Drugs affecting Gut Motility - Antiemetics, Laxatives, Antimotility

Question 1

Give 4 classes of antiemetics and relevant examples for each

Answer 1

1) Dopamine D2 receptor antagonists - Metoclopramide, Domperidone
2) Serotonin receptor antagonists - Ondansetron
3) Histamine H1 receptor antagonists - Cyclizine
4) Anti-muscarinics - Hyoscine

Question 2

What are dopamine D2 receptor antagonists particularly useful for?

Answer 2

N+V caused by reduced gut motility (e.g. opioids) or drugs such as chemotherapy

Question 3

What is the mechanism of action of dopamine D2 receptor antagonists?

Answer 3

• Block D2 receptors in the chemoreceptor trigger zone - prevents signals being sent to vomiting centres of medulla when emetogenic substances are detected
• Also promotes relaxation of stomach

Question 4

What is a problem with Metoclopramide in terms of PK and hence ADRs?

Answer 4

Crosses BBB - hence causes extrapyramidal symptoms

Question 5

Give 2 other ADRs of D2 receptor antagonists

Answer 5

Diarrhoea

Galactorrhoea - lack of inhibition on prolactin release as decreased dopamine

Question 6

Why can’t metoclopramide be given with Parkinson’s drugs?

Answer 6

Negates their effects - risk of worsening of symptoms/falls etc…

Question 7

What are serotonin receptor antagonists particularly good for?

Answer 7

N+V caused by GA and chemo/radio

Question 8

What is the mechanism of action of serotonin receptor antagonists?

Answer 8

• Blocks serotonin receptors in chemoreceptor trigger zone

- Also reduces serotonin release in gut in response to emetogenic stimuli

Question 9

Why are D2 receptor antagonists and serotonin receptor antagonists no good for motion sickness?

Answer 9

No role in vestibular-brain pathway

Question 10

What is an important DDI of Ondansetron?

Answer 10

May prolong QT interval so can’t be given with drugs that also do this, e.g. most of the psych drugs

Question 11

What class of drug does cyclizine belong to?

Answer 11

Histamine H1 receptor antagonist

Question 12

What is cyclizine particularly useful for?

Answer 12

Motion sickness/vertigo

Question 13

Outline the mechanism of action of cyclizine

Answer 13

Blocks H1 histamine receptors, and also has anti-muscarinic effects - these are the major NTs in the vomiting centre and in communications with vestibular system, hence reduces transmission via these pathways.

Question 14

What is the major problem with H1 receptor antagonists?

Answer 14

Crosses BBB - causes drowsiness

Question 15

Give an example of an anti-muscarinic drug used as an antiemetic

Answer 15

Hyoscine

Question 16

What is Hyoscine particularly useful for?

Answer 16

Motion sickness

Also good as antispasmodic in IBS

Question 17

How may hyoscine be administered?

What is a problem with one of these mechanisms?

Answer 17

Oral or transdermal patch

Transdermal - tolerance

Question 18

What are the 4 major classes of laxatives and give relevant examples

Answer 18

1) Bulk-forming - ispaghula husk
2) Faecal softeners - glycerol suppositories
3) Osmotic - lactulose, macrogols, phosphate enemas
4) Irritants/stimulants - castor oil, senna

Question 19

What is ispaghula husk useful for?

Answer 19

Chronic/simple constipation

Question 20

What is the mechanism of action of bulk-forming laxatives?

Answer 20

Contain hydrophilic substance which sits in gut lumen and attracts water into stool.
This distends gut - stimulates stretch receptors - hence results in peristalsis.

Question 21

What must patients ensure whilst taking bulk-forming laxatives?

Answer 21

Adequate fluid intake

Question 22

When must bulk-forming laxatives not be used?

Answer 22

Adhesions - risk of intestinal obstruction

Question 23

When might osmotically active laxatives be used?

Answer 23

Constipation/faecal impaction

Bowel preparation for surgery/endoscopy

Question 24

Outline the mechanism of action of osmotically active laxatives?

Answer 24

Contain osmotically active substances which remain in gut lumen, drawing water into stool - similar to bulk-forming.

Question 25

How are lactulose, movicol and phosphate enemas administered? How long do they take to work?

Answer 25

Lactulose - oral, 48 hours
Movicol - powder, dissolved and drunk - 2 - 4 days
Phosphate enema - enema, immediate (need I say more?)

Question 26

Give 3 ADRs of all osmotically active laxatives, and 1 specific to phosphate enemas

Answer 26

1) Flatulence
2) Abdo cramps
3) Nausea
Phosphate enemas can cause electrolyte/fluid balance disturbances

Question 27

Can osmotically active laxatives be used in intestinal obstruction?

Answer 27

NO

Question 28

Which laxatives are safe in obstruction?

Answer 28

Faecal softeners

Question 29

Outline the mechanism of action of stimulant laxatives

Answer 29

Increase water and electrolyte secretion from the colonic mucosa into gut lumen - increases volume - stimulates peristalsis

Question 30

How long does Senna take to work?

What is it useful for?

Answer 30

6 - 8 hours

Prevention of constipation with opioid use

Question 31

What can happen with long-term use of stimulant laxatives?

Answer 31

Colonic atony
Hypokalaemia
Melanosis coli

Question 32

What is the major class of drug used to treat diarrhoea?
Give an example

Answer 32

Anti-motility

Loperamide (Imodium)

Question 33

What is the mechanism of action of Imodium?

Answer 33

Opioid (but doesn’t penetrate CNS) - agonises mu receptors in GI tract
Reduces peristaltic contractions - bowel transit slows - anal sphincter tone increased.
Slower transit also means more water resorption, so harder stools

Question 34

When mustn’t loperamide be used?

Answer 34

In acute UC - risk of toxic megacolon

In bacterial infection