Laxatives

Question 1

What are 7 groups of drugs used as laxatives?

Answer 1

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

Question 2

What are 3 examples of bulk-forming agents?

Answer 2

1) Psyllium (fibre)
2) Methylcellulose (semi-synthetic)
3) Polycarbophil (synthetic)

Question 3

What is the moa of bulk-forming agents?

Answer 3

Indigestible, hydrophilic colloids (fibre)
→ absorbs water → form bulk, emollient gel → distend colon
→ promote peristalsis

Question 4

What are 3 AEs of bulk-forming agents?

Answer 4

Bacterial digestion of fibres in colon:
1) Flatus
2) Bloating
3) Abdo pain

Question 5

What should bulk-forming agents be administered with?

Answer 5

Lots of water

Question 6

When should bulk-forming agents be avoided?

Answer 6

1) Suspected obstruction
2) ↓absorption of other oral drugs (do not use within 2 hrs before or after)

Question 7

What are 2 examples of stool surfactant agents (softeners)?

Answer 7

1) Glycerin + NaCl (enema)
2) Mineral Oil (Oral)

Question 8

What is the moa of stool surfactant agents?

Answer 8

↓ surface tension → water and lipids can penetrate stool

• mineral oil lubricates + slows water reabsorption from stool

Question 9

What are 2 main AEs of stool surfactant agents?

Answer 9

Mineral oil:
1) Aspiration → sever lipid pneumonitis (aspiration pneumonia)

2) LT use → ↓fat-soluble vit ADEK absorption

Question 10

What are 3 examples of osmotic laxatives?

Answer 10

Nonabsorbable sugars
1) Lactulose
2) Sorbitol

Non-absorbable salts:
1) MgOH
2) Na2PO4
3) Magnesium citrate

Macrogol (balanced polyethylene glycol)

Question 11

What are 2 general AEs of osmotic laxative and 4 for Na2PO4?

Answer 11

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)

Question 11

What should osmotic laxatives be administered with?

Answer 11

Lots of water

Question 11

In which px should sodium phosphate be avoided?

Answer 11

1) Frail, elderly
2) Diuretics, cannot adequately hydrate
3) Renal insufficiency
4) Cardiac disease

Question 12

What is the moa of osmotic laxatives?

Answer 12

Osmosis of water into bowel → ↑stool liquidity & volume
→ stimulate peristalsis

Question 13

Which of the osmotic laxatives are the safest in terms of limited AEs and why?

Answer 13

Balanced macrogol
- contains sugar w electrolytes → avoids significant electrolyte shifts
- does not produce significant cramps or flatus

Question 14

What are 2 examples of stimulant laxatives (cathartics)?

Answer 14

1) Senna (anthraquinone derivatives)
2) Bisacodyl (diphenylmethane derivatives)

Question 15

What is the moa of stimulant laxatives?

Answer 15

Poorly understood
produce migrating colonic contractions by:
1) direct stimulation of enteric NS
2) Colonic electrolyte and fluid secretion

Question 16

What 2 laxatives are used for colonic cleansing prior to a colonscopy?

Answer 16

Bisacodyl (stimulant laxative)
Balanced Macrogol (PEG) (Osmotic laxative)

Question 17

What are 2 AEs of stimulant laxatives?

Answer 17

Anthraquinone derivatives (eg. senna):
1) Chronic use → brown pigmentation of colon
2) Possible carcinogenicity

Diphenylmethane derivatives (eg. Bisacodyl)
3) Cardiac toxicity

Question 18

What should px who are taking oral bisacodyl be advised of?

Answer 18

No milk product 1hr of taking bisacodyl
(milk product → break down enteric coating → gastric irritation/dyspepsia)

Question 19

What is an example of a chloride channel activator?

Answer 19

Lubiprostone

Question 20

What is the moa of lubiprostone?

Answer 20

1) Stimulate Type 2 Cl channels (ClC-2) in small intestine
2) ↑Cl-rich fluid secretions
3) Stimulates motility → ↓transit time

Question 21

What are 2 AEs of Cl channel activators?

Answer 21

1) Return of constipation after discontinuation
2) Nausea due to delayed gastric emptying

Question 22

When should Cl-channel activators be avoided?

Answer 22

Pregnant women

Question 23

Which laxatives induce soft stools in 1-3days?

Answer 23

1) Bulk laxatives
2) Osmotic laxatives (lactulose)
3) Stool surfactant agents

Question 24

Which laxative induce soft/semi-fluid stools in 6-8hrs?

Answer 24

Stimulant laxatives (oral)

Question 25

Which laxative induce watery stools in 1-3 hrs?

Answer 25

1) Osmotic laxatives
2) PEG/Balanced macrogol
3) Suppository (Bisacodyl)

Question 26

What is an example of an opioid receptor antagonist?

Answer 26

Methylnaltrexone bromide

Question 27

What is the specific indication of Methylnaltrexone bromide?

Answer 27

Opioid-induced constipation (µ-opioid receptor antagonist)
- subcut every 2 days

Question 28

Does Methylnaltrexone bromide block the CNS analgesic effects of opioids?

Answer 28

No, does not readily cross BBB

Question 29

What are 5 AEs of opioid receptor antagonists?

Answer 29

1) Abdo pain
2) Nausea
3) Diarrhoea
4) Flatulence
5) Sweating
6) GI perforation (rare but severe)

Question 30

What are 2 examples of 5-HT4 receptor agonists?

Answer 30

1) Prucalopride
2) Cisapride

Question 31

What is the moa of 5HT4 agonists?

Answer 31

Stimulate 5-HT4 receptors on nerve terminals in the GIT walls
→ ↑NT release and smooth muscle motor activity
→prokinetic/promotes GI motility

Question 32

What are 5 common AEs of 5HT4-receptor agonists?

Answer 32

1) Abdo pain
2) Nausea
3) Dizziness
4) Headache
5) Diarrhoea

Question 33

What is the difference in AEs of Cisapride and Prucalopride?

Answer 33

Cisapride: 5HT4 partial agonist
→ adverse cardiovascular effects (actions at hERG K+ channels)

Prucalopride: high-affinity 5-HT4 agonist (no CVS effects)

Question 34

When are 5-HT4 receptor agonists contraindicated?

Answer 34

During intestinal obstruction

Question 35

What are 2 laxative classes that should not be used in intestinal obstruction?

Answer 35

1) 5-HT4 receptor agonists (eg. prucalopride)
2) Bulk-forming agonists (eg. Psyllium)