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GI Liver Pharmacology > The Pharmacological Treatment of Constipation & Diarrhea > Flashcards

The Pharmacological Treatment of Constipation & Diarrhea Flashcards

1
Q

Intestinal absorption/secretion Water:

A

About 9 L water gut day, 2 L is dietary. The remainder is secreted by the mouth, stomach, biliary tree, pancreas, & jejunum.
Half of the 9 L is absorbed jejunum, & the ileum up all but 1 L. The colon absorbs 900 ml, so only about 100 to 200 ml excreted in stool.

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2
Q

Laxatives (5 groups)

MOSSD

A
  • Dietary fiber & Bulk-forming laxatives.
  • Surfactant laxatives
  • Osmotic laxatives
  • Stimulant laxatives.
  • Miscellaneous laxatives.
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3
Q

Dietary Fiber and Bulk-Forming Laxatives

A
  • Psyllium husk: Effer-syllium & Metamucil
  • Semisynthetic celluloses (carboxy-methylcellulose, methylcellulose): Citrucel Cologel
  • Polycarbophils: Mitrolan
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4
Q

Psyllium husk:

Characteristics

A

Hydrophilic muciloid that forms gelatinous mass when mixed with water

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5
Q

Psyllium husk:

Adverse Effects & Contraindications

A

Allergic reactions, flatulence, borborygmi, intestinal obstruction; May inhibit coumarin absorption.

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6
Q

Semisynthetic celluloses

Characteristics

A

Hydrophilic & digestible; forms a colloid mass with water

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7
Q

Semisynthetic celluloses

Adverse Effects & Contraindications

A

May bind & impede drug absorption.

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8
Q

Polycarbophils:

Characteristics

A

Hydrophilic polyacrylic resins; absorb 60-100x their weight in water.

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9
Q

Polycarbophils:

Adverse Effects & Contraindications

A

Ca+ polycarbophils release Ca+ that is contraindicated with tetracycline usage.

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10
Q

Surfactant Laxatives

A

Docusates:
Poloxamers:
Castor oil:

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11
Q

Docusates:

Characteristics

A

Anionic surfactant; Weakly active; Primary use is as stool softener; To reduce the strain of defecation. Has no effect on intestinal peristalsis.

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12
Q

Docusates:

Adverse Effects & Contraindications

A

Not for use during abdominal pain, nausea, or vomiting; Can irritate the intestinal mucosa & increase intestinal absorption of other drugs. Recommended for short-term use.

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13
Q

Poloxamers:

Characteristics

A

Non-ionic surfactant; Similar to docusates; Stool softener.

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14
Q

Poloxamers:

Adverse Effects & Contraindications

A

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

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15
Q

Castor oil:

Characteristics

A

Rapid-acting & effective anionic surfactant that produces catharsis: complete evacuation of the bowels. stimulates intestinal peristalsis

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16
Q

Castor oil:

Adverse Effects & Contraindications

A

Colic, dehydration, & electrolyte imbalance with overdose; Can induce uterine contraction in pregnant women.

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17
Q

Stimulant Laxatives

Mechanism of action:

A

a. Predominantly act on the large bowel.
b. Increase the permeability of intestinal mucosa;
c. Increase back diffusion of water & electrolytes.
d. Increase propulsive contractility of the colon by stimulating colonic mucosal myenteric plexus.
e. Stimulate prostaglandin synthesis & increase intestinal secretions.
* This is the most potent class of laxatives!*

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18
Q

Stimulant Laxatives

A
  • Diphenylmethanes (bisacodyl): Modane & Dulcolax

* Anthraquinones: Senokot™

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19
Q

Diphenylmethanes (bisacodyl)

Characteristics

A

Is a prodrug that is converted by enteric bacteria into the desacetyl active form. Administered in enteric coated tablets.

20
Q

Diphenylmethanes (bisacodyl)

Adverse Effects & Contraindications

A

Overdosing can cause excessive fluid & electrolyte loss, intestinal enterocyte damage leading to colonic inflammatory response.

21
Q

Anthraquinones

Characteristics

A

Natural derivatives of Lilliaceae plants (senna, cascara); More gentle than synthetic drugs. They act by promoting colonic motility

22
Q

Anthraquinones

Adverse Effects & Contraindications

A

Large doses can cause abdominal pain nephritis, melanotic pigmentation of the colonic mucosa, abnormal urine coloration

23
Q

Saline & Osmotic Laxatives

A
  • Magnesium laxatives:
  • Phosphate laxatives:
  • Nondigestible sugars & alcohols:
24
Q

Saline & Osmotic Laxatives

Mechanism of action:

A

They exert an osmotic effect which retains water in the lumen of the G. I. tract.

25
Q

Magnesium laxatives:

Special Mechanism of action:

A

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

26
Q

Magnesium laxatives:

Examples:

A
  • Magnesium sulfate: Epsom salt.
  • Magnesium hydroxide: Milk of Magnesia
  • Magnesium citrate: Citroma™, is a cathartic
27
Q

Phosphate laxatives:

Examples:

A

Given as enema. Fleet enema. or oral Sodium Phosphate tablets Visicol & OsmoPrep

28
Q

Nondigestible sugars & alcohols:

Examples:

A
  • Lactulose:
  • Glycerin:
  • Polyethylene glycol electrolyte solution (GOLYTELY™)
29
Q

Lactulose

Special Mechanism of action:

A

is metabolized by enteric bacteria to organic acids such as lactic, formic & acetic acid.
Fecal acidifier: Acidification of the stool traps ammonia in the ammonium form which is not toxic.

30
Q

Miscellaneous laxatives

A

Mineral oil: Is a mixture of hydrocarbons that penetrates & softens the stool.

31
Q

Laxatives used in the management of the Irritable Bowel Syndrome (IBS)

A

Lubiprostone:
Linaclotide:

32
Q

Lubiprostone:

Mechanism of action:

A

Lubiprostone specifically activates intestinal chloride channels, in a protein kinase A independent fashion. Activation of Cl- channels increases intestinal fluid secretion and motility & alleviates the symptoms associated with chronic idiopathic constipation.

33
Q

Linaclotide:

Mechanism of action:

A

Is a peptide agonist of guanylate cyclase 2C that acts on intestinal cells to indirectly (cGMP->PKG2 & PKA) activate the chloride channel.

34
Q

ANTIDIRRHEAL AGENTS

A
  1. Agents that absorb water:
  2. Adsorbers of etiological factors in the lumen:
  3. Agents that alter intestinal motility
35
Q

ANTIDIRRHEAL Agents that absorb water:

Examples:

A

Group 1. Laxative bulk formers such as Metamucil™

36
Q

ANTIDIRRHEAL Adsorbers of etiological factors in the lumen:

A

Bismuth subsalicylate (Pepto-Bismol™ & Kaopectate™) & charcoal are agents that adsorb harmful bacteria, viruses or toxin. Bismuth subsalicylate is effective in prevention of Traveler’s diarrhea & in treatment of Helicobacter pylori infections.

37
Q

ANTIDIRRHEAL Agents that alter intestinal motility

A

I. OPIATES:

II. ANTICHOLINERGICS:

38
Q

ANTIDIRRHEAL OPIATES:

Examples:

A
  1. Paregoric:
  2. Diphenoxylate with atropine (Lomotil™):
  3. Loperamide (Imodium™):
39
Q

Paregoric:

A

contains 0.04% morphine in benzoic acid, camphor, anise oil tincture.

40
Q

Diphenoxylate with atropine (Lomotil™):

A

Diphenoxylate is a meperidine congener that has effect similar to opiates. Marketed with atropine to reduce the dose & to prevent abuse of diphenoxylate.

41
Q

Loperamide (Imodium™):

A

Interacts with intestinal opioid receptors & binds to and inhibits the calcium-binding protein calmodulin.

42
Q

ANTIDIRRHEAL OPIATES:

Mechanism of action:

A

Opiates decrease:
• salivary, gastric & intestinal secretions.
• motility of the stomach & intestines.
• cramps = anti-spasmodics
Opiates increase:
• muscle tone
• tone of intestinal sphincters including EAS “reduce urgency”.
The sum effects is that opiates increase contact time between ingested matter & eabsorbtive intestinal epithelium

43
Q

ANTIDIRRHEAL ANTICHOLINERGICS:

Examples:

A

Quaternary ammonium derivatives of atropine

  1. Propantheline
  2. Dicyclomine
44
Q

ANTIDIRRHEAL ANTICHOLINERGICS:

Mechanism of action:

A

Block cholinergic receptors & reduce vagal stimulation. Their main use here is because they are anti-spasmodic.

45
Q

Quaternary ammonium derivatives of atropine?

A

They do not cross the blood brain barrier & have minimal CNS side effects. They are anti-spasmodics & alleviate CRAMPS.

GI Liver Pharmacology (9 decks)

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