Drugs affecting Gut Motility - Antiemetics, Laxatives, Antimotility Flashcards
Give 4 classes of antiemetics and relevant examples for each
1) Dopamine D2 receptor antagonists - Metoclopramide, Domperidone
2) Serotonin receptor antagonists - Ondansetron
3) Histamine H1 receptor antagonists - Cyclizine
4) Anti-muscarinics - Hyoscine
What are dopamine D2 receptor antagonists particularly useful for?
N+V caused by reduced gut motility (e.g. opioids) or drugs such as chemotherapy
What is the mechanism of action of dopamine D2 receptor antagonists?
- 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
What is a problem with Metoclopramide in terms of PK and hence ADRs?
Crosses BBB - hence causes extrapyramidal symptoms
Give 2 other ADRs of D2 receptor antagonists
Diarrhoea
Galactorrhoea - lack of inhibition on prolactin release as decreased dopamine
Why can’t metoclopramide be given with Parkinson’s drugs?
Negates their effects - risk of worsening of symptoms/falls etc…
What are serotonin receptor antagonists particularly good for?
N+V caused by GA and chemo/radio
What is the mechanism of action of serotonin receptor antagonists?
- Blocks serotonin receptors in chemoreceptor trigger zone
- Also reduces serotonin release in gut in response to emetogenic stimuli
Why are D2 receptor antagonists and serotonin receptor antagonists no good for motion sickness?
No role in vestibular-brain pathway
What is an important DDI of Ondansetron?
May prolong QT interval so can’t be given with drugs that also do this, e.g. most of the psych drugs
What class of drug does cyclizine belong to?
Histamine H1 receptor antagonist
What is cyclizine particularly useful for?
Motion sickness/vertigo
Outline the mechanism of action of cyclizine
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.
What is the major problem with H1 receptor antagonists?
Crosses BBB - causes drowsiness
Give an example of an anti-muscarinic drug used as an antiemetic
Hyoscine
What is Hyoscine particularly useful for?
Motion sickness
Also good as antispasmodic in IBS
How may hyoscine be administered?
What is a problem with one of these mechanisms?
Oral or transdermal patch
Transdermal - tolerance
What are the 4 major classes of laxatives and give relevant examples
1) Bulk-forming - ispaghula husk
2) Faecal softeners - glycerol suppositories
3) Osmotic - lactulose, macrogols, phosphate enemas
4) Irritants/stimulants - castor oil, senna
What is ispaghula husk useful for?
Chronic/simple constipation
What is the mechanism of action of bulk-forming laxatives?
Contain hydrophilic substance which sits in gut lumen and attracts water into stool.
This distends gut - stimulates stretch receptors - hence results in peristalsis.
What must patients ensure whilst taking bulk-forming laxatives?
Adequate fluid intake
When must bulk-forming laxatives not be used?
Adhesions - risk of intestinal obstruction
When might osmotically active laxatives be used?
Constipation/faecal impaction
Bowel preparation for surgery/endoscopy
Outline the mechanism of action of osmotically active laxatives?
Contain osmotically active substances which remain in gut lumen, drawing water into stool - similar to bulk-forming.
How are lactulose, movicol and phosphate enemas administered? How long do they take to work?
Lactulose - oral, 48 hours
Movicol - powder, dissolved and drunk - 2 - 4 days
Phosphate enema - enema, immediate (need I say more?)
Give 3 ADRs of all osmotically active laxatives, and 1 specific to phosphate enemas
1) Flatulence
2) Abdo cramps
3) Nausea
Phosphate enemas can cause electrolyte/fluid balance disturbances
Can osmotically active laxatives be used in intestinal obstruction?
NO
Which laxatives are safe in obstruction?
Faecal softeners
Outline the mechanism of action of stimulant laxatives
Increase water and electrolyte secretion from the colonic mucosa into gut lumen - increases volume - stimulates peristalsis
How long does Senna take to work?
What is it useful for?
6 - 8 hours
Prevention of constipation with opioid use
What can happen with long-term use of stimulant laxatives?
Colonic atony
Hypokalaemia
Melanosis coli
What is the major class of drug used to treat diarrhoea? Give an example
Anti-motility
Loperamide (Imodium)
What is the mechanism of action of Imodium?
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
When mustn’t loperamide be used?
In acute UC - risk of toxic megacolon
In bacterial infection
