Term
| how much fluid traverse the intestine per day? |
|
Definition
|
|
Term
| how much fluid in the intestine per day is from the diet? |
|
Definition
|
|
Term
| how much fluid in the intestines is from secretions? |
|
Definition
|
|
Term
| how much fluid is reabsorbed in the intestines? |
|
Definition
|
|
Term
|
Definition
| the failure to reabsorb fluid in the intestine |
|
|
Term
|
Definition
1. increased osmotic load
2. excessive secretion of electrolytes and water
3. exudation of protein and fluid from mucosa
4. altered intestinal motility |
|
|
Term
|
Definition
often self-limited
may require rehydration solution in elderly, infants, and severe cases |
|
|
Term
| how do rehydration solutions for the treatment of diarrhea differ? |
|
Definition
| in amounts of Na, K, Cl and other nutrients in the solution |
|
|
Term
| where do intraluminal agents work? |
|
Definition
|
|
Term
| 3 types of intraluminal agents? |
|
Definition
1. hydroscopic agents
2. bile acid resins
3. bismuth subsalicylate |
|
|
Term
|
Definition
1. psyllium
2. kaolin
3. pectin |
|
|
Term
| mechanism of hydroscopic agents? |
|
Definition
absorb water and increase stool bulk
may also bind bacterial toxins |
|
|
Term
|
Definition
1. cholestyramine
2. colestipol |
|
|
Term
|
Definition
used in treatment of lipid disorders
useful in bile salt-induced diarrhea |
|
|
Term
| mechanism of bile acid resins? |
|
Definition
bind bile acids
also bind bacterial toxins |
|
|
Term
| bile acid resins can also bind what? |
|
Definition
drugs (thyroxine, digoxin) and vitamins
decreases bioavailability |
|
|
Term
| what is bismuth subsalicylate also known as? |
|
Definition
|
|
Term
| what 2 things are formed with use of bismuth subsalicylate? |
|
Definition
1. bismuth oxychloride - that is not absorbed
2. salicyclic acid - that is absorbed |
|
|
Term
| activity of bismuth in the body? |
|
Definition
1. anti-secretory
2. anti-inflammatory
3. anti-microbial |
|
|
Term
| activity of salicylic acid? |
|
Definition
|
|
Term
| side effect of bismuth subsalicylate? |
|
Definition
| bismuth sulfide can turn the tongue and stool black |
|
|
Term
| what metabolite of bismuth subsalicylate is responsible for turning the tongue and stool black? |
|
Definition
|
|
Term
| 3 anti-motility and anti-secretory agents? |
|
Definition
1. opioids
2. alpha2 adrenergic agents
3. octreotide |
|
|
Term
| 2 opioids used as anti-motility and anti-secretory agents? |
|
Definition
1. loperamide
2. diphenoxylate |
|
|
Term
| mechanism of opioids as anti-motility and anti-secretory agents? |
|
Definition
activate intestinal mu receptors --> causes tonic contraction --> eliminates peristaltic action (decreases motility)
activate mu and delta receptors --> increases absorption |
|
|
Term
| are opioids used as anti-motility and anti-secretory agents more or less potent than morphine as an anti-diarrheal? |
|
Definition
|
|
Term
| does loperamide penetrate the CNS? |
|
Definition
|
|
Term
|
Definition
increases rectal sphincter tone
disrupts peristalsis |
|
|
Term
| can diphenoxylate penetrate the CNS? |
|
Definition
YES
can lead to resp depression |
|
|
Term
| which opioid used as an anti-motility and anti-secretory agent penetrates the CNS? |
|
Definition
|
|
Term
| diphenoxylate can lead to what side effect? |
|
Definition
resp depression
because it can penetrate CNS |
|
|
Term
| preparations of diphenoxylate include what? why? |
|
Definition
atropine
to reduce secretion, motility, and discourage abuse |
|
|
Term
| what is a potential side effect of atropine used in preparations with diphenoxylate? |
|
Definition
|
|
Term
| what is a side effect of opioids used as anti-motility and anti-secretory agents? |
|
Definition
|
|
Term
| what is an alpha2 adrenergic agent used as an anti-motility and anti-secretory agent? |
|
Definition
|
|
Term
| mechanism of clonidine as an anti-HTN medication? |
|
Definition
| binds to pre-synaptic receptors in the brain and reduces SNS output |
|
|
Term
| mechanism of clonidine as an anti-motility and anti-secretory agent? |
|
Definition
| activates receptors that stimulate absorption, inhibit secretion, and increase intestinal transit time |
|
|
Term
|
Definition
| used to treat diabetes with chronic diarrhea and peripheral autonomic neuropathy and lost adrenergic innervation in the periphery |
|
|
Term
|
Definition
long acting somatostatin analog
inhibitory peptide |
|
|
Term
|
Definition
| inhibitory peptide - inhibits secretion; decreases contractility |
|
|
Term
| administration of octreotide? |
|
Definition
| injected - subQ several times a day or IM |
|
|
Term
|
Definition
| carcinoid, VIPoma, AIDS, and diabetes induced diarrhea |
|
|
Term
| side effects of octreotide? |
|
Definition
1. formation of gallstones
2. pain at the injection site |
|
|
Term
|
Definition
1. bulk laxatives
2. lubricating agents
3. stimulant laxatives
4. osmotic agents
5. neuromuscular agents |
|
|
Term
| how do bulk laxatives work? |
|
Definition
| increase colonic residue and therefore peristalsis |
|
|
Term
| how do lubricating agents work as laxatives? |
|
Definition
|
|
Term
| how do stimulant laxatives work? |
|
Definition
| stimulate intestinal secretion |
|
|
Term
| how do osmotic agents work as laxatives? |
|
Definition
| draw water into the intestine |
|
|
Term
| how do neuromuscular agents work as laxatives? |
|
Definition
| directly or indirectly activate intestinal SM |
|
|
Term
| what is the ultimate mediator of neuromuscular agents as laxatives? |
|
Definition
|
|
Term
|
Definition
1. psyllium
2. methylcellulose |
|
|
Term
|
Definition
|
|
Term
| mechanism of bulk laxatives? |
|
Definition
not extensively metabolized
increase fecal mass |
|
|
Term
| adverse effects of bulk laxatives? |
|
Definition
1. can undergo bacterial degradation in the colon and cause bloating and flatulence
2. can be gritty and unpleasant to swallow
3. can bind drugs such as digoxin, thyroid hormone
4. can also bind bile acids and increase cholesterol excretion |
|
|
Term
| why do bulk laxatives cause bloating and flatulence? |
|
Definition
| they can undergo bacterial degradation in the colon |
|
|
Term
| what drugs can bulk laxatives bind in the colon? |
|
Definition
| digoxin and thyroid hormone |
|
|
Term
| how do bulk laxatives increase cholesterol excretion? |
|
Definition
|
|
Term
| onset of action of bulk laxatives? |
|
Definition
|
|
Term
| why are bulk laxatives slow acting agents? |
|
Definition
because their mechanism of action is dependent on bulk, softness, and water content of the feces
highly dependent on fiber content of the diet |
|
|
Term
| effect of bulk laxatives? |
|
Definition
1. increase stool bulk
2. shorten intestinal transit time |
|
|
Term
| what is a lubricating agent used as a laxative? |
|
Definition
|
|
Term
| how does mineral oil act as a laxative? |
|
Definition
| its an indigestible oil that softens stool over 2-3 days |
|
|
Term
| onset of action of mineral oil? |
|
Definition
|
|
Term
| adverse effects of mineral oil? |
|
Definition
1. may interfere with absorption of fat soluble substances
2. may lead to oil leakage past the anal sphincter and oil aspiration in young children |
|
|
Term
| why does mineral oil have to be used carefully in children? |
|
Definition
| can lead to oil aspiration in young children |
|
|
Term
|
Definition
1. docusate
2. bisacodyl
3. anthroquinones
4. ricinoleic acid |
|
|
Term
| mechanism of stimulant laxatives? |
|
Definition
| all cause local inflammation within the intestine mediated by PGE --> increase in cAMP and also inhibition of Na/K ATPase --> leads to electrolyte and water secretion |
|
|
Term
| mechanism of action of docusate? |
|
Definition
surface acting agent that softens stool (also a lubricating agent)
also increases electrolyte and water secretion into the intestinal lumen |
|
|
Term
| when is docusate effective? |
|
Definition
| only in mild constipation |
|
|
Term
|
Definition
| patients after colorectal surgery and acute MI to reduce straining |
|
|
Term
| mechanism of action of bisacodyl? |
|
Definition
like other stimulant laxatives
increase electrolyte and water secretion by a PGE-mediated increase in cAMP, inhibition of Na/K ATPase and low grade inflammation in the small and large bowel |
|
|
Term
|
Definition
|
|
Term
| administration of bisacodyl? |
|
Definition
| in enteric-coated capsules |
|
|
Term
| onset of laxative effect with bisacodyl? |
|
Definition
|
|
Term
|
Definition
1. senna
2. aloe
3. rhubarb |
|
|
Term
| onset of action of anthroquinones? |
|
Definition
|
|
Term
| anthroquinones can produce what? |
|
Definition
| giant, migrating, colonic contractions |
|
|
Term
| problem with anthroquinones? |
|
Definition
| they have tremendous abuse potential |
|
|
Term
| what type of drug is castor oil? |
|
Definition
|
|
Term
| mechanism of action of caster oil? |
|
Definition
| same as all stimulant laxatives |
|
|
Term
| 4 osmotic agents used as laxatives? |
|
Definition
1. saline laxatives
2. poorly absorbed sugars
3. polyethylene glycol
4. lubiprostone |
|
|
Term
| mechanism of osmotic agents? |
|
Definition
| pull water into the gut by osmotic drag |
|
|
Term
|
Definition
1. magnesium hydroxide
2. sodium phosphate
3. magnesium citrate |
|
|
Term
| mechanism of saline laxatives? |
|
Definition
| increase gut osmolality --> draw water into gut lumen by solute drag --> stimulates peristalsis |
|
|
Term
| use of magnesium hydroxide? |
|
Definition
| acute and chronic constipation |
|
|
Term
| use of magnesium citrate? |
|
Definition
| as a cathartic (in bowel preparation) |
|
|
Term
| 3 poorly absorbed sugars used as osmotic agents? |
|
Definition
1. lactulose
2. sorbitol
3. mannitol |
|
|
Term
| mechanism of poorly absorbed sugars as osmotic agents? |
|
Definition
| hydrolyzed by intestinal bacteria --> acidify --> osmotic drag pulls water into the intestine |
|
|
Term
| use of poorly absorbed sugars? |
|
Definition
|
|
Term
| onset of poorly absorbed sugars? |
|
Definition
|
|
Term
| poorly absorbed sugars may cause what side effects? |
|
Definition
|
|
Term
| magnesium has what type of properties? |
|
Definition
|
|
Term
| use of polyethylene glycol + electrolyte containing solutions? |
|
Definition
| as cathartic prior to bowel procedure |
|
|
Term
| when polyethylene glycol is used as cathartic prior to bowel procedure, what else is in the solution? |
|
Definition
|
|
Term
| polyethylene glycol + electrolytes = |
|
Definition
|
|
Term
| polyethylene glycol alone is what? |
|
Definition
|
|
Term
| use of polyethylene glycol alone? |
|
Definition
|
|
Term
| mechanism of polyethylene glycol? |
|
Definition
| isotonic PEG solution --> poorly absorbed --> retains water in colon |
|
|
Term
| what is a sulfate-free electrolyte lavage solution polyethylene glycol? |
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
| 3 liters PEG + ascorbic acid and Na sulfate |
|
|
Term
|
Definition
| fatty acid metabolite of PGE1 |
|
|
Term
| mechanism of lubiprostone? |
|
Definition
| activates a Cl channel in GI epithelium --> stimulates intestinal fluid secretion (water follows Cl) --> decreases intestinal transit time |
|
|
Term
|
Definition
1. chronic idiopathic constipation in adults
2. constipation a/w IBS |
|
|
Term
| side effects of lubiprostone? |
|
Definition
|
|
Term
| 4 types of neuromuscular agents used as laxatives? |
|
Definition
1. 5HT4 receptor agonists
2. misoprostol
3. cholinergic agents
4. opiate receptor antagonists |
|
|
Term
| how do 5HT4 receptor agonists act as laxatives? |
|
Definition
| activate M3 receptors eventually - increase SM contraction |
|
|
Term
| how does misoprostol act as a laxative? |
|
Definition
| its a PGE analog --> induces SM activity |
|
|
Term
| how do cholinergic agents act as laxatives? |
|
Definition
directly activate the receptor or indirectly by inhibiting breakdown of Ach
stimulate SM |
|
|
Term
| what is a selective mu receptor antagonist used as a laxative? |
|
Definition
|
|
Term
|
Definition
| opioid induced constipation in patients with advanced illness |
|
|
Term
| mechanism of methylnaltrexone? |
|
Definition
| blocks mu receptors in the intestinal tract without affecting analgesia |
|
|
Term
| why is methylnaltrexone good for patients with opioid induced constipation? |
|
Definition
| it blocks mu receptors in the intestinal tract WITHOUT affecting analgesia |
|
|
Term
| inflammatory bowel disease affects what part of the GI tract? |
|
Definition
| small and large intestine |
|
|
Term
| 2 inflammatory bowel diseases? |
|
Definition
1. ulcerative colitis
2. crohn's disease |
|
|
Term
| inflammatory bowel diseases are associated with what physical manifestations (4)? |
|
Definition
1. secretory diarrhea
2. ulcers
3. bleeding
4. malabsorption |
|
|
Term
| goal of treating inflammatory bowel disease? |
|
Definition
to relieve symptoms, induce remission, and prevent relapse
no single drug achieves these goals |
|
|
Term
| 6 types of drugs used to treat inflammatory bowel disease? |
|
Definition
1. sulfasalazine
2. mesalamine
3. glucocorticoids
4. immunomodulators
5. biologic reagents
6. antibiotics |
|
|
Term
| sulfasalazine is a conjugate of what 2 things? |
|
Definition
1. mesalamine
2. sulfapyridine |
|
|
Term
| 2 glucocorticoids used to treat inflammatory bowel disease? |
|
Definition
1. prednisone
2. budesonide |
|
|
Term
| immnunomodulator used in treatment of inflammatory bowel disease? |
|
Definition
|
|
Term
| 2 biologic reagents used in inflammatory bowel disease? |
|
Definition
1. Abs to TNF-alpha
2. Abs to alpha-4-integrins |
|
|
Term
| action of the mesalamine in sulfasalazine? |
|
Definition
inhibits cyclooxygenase and lipoxygenase --> reduction of LTB4 and 5-HETE levels
anti-inflammatory agent |
|
|
Term
| which part of sulfasalazine is responsible for most of the side effects? |
|
Definition
|
|
Term
|
Definition
| acute and maintenance therapy in ulcerative colitis |
|
|
Term
| side effects of sulfasalazine? |
|
Definition
1. fever - up to 45% of patients
2. malaise
3. headache
4. skin rash
5. bone marrow suppression |
|
|
Term
| how is mesalamine administered? |
|
Definition
| enteric coated or encapsulated |
|
|
Term
|
Definition
1. more effective in Crohn's disease than sulfasalazine - remission in as many as 45% of patients
2. acute and maintenance therapy in ulcerative colitis |
|
|
Term
| what drug is more effective in Crohn's disease? |
|
Definition
|
|
Term
| mesalamine leads to remission in what % of Crohn's patients? |
|
Definition
|
|
Term
| side effects of mesalamine? |
|
Definition
1. less than sulfasalazine - b/c don't have sulfapyridine
2. headache
3. rash
4. diarrhea |
|
|
Term
| problems with using oral prednisone in the treatment of inflammatory bowel disease? |
|
Definition
| can get systemic side effects including high BP, hypoglycemia, cataracts, and mood changes |
|
|
Term
| why is budesonide favored as a glucocorticoid to treat inflammatory bowel disease? |
|
Definition
| to avoid the side effects of oral prednisone - not absorbed as well from the intestine |
|
|
Term
| 4 immunomodulators used in the treatment of inflammatory bowel disease? |
|
Definition
1. mercaptopurine
2. azathioprine
3. methotrexate
4. cyclosporine |
|
|
Term
| mechanism of azathioprine in treatment of inflammatory bowel disease? |
|
Definition
| converted to mercaptopurine --> suppresses lymphocyte proliferation |
|
|
Term
| mechanism of methotrexate in treatment of inflammatory bowel disease? |
|
Definition
| dihydrofolate reductase inhibitor with anti-inflammatory and immunosuppressive activity |
|
|
Term
| mechanism of cyclosporine in the treatment of inflammatory bowel disease? |
|
Definition
| inhibits T cells activation |
|
|
Term
| 4 biological agents used in treatment of inflammatory bowel disease? |
|
Definition
1. infliximab
2. adalimumab
3. certolizumab
4. natalizumab |
|
|
Term
| administration of biologic agents used to treat inflammatory bowel disease? |
|
Definition
| have to be injected because they are immunoglobulins |
|
|
Term
|
Definition
| monoclonal Ab to tumor necrosis factor alpha --> neutralize TNFa |
|
|
Term
|
Definition
| a cytokine (inflammatory mediator) in the pathogenesis of inflammation |
|
|
Term
|
Definition
| humanized Ab to TNF-alpha |
|
|
Term
|
Definition
| used to treat rheumatoid arthritis and inflammatory bowel disease |
|
|
Term
|
Definition
| Fab fragment to TNF-alpha |
|
|
Term
|
Definition
| monoclonal Ab to alpha 4 integrins |
|
|
Term
| what is the role of alpha 4 integrins? |
|
Definition
| play a key role in leukocyte trafficking and cell to cell communication during inflammatory process |
|
|
Term
| other use of natalizumab (besides inflammatory bowel disease)? |
|
Definition
|
|
Term
| 2 antibiotics used in the treatment of inflammatory bowel disease? |
|
Definition
1. metronidazole
2. ciprofloxacin |
|
|
Term
|
Definition
| visceral hypersensitivity a/w diarrhea, constipation, or both and bloating |
|
|
Term
| treatment of constipation a/w IBS? |
|
Definition
1. tegaserod - 5HT4 agonist
2. osmotic agents - lactulose
3. lubiprostone - Cl channel activator |
|
|
Term
| treatment of diarrhea a/w IBS? |
|
Definition
1. alosetron - 5HT3 antagonist
2. loperamide - causes constant contraction
3. cholestyramine - bile acid resins |
|
|
Term
| treatment of bloating a/w IBS? |
|
Definition
| anti-spasmodics - anti-cholinergic agents |
|
|
Term
| treatment of abdominal pain a/w IBS? |
|
Definition
1. anti-cholinergics
2. TCAs
3. SSRIs |
|
|
Term
| 5HT3 and 4 receptors effect on intestinal motility? |
|
Definition
|
|
Term
| effect of 5HT3 and 4 receptor antagonists on motility? |
|
Definition
|
|
