Term
|
Definition
| - overuse of laxative> thorough evacuation> takes few days to build up bulk > lag of defecation is interpreted as continued constipation> take more laxative> etc.> continued use bowels become unresponsive |
|
|
Term
| best prophylaxis and treatment of constipation (non-pharmacological) (4): |
|
Definition
- diet rich in fiber
- sufficient fluid intake
- daily exercise
- bowel training |
|
|
Term
| Dietary fiber and bulk forming laxatives (3): |
|
Definition
- bran
- psyllium
- methylcellulose |
|
|
Term
| Osmotic laxatives such as ___ ___ __ ___ are the drug of choice for bowel prepartion for colonoscopy, barium enema, or colorectal surgery. |
|
Definition
| - polyethylene glycol-electrolyte solutions |
|
|
Term
| Magnesium oxide is also an __ ___. ___ is another ___ ___ used for hepatic encephalopathy. |
|
Definition
(this slide not in red)
- osmotic laxative
- Lactulose
- osmotic laxative
- hepatic encephalopathy |
|
|
Term
| Osmotic laxatives do NOT cause __ __. |
|
Definition
|
|
Term
| Surfactant Stool Softeners are also known as ____. These are wetting agents, like ___ __ and/or __ __. |
|
Definition
- Docusates (red)
- mineral oil and/or castro oil |
|
|
Term
| Lubipristone is a __ __ ___ (CIC-2) in the small intestine, and increases motility. |
|
Definition
| - chloride channel activator |
|
|
Term
| ___ is a chloride channel activator that works in the small intestine to increase motility. |
|
Definition
|
|
Term
| laxatives are only good when you’re using them, so no matter what the class is, you shouldn’t use them all the time. You should eat right, exercise, and have water. |
|
Definition
|
|
Term
| Constipation often occurs secondary to ___ __ because these drugs lead to decreased intestinal motility via the __ __ receptors. |
|
Definition
- opioid agonists
- mu opioid receptors |
|
|
Term
| To treat constipation that is secondary to opioid agonists, ___ __ __ __ ___ are used. Name one. |
|
Definition
- PERIPHERALLY ACTING mu opioid antagonists are used
- Methylnaltrexone |
|
|
Term
| Methylnaltrexone is a __ __ __ __ __ used to treat constipation in patients on opioids. This drug allows the opioids to still reduce pain in the CNS but eliminates their peripheral side effects like constipation. |
|
Definition
| - peripherally acting mu opioid antagonist/blocker |
|
|
Term
| ___ is also a peripherally acting mu opioid antagonist/blocker that is used to decrease post-op ileus in patients who have had bowel resection (limited to 7 day use due to ___ toxicity). |
|
Definition
|
|
Term
| name 2 peripherally acting mu opioid antagonists: |
|
Definition
- Methyltrexone (patients on opioids)
- Alvimopan (for post op ileus) |
|
|
Term
9 liters of fluid enter small intestine, only 0.1 liters pass with the stool.
Small intestine absorbs 8 liters.
Any reduction in this amount adds to the burden of the colon which can reabsorb 4-5 liters per day.
The presence of non-absorbable solutes will increase the passage of fluid and produce diarrhea. |
|
Definition
|
|
Term
| Colite / go lightly, poly ethylene glycol/electrolyte containing laxative> increases fluid in colon> diarrhea/watery stool |
|
Definition
|
|
Term
| electrolyte containing laxatives increase the ___ amount in the colon> watered down stool |
|
Definition
|
|
Term
| Excessive resorption of water causes ___. __ ___ dictates the time available for resorption of water and solutes. |
|
Definition
- constipation
- Intestinal motility |
|
|
Term
| Increased motility leads to ___, while decreased motility leads to ___. |
|
Definition
|
|
Term
| Nausea and vomiting causes __ ___ so antiemetic agents help this by ___ __. |
|
Definition
- decreased motility
- increasing motility |
|
|
Term
| ___ are the mainstay of nonspecific treatment of diarrhea. |
|
Definition
|
|
Term
| Opioids (for treatment of diarrhea) act at the __ receptors in the GI tract to __ ___. |
|
Definition
- mu receptors
- decrease motility |
|
|
Term
| List 2 opioids used for treatment of diarrhea: |
|
Definition
- Loperamide
- Diphenoxylate + atropine
These have poor CNS penetration so less abuse liability. |
|
|
Term
| Uncomplicated infectious diarrhea is usually __ __, treat with fluid replacement, bed rest, and __ ___ or ___. |
|
Definition
- self-limiting
- pepto-bismol or kaopectate |
|
|
Term
| Kaopectate adsorbs toxins so good antidiarrheal. |
|
Definition
|
|
Term
| ____ is a somatostatin analog for severe diarrhea. |
|
Definition
|
|
Term
|
Definition
Treatment for severe diarrhea seen with:
- Secretory Neuroendocrine tumors of the GI tract: decreases GI hormone secretion> reduces intestinal and pancreatic secretion> slowed motility> decreased secretion of anterior pituitary hormones
- also used in AIDs and Short Bowel Syndrome to slow motility |
|
|
Term
| Octreotide antidiarrheal used for (3): |
|
Definition
- Secretory neuroendocrine tumors in GI tract
- AIDs
- Short Bowel syndrome |
|
|
Term
| Irritable Bowel Syndrome: |
|
Definition
Abdominal pain, cramping, and bloating
Changes in bowel habits
Constipation, diarrhea, or both
String-like stools
Sense of incomplete evacuation
No structural anomalies = Functional Disorder
No diagnostic markers |
|
|
Term
| Irritable Bowel Syndrome (IBS) Rome Guidelilnes for Diagnosis: |
|
Definition
In 12 months, patient must experience 12 weeks of abdominal pain and discomfort with two of three features:
- defecation relieves symptoms
- change in stool frequency
- change in stool appearance |
|
|
Term
|
Definition
Abdominal pain, cramping, and bloating
Changes in bowel habits.
Constipation, diarrhea, or both
“constipation-predominant”, “diarrhea-predominant”, or “mixed”
String-like stools
Sense of incomplete evacuation
No structural anomalies = functional disorder
No diagnostic markers
~ 20 % of the U.S. population
Young adulthood
Greater incidence in women
Treatments not that effective |
|
|
Term
| Drug classifications for Treatment of IBS: |
|
Definition
- Anticholinergics aka muscarinic antagonists/blockers aka atropine like drugs
- 5-HT3 receptor antagonists
- TCAs
- MOA
- Peppermint capsules (England)
- Probiotics |
|
|
Term
| Example of anticholinergic used to treat IBS: |
|
Definition
|
|
Term
| Side effects of anticholinergics for treatment of IBS: |
|
Definition
- dry mouth
- dry eye
- tachycardia |
|
|
Term
| Dicyclomine is an ___ used to treat ___. |
|
Definition
| - anticholinergic used to treat IBS |
|
|
Term
| A 5HT-3 antagonist can be used to treat ___ b/c it ___ ___. |
|
Definition
|
|
Term
| What 5HT-3 blocker is used to treat diarrhea predominant IBS: |
|
Definition
Alosetron
- can cause constipation, which can be severe
- causes ischemic colitis in less than 1% |
|
|
Term
| ___ can be used for constipation predominant IBS. |
|
Definition
|
|
Term
TCAs can also be used for IBS. Not tested on but be aware of it.
The doses required for treating IBS are lower than those required for treating depression. |
|
Definition
|
|
Term
| MOA for IBS treatment: May be anticholinergic actions and alteration of processing of visceral afferent information |
|
Definition
|
|
Term
| side effects of using TCAs for treatment of IBS: |
|
Definition
- anticholinergic effects
- orthostatic hypotension
- overdose> conduction defects/arrhythmias, seizures |
|
|
Term
| 2 types of Inflammatory bowel disease: |
|
Definition
- Crohn's Disease (CD)
- Ulcerative Colitus (UC)
These are considered autoimmmune diseases. Cause is uknown, but there seems to be a genetic link.Pathology is also obsevered outside of the GI tract. |
|
|
Term
| Crohn's Disease is a ___ ___ __ that may occur in __ parts of the GI tract from __ to ___. The most common site is the __ __. |
|
Definition
- granulomatous inflammatory process
- all parts
- mouth to anus |
|
|
Term
| In Crohn's Disease there is __ __ __, meaning multiple tissue layers are involved. Ulcers may span the entire depth of the intestinal wall. This disease has ___ pattern or __ ___ pattern. |
|
Definition
- transmural granulomatous inflammation
- fibrostenotic pattern
- penetrating fistulous pattern |
|
|
Term
| most common site for Crohn's Disease: |
|
Definition
|
|
Term
| Ulcerative Colitis typically involves the ___ and extends __ to include part or all of the __ ___. |
|
Definition
- rectum
- proximally
- part or all of the large intestine |
|
|
Term
| Ulcerative Colitis is NOT ____, except in ___ disease. |
|
Definition
| - NOT transmural except in fulminant disease |
|
|
Term
| With ulcerative colitis there is an increase in __ __ and __ of the colon. |
|
Definition
- increase in polyp incidence
- narrowing of the colon |
|
|
Term
| Crohn's disease is ___ but ulcerative colitis is ___ ___. Crohn's is in the __ __ while ulcerative colitis is in the ___. |
|
Definition
- transmural
- NOT transmural
- terminal ileum
- rectum |
|
|
Term
| Goal of therapy for inflammatory bowel disease: |
|
Definition
| reduce inflammation to reduce ulceration and symptoms |
|
|
Term
| Aspirin is also known as ___ ____. |
|
Definition
|
|
Term
| A derivative of aspirin called _____ ___ is an active drug that only acts ___ not systemically. There are formulations designed to deliver drug to the ___ __ and ___. |
|
Definition
- 5-aminosalicyclic acid (5-ASA)
- locally
- distal small intestine and colon |
|
|
Term
| 5-ASA are formulated with some type of other bond so that it is not absorbed very well, which is the point. By not being absorbed it is able to act locally on the intestines to reduce inflammation. |
|
Definition
|
|
Term
|
Definition
- Sulfasalazine (5-ASA-sulfapyridene)
- Olsalazine |
|
|
Term
| 5-ASA has numerous anti-inflammatory mechanisms. It blockades ___ ___ by inhibiting ____. It blockades the ___ pathway which normally makes many inflammatory mediators. It inhibits the transcription factor ____, which is important for cyokine production. It may inhibit __ __ cells, ___ __, and ___. It may scavenge __ ___ species. |
|
Definition
- prostaglandin formation by inhibiting cyclooxygenase
- lipooxygenase
- factor NF-kB
- natural killer cells, mucosal lymphocytes, and macrophages
- reactive oxygen |
|
|
Term
| summary of 5-ASA mechanism of action (5): |
|
Definition
- inhibits cyclooxygenase so inhibits prostaglandin formation
- inhibits lipooxygenase so inhibits production of inflammatory mediators
- inhibits transcription factor NF-kB so inhibits cytokine production
- may inhibit natural killer cells, mucosal lymphocytes, and macrophages
- may scavenge reactive oxygen species |
|
|
Term
| 5-ASA is used for induction and maintenance of remission in ___ __ and in mild to moderate active disease. It is less efficacious with __ __ but still widely used. |
|
Definition
- Ulcerative colitis
- Crohn's disease |
|
|
Term
| For 5-ASA to be effective, __ concentrations must be reached. |
|
Definition
|
|
Term
| In disease localized to distal colon and rectum, a __ __ can be used. |
|
Definition
|
|
Term
| With 5-ASAs __ linkages reduce absorption so local inflammation can be acted on. This linkage gets cleaved by bacteria in the distal ileum/colon. |
|
Definition
|
|
Term
| Side effects of Sulfasalazine (a 5-ASA): |
|
Definition
- slow acetylator, so hard to dose
- GI distress/nausea
- headache
- arthralgia, myalgia, bone marrow suppression
- hypersensitivity- fever, dermatitis, pancreatitis, pneumonitis, hepatitis, pericarditis
- inhibition of folate absorption
THIS 5-ASA HAS BAD SIDE EFFECTS DUE TO THE SULFAPYRIDENE, OTHER 5-ASAs ARE MUCH BETTER TOLERATED. |
|
|
Term
| What 5-ASA is poorly tolerated due to its sulfapyridene linkage? |
|
Definition
|
|
Term
| Side effects of the well tolerated 5-ASAs: |
|
Definition
- secretory diarrhea: not associated with disease process (10% of patients)
- rare hypersensitivity, which occur with salicylates
- renal tubular damage and/or interstitial nephritis with higher serum 5ASA concentrations |
|
|
Term
| ___ are used for moderate to severe ACTIVE disease, not for maintenance of remission with inflammatory bowel diseases. |
|
Definition
|
|
Term
| Inflammatory bowel disease mild to moderate active or in remission use ___. Inflammatory bowel disease moderate to severe active use ___. |
|
Definition
|
|
Term
| Glucocorticoids can be given __, __, or __. Usually give ___ or ___ about 40-60mg/d, response in 1-2 weeks, and then taper off. Side effects are associated with HPA suppresion. |
|
Definition
- IV, PO, or rectally
- prednisone or prednisolone |
|
|
Term
| __ ___ is a controlled release low bioavailability glucocorticoid used for inflammatory bowel disease. |
|
Definition
|
|
Term
| With glucocoriticoids for inflammatory bowel disease the __ the bioavailability the better. |
|
Definition
|
|
Term
| 4 possible therapies for inflammatory bowel disease: |
|
Definition
- 5-ASA
- Glucocorticoids
- Purine analogs
- TNF-alpha antibody therapy |
|
|
Term
| Purine analogs like ___/___ are used for the maintenance and induction of remission in Ulcerative Colitis and Crohn's Disease. |
|
Definition
| - Azathioprine/6-Mercaptopurine |
|
|
Term
| Azathioprine is a __ __ that becomes ___ after absorption. Then the ___ becomes ___ ___. |
|
Definition
- purine analog
- 6-Meraptopurine
- 6-thioguanine nucleotides |
|
|
Term
purine analog:
- Azathioprine> 6-Mercaptopurine> 6-thioguanine nucleotides |
|
Definition
|
|
Term
| Azathiprine/6-Mercaptopurine are purine analogs that are __ __ or ___ __ that interfere with ___ nucleic acid metabolism by destroying ___ __ __ which inhibits the proliferation of lymphoid cells after antigen stimulation. |
|
Definition
- cytotoxic drugs or anti-metabolites
- purine
- activated lymphoid cells |
|
|
Term
| Major side effect of Azithiprine/6-Mercaptopurine: |
|
Definition
bone marrow suppression:
- leukopenia
- anemia
- thrombocytopenia
- may also cause liver disease |
|
|
Term
| TNF-alpha therapy for inflammatory bowel disease is based off of fact that __ __ __ __ is the key cytokine in IBD, especially Crohn's disease. |
|
Definition
| - tumor necrosis factor alpha |
|
|
Term
| The drug antibody to TNF-alpha: |
|
Definition
|
|
Term
| Infliximab is an __ to ___ and is given IV in moderate to severe UC or CD. |
|
Definition
|
|
Term
| 2 possible drugs used in remission or mild to moderate IBD: |
|
Definition
- 5-ASA
- purine analogs (just remission) |
|
|
Term
| 2 possible drugs used in moderate to severe IBD: |
|
Definition
- glucocorticoids
- TNF-alpha antibody therapy (Infliximab) |
|
|
Term
| Side effects of TNFalpha therapy (Infliximab): |
|
Definition
- 6% have serious side effects: infection due to reactivation of latent TB and Hep. B, and otehr infections
- other side effects include:
- fever, headache, dizziness, itching, chest pain, dyspnea, severy reactions, hypotension, sOB, delayed serum like sickness, myalgia, arthralgia, rash, edema, acute liver failure |
|
|
Term
| tumor necrosis factor alpha is on TH1 helper cells. |
|
Definition
|
|
Term
|
Definition
- Budesonide
- Topical corticosteroids
- antibiotics
- 5-ASA
last slide of lecture, not sure if need to memorize |
|
|
Term
| Moderate IBD disease tmt: |
|
Definition
TNF antagonists
oral corticosteroids
methotrexate
Azathioprine/6-Mercaptopurine |
|
|
Term
|
Definition
surgery
cyclosporine
TNF antagonists
intravenous corticosteroids |
|
|
