Term
| what are the different classes of laxatives? |
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Definition
| bulk-forming, stool surfacant, osmotic (laxatives/purgatives), stimulant, chloride channel activator, opioid receptor antagonist, and 5-HT receptor agonist |
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Term
| what are the bulk-forming laxatives and what characterizes them? |
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Definition
| bulk forming laxatives such as psyllium, methylcellulose, and polycarbophil are indigestable hydrophilic colloids that absorb water. this forms a gel in the GI which promotes peristalsis by incurring distention |
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Term
| what are the stool surfactant laxatives and what characterizes them? |
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Definition
| docusate, glycerin suppository, and mineral oil soften stool material - permitting water and lipds to penetrate (though long term use can impair absorption of fat soluble vitamins). they are mainly used to prevent straining and fecal impaction |
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Term
| what are the osmotic laxatives and what characterizes them? |
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Definition
| osmotic laxatives such as milk of magnesia (mag hydroxide), sorbitol, and lactulose are soluble but nonabsorbable compounds that result in increased stool liquidity (b/c fecal water isotonic and the colon can neither concentrate or dilute it). milk of magnesia if overused can cause hypermagnesia in pts w/renal insufficiency and and the non-absorbably sugars can be metabolized by colonic bacteria - producing gas |
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Term
| what are the osmotic purgatives and what characterizes them? |
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Definition
| magnesium citrate and sodium phosphate can be used in high doses as osmotically active agents producing an immediate and strong laxative effect (purgation). sodium phosphate can cause electrolyte imbalances (hyperphosphatemia, hypocalcemia, hypernatremia, and hypokalemia) and dehydration so pts with renal insufficiency or significant cardiac disease should not use it. |
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Term
| what is balanced polyethylene glycol? |
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Definition
| a balanced isotonic lavage solution containing polythethylene glycol (an inert, nonabsorbable, osmotically active sugar (PEG)) with sodium sulfate, sodium chloride, sodium bicarbonate, and potassium chloride - designed so that no significant intravascular fluid or electrolyte shifts occur. in large doses it an be used for colonic cleansing before procedures, in small doses, it can be used for tx of chronic constipation. in addition - it does not produce significant gas. |
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Term
| what are the stimulant laxatives (cathartics) and what characterizes them? |
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Definition
| anthraquinone and diphenylmethane derivatives are stimulant laxatives that induce bowel movements through poorly understood mechanisms including direct stimulation of the enteric nervous system and colonic electrolyte/fluid secretion. there is some concern that long-term use could lead to dependence and destruction of the myenteric plexus |
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Term
| what characterizes the anthraquinone derivative stimulant laxatives? |
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Definition
| aloe, senna, and cascara occur naturally in plants and are poorly absorbed and hydrolyzed in the colon - producing a BM in 6-12 hrs orally/2 hours rectally. chronic use can lead to "melanosis coli" or brown-stained colon |
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Term
| what characterizes the diphenylmethyl derivative stimulant laxatives? |
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Definition
| bisacodyl is used for acute/chronic constipation as well as along with PEG solution. bisacodyl has minimal systemic absorption and appears to be safe for acute/chronic use. phenolphthalein was in this class, but was removed due to concerns about cardiac toxcity |
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Term
| what are the chloride channel activators laxatives and what characterizes them? |
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Definition
| lubiprostone is a prostanoic acid which stimulates the type 2 chloride channel (ClC-2) in the small intestine, increasing Cl-rich secretions into its lumen which stimulates intestinal motility and shortens intestinal transit time. it is prescribed for pts with IBS w/predominant constipation and there appears to be no loss of efficacy with long term use, however it is contraindicated for pregnancy and may cause nausea in up to 30% of pts. |
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Term
| what are the opioid receptor antagonist laxatives and what characterizes them? |
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Definition
| methylnatrexone (subcu inj) and alvimopan (PO) block intestinal u-opioid (mu) receptors. methylnatrexone is used for opioid-induced constipation and alvimopan is used for post-operative ileus, though only short-term due to concerns about cardiac toxicity. neither agents cross the BBB (do not impact analgesis effects w/in CNS). |
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Term
| what are the 5-HT receptor agonists laxatives and what characterizes them? |
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Definition
| tegaserod, cisapride and prucalopride stimulate the 5-HT receptors on the presynaptic terminal of submucosal intrinsic primary afferent nerves - enhancing their NT release, including the calcitonin gene-related peptide which promotes the peristaltic reflex by stimulating enteric nerves to proximally contract and distally relax (via NO and VIP). tegaserod and cisapride were removed from the market and prucalopride is in development |
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Term
| what symptoms in pts contraindicate use of a antidiarrheal agent under normal circumstances? |
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Definition
| antidiarrheals should not be used in patients with bloody diarrhea, high fever, or systemic toxicity because of the risk of worsening the underlying condition. they should also be discontinued in patients whose diarrhea is worsening despite therapy |
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Term
| what are the different classes of anti-diarrheals? |
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Definition
| opioid agonists, colloidal bismuth compounds, kaolin & pectin, bile salt-binding resins, and octreotide |
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Term
| what are the opiod agonist anti-diarrheals and what characterizes them? |
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Definition
| loperamide and diphenoxylate increase colonic phase segmenting activity through inhibition of presynaptic cholinergic nerves in the submucosal and myenteric plexi and lead to increased colonic transit time and fecal water absorption. they also decrease mass colonic movements and the gastrocolic reflex. loperamide does not cross the BBB (no decrease in analgesic effect/addiction risk) and tolerance has not been reported. diphenoxylate has no CNS activity in small doses, but will w/higher doses - leading to the potential for dependence (which commercial preps include atropine to discourage and may boost the antidiarrheal effect) |
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Term
| what are the kaolin and pectin anti-diarrheals and what characterizes them? |
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Definition
| kaolin is a naturally occuring hydrated Mg Al silicate and pectin is an indigestible carbohydrate derived from apples. both appear to absorb bacterial toxins and fluid, which decreases stool liquidity and number. they may be useful in acute diarrhea but should not be taken w/in 2 hrs of other medications due to binding risks |
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Term
| what are the bile salt-binding anti-diarrheals and what characterizes them? |
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Definition
| cholestyramine, colestipol, and colesevelam bind bile salts that pts with defective or missing terminal ileums cannot reabsorb, decreasing diarrhea due to excess the bile salts. however pts w//diminished bile salts may experience fat malabsorption and these drugs with the exception of colesevelam can bind other drugs in the pt's system |
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Term
| what is octreotide? how does it work? |
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Definition
| octreotide is a synthetic octapeptide w/actions similar to somatostatin, whose actions include: 1) inhibition of secretion of gastrin, CCK, glucagon, growth hormone, insulin, secretin, pancreatic polypeptide, VIP, and 5-HT. 2) reduces intestinal fluid /pancreatic secretion 3) slows gastrointestinal motility and inhibits gallbladder contraction 4) induces direct contraction of vascular smooth muscle, reducing portal/splanchnic blood flow 5) inhibits secretion of some anterior pituitary hormones |
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Term
| how can octreotide inhibit diarrheal effects due to gastrointestinal neuroendocrine tumors (carcinoid, VIPoma) that cause secretory diarrhea and systemic symptoms such as flushing and wheezing? |
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Definition
| for pts with advanced symptomatic tumors that cannot be completely removed by surgery, octreotide decreases secretory diarrhea and systemic symptoms through inhibition of hormonal secretion and may slow tumor progression. |
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Term
| how does the effect of octreotide change depending on dose? |
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Definition
| in low doses, octreotide stimulates bowel motility, but inhibits in high doses. |
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Term
| what are other uses for octreotide? |
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Definition
| octreotide is effective in high doses for tx of diarrhea due to vagotomy, dumping syndrome, short bowel syndrome, or AIDS. in low (bowel-stimulatory) doses, octreotide can be used by pts w/small bowel bacterial overgrowth or intestinal pseudo-obstruction secondary to scleroderma. octreotide may also help with pancreatic secretion, pituitary tumors and GI bleeds |
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Term
| what ADRs are associated with octreotide? |
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Definition
| impaired pancreatic secretion may lead to steatorrhea and fat-soluble vit deficiency, as well as nausea, abdominal pain, flatulence, and diarrhea. b/c of inhibition of gallbladder contractility and alterations in fat absorption, octreotide can cause sludge/gallstone formation, which rarely results in the development of acute cholecystitis. b/c octreotide alters the balance among insulin, glucagon, and growth hormone, hyperglycemia or, less frequently, hypoglycemia (usually mild) can occur. prolonged treatment with octreotide may result in hypothyroidism. octreotide also can cause bradycardia. |
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