GIT - Drugs used in constipation & diarrhea Flashcards Preview

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Flashcards in GIT - Drugs used in constipation & diarrhea Deck (36):

Causes of constipation (3)

1. Insufficient intake of food & water
2. Poor bowel motility & contractibility
3. Obstruction (high/low, intrinsic lesions/extrinsic conditions)


Classes of laxatives & examples

1. Bulk-forming Laxatives (Psyllium, Methylcellulose, Polycarbophil)
2. Stool Surfactant Agents (Softeners) (Docusate, Glycerin, Mineral Oil)
3. Osmotic Laxatives (Sorbitol, lactulose, magnesium hydroxide, balanced polyethylene glycol - PEG)

4. Stimulant Laxatives (Cathartics) (Aloe, Senna, Cascara, Bisacodyl)
5. Chloride Channel Activators (Lubiprostone)
6. Opioid Receptor Antagonists (Methylnaltrexone bromide, Alvimopan)
7. Serotonin 5-HT4 Receptor Agonists (Tegaserod, Cisapride, Prucalopride)


Mechanism of action of bulk-forming laxatives

Indigestible, hydrophilic colloids (fiber) - absorb water, form bulk, emollient gel that distends colon (increased stool mass) - promotes peristalsis


Toxicity of bulk-forming laxatives (2)

1. Bacterial digestion of plant fibers in the colon - flatus, bloating, abdominal pain
2. Interacts with absorption of other drugs


Mechanism of action of stool surfactant agents

1. Lowers surface tension - allows water & lipids to penetrate
2. Mineral oil: lubricates bowel + retards water absorption from stool


Toxicity of mineral oil (3)

1. Not palatable (mix with fruit juice)
2. Aspiration - severe lipid pneumonia
3. Long term use - impair absorption of fat soluble vitamins A, D, E, K


Mechanism of action of osmotic laxatives

Osmotically-mediated water movement into bowel increases stool liquidity & volume - stimulates peristalsis


Toxicity of osmotic laxatives + Contraindications (3+1)

1. Colonic bacteria act on sugars to produce gas - severe flatus & abdominal cramps
2. Maintain adequate hydration by increasing oral fluid intake (more water moving into bowel)
3. Sodium phosphate - hyperphosphatemia, hypernatremia, hypocalcemia, hypokalemia, cardiac arrhythmias, acute renal failure (due to tubular deposition of calcium phosphate)

1. Frail, elderly patients/on diuretics, unable to maintain adequate hydration, have renal insufficiency/cardiac disease


Mechanism of action of stimulant laxatives

Produce migrating colonic contractions, poorly understood - may include direct stimulation of enteric nervous system or colonic electrolyte & fluid secretion


Uses of stimulant laxatives

1. Bisacodyl + PEG for colonic cleansing prior to colonoscopy


Toxicity of stimulant laxatives (3)

1. Long term/chronic use by neurologically impaired/bed bound - dependence, destruction of myenteric plexus - colonic atony & dilation
2. Aloe, Senna, Cascara - brown pigmentation of colon (melanosis coli) with chronic use & possible carcinogenesis
3. Phenolphthalein withdrawn - cardiac toxicity


Mechanism of action of chloride channel activators

Stimulate type 2 chloride channels (CIC-2) in small intestine - increases chloride-rich fluid secretions (water follows) & stimulates motility & shortens intestinal transit time


Toxicity of chloride channel activators + Contraindications (2+1)

1. Return of constipation after discontinuation
2. Nausea due to delayed gastric emptying (30% of patients)

1. Pregnancy - thought to cross placental barrier, possibly teratogenic


Mechanism of action of methylnaltrexone bromide & alvimopan

Blocks intestinal mu-opioid receptors


Uses of methylnaltrexone bromide

Opioid-induced constipation in patients receiving palliative care administered SQ every 2 days


Uses of alvimopan

Post operative ileus in hospitalised patients after GI surgery, orally ≤5h before surgery & twice daily after surgery

- does not readily cross BBB - does not block CNS analgesic effects


Toxicity of alvimopan

Cardiovascular toxicity - restricted to short term use in hospitalized patients


Mechanism of action of serotonin 5-HT4 receptor agonists

Stimulates presynaptic 5-HT4 receptors on submucosal intrinsic primary afferent neurone (IPAN) terminals - enhance release of neurotransmitters eg CGRP - stimulates enteric neurons to promote peristaltic reflex & colonic mass movement


Toxicity of serotonin 5-HT4 receptor agonists

1. Tegaserod, Cisapride - 5-HT4 partial agonists - adverse cardiovascular effects


Classes of anti-diarrheals & examples

1. Opioid Agonists (Loperamide, Diphenoxylate)
2. Colloidal Bismuth Compounds (Bismuth subsalicylate, bismuth subcitrate potassium)
3. Kaolin & Pectin
4. Bile Salt-Binding Resins (Cholestyramine, Colestipol, Colesevelam)
5. Somatostatin-like Peptides (Octreotide)
6. Lyophilizate of Lactobacillus acidophilus (Lacteol forte)


Mechanism of action of opioid agonists

Acts on enteric nervous system - increases colonic transit time


Toxicity of opioid agonists

1. Potential for CNS effects including addiction & abuse
- Loperamide: does not cross BBB
- Diphenoxylate: high dose - CNS effects, long term - dependence
- Preparation often includes atropine to discourage overdose (anticholinergic adverse effects eg dry mouth + antidiarrheal action)


Mechanism of action of colloidal bismuth compounds

Precise mechanisms unknown
1. Rapid dissociation of bismuth subsalicylate in stomach - absorption of salicylate
2. Salicylate inhibits intestinal PG production & Cl secretion
3. Reduces stool frequency & liquidity in acute infectious diarrhea


Uses of colloidal bismuth compounds (2)

1. Antimicrobial effects binds enterotoxins - Traveller's Diarrhea
2. Mucosal Protective agent in acid-peptic diseases


Toxicity of colloidal bismuth compounds (3)

1. Harmless blackening of stool & darkening of tongue (liquid formulations)
2. Bismuth toxicity (prolonged use, rare) - encephalopathy (ataxia, headaches, confusion, seizures)
3. Salicylate toxicity (high dose)


Mechanism of action of kaolin & pectin

Absorbs bacterial toxins & fluids - decreased stool liquidity & number


Uses of kaolin & pectin

1. Acute diarrhea, seldom used chronically


Toxicity of kaolin & pectin (2)

Not absorbed, little risk
1. Constipation
2. Binds & inhibits absorption of other medications


Mechanism of bile salt-binding resins (antidiarrheal)

1. Conjugated bile salts are normally absorbed in the terminal ileum
2. Diseases of the ileum (eg CD)/Surgical resection - malabsorption of bile salts - colonic secretory diarrhea
3. Binds to bile salts - alleviates diarrhea caused by excess fecal bile salts


Toxicity of bile salt-binding resins (antidiarrheal) (3)

1. Bloating, flatulence, constipation, fecal impaction
2. Exacerbation of malabsorption of fat if underlying deficiency is present
3. Binds to some drugs


Mechanism of action of octreotide

Similar to somatostatin
- inhibits release of transmitters & hormones eg gastrin, VIP, 5-HT
- reduces intestinal & pancreatic secretions
- slows GI motility & inhibits gall bladder contraction


Uses of octreotide (2)

1. Secretory diarrhea caused by GI neuroendocrine tumours (carcinoid, VIPoma)
2. Diarrhea due to vagotomy, gastric dumping syndrome, short bowel syndrome, AIDS


Toxicity of octreotide (5)

1. Steatorrhea - fat soluble vitamin deficiency - due to impaired pancreatic secretion
2. Nausea, abdominal pain, flatulence, diarrhea
3. Formation of gall sludge/stones
4. Hypothyroidism (long term)
5. Bradycardia


Mechanism of action of lacteol forte

Adheres onto the surface of intestinal cells - normalizes intestinal flora by competitive exclusion/prevents overcolonization of these organisms


Uses of lacteol forte

1. Bacterial/Traveler's Diarrhea


Toxicity of lacteol forte + Contraindications

Not systemically absorbed, little risk
- Important to maintain hydration

1. Lactose intolerance - formulation contains lactose monohydrate