Antiemetics

Question 1

Vomiting

Answer 1

Involuntary, forceful expulsion of gastric contents through the mouth

Question 2

Regurgitation

Answer 2

Effortless, bring something back up that was sat in the oesophagus/stomach

Question 3

Vomiting process

Answer 3

Vomiting centre in medulla signals to vomit

1. Nausea, salivation, sweating
2. Retrograde perstalsis- upper part of small bowel(duod and stomach)
3. Deep inspiration
4. Closure of glottis- present aspiration
5. Abd muscles contract
6. LOS relaxes- gastric contents out

Question 4

Chemo receptor trigger zone - vomiting zone

Answer 4

Part of brain involved
Floor of 4th ventricle
Blood side of BBB
Things in b stream hit CTZ, cause vomiting

Question 5

What activate CTZ

Answer 5

Sensory Afferent by midbrain: eww gross
Vestibular nuclei- inner ear (infection), motion sickness (car/sea sick/vertigo)
Visceral afferents from gut- vagus n. problem w gut
Direct triggers- drugs/hormone

Question 6

Stop CTZ

Answer 6

Avoidance

Drugs- work in diff places/ways eg CTZ/PNS

Question 7

Agents acting on vestibular nuclei

Answer 7

Muscarnic receptor antagonists

H1 receptor antagonists

Question 8

Muscarnic receptor antagonist

Answer 8

Eg: Hyoscine hydrobromide
Competitive blockade of muscarnic ACHR- work by PNS, found:
Vestibular nuclei/CTZ/PNS

Good for:
- not take tablets/ motion sickness/ bowel obs

Side effects:

• sedation = good in cancers agitated
• memory problems
• dry mouth/constipation = if D with V

Question 9

H1 receptor antagonist

Answer 9

Centrally:

• act on VN
• inhibits histaminergic signals from vestibular system to CTZ in medulla

Good for:

• motion sickness
• promethazine:morning sickness preg

Not good for:
Cyclizine- little old ladies/children

Question 10

H1 receptor antagonists

Answer 10

Cyclizine
Levomepomazine
Cinniarizine
Promethazine
Diphenhydramine

Side effects:

• sedation/excitation
• antomuscarinic- dry mouth/constipation/ urinary retention
• cardiac toxicity (long QT interval)

Question 11

Agents acting on visceral afferents in gut

Answer 11

5HT3 receptor antagonists

D2 receptor antagonists

Question 12

Serotonin (5HT) in gut :)

Answer 12

Production: enterochromaffin cells

Act: respond to parasymp stimulation: excite enteric neurones

• smooth muscle contraction: increase motility (except stomach)
• increase gut secretions

Regulates appetite

Question 13

5HT3 receptor antagonist

Answer 13

Peripherally
- reduce motility (stop retrograde peristalsis) and GI secretions

Centrally:
-inhibit CTZ

Good for:
- everyone: 1st line

Question 14

5HT3 receptor antagonists

Answer 14

Ondansetron (most common)
Granesitron
Palonosetron

Side effects- uncommon:

• constipation
• headache
• elevated liver enzymes
• long QT syndrome
• extra-pyramidal: dystonia, Parkinsonism

Question 15

D2 receptor antagonists- metoclopramide

Answer 15

• increase Ach at muscarnic receptor in gut
• promote gastric emptying:
  increase tone at LOS so it closes
  Increase tone and amplitude of gastric contractions
  Reduce tone of pylorus, so it opens

-increase peristalsis

Good for: GORD/ileus (gut go to sleep, no peristalsis= eg after laparotomy/infectuon/illness)

Question 16

D2 receptor antagonists- metoclopramide

Answer 16

Side effects:

• galactorrhoea: prolactin release
• extra pyramidal effects: dystopia, Parkinsonism

Question 17

D2 receptor antagonist- domperidone

Answer 17

• mechanism similar to metoclopramide
• get increase risk cardiac side effects

Good for:
- improve lactation in breast feeding mothers

Side effects:

• sudden cardiac death (long QT and VT)
• galactorrhoea

Question 18

Agents acting on the CTZ

Answer 18

5HT3 receptor antagonists
H1 receptor antagonists
Muscarnic receptor antagonist
D2 receptor antagonists
Corticosteroids 
Cannabinoids
NK1 receptor antagonists

Question 19

D2 receptor antagonists- 
Prochlorperazine
Chlorpromazine
Levomepromazine
Haloperidol

Answer 19

Zines:

• act:CTZ
• also block h1 and muscarnic receptors
• Good for: motion sickness/vertigo/prochloperazine=pregnancy

Haloperidol:

• act at CTZ
• Good for: chemotheapy and palliation

Question 20

D2 receptor antagonists- zines and haloperidol

Answer 20

Side effects:

• extra pyramidal effects- dystonia, Parkinsonism
• sedation
• hypotension

Question 21

Corticosteroids

Answer 21

Dexamethasone
Methylprednisolone

• act at CTZ, May also have D2 receptor antagonist properties

Good for:

• perioperative N and V (anaesthesia related)
• chemotherapy
• palliation (increased appetite in palliation)

Question 22

Corticosteroids-side effects

Answer 22

Insomnia
Increased appetite
Increased blood sugar

Question 23

Cannaboids

Answer 23

Nabilone

Act at CTZ
Good for: chemo, used as last line

Side effects:
- drowsy, dizziness

Question 24

Neurokinin 1 receptor antagonists

Answer 24

Aprepitant
Fosaprepitant
Netupitant

• prevent action of substance P at CTZ and in peripheral n.s
• boost effects of 5HT3 receptor antag
• anxiolytic and anti depressive properties

Good:
- chemo:esp in delayed eyes is

Question 25

NK1 receptor antagonists

Answer 25

Side effects:

• headache
• diarrhoea/ constipation
• Stevens-Johnson syndrome

Question 26

Random drugs used as antiemetics

Answer 26

Midazolam- benzodiazepine

• act at CTZ, bind to GABA receptor, reduce serotonin secretion
• used perioperatvely

Gabapentin:

• mitigation of effects of neurokinins and tachykinins
• used perioperatively and hyperemosis gravidarum

Cisapride:

• prokinetic
• chemo

Mirtazepine:

• tetracyclic antidepressant
• effect serotonin