A-33. Drugs used in constipation(laxatives) and diarrhea. Drugs promoting digestion. Pharmacology of liver and biliary tract Flashcards
What are the 4 main groups of laxatives?
Stool softeners
Bulk forming laxatives
Stimulant/Irritant laxatives
Osmotic laxatives
Stool softeners.
Drugs with duration?
Docusate - onset 1-3 days
Mineral oil - onset 6-12 hours
Stool softeners.
MOA + Side effects?
Softened stool → permit water + lipids to penetrate it
Side effects:
● Lipid pneumonia - due to aspiration (elderly/kids)
● ↓ Lipid-soluble vitamin absorption
Bulk forming laxatives.
Drugs?
Natural: Psyllium
Semisynthetic: Methylcellulose
Synthetic: Polycarbophil
Bulk forming laxatives.
MOA and side effects?
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
Stimulant/Irritant laxatives 1.
Natural Anthraquinone Derivative drugs?
Special side effect?
Senna
Aloe vera
Cascara sagrada
Side effect
melanosis coli - brown pigmentation of colon
Stimulant/Irritant laxatives 2.
Diphenylmethane Derivative drugs?
Properties?
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● might be cardiotoxic (withdrawn in US)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
Stimulant/Irritant laxatives 3.
Castor oil. Properties?
Hydrolyzed into ricinoleic acid → local irritant + inhibits water reabsorption
Effect in 1-6 hours; very strong, rarely used; also contracts uterus (for atonic bleeding)
General MOA of Stimulant/Irritant laxatives?
They induce colonic motility by stimulating enteral nervous system; inhibit Na/K ATPases and Na/water reabsorption from GI tract
General MOA of Osmotic Laxatives?
They influence epithelial transport of water / electrolytes
Osmotic Laxatives 1.
Inorganic salts. Drugs, properties?
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.
Inorganic salts. Side effects?
Minimal side effects in short term use
Increased BP - Na absorbed long term use → fluid retention
Mg salts are CI in renal disease
Osmotic Laxatives 2.
Non-absorbable sugars. Drugs?
i. Mannitol
ii. Glycerin
iii. Sorbitol
iv. Lactulose (the most important one ac. to Timár)
Glycerin properties?
Increased rectal contractions; available as suppository
Lactulose properties?
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
Osmotic laxatives 3. Polyethylene glycol (PEG). Properties and usage?
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
Two opioids acting as antidiarrheal agents.
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.
What are bismuth salts used for? MOA?
They are used as antidiarrheal agenst and against H pylori/Peptic Ulcer.
They form a protective coat on the mucosa and inactivate toxins.
Examples of hepatotoxins?
Paracetamol, cytotoxic agents, alcohol, mushroom alkaloids, antituberculotics
List some hepatoprotective compounds!
Silymarin/silibinin, Lactulose, N-Acetylcysteine, Rixamixin, Neomycin.
The action of Silymarin and silibinin?
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
The action of Lactulose?
GI flora metabolize it to form organic acids → ↓ GI tract pH → ↑ NH3 to NH4+ conversion → ↓ ammonia load → ↓ hepatic encephalopathy
The action of N-Acetylcysteine?
contains -SH groups which aid in sulfhydryl conjugation of hepatotoxins such as the toxic metabolite of paracetamol (NAPQI)
The action of Rifamixin/Neomycin?
They are not absorbed from GI tract; kill ammonia-producing flora in GI tract
Example of a bile binding resin and MOA?
Cholestyramine
↓ enterohepatic circulation + ↑ fecal excretion of bile; used to ↓ cholesterol levels and treat diarrhea due to upper small intestine resection
Two bile production increasing agents that can also help dissolving small bile stones?
Chenodiol and Ursodeoxycholic acid
