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Gastrointestinal 2 > Laxatives and Anti-Diarrheals > Flashcards

Laxatives and Anti-Diarrheals Flashcards

1
Q

What is IBS?

A

abdominal pain associated with constipation or diarrhea

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2
Q

What is inflammatory bowel disease (IBD)?

A
  • Crohn’s disease= infiltration of lymphocytes, macrophages, and submucosal fibrosis. Lesions are not confluent and contain “skip areas” of normal colon.
  • OR-
  • ulcerative colitis= lymphocytic and neutrophilic infiltrates (usually more distal than Crohn’s). Lesions are usually confluent.
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3
Q

How much water does normal peristalsis allow to be absorbed?

A

4 L

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4
Q

What happens to water absorption with inhibition of peristalsis (decreased motility)?

A

more water is extracted leading to harder stools (constipation)

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5
Q

What happens to water absorption with increased GI motility?

A

less water is extracted leading to watery stools (diarrhea)

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6
Q

*** What are the bulk-forming laxatives?

A
  • natural= PSYILLIUM and METHYLCELLULOSE
  • synthetic= POLYCARBOPHIL
  • these are indigestible, hydrophilic colloids that absorb water and form a bulky and lubricating gel that distends the colon and promotes peristalsis.
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7
Q

What can bacterial digestion of plant fibers (psyllium or methylcellulose) cause?

A

increased bloating and flatus

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8
Q

*** What are the osmotic laxatives?

A
  • drugs that increase water content of stool; used in acute constipation and cleanse bowel prior to colonoscopy.
  • nonabsorbable sugars/salts= MAGNESIUM HYDROXIDE (milk of magnesia), SORBITOL, LACTULOSE, PREPOPIK.
  • balanced POLYETHYLENE GLYCOL (PEG)= used for bowel prep for colonoscopy.
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9
Q

*** What are the surfactant agent laxatives (stool softeners)?

A
  • soften stool by permitting entrance of excess lipids and water.
  • used in children and debilitated adults to treat fecal impaction.
  • DOCUSATE (oral or enema)
  • GLYCERIN suppository
  • MINERAL OIL
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10
Q

What can long term use of surfactant laxatives (such as docusate) lead to?

A

impairment of fat-soluble vitamin (A, D, E, and K) absorption

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11
Q

*** What are the stimulant laxatives (cathartics)?

A
  • increase NO synthase activity and platelet activating factor (PAF); induce mild inflammatory response.
  • given PO and poorly absorbed.
  • SENNA
  • ALOE
  • CASCARA
  • mainly used in neurologically impaired pts
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12
Q

What can chronic use of stimulant laxatives (such as senna) lead to?

A

melanotic pegmentation of colon mucosa

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13
Q

What agent is used in conjunction with PEG for colonoscopy?

A
  • BISACODYL (diphenylmethane derivative)
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14
Q

*** What are the opioid receptor antagonist laxatives?

A
  • METHYLNALTREXONE= used to counteract opioid induced constipation. Given as a subcutaneous injection every 2 days.
  • ALVIMOPAN= short-term use to shorten the period of postoperative ileus in hospitalized patients who have undergone small or large bowel resection. Given orally, but not more than 7 days due to cardiovascular toxicity.
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15
Q

*** What are the opioid agonist antidiarrheal agents?

A
  • LOPERAMIDE= OTC and doesn’t cross the BBB, making it safe since there is no analgesic properties.
  • DIPHENOXYLATE= prescription needed.
  • All work by inhibiting presynaptic ACh release in submucosal and myenteric plexuses; increase colonic transit time and fecal H2O absorption.
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16
Q

What can higher doses of diphenoxylate (opioid agonist) cause?

A

CNS effects and lead to opioid dependence.

*commercial preps contain small amounts of atropine to discourage overdosage.

17
Q

** What drug is used in pts who are refractory to antimotility drugs like loperamide?

A

5-HT3 antagonists (ALOSETRON)= blocks 5-HT3 receptor of enteric cholinergic neurons, thus inhibiting colonic motility and increasing colonic transit time.

  • used to treat IBS in women when diarrhea is the main complaint.
  • metabolized by P450 enzymes
18
Q

** What does the GI serotonin 5-HT3 receptor do?

A
  • activates visceral afferent pain sensation resulting in unpleasant sensations (nausea, bloating, and pain).
  • increases colonic motility (left colon).
  • so using an antagonist to this will reduce the pain and prevent diarrhea.
19
Q

For what are the other “TRONs” used?

A

anti-emic agents

20
Q

*** What is a bad ADR of alesetron?

A

ischemic colitis (RARE). This is why it is reserved only for pts who do not respond to loperamide.

21
Q

What drugs are used to treat IBD?

A
  • 5-aminosalicylic acids (5-ASA)
  • antimicrobials (metronidazole, ciprofloxacin)
  • corticosteroids for ACUTE FLARES
  • immunosuppressives (azathioprine, mercaptopurine)= anti-tumor necrosis factor receptor antagonists.
  • methotrexate (Crohn’s) or cyclosporine (ulcerative colitis
22
Q

** What is the first line treatment drug for IBD?

A

5-ASA

23
Q

*** How do the 5-aminosalicylates work?

A
  • anti-inflammatory that works topically, not systemically in areas of diseased GI mucosa.
  • inhibits activity of nuclear factor-kB (NF-kB); transcription factor to induce pro-inflammatory cytokine expression.
  • sulfaSALAZINE, balSALAZINE, olSALAZINE…
  • you pick the drug based on the site where the lesion is (different drugs are coated to go further in the colon).
24
Q

What are some ADRs of aminosalicylates?

A
  • adverse effects of sulfonamides (allergy, rash, hemolytic anemia; interference with folic acid absorption).
25
Q

*** What are the TNF antagonists?

A
  • indicated for acute/chronic Crohn’s disease in moderate to severe conditions.
  • infliximab or adalimbumab for ulcerative colitis
  • work by preventing TNF from binding to receptors to inhibit pro-inflammatory cytokine expression.
26
Q

When are TNF antagonists used?

A
  • remission/maintenance in pts with inadequate response to mesalamine/steroids
27
Q

What are some anti-integrin therapies?

A

Natalizumab= monoclonal antibody against alpha-4 subunit of integrin on the surface of leukocytes. Prevents leukocyte binding to vascular endothelium (p-selectins and ICAM-1).

28
Q

When are anti-integrin therapies used?

A
  • when pts are refractory to TNF antagonists
29
Q

What is an ADR of anti-integrin therapy (natalizumab)?

A

multi-focal leukoenceophalopathy= degeneration of white matter in the brain

30
Q

*** How do you treat ulcerative colitis (IBD) that is less than 40 cm?

A

budesonide= newer corticosteroid formulated to release steroid in intestines to minimize systemic steroidal ADRs.
*coticosteroids inhibit production of inflammatory cytokines (TNF-a, IL-1, IL-8) and cell adhesion molecules.

31
Q

How do you treat ulcerative colitis (IBD) that is greater than 40 cm?

A
  • mild= oral mesalamine or sulfasalazine
  • moderate= steroids
  • severe= mercaptopurine or azathioprine
32
Q

How do you treat Crohn’s disease (IBD)?

A
  • mild= mesalamine or budesonide
  • moderate= steroids
  • severe= IV steroids, azathioprine, mercaptopurine, or anti-TNF drugs for longer term use for refractory cases to conventional therapy.

Gastrointestinal 2 (18 decks)

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