A- 33. Laxatives + Anti-diarrheals. Drugs promoting digestion. Liver and biliary drugs.

Question 1

Laxatives (groups)

Answer 1

1. Stool softeners - soften stool → permit water + lipids to penetrate it.
2. Bulk-forming Laxatives - indigestible hydrophilic colloids; absorb water + form emollient gel → bowel distension.
   * effect in 1-3 days; must take with adequate water to avoid mechanical obstruction.
   * not degraded in GI tract → bacterial fermentation → bloating.
3. Stimulant / Irritant Laxatives ( = cathartics)- induce colonic motility by stimulating enteral nervous system; inhibit Na/K ATPases and Na/water reabsorption from GI tract.
4. Osmotic Laxatives - effect epithelial transport of water / electrolytes.

Question 2

Stool softeners

Answer 2

1. Docusate - onset 1-3 days.
2. Mineral oil - onset 6-12 hours.
   * Side Effects:
   
   • Lipid pneumonia - due to aspiration (elderly/kids)
   • ↓ Lipid-soluble vitamin absorption

Question 3

Bulk-forming Laxatives

Answer 3

1. Natural: Psyllium
2. Semisynthetic: Methylcellulose
3. Synthetic: Polycarbophil

Question 4

Stimulant / Irritant Laxatives ( = cathartics)

Answer 4

1. Natural Anthraquinone Derivatives: 
(prodrugs transformed by bacteria into emodins; onset in 6 hours).
Side Effect:
melanosis coli - brown pigmentation of colon
Drugs: 
 a. Senna
 b. Aloe vera
 c. Cascara sagrada

2. Diphenylmethane Derivatives:
   a. Phenolphthalein - still has effect 2-3 day after administration
   * given in pregnancy / children
   * might be cardiotoxic (withdrawn in US)

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

c. Castor oil - 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 5

Osmotic Laxatives

Answer 5

1. Inorganic salts - not absorbed from GI tract
   a. Mg hydroxide - milk of magnesia; weak effect
   b. Mg sulfate - stronger; 1-3 hr onset
   
   • 25 g in water → ↓ ICP
     c. Na sulfate - stronger; 1-3 hr onset

Side Effects: (minimal sfx in short term use)

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

2. Non-absorbable sugars - normal doses → 1-3 day onset
   a. Mannitol - osmotic diuretic given parenterally; laxative orally
   b. Glycerin - ↑ rectal contractions; available as suppository
   c. Sorbitol
   d. Lactulose - 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
3. Polyethylene glycol (PEG)
   * combined with different ions → isotonic solution → no change to electrolyte levels
   * Indications:
   Pre-endoscopy - 2-4 L in 2-4 hours to clear GI tract

Question 6

Anti-diarrheals

Answer 6

1. Loperamide (no CNS entry)
2. Diphenoxylate (some CNS entry at high dose)
   * opioids used to decrease motility
3. Bismuth salts - kill some GI tract bacteria;

Question 7

Drugs promoting digestion

Answer 7

1. HCl - 10% HCl solution for supplementation in gastric hypoacidity; drink with straw to avoid dental damage
2. Pancreatic Enzymes (“Pancrelipase”) - taken orally to treat impaired digestion in steatorrhea, etc.; contain amylase, lipase, protease

Question 8

Hepatotoxins + Hepatoprotective Agents

Answer 8

1. Toxins: can cause acute or chronic hepatotoxicity; paracetamol, cytotoxic agents, alcohol, mushroom alkaloids, antituberculotics.
2. Silymarin and silibinin - from Milk Thistle herb; have hepatoprotective / antioxidative effect, help hepatocytes regenerate etc.; effects are more prevalent in long-term rather than acute use; given to alcoholics, etc. with chronic liver damage.
3. Lactulose - an osmotic laxative; GI flora metabolize it to form organic acids → ↓ GI tract pH → ↑ NH3 to NH4+ conversion → ↓ ammonia load → ↓ hepatic encephalopathy
4. Neomycin / Rifaximin - not absorbed from GI tract; kill ammonia-producing flora in GI tract.
5. N-Acetyl Cysteine - contains -SH groups which aid in sulfhydryl conjugation of hepatotoxins such as the toxic metabolite of paracetamol.

Question 9

Bile Drugs

Answer 9

1. Bile-acid binding resins such as cholestyramine - ↓ enterohepatic circulation + ↑ fecal excretion of bile; used to ↓ cholesterol levels and treat diarrhea due to upper small intestine resection.
2. Chenodiol and ursodeoxycholic acid - help dissolve small gallstones.