Antiemetics And Antidiarrhoeals

Question 1

What drugs at on the vestibular nuclei?

Answer 1

Muscarinic Receptor Antagonists

H1 receptor antagonists

Question 2

What is the main Muscarinic receptor antagonist?

Answer 2

Hyosine hycobromide

Question 3

How does hyosine hycobromide work?

Answer 3

Competitive blockade of Muscarinic ACh receptors in the vestibular nuclei and the CTZ.

Question 4

Who is hyosine good for?

Answer 4

People who cant take tablets (patch)
Motion sickness
Bowel obstruction

Question 5

What are the side effects of hyosine?

Answer 5

Dry mouth and constipation
Sedation
Memory problems
Glaucoma

Question 6

What are the main H1 receptor antagonists?

Answer 6

Cyclizine (not children or old ladies as sedation and excitation are more prominent) 
Levomepromazine
Cinnirazine
Promethazine
Diphenhydramine

Question 7

How do H1 receptor antagonists work?

Answer 7

Centrally:
Vestibular nuclei
Inhibits histaminergic signals from the vestibular system to the CTZ in medulla

Question 8

Why are H1 good for / not good for?

Answer 8

Good:
Motion sickness - long place journeys
Promethazine - morning sickness in pregnancy

Not good:
Cyclizine -little old ladies and children

Question 9

What are the side effects of H1?

Answer 9

Sedation
Excitation
Antimuscarinic - dry mouth, constipation, urinary retention
Cardiac toxicity (long QT)

Question 10

What agents act on visceral afferents?

Answer 10

5HT3 receptor antagonists

D2 receptor antagonists

Question 11

How does serotonin normally work?

Answer 11

95% of serotonin in the body is located int he gut and produced by enterochromaffin cells.

In response to parasympathetic stimulation, serotonin excited exterior neurones:
Smooth muscle contraction increases motility (except in stomach)
Increases gut secretions.

It also regulates appetite.

Question 12

What are the main 5HT3 receptor antagonists?

Answer 12

Ondansetron
Granesitron
Palonosetron

Question 13

How do 5HT3 receptor antagonists work?

Answer 13

They work peripherally to reduce GI motility and secretions.

They work centrally to inhibit the CTZ.

Question 14

Side effects of 5HT3 receptor antagonists?

Answer 14

Constipation
Headache
Elevated liver enzymes
Long QT syndrome
Extra-pyramidal effects - dystonia, parkinsonism

Question 15

Main D2 receptor antagonists?

Answer 15

Metaclopramide

Domperidone

Question 16

How does metaclipramide work?

Answer 16

Increases acetylcholine at muscarinic receptors in the gut.

Promotes gastric emptying - Increases tone at LOS so it closes, Increases time and amplitude of gastric contractions, Decreases tone of pylorus so it opens.

Increases peristalsis

Good for:
GORD
Ileus

Question 17

What are the side effects of metaclopromide?

Answer 17

Galactorrhoea via prolactin release

Extra-pyramidal effects - dystonia, Parkinsonism

Question 18

How does domperidone work?

Answer 18

Similar to metoclopramide - increases ACh at mAChR in gut.
Promote gastric emptying
Increase peristalsis

Used to be popular but increased risk of significant cardiac effects.

Good for improving lactation in breastfeeding mothers

Question 19

What are the side effects of Domperidone?

Answer 19

Sudden cardiac death - long QT and VT (because of this, now used less)

Galactorrhoea

Question 20

How does Haloperidol work and who is it good for?

Answer 20

Act on CTZ
Good for chemo and palliative.

This is also an antipsychotic.

Question 21

Steroid examples?

Answer 21

Dexamethasone

Methylprednisolone

Question 22

How do steroids work as antiemmetics?

Answer 22

Assumed to act on CTZ.

May also have properties of D2 receptor antagonists.

Question 23

Who are corticosteroids used for?

Answer 23

Peri-operative nausea and vomiting
Chemotherapy
Palliation

Question 24

Side effects of steroids?

Answer 24

Insomnia
Increased appetite
Increased blood sugar

Question 25

Cannabinoids example

Answer 25

Nabolone

Question 26

How do cannabinoids work and what are the side effects?

Answer 26

Act on CTZ (assumed) Good for chemotherapy Side effects: Dizziness Drowsiness

Question 27

Give examples of neurokinin 1 receptor antagonists

Answer 27

Aprepitant Fosaprepitant Netupitant

Question 28

How do Neurokinin 1 receptor antagonists work?

Answer 28

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

Question 29

Side effects of Neurokinin 1 receptor antagonists?

Answer 29

Headache Diarrhoea / Constipation Stevens-Johnson syndrome

Question 30

Different between motion sickness drugs?

Answer 30

Hyosine - 1st line but drowsy Cinnirazine - less drowsy

Question 31

What are prokinetics?

Answer 31

``` Domperidone Metaclopramide (Cisapride) ```

Question 32

When are prokinetcs useful?

Answer 32

GORD | Ileus

Question 33

When dont you use prokinetics?

Answer 33

Obstruction | Risk of perforation

Question 34

How do you treat sickness?

Answer 34

Ondansetron (5HT receptor antagonist) snd/or Cyclizine (H1 receptor antagonist) Then add: Dexamethasone (corticosteroid)

Question 35

What can directly trigger CTZ?

Answer 35

Hormones - hyperemesis gravidarum ``` Drugs Chemotherapy Anaesthetics Opiates Many others! ```

Question 36

What is hyperemesis Gravidarum?

Answer 36

Rapid rise in beta hCG stimulates CTZ. Typically weeks 4-16 but may continue beyond Higher risk with multiple pregnancies More than just 'morning sickness' - dehydration, 5% weight loss, electrolyte imbalance, urinary ketones

Question 37

What are the best drugs for hyperemesis Gravidarum?

Answer 37

Promethazine (H1 receptor antagonist) or Prochlorperazine (D2 receptor antagonist) Then add: Metaclopramide (D2 receptor antagonist) Then add: Ondansetron (5HT3 receptor antagonist)

Question 38

What are the risk factors for post-operative nausea and vomiting?

Answer 38

Female Phobia Young age Non Smoker General> Regional anaesthetic Volatile anaesthetics Post-operative opioids Duration of operation Laparoscopic Surgery

Question 39

What is the most common class of drugs used to treat diarrhoea?

Answer 39

Opioid receptor agonist

Question 40

Give examples of opioid receptor agonist

Answer 40

Loperamide (most common)

Question 41

How does loperamide work?

Answer 41

It is specific to the u (MOR / mu) receptors in the myenteric plexus Decreases tone of longitudinal circular smooth muscle Reduces peristalsis but increases segmental contractions Decreases colonic mass movements by suppressing gastrocolic reflex.

Question 42

How do opioid receptor agonist (morphone / codine ) work?

Answer 42

Act on u and d receptors Similar to loperamide. More often used for patients that also have pain.

Question 43

SIde effects of opioid receptor agonist?

Answer 43

Paralytic Ileus Nausea and Vomiting Sedation and Addiction (codeine and morphine)

Question 44

What effect does fibre have on your stools?

Answer 44

Lots - loose stools Not much - constipated

Question 45

What is the diet for people with long term loose stools?

Answer 45

(IBS, IBD, short bowel, hyper mobility, drugs side effects.) White rice - Binds in stool White bread/pasta - Low in fibre Limit fruit to 3 portions per day Avoid caffeine, sorbitol, fatty or spicy foods and fizzy drinks. Consider probiotics to reinstate a balanced intestinal flora

Question 46

What lifestyle things can you do to reduce constipation?

Answer 46

Drink more water Increase fibre intake - wholegrain foods, fruit and veg, nuts, pulses Regular exercise Toilet routine (same each day) and positioning

Question 47

What medications can you get for constipation?

Answer 47

Laxatives (osmotic, stimulants, bulk forming, stool softeners) Enemas (Osmotic / stimulants)

Question 48

Give examples of osmotic laxatives

Answer 48

Lactulose Moviol Cosmocol

Question 49

How do osmotic laxatives work?

Answer 49

Increase the amount of fluid int he large bowl by: Drawing fluids in (lactulose) OR Retaining the fluids they came with (Macrogols)

Question 50

Give examples of stimulant laxatives

Answer 50

``` Bisacodyl Sodium pocosulphate Senna Co-Danthromer Docusate Sodium Glycerin ```

Question 51

How do stimulant laxatives work?

Answer 51

Increase intestinal motility May be given orally to PR Docusate sodium acts as stimulant and stool softener Glycerin suppositories cause rectal irritation and lubrication

Question 52

Give examples of bulk forming laxatives

Answer 52

Basically medicine fibre Ispaghula Methylcellulose

Question 53

Give examples of stool softeners

Answer 53

Docusate sodium Glycerin suppositories Arachis oil Liquid paraffin

Question 54

How do stool softeners work?

Answer 54

Decrease surface tension of stool | Increase penetration of fluid into stool

Question 55

What is vomiting?

Answer 55

Involuntary, forceful expulsion of gastric contents through the mouth

Question 56

What happens when we vomit?

Answer 56

Vomiting centre in medulla signals to vomit: 1. Nausea, salivation, sweating 2. Retrograde peristalsis 3. Deep inspiration 4. Closure of glottis 5. Abdominal muscles contract 6. Lower oesophageal sphincter relaxes

Question 57

What things can make the vomiting centre (chemoreceptor trigger zone / CTZ) go?

Answer 57

Sensory afferents via midbrain Vestibular nuclei Direct triggers Visceral afferents from gut