Drugs for constipation

Question 1

List SEVEN major groups of drugs used to treat constipation.

Answer 1

(1) Bulk-Forming Laxatives
(2) Stool Surfactant Agents
(3) Osmotic Laxatives
(4) Stimulant Laxatives
(5) Chloride Channel Activators
(6) Opioid Receptor Antagonists
(7) Serotonin 5-HT4-Receptor Agonists

Question 2

Name examples of bulk-forming laxatives that are (1) natural plant products/fibres; (2) Semi-synthetic plant fibres; and (3) Synthetic fibres

Answer 2

Examples of bulk-forming laxatives that are:

(1) Natural plant products/fibres: PSYLLIUM, Sterculia, Agar, Bran
(2) Semi-synthetic plant fibres: METHYLCELLULOSE
(3) Synthetic fibres: POLYCARBOPHIL

Question 3

bulk-forming laxatives MOA

Answer 3

• Indigestible, hydrophilic colloids (fibre) -> absorb water and form bulk, emollient gel -> distends colon (increases stool mass)
• Promotes peristalsis

Question 4

bulk-forming laxatives adverse effects

Answer 4

• bacterial digestion of plant fibres within the colon -> lead to flatus, bloating and abdominal pain
• avoid if an obstruction is suspected
• interaction with the absorption of other drugs

Question 5

stool surfactant agents examples

Answer 5

DOCUSATE (oral), Mineral oil(oral), glycerin

Question 6

stool surfactant agents MOA

Answer 6

• lower surface tension -> allow water/ lipids to penetrate stool
• mineral oil: lubricate + prevent water absorption from stool

Question 7

mineral oil adverse effects

Answer 7

• not palatable
• aspiration can cause lipid pneumonitis (aspiration pneumonia)
• long term -> impair absorption of fat soluble vitamins (A,D,E,K)

Question 8

examples of (1) sugar, (2) salt, and (3) balanced osmotic laxatives.

Answer 8

(1) Nonabsorbable Sugars: Sorbitol, LACTULOSE

(2) Nonabsorbable Salts: Magnesium hydroxide (milk of magnesia); Magnesium citrate; Sodium phosphate

(3) Balanced: Balanced Polyethylene Glycol (PEG)
* Balanced, isotonic solution of osmotically active sugar (PEG) and various salts

Question 9

osmotic laxatives MOA

Answer 9

• Osmotically-mediated water movement into the bowel increases stool liquidity (softer stool) and volume
• Increased volume stimulates peristalsis
• High doses can produce bowel evacuation (purgation) within 1 to 3 hours

Question 10

osmotic laxatives adverse effects

Answer 10

• colon bacteria act on sugars - FLATUS & ABDOMINAL CRAMPS
• must maintain adequate hydration

*PEG does not produce significant cramps/ flatus

Question 11

stimulant laxatives examples

Answer 11

(1) Natural product, Anthraquinone Derivatives:
- Aloe, Senna and Cascara (oral or per rectum)

(2) Synthetic, Diphenylmethane Derivatives
- Bisacodyl (oral or per rectum)
- Used in conjunction with PEG for colonic cleansing prior to colonoscopy

Question 12

stimulant laxatives MOA

Answer 12

• produce migrating colonic contractions
• stimulate enteric NS
• colonic electrolyte and fluid secretion

Question 13

stimulant laxatives adverse effects

Answer 13

• anthraquinone derivatives -> chronic use cause BROWN PIGMENTATION of colon

Question 14

laxatives comparison

Answer 14

bulk laxatives
- soft stool in 1-3 days

stimulant laxatives
- soft stool in 6-8hr

osmotic laxatives, PEG, suppositories (bisacodyl)
- watery stool in 1-3hr

Question 15

chloride channel activators examples

Answer 15

• LUBIPROSTONE
  *50% of patients have bowel movement within 24hrs of first dose

Question 16

chloride channel activators MOA

Answer 16

• Stimulates type 2 chloride channels (ClC-2) in the small intestine
• Increases chloride-rich fluid secretions
• stimulate motility, shorten intestinal transit time

Question 17

chloride channel activators adverse effects

Answer 17

• return of constipation after discontinuation
• AVOID in pregnancy
• nausea due to delayed gastric emptying

Question 18

lubiprostone indications (3)

Answer 18

• chronic idiopathic constipation
• irritable bowel syndrome with constipation
• constipation caused by opioid medications (other than diphenylheptane opioids e.g., methadone) in people with ongoing pain due to medical conditions other than cancer

Question 19

opioid receptor antagonists examples

Answer 19

• METHYLNALTREXONE
• subcutaneous every 2 days

Question 20

methylnatrexone indications

Answer 20

• OPIOID INDUCED constipation in patients receiving palliative care

Question 21

methylnatrexone MOA

Answer 21

• block intestinal mu (u) opioid receptors

Question 22

does methylnatrexone block CNS analgesic effects?

Answer 22

NO. does not cross BBB

Question 23

methylnatrexone adverse effects

Answer 23

common:
- stomach/ abdominal pain, nausea, diarrhea, flatulence, sweating

Question 24

serotonin 5-HT4 receptor agonist examples

Answer 24

PRUCALOPRIDE, cisapride

Question 25

serotonin 5-HT4 receptor agonist MOA

Answer 25

• stimulate 5-HT4 receptors on nerve terminals in GI wall -> increase neurotransmitter release & smooth muscle activity
• prokinetic effect -> promote GI motility

Question 26

5HT4 agonist indication

Answer 26

• Chronic idiopathic constipation.
• Constipation refractory to treatment with other laxatives

Question 27

5HT4 receptor agonist contradindication

Answer 27

INTESTINAL OBSTRUCTION

Question 28

5HT4 agonist adverse effects

Answer 28

• stomach pain, nausea, dizzy, headache, diarrhea

cisapride
- adverse CARDIOVASCULAR event due to action at hERG K+ channel