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systemic pharmaco > GIT - Drugs used in constipation & diarrhea > Flashcards

GIT - Drugs used in constipation & diarrhea Flashcards

1
Q

Causes of constipation (3)

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

Classes of laxatives & examples

A

Physical

  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)

Physiological

  1. Stimulant Laxatives (Cathartics) (Aloe, Senna, Cascara, Bisacodyl)
  2. Chloride Channel Activators (Lubiprostone)
  3. Opioid Receptor Antagonists (Methylnaltrexone bromide, Alvimopan)
  4. Serotonin 5-HT4 Receptor Agonists (Tegaserod, Cisapride, Prucalopride)
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3
Q

Mechanism of action of bulk-forming laxatives

A

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

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4
Q

Toxicity of bulk-forming laxatives (2)

A
  1. Bacterial digestion of plant fibers in the colon - flatus, bloating, abdominal pain
  2. Interacts with absorption of other drugs
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5
Q

Mechanism of action of stool surfactant agents

A
  1. Lowers surface tension - allows water & lipids to penetrate
  2. Mineral oil: lubricates bowel + retards water absorption from stool
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6
Q

Toxicity of mineral oil (3)

A
  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
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7
Q

Mechanism of action of osmotic laxatives

A

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

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8
Q

Toxicity of osmotic laxatives + Contraindications (3+1)

A
  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)
  4. Frail, elderly patients/on diuretics, unable to maintain adequate hydration, have renal insufficiency/cardiac disease
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9
Q

Mechanism of action of stimulant laxatives

A

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

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10
Q

Uses of stimulant laxatives

A
  1. Bisacodyl + PEG for colonic cleansing prior to colonoscopy
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11
Q

Toxicity of stimulant laxatives (3)

A
  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
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12
Q

Mechanism of action of chloride channel activators

A

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

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13
Q

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

A
  1. Return of constipation after discontinuation
  2. Nausea due to delayed gastric emptying (30% of patients)
  3. Pregnancy - thought to cross placental barrier, possibly teratogenic
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14
Q

Mechanism of action of methylnaltrexone bromide & alvimopan

A

Blocks intestinal mu-opioid receptors

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15
Q

Uses of methylnaltrexone bromide

A

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

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16
Q

Uses of alvimopan

A

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
17
Q

Toxicity of alvimopan

A

Cardiovascular toxicity - restricted to short term use in hospitalized patients

18
Q

Mechanism of action of serotonin 5-HT4 receptor agonists

A

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

19
Q

Toxicity of serotonin 5-HT4 receptor agonists

A
  1. Tegaserod, Cisapride - 5-HT4 partial agonists - adverse cardiovascular effects
20
Q

Classes of anti-diarrheals & examples

A
  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)
21
Q

Mechanism of action of opioid agonists

A

Acts on enteric nervous system - increases colonic transit time

22
Q

Toxicity of opioid agonists

A
  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)
23
Q

Mechanism of action of colloidal bismuth compounds

A

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
24
Q

Uses of colloidal bismuth compounds (2)

A
  1. Antimicrobial effects binds enterotoxins - Traveller’s Diarrhea
  2. Mucosal Protective agent in acid-peptic diseases
25
Q

Toxicity of colloidal bismuth compounds (3)

A
  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)
26
Q

Mechanism of action of kaolin & pectin

A

Absorbs bacterial toxins & fluids - decreased stool liquidity & number

27
Q

Uses of kaolin & pectin

A
  1. Acute diarrhea, seldom used chronically
28
Q

Toxicity of kaolin & pectin (2)

A

Not absorbed, little risk

  1. Constipation
  2. Binds & inhibits absorption of other medications
29
Q

Mechanism of bile salt-binding resins (antidiarrheal)

A
  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
30
Q

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

A
  1. Bloating, flatulence, constipation, fecal impaction
  2. Exacerbation of malabsorption of fat if underlying deficiency is present
  3. Binds to some drugs
31
Q

Mechanism of action of octreotide

A

Similar to somatostatin

  • inhibits release of transmitters & hormones eg gastrin, VIP, 5-HT
  • reduces intestinal & pancreatic secretions
  • slows GI motility & inhibits gall bladder contraction
32
Q

Uses of octreotide (2)

A
  1. Secretory diarrhea caused by GI neuroendocrine tumours (carcinoid, VIPoma)
  2. Diarrhea due to vagotomy, gastric dumping syndrome, short bowel syndrome, AIDS
33
Q

Toxicity of octreotide (5)

A
  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
34
Q

Mechanism of action of lacteol forte

A

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

35
Q

Uses of lacteol forte

A
  1. Bacterial/Traveler’s Diarrhea
36
Q

Toxicity of lacteol forte + Contraindications

A

Not systemically absorbed, little risk
- Important to maintain hydration

  1. Lactose intolerance - formulation contains lactose monohydrate

systemic pharmaco (18 decks)

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