A-33. Drugs used in constipation(laxatives) and diarrhea. Drugs promoting digestion. Pharmacology of liver and biliary tract

Question 1

What are the 4 main groups of laxatives?

Answer 1

Stool softeners
Bulk forming laxatives
Stimulant/Irritant laxatives
Osmotic laxatives

Question 2

Stool softeners.

Drugs with duration?

Answer 2

Docusate - onset 1-3 days

Mineral oil - onset 6-12 hours

Question 3

Stool softeners.

MOA + Side effects?

Answer 3

Softened stool → permit water + lipids to penetrate it

Side effects:
● Lipid pneumonia - due to aspiration (elderly/kids)
● ↓ Lipid-soluble vitamin absorption

Question 4

Bulk forming laxatives.

Drugs?

Answer 4

Natural: Psyllium

Semisynthetic: Methylcellulose

Synthetic: Polycarbophil

Question 5

Bulk forming laxatives.

MOA and side effects?

Answer 5

Indigestible hydrophilic colloids; absorb water + form emollient gel → bowel distension

Effect in 1-3 days; must take with adequate water to avoid mechanical obstruction

SIde effect:
not degraded in GI tract → bacterial fermentation → bloating

Question 6

Stimulant/Irritant laxatives 1.

Natural Anthraquinone Derivative drugs?
Special side effect?

Answer 6

Senna
Aloe vera
Cascara sagrada

Side effect
melanosis coli - brown pigmentation of colon

Question 7

Stimulant/Irritant laxatives 2.

Diphenylmethane Derivative drugs?
Properties?

Answer 7

Phenolphthalein - still has effect 2-3 day after administration
● given in pregnancy / children
● might be cardiotoxic (withdrawn in US)

Bisacodyl - effect in 8 hours (enterohepatic circulation)
● prodrug → active metabolite is eliminated in GI tract, causing effect

Question 8

Stimulant/Irritant laxatives 3.

Castor oil. Properties?

Answer 8

Hydrolyzed into ricinoleic acid → local irritant + inhibits water reabsorption

Effect in 1-6 hours; very strong, rarely used; also contracts uterus (for atonic bleeding)

Question 9

General MOA of Stimulant/Irritant laxatives?

Answer 9

They induce colonic motility by stimulating enteral nervous system; inhibit Na/K ATPases and Na/water reabsorption from GI tract

Question 10

General MOA of Osmotic Laxatives?

Answer 10

They influence epithelial transport of water / electrolytes

Question 11

Osmotic Laxatives 1.

Inorganic salts. Drugs, properties?

Answer 11

Mg hydroxide - milk of magnesia; weak effect

Mg sulfate - stronger; 1-3 hr onset
● 25 g in water → ↓ ICP

Na sulfate - stronger; 1-3 hr onset

They are not absorbed in the GI tract.

Question 12

Inorganic salts. Side effects?

Answer 12

Minimal side effects in short term use

Increased BP - Na absorbed long term use → fluid retention
Mg salts are CI in renal disease

Question 13

Osmotic Laxatives 2.

Non-absorbable sugars. Drugs?

Answer 13

i. Mannitol
ii. Glycerin
iii. Sorbitol
iv. Lactulose (the most important one ac. to Timár)

Question 14

Glycerin properties?

Answer 14

Increased rectal contractions; available as suppository

Question 15

Lactulose properties?

Answer 15

Degraded to organic acids in GI tract (lactic, acetic) → ↓ pH → stimulates motility; osmotic effect via non-absorbability

In liver damage → ↑ risk of hepatic encephalopathy → ↓ pH with lactulose in GI tract → ↑ ammonia-to-ammonium conversion → ↓ ammonia reabsorption

Question 16

Osmotic laxatives 3. 
Polyethylene glycol (PEG). Properties and usage?

Answer 16

Combined with different ions → isotonic solution → no change to electrolyte levels

Indicated Pre-endoscopy - 2-4 L in 2-4 hours to clear GI tract

Question 17

Two opioids acting as antidiarrheal agents.

Answer 17

Loperamide (no CNS entry) and Diphenoxylate (some CNS entry at high dose)

They decrease motility

Loperamide is the only off label opioid

Diphenoxylate is much stronger and rarely used.

Question 18

What are bismuth salts used for? MOA?

Answer 18

They are used as antidiarrheal agenst and against H pylori/Peptic Ulcer.

They form a protective coat on the mucosa and inactivate toxins.

Question 19

Examples of hepatotoxins?

Answer 19

Paracetamol, cytotoxic agents, alcohol, mushroom alkaloids, antituberculotics

Question 20

List some hepatoprotective compounds!

Answer 20

Silymarin/silibinin, Lactulose, N-Acetylcysteine, Rixamixin, Neomycin.

Question 21

The action of Silymarin and silibinin?

Answer 21

They have hepatoprotective / antioxidative effect, help hepatocytes regenerate.

The effects are more prevalent in long-term rather than acute use; given to alcoholics, etc. with chronic liver damage

Question 22

The action of Lactulose?

Answer 22

GI flora metabolize it to form organic acids → ↓ GI tract pH → ↑ NH3 to NH4+ conversion → ↓ ammonia load → ↓ hepatic encephalopathy

Question 23

The action of N-Acetylcysteine?

Answer 23

contains -SH groups which aid in sulfhydryl conjugation of hepatotoxins such as the toxic metabolite of paracetamol (NAPQI)

Question 24

The action of Rifamixin/Neomycin?

Answer 24

They are not absorbed from GI tract; kill ammonia-producing flora in GI tract

Question 25

Example of a bile binding resin and MOA?

Answer 25

Cholestyramine

↓ enterohepatic circulation + ↑ fecal excretion of bile; used to ↓ cholesterol levels and treat diarrhea due to upper small intestine resection

Question 26

Two bile production increasing agents that can also help dissolving small bile stones?

Answer 26

Chenodiol and Ursodeoxycholic acid