Therapeutic Intervention in the Lower GI tract Flashcards

1
Q

Your patient has diarrhea.

Do you prescribe drugs as first-line tx?

A
  • First, acutely treat with rehydration and electrolyte balance (glucose, salts)
  • Reserve drugs for significant, persistant symptoms.
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2
Q

Anti-diarrheal tx:

list categories (6)

A
  1. Opioids (loperamide, diphenoxylate)
  2. Bulk forming and absorbents (fiber)
  3. Antibiotics
  4. Probiotics
  5. Bismuth subsalicylate (pepto-bismol)
  6. octreotide
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3
Q

What 2 narcotics are used to tx diarrhea?

  • mech
  • what’s the difference between them?
A
  1. Loperamide (Imodium)
  2. Diphenoxylate (Lomotil)
    - both are Mu agonists
    - Loperamide has no CNS penetration.
    - Diphenoxylate has CNS penetration, so risk of abuse. Give atropine (this is why Lomotil has atropine in it)
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4
Q

What OTC GI drug has abuse potential, and how it this prevented?

A

Diphenoxylate (Lomotil OTC)

  • opioid that has CNS penetration
  • Lomotil OTC has atropine in it. Atropine is an abuse deterrent b/c of anticholinergic symptoms
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5
Q

Anti-diarrhea tx:

-what are the 2 bulk forming and absorbent treatments?

A
  1. Kaopectin (not bolded)
  2. Fiber
    - absorb water, increase stool bulk
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6
Q

Loperamide

  • mech
  • tx what
A

(Imodium)

  • opioid, mu agonist. No CNS penetration
  • anti diarrhea
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7
Q

Diphenoxylate

  • mech
  • tx what
A
  • Opioid, mu agonist
  • anti diarrhea
  • CNS penetration so give with atropine to prevent abuse
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8
Q

Fiber

-how does it prevent diarrhea? (2)

A
  1. increases stool bulk
  2. may bind toxins
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9
Q

Bismuth subsalicylate

  • mech
  • tx what
A
  • mech still unknown, but thought to have anti secretory, anti-inflammatory, anti-microbial effects
  • Prevention/tx of episodic diarrhea (eg traveler’s diarrhea)
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10
Q

Octreotide

  • mech
  • tx of what (2)
A
  • somatostatin analog–inhibits hormone secretion from tumors of pancreas/GI tract
    1. Tumor-related secretory diarrhea (eg Carcinoid syndrome)
    2. also tx for variceal bleeding
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11
Q

Pt with carcinoid syndrome:

-Tx with what?

A

Octreotide

-somatostatin analog

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12
Q

Laxatives:

-general mechanisms (3)

A
  1. osmotic retention of luminal fluid
  2. decrease absorption/increase secretion of fluid
  3. alter motility
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13
Q

Fiber:

-divided into what types?

A

Fermented and Nonfermented fiber

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14
Q

Fermented fiber:

-mech as laxative (3)

A
  1. SCFA: prokinetic
  2. SCFA: trophic for endothelium
  3. Increase bacterial stool mass

Colonic bacteria produce SCFA (short chain fatty acids) by fermentation

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15
Q

Non-fermented fiber

-mech as laxative (2)

A
  1. retention of water
  2. increase stool bulk
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16
Q

Saline carthartics:

  • mech
  • list them (1 bolded, 3 others listed)
A
  • Laxatives–cause water retention with non-absorbable inorganic salts (magnesium or phosphate)
    1. Mg(OH)2–Milk of Magnesia
    2. MgSO4 –Epsom salt
    3. Mg citrate
    4. PO4 salts
17
Q

Lactulose

  1. mech
  2. tx what (2)
  3. side effects
A
  1. osmotic laxative. lactulose is a carb that cannot be absorbed, so gut bacteria ferment it to SCFA.
  2. -Constipation.
    - Hepatic encephalopathy (buildup of SCFA acidifies gut, decreaseing ammonia levels)
  3. gas, cramping (just like lactose intolerance)
18
Q

Polyethylene Glycol (PEG)

  • mech
  • give with what
A

(Miralax)

  • osmotic laxative
  • Can give with isotonic Na and K salts to prevent net ionic shift
19
Q

Ducosate salts

-mech

A
  • laxative
  • anionic surfactant of fat. This decreases the surface tension of stool, enhancing propulsion/mixing.
20
Q

Contact cathartics

  • mech
  • list them (2)
A
  • stimulant laxatives. Cause mucosal irritation/inflammation in colon
    1. Bisacodyl
    2. Senna
21
Q

Bisacodyl

-mech

A
  • “Contact cathartic”–stimulant laxative
  • causes mucosal irritation/inflammation
22
Q

Senna

-mech

A
  • “contact cathartic”–stimulant laxative
  • causes mucosal irritation/inflammation
  • prodrug–requires colonic bacteris.
23
Q

Lubiprostone

  • mech
  • Tx what? (2)
A
  • activtes Cl channels to increase fluid secretion
  • Tx for adult chronic constipation and women with IBS
  • this is a brand new drug
24
Q

Linaclotide

  • mech (2)
  • Tx what? (2)
A
  • increases cGMP by activating guanylate cyclase C on intestinal epithelial surface:
    1. increased intracellular cGMP–increase Cl and HCO3 secretion
    2. increased extracellular cGMP–decrease visceral pain of constipation

Tx:

  1. chronic idiopathic constipation
  2. IBS with constipation
25
Q

Opioid receptor antagonists:

  • list them (1 bolded, 1 other)
  • what does each tx?
A
  1. Methylnaltrexone
    - tx constipation
  2. Alvimopan (not bolded)
    - specifically tx post-op ileus, post bowel resection
26
Q

Methylnaltrexone

-mech

A
  • opioid receptor antagonist (mu receptor)
  • tx constipation
27
Q

IBS

  • tx based on serotonin
  • what is the concern with this drug?
A
  • Alosetron–5-HT3 antagonist
  • Restricted use, only for IBS. There is increased incidence of ischemic colitis with Alosetron
28
Q

IBD:
-how do patients respond to prednisone? (3)

A
  1. steroid-responsive: pts improves and remain in remission
  2. steroid-dependent: pts improve but relapse when dose is tapered
  3. steroid-unresponsive: no improvement even with high dose
29
Q

Budesonide

  • mech
  • tx what
A
  • enteric release steroid to target inflamed gut
  • Crohn’s disease
30
Q

5-aminosalicylates

  • mech
  • tx what
  • when contraindicated?
A

Mesalamine, Olsalazine, Sulfasalazine

  • mech unknown–possible IL1 and TNF production. NOT related to COX inhibition
  • Tx for IBD
  • contraindicated in salicylate allergy. (aspirin)
31
Q

5-aminosalicylates

  • list them (3)
  • what’s the difference
A
  1. Mesalamine
  2. Olsalazine (prodrug to mesalamine)
  3. Sulfasalazine (prodrug to mesalamine)

Mesalamine acts on jejunum and ileum, while Olsalazine and Sulfasalazine act on the colon (prodrugs must be acted on by colonic bacteria).

32
Q

Immunosuppresive drugs for IBD, list them:

  • non biologic (3 non-bolded)
  • biologic (1 bolded, 3 others)
A

non-biologic:

  1. 6-MP (azathioprine)–purine analog
  2. methotrexate–DHFR inhibitor
  3. cyclosporine–calcineurin inhibitor

biologic:

  1. Infliximab (bolded)–TNF-A inhibitor
  2. Adalimumab–TNF-A inhibitor
  3. Certolizumab–TNF-A inhibitor
  4. Natalizumab–4-integrin inhibitor
33
Q

Infliximab

  • mech
  • tx what?
  • side effects (including 2 black box warnings)
A
  • TNF-A inhibitor (immunoglobulin)
  • Tx IBD–UC and Crohn’s
  • Side effects: Lupus-like symptoms, delayed hypersensitivity, infection
  • black box: 1. increased TB
    2. increased non-H lymphoma
34
Q

What’s currently under investigation as potential tx for IBD?

A

-helminths and helminth-associated molecules

35
Q

How can antibiotics and probiotics treat IBD?

A

Certain bacteria can be pro- or anti-inflammatory. Antibiotics and probiotics are used to manipulate the colonic flora of IBD patients.