The Pharmacological Treatment of Constipation & Diarrhea Flashcards Preview

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

Flashcards in The Pharmacological Treatment of Constipation & Diarrhea Deck (45):
1

Intestinal absorption/secretion Water:

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.

2

Laxatives (5 groups)
(MOSSD)

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

3

Dietary Fiber and Bulk-Forming Laxatives

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

4

Psyllium husk:
Characteristics

Hydrophilic muciloid that forms gelatinous mass when mixed with water

5

Psyllium husk:
Adverse Effects & Contraindications

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

6

Semisynthetic celluloses
Characteristics

Hydrophilic & digestible; forms a colloid mass with water

7

Semisynthetic celluloses
Adverse Effects & Contraindications

May bind & impede drug absorption.

8

Polycarbophils:
Characteristics

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

9

Polycarbophils:
Adverse Effects & Contraindications

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

10

Surfactant Laxatives

Docusates:
Poloxamers:
Castor oil:

11

Docusates:
Characteristics

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

12

Docusates:
Adverse Effects & Contraindications

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.

13

Poloxamers:
Characteristics

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

14

Poloxamers:
Adverse Effects & Contraindications

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

15

Castor oil:
Characteristics

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

16

Castor oil:
Adverse Effects & Contraindications

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

17

Stimulant Laxatives
Mechanism of action:

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!*

18

Stimulant Laxatives

• Diphenylmethanes (bisacodyl): Modane & Dulcolax
• Anthraquinones: Senokot™

19

Diphenylmethanes (bisacodyl)
Characteristics

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

20

Diphenylmethanes (bisacodyl)
Adverse Effects & Contraindications

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

21

Anthraquinones
Characteristics

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

22

Anthraquinones
Adverse Effects & Contraindications

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

23

Saline & Osmotic Laxatives

• Magnesium laxatives:
• Phosphate laxatives:
• Nondigestible sugars & alcohols:

24

Saline & Osmotic Laxatives
Mechanism of action:

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

25

Magnesium laxatives:
Special Mechanism of action:

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

26

Magnesium laxatives:
Examples:

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

27

Phosphate laxatives:
Examples:

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

28

Nondigestible sugars & alcohols:
Examples:

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

29

Lactulose
Special Mechanism of action:

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

Miscellaneous laxatives

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

31

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

Lubiprostone:
Linaclotide:

32

Lubiprostone:
Mechanism of action:

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

Linaclotide:
Mechanism of action:

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

34

ANTIDIRRHEAL AGENTS

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

35

ANTIDIRRHEAL Agents that absorb water:
Examples:

Group 1. Laxative bulk formers such as Metamucil™

36

ANTIDIRRHEAL Adsorbers of etiological factors in the lumen:

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

ANTIDIRRHEAL Agents that alter intestinal motility

I. OPIATES:
II. ANTICHOLINERGICS:

38

ANTIDIRRHEAL OPIATES:
Examples:

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

39

Paregoric:

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

40

Diphenoxylate with atropine (Lomotil™):

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

41

Loperamide (Imodium™):

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

42

ANTIDIRRHEAL OPIATES:
Mechanism of action:

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

ANTIDIRRHEAL ANTICHOLINERGICS:
Examples:

Quaternary ammonium derivatives of atropine
1. Propantheline
2. Dicyclomine

44

ANTIDIRRHEAL ANTICHOLINERGICS:
Mechanism of action:

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

45

Quaternary ammonium derivatives of atropine?

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