, hypotension

Question 11

How do corticosteroids work to prevent vomiting? Give examples, uses and side effects

Answer 11

Act on CTZ

E.g. dexamethosone, methylprednisolone

Assumed act on CTZ, May also properties D2 receptor antagonists

Uses: perioperative nausea & vomiting, chemotherapy and palliation

Side effects: insomnia, increased appetite, increased blood sugar

Question 12

How do cannabinoids work? Give an example, uses and side effects

Answer 12

Synthetic compounds assumed to act on the CTZ

E.g. Nabilone

Good for chemotherapy as last line

Side effects: dizziness, drowsiness

Question 13

How do neurokinin 1 receptor antagonists work, give examples, uses and side effects?

Answer 13

Act on CTZ

Prevent action of substance P at CTZ and in peripheral nerves (painkillers), boosts effects of 5HT3 receptor antagonists, anxiolytic (reduces anxiety) + antidepressant properties

E.g. aprepitant, fosaprepitant, netupitant

Good for chemotherapy particularly delayed emesis

Side effects: headache, diarrhoea/ constipation, stevens- Johnson syndrome (rare, serious disorder of skin)

Question 14

Best methods to treat motion sickness?

Answer 14

Prevention is better than cure - take before journey

1st line: Hyoscine hydrobromide - sedating

If driving/ need to concentrate: connirazine - fewer side effects

Trial & error

Question 15

What are prokinetics useful for? Give examples. When should you use them?

Answer 15

Increase gut motility

E.g. Domperidone, metoclopramide

Uses: GORD, ileus (gum may help first)

Don’t use: obstruction, risk of perforation

Question 16

What should you consider trying before medication for a lot of gut pathology if they are being sick?

Answer 16

A nasogastric tube - mechanical decompression of the stomach

Question 17

What antiemetics are used normally for gut pathology bar prokinetics?

Answer 17

1st ondansetron (5HT3 receptor antagonist)

&/ or cyclizine (H1 R antagonist - not old ladies/ children)

Then add: dexamethasone if needed (corticosteroid)

Different classes

Question 18

What is hyperemesis gravidarum?

Answer 18

V severe morning sickness

Rapid rise beta- hcg-> stimulates CTZ
Typically weeks 4-16
Higher risk with multiple pregnancies

Dehydration, weight loss, electrolyte imbalance, urinary ketones

Question 19

Treatment of hyperemesis gravidarum

Answer 19

Promethazine (H1 R antagonist) Or prochlorperazine (D2 R antagonist)

Then add: metoclopramide (D2 R antagonist)

Then add: ondansetron (5HT3 R antagonist - 1st trimester risk cleft lip/ palate)

Question 20

Treatment of emesis in chemotherapy

Answer 20

Low risk chemo: dexamethasone (if needed + metoclopramide)

Moderate: dexamethasone & ondasetron (+ metoclopramide)

High risk: dexamethasone & ondansetron & aprepitant (+ metoclopramide)

Dexamethasone - corticosteroid
Ondansetron - 5HT3 R antagonist
Aprepitant - NK1 antagonist
Metoclopramide - D2 R antagonist

Question 21

Risk factors for post- operative nausea & vomiting

Answer 21

Female

History of PONV/ motion sickness

Younger

Non smoker

Genera anaesthetic

Volatile anaesthetic gases/ NO

PO opioids

Longer op

Laparoscopic surgery

Question 22

Post- op N&V treatment

Answer 22

Low risk: wait and see

Moderate: pick 1/ 2 antiemetic agents

High: 3+ agents

If prophylaxis fails use antiemetic of different class

Question 23

What do you use to treat infective gastritis?

Answer 23

Osmotic or secretory agents

Question 24

Give examples of opioid receptor agonists, how do they work

Answer 24

Loperamide - specific to mu receptors in myenteric plexus

Decreases tone longitudinal/ circular SM, reduces peristalsis but increases segmental contractions, decreases colonic mass movement by suppressing gastrocolic reflex

Works just in the gut

Max effects in 24hrs

Also: codeine, morphine - mu and delta receptors - similar effects, more often used wine patients also have pain

Works all over body

Question 25

Side effects of opioid receptor agonists

Answer 25

Paralytic ileus

N&V

Sedation

Addiction (codeine & morphine)

Question 26

For those with long term loose stools what should they consider adding and limiting from their diet?

Answer 26

E.g. IBS, IBD, short bowel, hypermotility, drug side effects

The constipating diet:
Bananas, white rice, white bread/ pasta

Limit fruit 3per day
Avoid: caffeine, sorbitol, fatty/ spicy foods, fizzy drinks

Consider probiotics

Question 27

Lifestyle/ diet changes for those with chronic idiopathic constipation?

Answer 27

More water

Increase fibre: whole grain foods, f&v, nuts, pulses

Regular exercise

Toilet routine and positioning

Consider probiotics

Question 28

Categorise the medications for constipation

Answer 28

Laxatives - orally - osmotic, stimulants, bulk forming, stool softeners

Enemas - rectally - osmotic, stimulants

Question 29

Give examples of osmotic laxatives, how do they work?

Answer 29

Lactulose (draws H2O in, mild constipation),

1st line: movicol (retains H2O, up to 12 sachets a day, bad constipation),

cosmocol (retains H2O)

Increases water in large bowel

Question 30

Give examples of stimulant laxatives, how do they work?

Answer 30

Bisacodyl

Dosimeter picosulphate

Senna

Docusate sodium - stimulant & stool softener

Glycerine - rectal irritation & lubrication & stool softener

If need more help, increase intestinal motility, orally or rectally

Question 31

Give examples of bulk forming laxatives, how do they work?

Answer 31

Ispaghula husk

Methylcellulose

Medicinal fibre - sometimes also helpful for diarrhoea

Ideally just get from diet or increase H2O

Question 32

Give examples of stool softeners, how do they work?

Answer 32

Docusate sodium - stimulant

Glycerine - rectal irrational, lubrication, stimulant

Liquid paraffin

Decrease surface tension of stool

Increase penetration of fluid into stool