Session 11 Antiemetics And Antidiarrhoeals

Question 1

What is vomiting?

Answer 1

Involuntary, forceful expulsion of gastric contents through the mouth

Question 2

Describe how vomiting occurs

Answer 2

Vomiting centre in medulla —> vomit

1. Nausea, salivation and sweating
2. Retrograde peristalsis
3. Deep inspiration
4. Closure of glottis
5. Abdominal muscles contract
6. Lower oesophageal sphincter relaxes

Question 3

What makes the vomiting centre ‘go’?

Answer 3

Sensory afferents via midbrain

Direct Triggers (needles etc)

Vestibular nuclei

Visceral afferents from gut

Question 4

What agents (drugs) act on the vestibular nuclei?

Answer 4

Muscarinic receptor antagonists

H1 receptor antagonist

Question 5

What is an example of a muscarinic receptor antagonist?

Answer 5

Hyoscine hydrobromide

Question 6

Muscarinic receptor antagonists MoA?

Answer 6

Competitive blockade of muscarinic acetylcholine receptors in the vestibular nuclei and at the CTZone

Question 7

Good uses of muscarinic receptor antagonists?

Answer 7

For people who cant take tablets

Motion sickness

Bowel obstruction

Question 8

Side effects of muscarinic receptor antagonists?

Answer 8

Sedation

Memory problems

Glaucoma

Dry mouth and constipation

Question 9

How do H1 receptor antagonists work?

Answer 9

Centrally

• acts on the vestibular nuclei
• inhibits histaminergic signals from the vestibular system to the CTZ in medulla

Question 10

What are H1 receptor antagonists good for?

Answer 10

Motion sickness - long plane journeys

Promethazine = morning sickness in pregnancy

Question 11

Names of some H1 receptor antagonists?

Answer 11

Cyclizine
Levomepromazine
Cinnirazine
Promethazine
Diphenhydramine

Question 12

Side effects of H1 receptor antagonists?

Answer 12

Sedation

Excitation

Antimuscarinic - dry mouth, constipation, urinary retention

Cardiac toxicity (long QT interval)

Question 13

What are the two agents that act on visceral afferents in the gut?

Answer 13

5HT3 receptor antagonist

D2 receptor antagonists

Question 14

What cell type produces serotonin? (5-HT)

Answer 14

Enterochromaffin cells

Question 15

What does serotonin do in response to parasympathetic stimulation?

Answer 15

Excites enteric neurones

• smooth muscle contraction increases motility (except in stomach)
• increases gut secretions
• regulates appetite

Question 16

How do 5HT3 receptor antagonists work

A) peripherally
B) centrally

Answer 16

Peripherally
* reduced GI motility and reduces GI secretions

Centrally
* acts to inhibit to CTZ

Good for: almost everyone (1st line treatment most of the time)

Question 17

Examples of names of 5 HT3 receptor antagonists?

Answer 17

Ondansetron
Granesitron
Palonosetron

Question 18

Side effects of 5 HT3 receptor antagonists?

Answer 18

Uncommon!

Constipation 
Headache
Elevated liver enzymes
Long QT syndrome 
Extra-pyramidal effects (dystonia, Parkinsonism)

Question 19

How do the D2 receptor antagonists metoclopramide and domperidone work?

Answer 19

Increase ACh at muscarinic receptors in the gut

Promote gastric emptying

• increase tone at LOS so it closes
• increase tone and amplitude of gastric contractions
• decrease tone of pylorus so it opens
• increase peristalsis

Question 20

What is metoclopramide good for?

Answer 20

GORD

Ileus

Question 21

Side effects of metoclopramide?

Answer 21

Galactorrhoea via prolactin release

Extra-pyramidal effects - dystonia, Parkinsonism

Question 22

What is domperidone good for?

Answer 22

Improving lactation in breastfeeding mothers

Question 23

Side effects of domperidone?

Answer 23

Sudden cardiac death (long QT and VT)

Galactorrhoea

Question 24

What agents act on the CTZ?

Answer 24

5HT3 receptor antagonists

H1 receptor antagonists

Muscarinic receptor antagonists

D2 receptor antagonists

Corticosteroids

Cannabinoids

NK1 Receptor antagonists

Question 25

Which drugs are good for chemotherapy sickness?

Answer 25

D2 receptor antagonists - Haloperidol Corticosteroids (also perioperative N+V and palliation Cannabinoids Neurokinin 1 receptor antagonists

Question 26

How do NK1 receptor antagonists work?

Answer 26

Prevent the action of substance P at CTZ and in peripheral nerves Boosts effects of 5HT3 receptor antagonists Anxiolytic an antidepressant properties

Question 27

Side effects of NK1 receptor antagonists?

Answer 27

Headache Diarrhoea or constipation Stevens - Johnson Syndrome

Question 28

Names of some NK1 receptor antagonists?

Answer 28

Aprepitant fosaprepitant Netupitant

Question 29

Name of a cannabinoid?

Answer 29

Nabilone

Question 30

Side effects of corticosteroids (when treating vomiting) - dexamethasone and methylprednisolone

Answer 30

Insomnia Increased appetite Increase blood sugar

Question 31

What is first line treatment for motion sickness?

Answer 31

Hyoscine hydrobromide

Question 32

What is hyperemeesis Gravidarum?

Answer 32

Excessive nausea and vomiting * rapid rise in b-HCG stimulates the CTZ Typically occurs in weeks 4-16 Higher risk with multiple pregnancies - also dehydration, weight loss, electrolyte imbalance and urinary ketones

Question 33

Treatment of hyperemesis Gravidarum?

Answer 33

Promethazine (H1 RAnt) or Prochlorperazine(D2 RAnt) Then add: metoclopramide (D2 RAnt) Then add: ondansetron (5HT3 RAnt)

Question 34

What are some risk factors for post-operative nausea and vomiting? split up into patient, anaesthetic and surgery

Answer 34

patient * female * history of PONV or motion sickness * younger age * non smoker anaesthetic * general > regional * use of volatile gases or NO * post op opioids Surgery * duration of operation * laparoscopic surgery

Question 35

How does loperamide work in treating diarrhoea? What type of drug is it?

Answer 35

= opioid receptor agonist decreases tone of longitudinal and circular smooth muscle reduces peristalsis but increases segmental contractions (more contact with enterocytes for longer) decreases colonic mass movement by suppressing gastrocolic reflex (stops the urge)

Question 36

Morphine and codeine can also be given to treat diarrhoea. What type of drugs are they and what are some side effects?

Answer 36

Opioid receptor agonists ADR * paralytic ileus * N+V * sedation and addiction

Question 37

What could you recommend for people with chronic diarrhoea (could be IBS, IBD, short bowel, drug side effects etc)

Answer 37

To follow the constipating diet * white rice - binds stool * white bread / pasta - low in fibre limit fruit to 3 portions per day avoid caffeine, sorbitol, fatty or spicy foods and fizzy drinks

Question 38

How do osmotic laxatives work? (general)

Answer 38

they increase the amount of water in the large bowel

Question 39

How does lactulose work (an osmotic laxative)?

Answer 39

draws fluid IN

Question 40

how do macrogols (movicol and cosmocol) work? * osmotic laxatives

Answer 40

they retain the fluid they came in movicol is first line - come in sachet form

Question 41

How do stimulant laxatives work?

Answer 41

increase intestinal motility

Question 42

What are names of some laxatives?

Answer 42

``` bisacodyl sodium picosulphate senna co-danthromer docusate sodium Glycerin suppository ```

Question 43

Which laxative is a stimulant and a stool softener?

Answer 43

docusate sodium

Question 44

Which laxative causes rectal irritation and lubrication?

Answer 44

glycerin suppositories

Question 45

What are two names of bulk forming laxatives?

Answer 45

ispaghula husk | methylcellulose

Question 46

How do stool softeners work?

Answer 46

decrease surface tension of stool | increase penetration of fluid into stool