The Pharmacological Treatment of Constipation & Diarrhea Flashcards
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.
Laxatives (5 groups)
MOSSD
- Dietary fiber & Bulk-forming laxatives.
- Surfactant laxatives
- Osmotic laxatives
- Stimulant laxatives.
- Miscellaneous laxatives.
Dietary Fiber and Bulk-Forming Laxatives
- Psyllium husk: Effer-syllium & Metamucil
- Semisynthetic celluloses (carboxy-methylcellulose, methylcellulose): Citrucel Cologel
- Polycarbophils: Mitrolan
Psyllium husk:
Characteristics
Hydrophilic muciloid that forms gelatinous mass when mixed with water
Psyllium husk:
Adverse Effects & Contraindications
Allergic reactions, flatulence, borborygmi, intestinal obstruction; May inhibit coumarin absorption.
Semisynthetic celluloses
Characteristics
Hydrophilic & digestible; forms a colloid mass with water
Semisynthetic celluloses
Adverse Effects & Contraindications
May bind & impede drug absorption.
Polycarbophils:
Characteristics
Hydrophilic polyacrylic resins; absorb 60-100x their weight in water.
Polycarbophils:
Adverse Effects & Contraindications
Ca+ polycarbophils release Ca+ that is contraindicated with tetracycline usage.
Surfactant Laxatives
Docusates:
Poloxamers:
Castor oil:
Docusates:
Characteristics
Anionic surfactant; Weakly active; Primary use is as stool softener; To reduce the strain of defecation. Has no effect on intestinal peristalsis.
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.
Poloxamers:
Characteristics
Non-ionic surfactant; Similar to docusates; Stool softener.
Poloxamers:
Adverse Effects & Contraindications
Diarrhea; Not for use during abdominal pain, nausea, or vomiting.
Castor oil:
Characteristics
Rapid-acting & effective anionic surfactant that produces catharsis: complete evacuation of the bowels. stimulates intestinal peristalsis
Castor oil:
Adverse Effects & Contraindications
Colic, dehydration, & electrolyte imbalance with overdose; Can induce uterine contraction in pregnant women.
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!*
Stimulant Laxatives
- Diphenylmethanes (bisacodyl): Modane & Dulcolax
* Anthraquinones: Senokot™
Diphenylmethanes (bisacodyl)
Characteristics
Is a prodrug that is converted by enteric bacteria into the desacetyl active form. Administered in enteric coated tablets.
Diphenylmethanes (bisacodyl)
Adverse Effects & Contraindications
Overdosing can cause excessive fluid & electrolyte loss, intestinal enterocyte damage leading to colonic inflammatory response.
Anthraquinones
Characteristics
Natural derivatives of Lilliaceae plants (senna, cascara); More gentle than synthetic drugs. They act by promoting colonic motility
Anthraquinones
Adverse Effects & Contraindications
Large doses can cause abdominal pain nephritis, melanotic pigmentation of the colonic mucosa, abnormal urine coloration
Saline & Osmotic Laxatives
- Magnesium laxatives:
- Phosphate laxatives:
- Nondigestible sugars & alcohols:
Saline & Osmotic Laxatives
Mechanism of action:
They exert an osmotic effect which retains water in the lumen of the G. I. tract.
Magnesium laxatives:
Special Mechanism of action:
Produce laxation by their osmotic effect & through the release of cholecystokinin. CCK increases intestinal motility & secretion.
Magnesium laxatives:
Examples:
- Magnesium sulfate: Epsom salt.
- Magnesium hydroxide: Milk of Magnesia
- Magnesium citrate: Citroma™, is a cathartic
Phosphate laxatives:
Examples:
Given as enema. Fleet enema. or oral Sodium Phosphate tablets Visicol & OsmoPrep
Nondigestible sugars & alcohols:
Examples:
- Lactulose:
- Glycerin:
- Polyethylene glycol electrolyte solution (GOLYTELY™)
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.
Miscellaneous laxatives
Mineral oil: Is a mixture of hydrocarbons that penetrates & softens the stool.
Laxatives used in the management of the Irritable Bowel Syndrome (IBS)
Lubiprostone:
Linaclotide:
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.
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.
ANTIDIRRHEAL AGENTS
- Agents that absorb water:
- Adsorbers of etiological factors in the lumen:
- Agents that alter intestinal motility
ANTIDIRRHEAL Agents that absorb water:
Examples:
Group 1. Laxative bulk formers such as Metamucil™
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.
ANTIDIRRHEAL Agents that alter intestinal motility
I. OPIATES:
II. ANTICHOLINERGICS:
ANTIDIRRHEAL OPIATES:
Examples:
- Paregoric:
- Diphenoxylate with atropine (Lomotil™):
- Loperamide (Imodium™):
Paregoric:
contains 0.04% morphine in benzoic acid, camphor, anise oil tincture.
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.
Loperamide (Imodium™):
Interacts with intestinal opioid receptors & binds to and inhibits the calcium-binding protein calmodulin.
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
ANTIDIRRHEAL ANTICHOLINERGICS:
Examples:
Quaternary ammonium derivatives of atropine
- Propantheline
- Dicyclomine
ANTIDIRRHEAL ANTICHOLINERGICS:
Mechanism of action:
Block cholinergic receptors & reduce vagal stimulation. Their main use here is because they are anti-spasmodic.
Quaternary ammonium derivatives of atropine?
They do not cross the blood brain barrier & have minimal CNS side effects. They are anti-spasmodics & alleviate CRAMPS.
