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DEMS: Unit 1 > Lower GI Pharmacology > Flashcards

Lower GI Pharmacology Flashcards

1
Q

Treatment of most simple constipation

A
  • proper diet
    • high fiber
  • exercise
  • adequate fluid intake
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2
Q

Classes of laxatives

A
  • bulk-forming
  • stimulant (irritant)
  • saline (osmotic)
  • wetting agents
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3
Q

Examples of bulk-forming/fiber laxatives

A
  • psyllium (metamucil)
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4
Q

Mechanism of ation of fiber/bulk-forming laxatives (psylium(Metamucil))

A
  • ~physiologic mechanism
  • facilitate passage and stimulate peristalsis via absorption of water ==> bulk expansion ==> swells and distends colon
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5
Q

MOA of saline (osmotically active agents) cathartics

A
  • Nonabsorbable ions in lumen ==> osmotic retention of water in intestine ==> increased peristalsis
  • Can be used in purging doses for food / drug poisoning
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6
Q

Examples of saline (osmotic) cathartics

A
  • Milk of magnesia [Mg(OH2)]
  • Phosphate enemas
  • Polyethlyene Glycol – electrolyte solutions (Miralax)
  • Lactulose (Chronulac)
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7
Q

Milk of Magnesia MOA/use

A
  • Most commonly used cathartics for mild to moderate constipation.
  • Avoid in renal dysfunction as long term use can lead to electrolyte imbalances.
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8
Q

Polyethlene Glycol – Electrolyte Solutions (PEGs): Examples & MOA

A
  • High volume solutions (4 liters of Colyte)
    • bowel cleansing prior to procedures.
    • sodium and potassium salts prevent net transfer of electrolytes into lumen.
  • Smaller volume solutions (250-500 ml of Miralax)
    • used for difficult to treat constipation
    • Prolonged, frequent, or excessive use may lead to electrolyte depletion.
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9
Q

Typical uses for each class of laxatives

A
  • laxatives used for tx of acute constipation
  • Fiber/bulk forming = usually first-line
  • saline (osmotic) cathartics = added to fiber as a second step
  • stimulant/irritants = try if fiber/saline fail
  • stool-wetting agents = prevention agents
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10
Q

Administration of fiber/bulk-forming laxatives

A
  • Effective in 12-24 hrs to 3 days
  • take with 8 oz water/juice
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11
Q

Drawbacks of fiber/bulk-forming laxatives

A
  • May combine and interact with other drugs (digoxin / salicylates)
  • requires spacing of doses
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12
Q

Examples of stimulat/irritant laxatives

A
  • Bisacodyl (Dulcolax)
  • castor oil
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13
Q

MOA, onset of Bisacodyl (Dulcolax)

A
  • = stimulant/irritant laxative
  • ==> increase in peristaltic activity by inducing low-grade inflammation (local irritation) in bowel to promote accumulation of water and electrolytes and stimulation of intestinal motility.
  • Proposed mechanisms include activation of prostaglandin-cAMP and NO-cGMP pathways.
  • Usually active within 6-10 hrs orally or 15-60 min rectally
  • Safe for chronic use in recommended doses
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14
Q

Drawbacks of bisacodyl

A
  • Effective, but potentially dangerous side effects (electrolyte / fluid deficiencies, severe cramping).
  • BUT most widely abused class
  • wide variation in the effective dose in individual patients ==> same dose may result in a lack of effect in some, but may produce cramping and fluid loss side effects in others
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15
Q

Examples of wetting agents and emollients

A
  • sufractant (docusate [Colace])
  • lubricant (mineral oil, olive oli)
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16
Q

Surfactant: examples, MOA

A
  • ex: docusate [Colace]
  • Acts as stool-softener (facilitates admixture of aqueous and fatty substances)
  • Role is primarily prevention.
  • Used in patients with cardiovascular disease / hernia / postpartum patients.
  • Often used in combination with stimulant laxative when initiating opioid analgesic therapy.
17
Q

Lubricant: Examples, MOA, drawbacks

A
  • e.g.: mineral oil, olive oil
  • coats fecal contents preventing colonic absorption of fecal water.
  • Use with caution in very young / elderly due to potential for aspiration into lungs.
18
Q

General approach to diarrhea tx

A
  • most patients w/sudden onset of diarrhea have benign, self-limiting illness that requires no tx/evaluation
  • severe cases w/infants, children, elderly: tx = oral rehydration therapy
  • most agents provide symptomatic relief of mild causes of acute diarrhea, but do not address underlying cause
19
Q

Opioids: Examples & MOA

A
  • e.g.: loperamide (Imodium)
  • MOA: mediated via opioid receptors, including effects on intestinal motility (m), intestinal secretion (d), and absorption (m and d).
  • Loperamide also has anti-secretory activity against cholera toxin
20
Q

Opioids: typical use

A
  • Loperamide is effective against traveler’s diarrhea
    • alone or in combination w/antimicrobial agents
  • Use should be discontinued if no improvement in 48 hours.
21
Q

Opioids: side effects

A
  • Low addiction liability for acute use due to low water solubility (difficult to dissolve and then inject)
  • Few adverse effects but overdosage can cause CNS depression (esp. in children) and paralytic ileus
  • May worsen Shigella infections
22
Q

Polycarbophil (Mitrolarr): MOA, use

A
  • Recognized by FDA as safe and effective (marked capacity to bind free fecal water).
  • Useful in diarrhea (absorbs 60X weight in H2O) and constipation (prevents fecal desiccation).
23
Q

Examples of adsorbents

A
  • kaolin/pectin (Kapectolin)
  • Bismuth subsalicylate (PeptoBismol)
24
Q

Adsorbents: MOA, use

A
  • adsorb “toxins” that cause irritation (of doubtful value); can also adsorb drugs, nutrients, digestive enzymes.
  • Generally, take after each loose bowel movement until diarrhea controlled.
  • Can usually manage mild to moderate diarrhea (promote “formed stools” and perception of decreased fluidity, but small effect on fluid volume excreted).
25
Q

Adsorbents: drawbacks

A
  • little effects on actual fluid volume excreted
  • avoid use of bismuth subsalicylate in children under 12
    • risk for Reye’s syndrome
26
Q

General pharm tx for IBS

A
  • low dose tricyclic antidepressants
    • goal: relieving abdominal pain and discomfort
  • antidiarrheal agents [loperamide] if diarrhea
    • goal: improving bowel function
  • fiber supplements / osmotic laxatives if constipation
    • goal: improving bowel function
  • Serotonin 5-HT3 Antagonists (Alosetron [Lotronex])
  • Serotonin 5-HT4 Agonists (Tegaserod [Zelnorm])
27
Q

Alostetron [Lotronex]: MOA & use

A
  • MOA: Block of 5-HT3 receptors on sensory and motor neurons reduces pain and inhibits colonic motility.
  • Use: Currently restricted to use only for treatment of severe IBS in women with diarrhea as the prominent symptom that have not responded to conventional therapies.
28
Q

Alosetron [Lotronex]: Side effects

A
  • Constipation in 30% of patients, requiring discontinuation in 10%.
  • I_schemic colitis_ in 3 of 1000 patients with some fatalities has led to restricted use
29
Q

Tegaserod[Zelnorm]: MOA, use

A
  • MOA: Agonist at serotonin 5-HT4 receptors that leads to stimulation of release of neurotransmitters involved in peristaltic reflex, promoting gastric emptying and intestinal motility
  • Use: Use is now restricted (as is alosetron) to women under 55, approved for treatment of I_BS patients with predominant constipation_ or chronic idiopathic constipation who haven’t responded to other treatments.
30
Q

Tegaserod [Zelnorm]: Side effects

A
  • Some diarrhea (10%) early in therapy that resolves within first few days of treatment.
  • Linked with heart attacks, strokes, and unstable angina leading to restricted use.

DEMS: Unit 1 (29 decks)

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