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GI- Week 2 > Anti-Diarrheal Therapy > Flashcards

Anti-Diarrheal Therapy Flashcards

1
Q
A
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2
Q

Describe absorption of fluids in different segments of the gut

A

About 9 L of water enters the gut each day, of which only approximately 2 L is dietary. The remainder is secreted by the mouth, stomach, biliary tree, pancreas, and jejunum. Close to 4.5 L is absorbed by the jejunum, and the ileum takes up all but about 1 L of the remaining water (~3.5L). The colon absorbs nearly 900 ml, so that only about 100 to 200 ml is normally excreted in stool

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3
Q

What are the main groups of laxatives?

A
  • Dietary fiber and Bulk-forming laxatives.
  • Surfactant laxatives
  • Osmotic laxatives
  • Stimulant laxatives.
  • Miscellaneous laxatives.
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4
Q

What are some common bulk-forming laxatives?

A
  • Psyllium husk
  • Semisynthetic celluloses (Carboxymethylcellulose, methylcellulose)
  • Poylcarbophils
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5
Q

How does psyllium husk work (Metamucil; Effer-syllium)?

A

This is a hydrophilic muciloid that forms gelatinous mass when mixed with water and bulks up stool to activate stretch receptors in the GI

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6
Q

What are some AEs of psyllium husk?

A

Allergic reactions,

flatulence,

borborygmi,

intestinal obstruction;

May inhibit coumarin absorption

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7
Q

How do Semisynthetic celluloses work (Citrucel and Cologel)?

A

Hydrophilic and digestible; forms a colloid mass with water

May bind and impede drug absorption.

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8
Q

How do Polycarbophils work (Mitrolan)?

A

Hydrophilic polyacrylic resins; absorb 60-100x their weight in water to bulk stool

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9
Q

Ca+ polycarbophils are contraindicated in which pts?

A

They release Ca+ that is contraindicated with tetracycline usage.

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10
Q

How does fiber promote defecation?

A

*Increase delivery of water to the colon.

*Increase bulk by consisting of non-digestable carbs

*Reduce pressure in sigmoid Colon

*Net result: more formed stools.

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11
Q

What are the main surfactant laxatives?

A
  • docusates
  • poloxamers
  • Castor oil
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12
Q

How do Docusates work (Colace, Surfak)?

A

They are anionic surfactants primarily used as a stool softener to reduce the strain of defecation (in e.g. HA pts.) by reducing water tension with epithelium

*Has no effect on intestinal peristalsis.

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13
Q

What are some AEs of Docusates?

A

Not for use during abdominal pain or vomiting;

*Can irritate the intestinal mucosa and increase absorption of other drugs.

*Recommended for short-term use ONLY

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14
Q

How do Poloxamers work (Poloxamer 188)?

A

Non-ionic surfactant similar to docusates that acts as a Stool softener.

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15
Q

What are the AEs of poloxamers?

A

Diarrhea; Not for use during abdominal pain, nausea, or vomiting.

dont use for a long time, they irriatate the mucosa- give 2-4 weeks max;

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16
Q

How does castor oil work?

A

Rapid-acting and effective anionic surfactant that produces catharsis i.e. complete evacuation of the bowels. DOES stimulate intestinal peristalsis (unlike docusates)

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17
Q

What are some AEs of castor oil?

A

Colic, dehydration, and electrolyte imbalance with overdose;

Can induce uterine contraction in pregnant women.

This is an emulsion that irritates the mucosa and produces a cathartic effect.

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18
Q

How do stimulant laxatives work?

A

These predominantly act on the large bowel and increase the permeability of intestinal mucosa by weakening tight junctions to increase back diffusion of water and electrolytes.

they also increase propulsive contractility of the colon by stimulating colonic mucosal myenteric plexus and stimulate prostaglandin synthesis and increase intestinal secretions.

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19
Q

What is the most potent class of laxatives?

A

stimulants

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20
Q

What are some types of stimulant laxatives?

A
  • Diphenylmethanes (Bisacodyl)
  • Antraquinones
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21
Q

How do Diphenylmethanes like bisacodyl work (Modane, Dulcolax)?

A

This is a prodrug, converted by enteric bacteria into the desacetyl active form.

*Administered in enteric coated tablets- want it to be released in large intestine.

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22
Q

What are the AEs of Diphenylmethanes?

A

Overdosing can cause excessive fluid and electrolyte loss and/or intestinal enterocyte damage leading to colonic inflammatory response.

23
Q

How do Anthraquinones (Senokot) work?

A

These are natural derivatives of Lilliaceae plants (senna, cascara) that are stimulants that act by promoting colonic motility

•More gentle than synthetic drugs.

24
Q

What are the AEs of Anthraquinones?

A

May cause melanotic (dark) pigmentation of the colonic mucosa, abnormal urine coloration (brownish)

25
Q

What are saline/osmotic laxatives?

A

Saline laxatives are laxatives containing magnesium cations or other nonabsorbable molecules. They exert an osmotic effect which retains water in the lumen of the G. I. tract.

26
Q

How do Mg2+ containing laxatives work?

A

Produce laxation by their osmotic effect and through the release of cholecystokinin. CCK increases intestinal motility and secretion

27
Q

What are some examples of magnesium containing laxatives?

A

i. Magnesium sulfate: Epsom salt.
ii. Magnesium hydroxide: milk of magnesia (dose = 30 ml) Take in evening= diarrhea in morning.
iii. Magnesium citrate: Citroma™, is a cathartic (dose 4-8 oz)

28
Q

What is another type of osmotic laxative?

A

Phosphate containing laxatives

Given as enema or oral Sodium Phosphate tablets (Visicol, OsmoPrep etc.)

29
Q

Nondigestible sugars and alcohols are also used as osmotic laxatives. What is the most common type?

A

lactulose (cephulac)

30
Q

What is lactulose?

A

a semisynthetic disaccharide which is not absorbed and produces an osmotic laxative effect.

It is metabolized by enteric bacteria to organic acids such as lactic, formic, and acetic acid.Therefore, it is a fecal acidifier, that is used in management of symptoms of liver failure [portal systemic encephalopathy]).

31
Q

How is lactulose used in the tx of PSE?

A

The liver normally converts ammonia to urea but in liver failure the ammonia begins to increase leading to PSE (above-pt gets sleepy).

Lactulose causes acidification of the stool which traps ammonia in the ammonium (NH4+) form (prevents its conversion) which is not toxic, and retards the non ionic diffusion of ammonia from colon to blood because NH3 is in the ammonium form which is non diffusable, and thus is lost in feces.

32
Q

What are some other types of nondigestible sugars and alcohols?

A

Glycerin: osmotic and lubricant effects, suppository. Glycerin draws water making stool passage easier especially in children

Polyethylene glycol electrolyte solution (GOLYTELY™) perscription: Dissolved into 4 L and ingested 8 Oz ~10 min for colonoscopy, where complete evacuation is needed. Prep for colonoscopy usually. Miralax used for colonic cleanse (trendy- OTC)

33
Q

What is Haley’s M.O. (mineral oil)?

A

a mixture of hydrocarbons that penetrates and softens the stool.

34
Q

What are the main tx options for IBS-C?

A

Cl- channel regulators such as:

  • Lubiprostone (Amitiza)
  • Linaclotide (Linzess)
35
Q

How does Lubiprostone work?

A

•Lubiprostone directly activates intestinal chloride channels (CICs), in a protein kinase A–independent fashion. Activation of Cl- channels increases intestinal fluid secretion and motility and alleviates the symptoms associated with chronic idiopathic constipation.

36
Q

How oes Linaclotide work?

A

it is a peptide agonist of guanylate cyclase 2C that acts on intestinal cells to indirectly activate CFTRs.

37
Q

What are the general AEs of laxatives?

A

Laxative abuse:

Overuse of laxative leads to thorough constipation that requires several days to accumulate bulk. Often times there is subsequent lag in defecation after 1st use (because the bowel is empty) and is interpreted as continued constipation. Pts. then take more laxatives-vicious cycle.

-If continued, bowel becomes unresponsive.

Laxatives should only be taken short term!!

38
Q

What are some antidiarrheal agents that work by absorbing water from the GI lumen?

A

Cellulose derivatives, semisynthetic polysaccharides (metamucil™)

These agents pull water and swell, producing more formed stool.

39
Q

What are some antidiarrheal agents that work by absorbing etiological factors from the GI lumen?

A

Bismuth subsalicylate (Pepto-Bismol™, Kaopectate™) and charcoal are agents that absorb harmful bacteria, viruses or toxin. This is bacteriostatic in peptic ulcer disease with H. pylori (helpful!!)

*Bismuth subsalicylate is effective in prevention of Traveler’s diarrhea and in treatment of Helicobacter pylori infections.

40
Q

What are some antidiarrheal agents that work by altering GI motility?

A

Opiates

41
Q

How do opiates work in the GI?

A

Opiates:

  • decrease salivary, gastric and intestinal secretions.
  • decrease the motility of the stomach and intestines.
  • increase muscle tone.
  • increase the tone of intestinal sphincters including the tone of the external anal sphincter to“reduce urgency”.
  • are anti-spasmodics and decrease cramps

The sum of these effects is that opiates increase the contact time between ingested matter and the reabsorbtive intestinal epithelium

42
Q

What are some opiods specifically formulates for diarrhea tx?

A
  1. Paregoric: contains 0.04% morphine in benzoic acid, camphor, anise oil tincture.
  2. Diphenoxylate with atropine (Lomotil™): Diphenoxylate is a meperidine congener that has effect similar to opiates. Marketed with atropine to reduce the dose and to prevent abuse of diphenoxylate.
  3. Loperamide (Imodium™) Interacts with intestinal opioid receptors and binds to and inhibits the calcium-binding protein calmodulin. OTC
43
Q

How do anticholinergic prevent diarrhea?

A

Block cholinergic receptors and reduce vagal stimulation. Their main use here is because they are anti-spasmodic (Causes SM relaxation but doesn’t inhibit motility or secretions!)

44
Q

What are some examples of anticholinergics used for diarrhea tx?

A

Quaternary ammonium derivatives of atropine, such as Propantheline (Pro-Banthine); Dicyclomine (Bentyl™). Do not cross the BBB and have minimal CNS side effects. They are anti-spasmodics and alleviate CRAMPS.

—They are popular as a combination with a benzodiazepine sedative (Librax™), a sedative, to help with stress/anxiety!

45
Q

T or F. Dicyclomine is more suited to alleviate cramps than propantheline which is used frequently for promoting urinary retention.

A

T.

46
Q

Two drugs with different MOA are used for IBS-D, namely:

A
  • Rifaximin (Xifacan)
  • Eluxadoline (Viberzi)
47
Q

What is Rifaximin?

A

Locally acting antibiotic that is not absorbed systemically. It has broad spectrum of activity that target various strain of E. Coli bacteria.

Widely used in Rx of hepatic encephalopathy (inhibits the bugs that produce ammonia), traveller’s diarrhea (dose lower), and IBS-D.

48
Q

What is the dose of Rifaximin used for IBS-D tx?

A

550 mg tablet twice daily, usually for a week to 10 d.

49
Q

What are the AEs of Rifaximin?

A

peripheral edema (swelling, usually in ankles or lower limbs), nausea , dizziness, fatigue, and abdominal ascites

50
Q

When is Rifaximin contraindicated?

A

avoid in pregnancy

51
Q

How does Eluxadoline work?

A

It is a mixed opioid receptor regulator that targets opiate receptors in the GI tract, with minimal central effects (degraded by liver first pass). It acts as an agonist mainly on µ- and k-opioid receptors and as an antagonist on delta-opioid-R (C-IV ).

  • It decreases GI motility and reduces the sensitivity of myenteric plexi.
  • It is indicated for the treatment of IBS-D in adults.
52
Q

What dose of Eluxadoline is used for IBS-D?

A

75 -100 mg twice daily for no more than 2 weeks

53
Q

What are the AEs of Eluxadoline?

A

Activation of µ-opioid receptors is associated with gall bladder constriction and increased risk of sphincter of Oddi spasm, resulting in abdominal pain, pancreatitis or hepatic enzyme elevation.

54
Q

What are the contraindications of Eluxadoline?

A
  • Patients with gallbaldder disease need to be monitored for abdominal pain or pancreatitis. Don’t give in pts without a gallbladder b/c of increased pancreatitis risk
  • Alcoholics or patients who drink more than 3 alcoholic beverages per day. These patients are at increased risk for acute pancreatitis.
  • Pregnant patients.

GI- Week 2 (27 decks)

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