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GI > Bahouth - Diarrhea and Constipation > Flashcards

Bahouth - Diarrhea and Constipation Flashcards

1
Q

How much water is normally excreted in the stool? Where does it all go?

A
  • Normal stool water: 125mL +/- 75mL (so, diarrhea when H2O in stool exceeds 200mL)
  • About 9L enters gut each day (2L dietary)
    1. 4.5L absorbed by jejunum
    2. 3.5L by ileum
    3. 900mL by colon
  • NOTE: PNS activity wanes as we age, INC chances of constipation (diabetes also a contributing factor)
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2
Q

What are the 5 groups of laxatives?

A
  • Dietary fiber and bulk-forming: all taken orally, and INC water delivery to the colon
  • Surfactant: stool softeners that lower surface tension b/t gut contents and intestinal wall
  • Osmotic: contain Mg cations or o/non-absorbable molecules, and exert an osmotic effect that retains water in the lumen of the G. I. tract
  • Stimulant: predominantly act on lg bowel, and INC intestinal permeability, back diffusion of water and electrolytes, and propulsive contractility
  • Miscellaneous
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3
Q

What are the 4 dietary fiber/bulk-forming laxatives?

A
  • Psyllium husk
  • Semisynthetic celluloses
  • Polycarbophils
  • Functional fiber
  • NOTE: all taken orally, and form gritty substance when added to water (except new formulation of functional fiber that completely dissolves and has no taste)
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4
Q

What are the class, characteristics, AE’s for psyllium husk?

A
  • CLASS: dietary fiber/bulk-forming laxatives
  • CHARACTERISTICS: hydrophilic muciloid that forms gelatinous mass when mixed with water
  • AE’s: allergic rxns, flatulence, borborygmi, intestinal obstruction
    1. May INH coumadin (Warfarin) absorption
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5
Q

What are the class, characteristics, AE’s for semi-synthetic celluloses (carboxymethyl and methyl)?

A
  • CLASS: dietary fiber/bulk-forming laxatives
  • CHARACTERISTICS: hydrophilic and digestable; form a colloid mass with water
  • AE’s: may bind and impede drug absorption
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6
Q

What are the class, characteristics, AE’s for polycarbophils?

A
  • CLASS: dietary fiber/bulk-forming laxatives
  • CHARACTERISTICS: hydrophilic, polyacrylic resins; absorb 60-100x their weight in water
  • AE’s: Ca+ polycarbophils release Ca+ that is contraindicated with tetracycline usage
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7
Q

What are the class, characteristics, MOA, and net result of functional fiber?

A
  • CLASS: dietary fiber/bulk-forming laxatives
  • CHARACTERISTICS: isolated, non-digestible carbs that have beneficial effects in humans
    1. Best type of fiber is dietary fiber -> advise to INC intake b/c diet with sufficient amt of fiber should foster normal bowel function (25-38g/d)
  • MOA: INC delivery of water to colon, INC bulk, and reduce pressure in sigmoid colon
  • NET RESULT: more formed stools
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8
Q

What are the 3 surfactant laxatives? MOA?

A
  • Docusates: dioctyl sodium (Ca2+) sulfo-succinate
  • Poloxamers
  • Castor oil
  • MOA: reduce water tension b/t stool and intestinal epithelium
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9
Q

What are class, characteristics, and AE’s for the docusates?

A
  • CLASS: surfactant laxatives (capsules)
  • CHARACTERISTICS: anionic surfactant primarily used as stool softener
    1. Reduce strain of defecation, and DEC water tension b/t stool and intestinal epithelium
    2. No effect on intestinal peristalsis
  • AE’s: not for use during abdominal pain or vomiting
    1. Can irritate intestinal mucosa and INC absorption of other drugs
    2. Recommended for SHORT-TERM USE: w/use <1 (to 2) wks, no long-term consequences, but can cause epithelial damage and inflammation when used long-term
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10
Q

What are the class, characteristics, and AE’s for the poloxamers?

A
  • CLASS: surfactant laxatives
  • CHARACTERISTICS: non-ionic surfactant similar to docusates; stool softener
  • AE’s: diarrhea
    1. Not for use during abdominal pain or N/V
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11
Q

What are the class, characteristics, and AE’s for castor oil?

A
  • CLASS: surfactant laxatives
  • CHARACTERISTICS: rapid-acting, effective anionic surfactant that produces CATHARSIS (complete evacuation of the colon; much more potent)
    1. Stimulates intestinal peristalsis
  • AE’s: colic, dehydration, and electrolyte imbalance with OD
    1. Can induce uterine contraction in pregnant women
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12
Q

What are the 2 stimulant laxatives? MOA?

A
  • Diphenylmethanes (bisacodyl)
  • Anthraquinones
  • MOA: predominantly act on LARGE BOWEL
    1. INC permeability of intestinal mucosa
    2. Act on tight junctions to INC back-diffusion of water and electrolytes
    3. INC propulsive contractility of colon by stimulating colonic mucosal myenteric plexus: food matter travels through the colon faster, allowing less absorption
    4. Stimulate PG synthesis, and INC intestinal secretions
  • MOST POTENT class of laxatives
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13
Q

What are the class, characteristics, and AE’s for diphenylmethans (bisacodyl)?

A
  • CLASS: stimulant laxatives
  • CHARACTERISTICS: prodrug converted by enteric bacteria into deacetyl active form
    1. Administered in enteric-coated tablets so it doesn’t dissolve until it gets to intestine
    2. Taken at night, like all laxatives, and produces effects in the morning
  • AE’s: OD can cause excessive fluid and electrolyte loss, intestinal enterocyte damage leading to colonic inflammatory response
    1. Need to ensure pt. has high enough fluid intake
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14
Q

What are the class, characteristics, and AE’s for anthraquinones?

A
  • CLASS: stimulant laxatives
  • CHARACTERISTICS: natural derivatives of Lilliaceae plants (senna, cascara); more gentle than synthetic drugs -> acts by promoting colonic motility
  • AE’s: may cause melanotic (dark) pigmentation of colonic mucosa and abnormal urine coloration, at least for the first couple of days
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15
Q

What are the 3 types of saline/osmotic laxatives? MOA?

A
  • Mg-containing
  • Phosphate-containing
  • Non-digestible sugars/alcohols: lactulose, glycerin, and PEG electrolyte solution (GOLYTELY)
  • MOA: contain Mg cations or other non-absorbable molecules, and exert osmotic effect that retains water in lumen of GI tract
    1. Largest class, and each has a different use
    2. REMEMBER: absorption in colon is iso-osmotic; ions not normally absorbed by the gut
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16
Q

Class, MOA, and examples of Mg-containing laxatives?

A
  • Saline/osmotic laxatives
  • MOA: produce laxation by osmotic effect + release of CCK, which INC intestinal motility and secretion
  • Mg sulfate: epsom salt (poor man’s laxative)
  • Mg hydroxide: type of thing dr. prescribes; take at night (pts after surgery)
  • Mg citrate: cathartic (4-8oz dose)
17
Q

Phosphate-containing laxatives?

A
  • Saline/osmotic laxatives
  • Given as enema (fleet) or oral sodium phosphate tablets
  • Enemas traditionally used in severe constipation, or in prep for lower colonic exams
  • Now have oral tablets, which are used in prep for colonoscopy, providing complete evacuation of the bowel (take 32 tablets overnight)
18
Q

Lactulose class, characteristics, and MOA?

A
  • CLASS: saline/osmotic laxatives
  • CHARACTERISTICS: semi-synthetic disaccharide that is not absorbed, and has osmotic laxative effect + diarrhea that discharges ammonium ions
    1. Metabolized by enteric bacteria to organic acids like lactic, formic, and acetic acid
  • MOA: fecal acidifier used in mgmt of symptoms of liver failure (portal systemic encephalopathy)
    1. Acidification of stool traps ammonia in non-toxic ammonium form (ammonia detoxification is important func of liver, which converts it to urea)
    2. Retards non-ionic diffusion of ammonia from colon to blood b/c NH3 is in ammonium form, which is non-diffusable
  • REMEMBER: the sources of ammonia are proteins and enteric bacteria, and it diffuses freely -> pts with liver failure can get lethargic, and even go into coma
19
Q

Glycerin class and characteristics?

A
  • CLASS: saline/osmotic laxatives
  • CHARACTERISTICS: osmotic and lubricant effects
    1. Suppository
20
Q

Polyethylene glycol electrolyte solution class and characteristics?

A
  • CLASS: saline/osmotic laxatives
  • CHARACTERISTICS: dissolved into 4L and ingested for colonoscopy, where complete evacuation is needed
    1. Collapsed, plastic gallon they have to fill with water, and drink overnight
  • Aka, GOLYTELY
21
Q

What are the 2 miscellaneous laxatives?

A
  • Mineral oil: mixture of hydrocarbons that penetrates and softens stool
  • Castor oil: an emulsion that irritates mucosa and produces a cathartic effect
    1. INC mucous secretion
22
Q

What laxatives are used in the mgmt of IBS?

A
  • IBS: bloating and constipation of unknown etiology; 10:1 female
  • 2 drugs currently approved: target Cl- channel (Lubiprostone) or GC system (Linaclotide)
    1. LUBIPROSTONE: acts directly on Cl- channels, activating them in protein kinase A-independent fashion -> INC intestinal fluid secretion, motility, and alleviates the symptoms associated with chronic idiopathic constipation
    2. LINACLOTIDE: peptide agonist of guanylate cyclase 2C that acts on intestinal cells to indirectly activate the Cl- channel
23
Q

Why is laxative abuse a problem?

A
  • Overuse leads to thorough constipation that requires several days to accumulate bulk
  • Lag in defecation interpreted as continued constipation, so pts take more laxatives, leading to a vicious cycle
  • If continued, the bowel becomes unresponsive
    1. Colon damage + psych effect -> need to INC fiber in diet to repair GI tract, and overcome constipation
24
Q

What are the 3 groups of anti-diarrheals?

A
  • Absorb/adsorbers: pull in water, bacteria, viruses, or toxin
  • Opiates
  • Anti-cholinergics
25
Q

Describe the absorptive/adsorptive anti-diarrheal agents.

A
  • Agents that ABSORB water: pull water and swell, producing more formed stool
    1. Cellulose derivatives, semi-synthetic poly-saccharides, fiber
    2. Before pts take these, need to rule out C. diff/bacterial infection
  • ADSORBERS of etiological factors in lumen: bismuth subsalicylate (Pepto-Bismol, Kaopectate) & charcoal
    1. Adsorb harmful bacteria, viruses, or toxin
    2. Bismuth subsalicylate effective in prevention of Traveler’s diarrhea and in tx of H. pylori
26
Q

What are the MOA’s of the opiates?

A
  • DEC salivary, gastric, and intestinal secretions
  • DEC motility of stomach and intestines, allowing more time for absorption
  • INC muscle tone
  • INC tone of intestinal sphincters, incl. the tone of the external anal sphincter, reducing urgency
  • Anti-spasmodics and DEC cramps
  • SUM OF THESE EFFECTS is that opiates INC contact time b/t ingested matter and the reabsorptive intestinal epithelium
  • NOTE: can give much lower dose than what would be needed for analgesic effects
27
Q

What are the 3 anti-diarrheal opiates?

A
  • PAREGORIC: contains 0.04% morphine in benzoic acid, camphor, anise oil tincture
  • DIPHENOXYLATE with atropine: diphenoxylate is a meperidine congener that has effect similar to opiates; marketed with atropine to reduce the dose and to prevent abuse of diphenoxylate
  • LOPERAMIDE: interacts w/intestinal opioid receptors, and binds to and INH Ca-binding protein, calmodulin -> reduces Ca available to smooth muscle, reducing motility
28
Q

What is the MOA of the anti-cholinergics? Example?

A
  • MOA: block cholinergic receptors and reduce vagal stimulation -> main anti-diarrheals use anti-spasmodic
  • EXAMPLES: quaternary ammonium derivatives of atropine, like Propantheline and Dicyclomine
    1. Do not cross BBB and have minimal CNS side effects; anti-spasmodics, and alleviate CRAMPS
    2. Dicyclomine more suited to alleviate cramps than propantheline, which is used frequently for urinary retention
    3. Popular as combo with a benzodiazepine sedative -> some of these causes are PSYCH in nature, so combos with mood-altering drugs common

GI (25 decks)

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