GIT - Drugs used in constipation & diarrhea Flashcards
Causes of constipation (3)
- Insufficient intake of food & water
- Poor bowel motility & contractibility
- Obstruction (high/low, intrinsic lesions/extrinsic conditions)
Classes of laxatives & examples
Physical
- Bulk-forming Laxatives (Psyllium, Methylcellulose, Polycarbophil)
- Stool Surfactant Agents (Softeners) (Docusate, Glycerin, Mineral Oil)
- Osmotic Laxatives (Sorbitol, lactulose, magnesium hydroxide, balanced polyethylene glycol - PEG)
Physiological
- Stimulant Laxatives (Cathartics) (Aloe, Senna, Cascara, Bisacodyl)
- Chloride Channel Activators (Lubiprostone)
- Opioid Receptor Antagonists (Methylnaltrexone bromide, Alvimopan)
- 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)
- Bacterial digestion of plant fibers in the colon - flatus, bloating, abdominal pain
- Interacts with absorption of other drugs
Mechanism of action of stool surfactant agents
- Lowers surface tension - allows water & lipids to penetrate
- Mineral oil: lubricates bowel + retards water absorption from stool
Toxicity of mineral oil (3)
- Not palatable (mix with fruit juice)
- Aspiration - severe lipid pneumonia
- 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)
- Colonic bacteria act on sugars to produce gas - severe flatus & abdominal cramps
- Maintain adequate hydration by increasing oral fluid intake (more water moving into bowel)
- Sodium phosphate - hyperphosphatemia, hypernatremia, hypocalcemia, hypokalemia, cardiac arrhythmias, acute renal failure (due to tubular deposition of calcium phosphate)
- 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
- Bisacodyl + PEG for colonic cleansing prior to colonoscopy
Toxicity of stimulant laxatives (3)
- Long term/chronic use by neurologically impaired/bed bound - dependence, destruction of myenteric plexus - colonic atony & dilation
- Aloe, Senna, Cascara - brown pigmentation of colon (melanosis coli) with chronic use & possible carcinogenesis
- 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)
- Return of constipation after discontinuation
- Nausea due to delayed gastric emptying (30% of patients)
- 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
- Tegaserod, Cisapride - 5-HT4 partial agonists - adverse cardiovascular effects
Classes of anti-diarrheals & examples
- Opioid Agonists (Loperamide, Diphenoxylate)
- Colloidal Bismuth Compounds (Bismuth subsalicylate, bismuth subcitrate potassium)
- Kaolin & Pectin
- Bile Salt-Binding Resins (Cholestyramine, Colestipol, Colesevelam)
- Somatostatin-like Peptides (Octreotide)
- 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
- 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
- Rapid dissociation of bismuth subsalicylate in stomach - absorption of salicylate
- Salicylate inhibits intestinal PG production & Cl secretion
- Reduces stool frequency & liquidity in acute infectious diarrhea
Uses of colloidal bismuth compounds (2)
- Antimicrobial effects binds enterotoxins - Traveller’s Diarrhea
- Mucosal Protective agent in acid-peptic diseases
Toxicity of colloidal bismuth compounds (3)
- Harmless blackening of stool & darkening of tongue (liquid formulations)
- Bismuth toxicity (prolonged use, rare) - encephalopathy (ataxia, headaches, confusion, seizures)
- Salicylate toxicity (high dose)
Mechanism of action of kaolin & pectin
Absorbs bacterial toxins & fluids - decreased stool liquidity & number
Uses of kaolin & pectin
- Acute diarrhea, seldom used chronically
Toxicity of kaolin & pectin (2)
Not absorbed, little risk
- Constipation
- Binds & inhibits absorption of other medications
Mechanism of bile salt-binding resins (antidiarrheal)
- Conjugated bile salts are normally absorbed in the terminal ileum
- Diseases of the ileum (eg CD)/Surgical resection - malabsorption of bile salts - colonic secretory diarrhea
- Binds to bile salts - alleviates diarrhea caused by excess fecal bile salts
Toxicity of bile salt-binding resins (antidiarrheal) (3)
- Bloating, flatulence, constipation, fecal impaction
- Exacerbation of malabsorption of fat if underlying deficiency is present
- 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)
- Secretory diarrhea caused by GI neuroendocrine tumours (carcinoid, VIPoma)
- Diarrhea due to vagotomy, gastric dumping syndrome, short bowel syndrome, AIDS
Toxicity of octreotide (5)
- Steatorrhea - fat soluble vitamin deficiency - due to impaired pancreatic secretion
- Nausea, abdominal pain, flatulence, diarrhea
- Formation of gall sludge/stones
- Hypothyroidism (long term)
- 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
- Bacterial/Traveler’s Diarrhea
Toxicity of lacteol forte + Contraindications
Not systemically absorbed, little risk
- Important to maintain hydration
- Lactose intolerance - formulation contains lactose monohydrate
