A/37. Drugs used in constipation (laxatives) and diarrhea. Drugs promoting digestion. Pharmacology of liver and biliary tract

Question 1

Drugs need to know in this topic

Answer 1

plant fibers

MgSO4 magnesium-sulfate

lactulose

paraffin oil

sennoside

bisacodyl

diphenoxilate

loperamide

active charcoal

ursodeoxycholoc acid

acetylcysteine

silimarin

Question 2

Laxatives

Answer 2

1. Laxatives are commonly used in constipation, to accelerate the movement of food through the gastrointestinal tract.
2. Laxatives increase the potential for loss of pharmacologic effect of poorly absorbed, delayed-acting, and extended-release oral preparations by accelerating
   their transit through the intestines. May also cause electrolyte imbalances when used chronically.
3. Classified on the basis of their mechanism of action:

1. Irritants and stimulants

2. Bulk-forming laxatives

3. Osmotic laxatives

4. Stool softeners

5. Lubricant laxatives

Question 3

Antidiarrheal agents

Answer 3

all antidiarrheal agents are contraindicated in the management of bloody-diarrhea (ex. infectious colitis, erosive colitis);

Loperamide

Diphenoxylate

Activated charcoal

Question 4

Pharmacology of liver and biliary tract

Answer 4

N-Acetylcysteine

Ursodeoxycholicacid

Silymarin

Question 5

Sennoside

Answer 5

1. degradation product of senna acts directly as irritant on the colonic wall to induce fluid secretion and colonic motility
2. Taken orally (causes evacuation of the bowels within 8-10 h’) or rectally (effects within minutes)
3. May induce darkening of the stool and urine
4. Can be used in the treatment of opioid-induced constipation, and in evacuation of the bowel prior to surgery or invasive rectal/colonic examinations

Question 6

Bisacodyl

Answer 6

1. Potent stimulant of the colon, acts directly on nerve fibers in the colonic mucosa
2. Adverse effects include abdominal cramps, potential for atonic colon with prolonged use, and potential damage to the enteric protective coating
3. Can be used in treatment of chronic constipation, neurologic bowel dysfunction, and pre-operative preparation

Question 7

Plant fiber

Answer 7

1. Indigestible parts of fruits and vegetables
2. Form gels in the large intestine → causing water retention (absorb water from the colon) → intestinal distension → increased peristaltic activity

Question 8

Magnesium-sulphate
Magnesium-citrate
Magnesium-hydroxide

Answer 8

1. Non-absorbable salts that hold water in the intestinal lumen by means of osmosis
2. This distends the bowel → increasing intestinal activity → produces defecation in a few hours

Question 9

Lactulose

Answer 9

1. Semisynthetic disaccharide sugar, cannot be hydrolyzed by intestinal enzymes
2. Oral doses are degraded in the colon by colonic bacteria into lactic, formic, and acetic acids
3. This increases osmotic pressure, causing fluid accumulation, colon distension, soft stools, and defecation
   *Lactulose is also used in the management of hepatic encephalopathy (reduces ammonia levels

Question 10

Docusate(not in the list)

Answer 10

1. Surface-active agents that become emulsified with stool, produce softer feces and ease passage
2. May take days to become effective; used for prophylaxis rather than acute treatment

Question 11

Paraffin oil

Answer 11

1. Act by facilitating the passage of hard stools (lubricant activity)
2. Should be taken orally in an upright position to avoid aspiration and potential lipoid pneumonia

Question 12

Loperamide

Answer 12

1. Synthetic opioid derivatives
2. Activate μ receptors in the enteric nervous system → inhibit Ach release
   → decrease motility
3. Minimal analgesic effects
4. Oral
5. Hepatic P450 metabolism
6. Does not cross the blood-brain-barrier
7. Non-specific, non-infectious diarrhea
   * *Side effects:**
8. Abdominal cramps

Question 13

Diphenoxylate

Answer 13

1. Synthetic opioid derivatives
2. Activate μ receptors in the enteric nervous system → inhibit Ach release
→ decrease motility
3. Minimal analgesic effects

1. Oral
2. Hepatic P450 metabolism
3. Crosses the blood-brain-barrier at high
   doses
   #Formulated with muscarinic antagonist
   (atropine) to reduce abuse liability
4. Non-specific, non-infectious diarrhea
   * *Side effects:**
5. Abdominal cramps
6. CNS effects and toxicity with higher doses

Question 14

Activated charcoal

Answer 14

Attract and expel ingested toxins from the gastrointestinal tract

Oral

1. Non-specific, non-infectious diarrhea

Question 15

N-Acetylcysteine

Answer 15

Provides -SH groups

1. Oral, IV, inhaled
2. T1/2 5-6 h’
3. Hepatic P450 metabolism
4. Acetaminophen toxicity
   (best given within 8-10 h’ of overdose)
5. Mucolytic agent (used in COPD and CF)
   Side effects:
6. Nausea, vomiting
7. Anaphylaxis-like allergic reaction

Question 16

Ursodeoxycholic acid (Ursodiol)

Answer 16

1. Reduces cholesterol absorption
2. Used to dissolve cholesterol gallstones
3. Potential anti-inflammatory effects
   in the GI
4. Oral
   * *Contraindications:**
5. Acute hepatitis
6. Biliary obstruction
7. Cholelithiasis (patients unfit for cholecystectomy)
8. Prophylaxis (patients undergoing rapid weight loss or
   bariatric surgery – biliary cholesterol oversaturation)
9. Primary biliary cirrhosis (PBC)

• *Side effects (generally well-tolerated)**
  1. Diarrhea

Question 17

Silymarin

Answer 17

1. Milk thistle extract derived from the fruit and seeds of ‘Silybum marianum’
2. Support liver function
3. Oral
4. Potentially protects against liver injury caused by alcohol, acetaminophen, and Amanita mushrooms
5. Antidote to Amanita phalloides mushroom poisoning