Laxatives: drugs used in constipation

Question 1

List out PHYSICAL drugs for constipation

Answer 1

• bulk-forming laxatives
• stool surfactant agents (softeners)
• osmotic laxatives

Question 2

List out PHYSIOLOGICAL drugs for constipation

Answer 2

• stimulant laxatives
• chloride channel activators
• opioid receptor antagonists
• serotonin 5-HT4- receptor agonists

Question 3

Examples of bulk-forming laxatives

• Plant products/fibers:
• Synthetic fibers:

Answer 3

1. Plant products/fibers:
   - psyllium (ispaghula husk), sterculia, agar, bran
   - methylcellulose (semi-synthetic)
2. Synthetic fibers: polycarbophil

Question 4

Mechanism of bulk-forming laxatives

Answer 4

• Bulk-forming laxatives are not digested but absorb liquid in the intestines and swell to form a soft, bulky stool.
• The bowel is then stimulated normally by the presence of the bulky mass. (promotes peristalsis)

Question 5

Main concerns of bulk-forming laxatives

Answer 5

• bacterial digestion of plant fibers within colon may lead to flatus, bloating & abdominal pain
• interference with absorption of other drugs

Question 6

What drugs are the safest & most natural way for patients with occasional constipation?

Answer 6

bulk-forming agents

Question 7

Examples of stool surfactant agents (softeners)

Answer 7

• docusate (oral or enema)
• glycerin (rectal suppository)
• mineral oil (oral)

Question 8

Mechanism of stool surfactant agents

Answer 8

• lowers surface tension, allowing water & lipids to penetrate
• mineral oil lubricates + retards water absorption from stool
• soften stool mass, promote peristalsis

Question 9

Main concerns of stool surfactant agents:

• if drug accidentally gets into lungs:
• long-term use:

Answer 9

Mineral oil:

• if drug accidentally gets into lungs: aspiration can result in severe lipid pneumonitis (aspiration pneumonia)
• long-term use: impairs absorption of fat-soluble vitamins (A,D,E & K)

Question 10

Examples of osmotic laxatives
1. Non-absorbable sugars or salts:
2.

Answer 10

1. Non-absorbable sugars or salts:
   - sugars: sorbitol, lactulose
   - salts: magnesium hydroxide; Mg citrate; sodium phosphate
2. Balanced Polyethene Glycol (PEG)

Question 11

Mechanism of osmotic laxatives

• osmotically-mediated water movement into the bowel increases ________________
• increased vol. stimulates _________
• high doses can produce ___________ within _______

Answer 11

• osmotically-mediated water movement into the bowel increases stool liquidity & volume
• increased vol. stimulates peristalsis
• high doses can produce bowel evacuation (purgation) within 1-3hrs

Question 12

Main concerns of osmotic laxatives

1. colonic bacteria act on _____, causing ___________
2. sodium phosphate:

Answer 12

• colonic bacteria act on sugars — causing severe flatus & abdominal pain
• sodium phosphate: can cause overabsorption of phosphate, sodium and under absorption of calcium, potassium
• Na phosphate can also cause cardiac arrythmias or acute renal failure (nephrocalcinosis)

Question 13

In osmotic laxatives,

• it is important to maintain ________ by increasing ______
• should not be used in patients who are _________, unable to ________ or who have ________ or ______

Answer 13

• maintain adequate hydration by increasing oral fluid intake
• should not be used in patients who are frail, elderly, on diuretics, unable to maintain adequate hydration or who have renal insufficiency or cardiac disease

Question 14

1. Non-absorbable sugars or salts:
   vs
2. Balanced Polyethene Glycol (PEG)

which is safer?
why?

Answer 14

Balanced Polyethene Glycol (PEG)

• avoid significant electrolyte shifts
• PEG altho an osmotically active sugar, does not produce sig. cramps or flatus

Question 15

Examples of stimulant laxatives

1. Anthraquinone derivatives
2. Diphenylmethane derivatives

Answer 15

1. Anthraquinone derivatives:
   - aloe, senna or cascara (oral or rectum)
2. Diphenylmethane derivatives
   - bisacodyl (oral or rectum)

Question 16

1. Anthraquinone derivatives
2. Diphenylmethane derivatives
   produce bowel movements in:
   _____ (oral)
   _____ (rectal)

Answer 16

1. Anthraquinone derivatives
6-12 hrs (oral)
2 hrs (rectal)

2. Diphenylmethane derivatives
   6-10 hrs (oral)
   30-60 mins (rectal)

Question 17

______ is used in conjunction with PEG for colonic cleansing prior to colonoscopy

Answer 17

Bisacodyl (stimulant laxative)

Question 18

Mechanisms of stimulant laxatives

• produce ______________
• ______________ of enteric nervous system
• ______________ secretion

Answer 18

• produce migrating colonic contractions
• direct stimulation of enteric nervous system
• colonic electrolyte & fluid secretion

Question 19

Main concerns of stimulant laxatives

• long-term use: may lead to ________ and ________of myenteric plexus → colonic atony & dilation
• anthraquinone derivatives: chronic use leads to __________
• diphenylmethane derivatives: phenolphthalein withdrawn due to __________

Answer 19

• long-term use: (may be needed in pts who are bed bound) may lead to dependence and destruction of myenteric plexus → colonic atony & dilation
• anthraquinone derivatives: chronic use leads to brown pigmentation of colon
• diphenylmethane derivatives: phenolphthalein withdrawn due to cardiac toxicity

Question 20

Examples of chloride channel activators

Answer 20

lubiprostone

Question 21

Mechanisms of chloride channel activators

• stimulate
• increases
• stimulates _____ & shortens __________

Answer 21

• stimulate type 2 chloride channels in small intestine
• increases chloride-rich fluid secretions
• stimulates motility & shortens intestinal transit time

Question 22

Main concerns of chloride channel activators

Answer 22

• return of constipation after discontinuation

- nausea due to delayed gastric emptying

Question 23

Avoid chloride channel activators in ______ patients

Answer 23

pregnant

Question 24

Example of opioid receptor antagonists

Answer 24

methylnaltrexone bromide

Question 25

Opioid receptor antagonists are administered _________ every ____

Answer 25

subcutaneously every 2 days

Question 26

Opioid receptor antagonists are used to treat opioid-induced constipation in ________ patients

Answer 26

palliative care

Question 27

Mechanisms of opioid receptor antagonists - they block ______________ - do not ______________ thus they do not ______________

Answer 27

- they block intestinal mu opioid receptors | - do not readily cross blood-brain barrier so do not block CNS analgesics effects

Question 28

Side effects of opioid receptor antagonists 1. Common: 2. Rare but severe:

Answer 28

1. Common: abdominal pain, nausea, diarrhoea, flatulence, sweating 2. Rare but severe: GI perforation

Question 29

Examples of serotonin 5-HT4- receptor agonists

Answer 29

cisapride, prucalopride

Question 30

Mechanisms of serotonin 5-HT4- receptor agonists - stimulate 5-HT4 receptors on __________ in the GI walls → increases ____________ & ____________ → ____________ → promotes ____________

Answer 30

- stimulate 5-HT4 receptors on nerve terminals in the GI walls → increases neurotransmitter release & smooth muscle motor activity → prokinetic effect → promotes GI motility

Question 31

Do NOT use serotonin 5-HT4- receptor agonists in the event of _________

Answer 31

intestinal obstruction

Question 32

Side effects of serotonin 5-HT4- receptor agonists 1. Common: 2. Severe-- - cisapride:

Answer 32

1. Common: abdominal pain, nausea, diarrhoea, dizziness, headache 2. Severe-- - cisapride: is a 5-HT4 partial agonist → adverse cardio events due to actions at hERG K+ channel

Question 33

Are there any side effects of prucalopride? Why?

Answer 33

prucalopride: high affinity 5-HT4 agonist → does not appear to have sig. cardio affects