Laxatives Flashcards
What are 7 groups of drugs used as laxatives?
Physical:
1) Bulk-forming
2) Stool surfactant
3) Osmotic
Physiological:
4) Stimulant
5) Cl channel activators
6) Opioid receptor antagonists
7) 5-HT4 receptor antagonists
What are 3 examples of bulk-forming agents?
1) Psyllium (fibre)
2) Methylcellulose (semi-synthetic)
3) Polycarbophil (synthetic)
What is the moa of bulk-forming agents?
Indigestible, hydrophilic colloids (fibre)
→ absorbs water → form bulk, emollient gel → distend colon
→ promote peristalsis
What are 3 AEs of bulk-forming agents?
Bacterial digestion of fibres in colon:
1) Flatus
2) Bloating
3) Abdo pain
What should bulk-forming agents be administered with?
Lots of water
When should bulk-forming agents be avoided?
1) Suspected obstruction
2) ↓absorption of other oral drugs (do not use within 2 hrs before or after)
What are 2 examples of stool surfactant agents (softeners)?
1) Glycerin + NaCl (enema)
2) Mineral Oil (Oral)
What is the moa of stool surfactant agents?
↓ surface tension → water and lipids can penetrate stool
- mineral oil lubricates + slows water reabsorption from stool
What are 2 main AEs of stool surfactant agents?
Mineral oil:
1) Aspiration → sever lipid pneumonitis (aspiration pneumonia)
2) LT use → ↓fat-soluble vit ADEK absorption
What are 3 examples of osmotic laxatives?
Nonabsorbable sugars
1) Lactulose
2) Sorbitol
Non-absorbable salts:
1) MgOH
2) Na2PO4
3) Magnesium citrate
Macrogol (balanced polyethylene glycol)
What are 2 general AEs of osmotic laxative and 4 for Na2PO4?
General: bacterial digestion of sugars
1) Flatus
2) Abdo cramps
Na2PO4:
1) HyperPO4
2) HyperNa
3) HypoCa
4) HypoK
5) Cardiac arrythmia, ARF 2° to nephrocalcinosis)
What should osmotic laxatives be administered with?
Lots of water
In which px should sodium phosphate be avoided?
1) Frail, elderly
2) Diuretics, cannot adequately hydrate
3) Renal insufficiency
4) Cardiac disease
What is the moa of osmotic laxatives?
Osmosis of water into bowel → ↑stool liquidity & volume
→ stimulate peristalsis
Which of the osmotic laxatives are the safest in terms of limited AEs and why?
Balanced macrogol
- contains sugar w electrolytes → avoids significant electrolyte shifts
- does not produce significant cramps or flatus
What are 2 examples of stimulant laxatives (cathartics)?
1) Senna (anthraquinone derivatives)
2) Bisacodyl (diphenylmethane derivatives)
What is the moa of stimulant laxatives?
Poorly understood
produce migrating colonic contractions by:
1) direct stimulation of enteric NS
2) Colonic electrolyte and fluid secretion
What 2 laxatives are used for colonic cleansing prior to a colonscopy?
Bisacodyl (stimulant laxative)
Balanced Macrogol (PEG) (Osmotic laxative)
What are 2 AEs of stimulant laxatives?
Anthraquinone derivatives (eg. senna):
1) Chronic use → brown pigmentation of colon
2) Possible carcinogenicity
Diphenylmethane derivatives (eg. Bisacodyl)
3) Cardiac toxicity
What should px who are taking oral bisacodyl be advised of?
No milk product 1hr of taking bisacodyl
(milk product → break down enteric coating → gastric irritation/dyspepsia)
What is an example of a chloride channel activator?
Lubiprostone
What is the moa of lubiprostone?
1) Stimulate Type 2 Cl channels (ClC-2) in small intestine
2) ↑Cl-rich fluid secretions
3) Stimulates motility → ↓transit time
What are 2 AEs of Cl channel activators?
1) Return of constipation after discontinuation
2) Nausea due to delayed gastric emptying
When should Cl-channel activators be avoided?
Pregnant women
Which laxatives induce soft stools in 1-3days?
1) Bulk laxatives
2) Osmotic laxatives (lactulose)
3) Stool surfactant agents
Which laxative induce soft/semi-fluid stools in 6-8hrs?
Stimulant laxatives (oral)
Which laxative induce watery stools in 1-3 hrs?
1) Osmotic laxatives
2) PEG/Balanced macrogol
3) Suppository (Bisacodyl)
What is an example of an opioid receptor antagonist?
Methylnaltrexone bromide
What is the specific indication of Methylnaltrexone bromide?
Opioid-induced constipation (µ-opioid receptor antagonist)
- subcut every 2 days
Does Methylnaltrexone bromide block the CNS analgesic effects of opioids?
No, does not readily cross BBB
What are 5 AEs of opioid receptor antagonists?
1) Abdo pain
2) Nausea
3) Diarrhoea
4) Flatulence
5) Sweating
6) GI perforation (rare but severe)
What are 2 examples of 5-HT4 receptor agonists?
1) Prucalopride
2) Cisapride
What is the moa of 5HT4 agonists?
Stimulate 5-HT4 receptors on nerve terminals in the GIT walls
→ ↑NT release and smooth muscle motor activity
→prokinetic/promotes GI motility
What are 5 common AEs of 5HT4-receptor agonists?
1) Abdo pain
2) Nausea
3) Dizziness
4) Headache
5) Diarrhoea
What is the difference in AEs of Cisapride and Prucalopride?
Cisapride: 5HT4 partial agonist
→ adverse cardiovascular effects (actions at hERG K+ channels)
Prucalopride: high-affinity 5-HT4 agonist (no CVS effects)
When are 5-HT4 receptor agonists contraindicated?
During intestinal obstruction
What are 2 laxative classes that should not be used in intestinal obstruction?
1) 5-HT4 receptor agonists (eg. prucalopride)
2) Bulk-forming agonists (eg. Psyllium)
