Diarrhea Pharmacology Flashcards
Accurate diagnosis of diarrhea must rule out the following two conditions which are not considered diarrhea since feces output is typically < 200g/day:
Fecal incontinence: involuntary passing of rectal contents, commonly associated with neuromuscular, or structural anorectal disorders.
Pseudo-diarrhea: frequent passages of small amounts of feces caused by rectal urgencies or feelings of incomplete rectal evacuation
Narcotic Member Names
Diphenoxylate, difenoxin and loperamide
Narcotics MOA
All opioid narcotics inhibit GI motility, decrease secretion and absorption secondary to stimulation of opioid receptors within the enteric nervous system.
Decreasing GI motility allows enough time for water, nutrients and electrolytes to be absorbed from the intestine, thereby alleviating symptoms of diarrhea.
Major opioids receptors (µ, δ and κ) are generally _____ and their stimulation leads to
Major opioids receptors (µ, δ and κ) are generally inhibitory and their stimulation leads to decrease intracellular cAMP, increase K+ conductance, decrease intracellular Ca2+ and hyperpolarization.
These actions amount reduced contractility of smooth muscles within the GI and subsequent decrease in motility.
Actions of the opioid receptors
The µ receptor affects intestinal motility, δ receptor affects intestinal secretion, absorption is modulated by both µ and δ.
_____ is rapidly metabolized to its active metabolite _____ after an oral administration.
Diphenoxylate is rapidly metabolized to its active metabolite difenoxin after an oral administration.
Both diphenoxylate and difenoxin are more potent than morphine for treatment of diarrhea.
Why are small doses of atropine commonly added to the opioids?
CNS effects (albeit at very high doses) can occur with use of both diphenoxylate and difenoxin as a result, the risk for addiction and abuse associate with their use is significant
Small doses of atropine are occasionally added to these drugs as a way to discourage deliberate overdose or abuse.
Narcotics ADES
Constipation, toxic megacolon, CNS effects.
Anti-cholinergic effects (blurred vision, xerostomia etc.) may occur due to the included atropine.
What drug increases anal sphincter tone?
Loperamide
Loperamide MOA
In addition to stimulating µ receptors in the GI, loperamide also stimulates Gi receptor which counter the cholera and E. coli – induced increase in cellular cAMP that leads to diarrhea.
More effective in treating diarrhea than diphenoxylate
One plus of using Loperamide for constipation
Poor CNS penetration (a plus).
Lacks significant abuse potential, has low adverse effect profile and is available over the counter.
Clinical Application of Loperamide
Effective against traveler’s diarrhea (either as a monotherapy or in combination with antibiotics).
Loperamide ADES
Not recommended for use in children under 2
CNS depression may occur in case of overdose
Bile Acid Sequestrate Members
Cholestyramine, colestipol and colesevalam
Bile Acid Sequestrates MOA
Bind and form complexes with bile acids and some bacterial toxins thereby facilitating their excretion.
If allowed to accumulate in the GI, bile salts usually stimulate excessive water and electrolyte secretion in the colon leading to diarrhea.
Bile Acid Sequestrates Clinical Applications
Treatment of bile acid-induced diarrhea as in patients with resection of distal ileum – where excess bile salt is delivered to the colon as a result of decrease enterohepatic circulation.
What drug is effective in treating mild antibiotic-induced diarrhea?
Cholestyramine
Bile Acid Sequestrates ADES
May cause steatorrhea, depletion of fat-soluble vitamins (ADEK) with corresponding manifestations of deficits e.g. night blindness(with vitamin A defficiency), bleeding (with vitamin K deffiency)
In patients with extensive ileal resection, steatorrhea is present secondary to significant bile salt depletion. Thus use of cholestyramine in such patients will aggravate diarrhea instead.
Minerals Members
Attapulgite and kaolin
Minerals MOA
Attapulgite (a magnesium-aluminum disilicate) and kaolin (a hydrated aluminum silicate) are extremely hygroscopic and avidly bind water within the GI tract.
Both attapulgite and kaolin can also bind to endotoxins, nutrients and even other drug molecules within the GI.
A mixture of _______ is available over the counter for treatment of mild diarrhea.
A mixture of kaolin and pectin (a plant polysaccharide) is available over the counter for treatment of mild diarrhea.
Minerals ADEs
Well tolerated.
May decrease absorption of nutrients and other drug molecules with the GI tract.
What drugs are suitable for diarrhea associated with irritable bowel syndrome?
Plants extracts and minerals
Plant Extracts Members
Carboxymethylcellulose, pectin, calcium polycarbophil (not a plant extract but fit this category otherwise)
Plant Extracts MOA
Hydrophilic, resistant to enzymatic break-down within the GI, absorb water and increase stool bulk.
Calcium polycarbophil absorbs up to 60 or so times its own weight in water.
Plant Extracts Clinical ADES
May also bind to nutrients, and other drug molecules within the GI thereby decreasing their absorption.
Bismuth Subsalicylate MOA
Has anti bacterial (H. pylori), anti inflammatory effects, as well as antacid effects
Decrease hypersecretion, stimulate absorption, slow hyper-motility of the stomach
What drug is used prophylactically against traveler’s diarrhea?
Bismuth Subsalicylate
Bismuth Subsalicylate ADES
Black stool and black tongue
Clonidine MOA
Stimulates alpha-2 adrenergic receptors on enteric neurons and enterocytes, inhibiting secretion of fluids and electrolytes as well as increasing intestinal transit time.
What drug is effective against diabetic chronic diarrhea where autonomic neuropathy may lead to loss of adrenergic innervation in the GI?
Clonidine
What drug is effective in patients with diarrhea caused by opioid withdrawal?
Clonidine
One main ADE of Clonidine
Can cause severe withdrawal syndrome characterized by hypertensive crisis.
Somatostatin (grow hormone inhibiting hormone), octreotide MOA
Inhibition of hormone secretion (serotonin, gastrin, VIP, insulin etc.)
Why is octreotide commonly chosen over somatostatin?
Somatostatin itself is rarely used clinically because of a very short half-life (few minutes). Octreotide a synthetic analog with a longer plasma half-life is a better alterative.
Clinical applications of somatostatin and octreotide
Effective against secretory diarrheas (chemotherapy-induced diarrhea, diarrhea associated with HIV, and diabetes associated diarrhea)
Effective in managing the dumping syndrome seen in patients after gastric surgery
Somatostatin and Octreotide ADES
GI cramps, hypothyroidism, and headaches
