Laxatives and Anti-Diarrheals Flashcards
What is IBS?
abdominal pain associated with constipation or diarrhea
What is inflammatory bowel disease (IBD)?
- Crohn’s disease= infiltration of lymphocytes, macrophages, and submucosal fibrosis. Lesions are not confluent and contain “skip areas” of normal colon.
- OR-
- ulcerative colitis= lymphocytic and neutrophilic infiltrates (usually more distal than Crohn’s). Lesions are usually confluent.
How much water does normal peristalsis allow to be absorbed?
4 L
What happens to water absorption with inhibition of peristalsis (decreased motility)?
more water is extracted leading to harder stools (constipation)
What happens to water absorption with increased GI motility?
less water is extracted leading to watery stools (diarrhea)
*** What are the bulk-forming laxatives?
- natural= PSYILLIUM and METHYLCELLULOSE
- synthetic= POLYCARBOPHIL
- these are indigestible, hydrophilic colloids that absorb water and form a bulky and lubricating gel that distends the colon and promotes peristalsis.
What can bacterial digestion of plant fibers (psyllium or methylcellulose) cause?
increased bloating and flatus
*** What are the osmotic laxatives?
- drugs that increase water content of stool; used in acute constipation and cleanse bowel prior to colonoscopy.
- nonabsorbable sugars/salts= MAGNESIUM HYDROXIDE (milk of magnesia), SORBITOL, LACTULOSE, PREPOPIK.
- balanced POLYETHYLENE GLYCOL (PEG)= used for bowel prep for colonoscopy.
*** What are the surfactant agent laxatives (stool softeners)?
- soften stool by permitting entrance of excess lipids and water.
- used in children and debilitated adults to treat fecal impaction.
- DOCUSATE (oral or enema)
- GLYCERIN suppository
- MINERAL OIL
What can long term use of surfactant laxatives (such as docusate) lead to?
impairment of fat-soluble vitamin (A, D, E, and K) absorption
*** What are the stimulant laxatives (cathartics)?
- increase NO synthase activity and platelet activating factor (PAF); induce mild inflammatory response.
- given PO and poorly absorbed.
- SENNA
- ALOE
- CASCARA
- mainly used in neurologically impaired pts
What can chronic use of stimulant laxatives (such as senna) lead to?
melanotic pegmentation of colon mucosa
What agent is used in conjunction with PEG for colonoscopy?
- BISACODYL (diphenylmethane derivative)
*** What are the opioid receptor antagonist laxatives?
- METHYLNALTREXONE= used to counteract opioid induced constipation. Given as a subcutaneous injection every 2 days.
- ALVIMOPAN= short-term use to shorten the period of postoperative ileus in hospitalized patients who have undergone small or large bowel resection. Given orally, but not more than 7 days due to cardiovascular toxicity.
*** What are the opioid agonist antidiarrheal agents?
- LOPERAMIDE= OTC and doesn’t cross the BBB, making it safe since there is no analgesic properties.
- DIPHENOXYLATE= prescription needed.
- All work by inhibiting presynaptic ACh release in submucosal and myenteric plexuses; increase colonic transit time and fecal H2O absorption.
What can higher doses of diphenoxylate (opioid agonist) cause?
CNS effects and lead to opioid dependence.
*commercial preps contain small amounts of atropine to discourage overdosage.
** What drug is used in pts who are refractory to antimotility drugs like loperamide?
5-HT3 antagonists (ALOSETRON)= blocks 5-HT3 receptor of enteric cholinergic neurons, thus inhibiting colonic motility and increasing colonic transit time.
- used to treat IBS in women when diarrhea is the main complaint.
- metabolized by P450 enzymes
** What does the GI serotonin 5-HT3 receptor do?
- activates visceral afferent pain sensation resulting in unpleasant sensations (nausea, bloating, and pain).
- increases colonic motility (left colon).
- so using an antagonist to this will reduce the pain and prevent diarrhea.
For what are the other “TRONs” used?
anti-emic agents
*** What is a bad ADR of alesetron?
ischemic colitis (RARE). This is why it is reserved only for pts who do not respond to loperamide.
What drugs are used to treat IBD?
- 5-aminosalicylic acids (5-ASA)
- antimicrobials (metronidazole, ciprofloxacin)
- corticosteroids for ACUTE FLARES
- immunosuppressives (azathioprine, mercaptopurine)= anti-tumor necrosis factor receptor antagonists.
- methotrexate (Crohn’s) or cyclosporine (ulcerative colitis
** What is the first line treatment drug for IBD?
5-ASA
*** How do the 5-aminosalicylates work?
- anti-inflammatory that works topically, not systemically in areas of diseased GI mucosa.
- inhibits activity of nuclear factor-kB (NF-kB); transcription factor to induce pro-inflammatory cytokine expression.
- sulfaSALAZINE, balSALAZINE, olSALAZINE…
- you pick the drug based on the site where the lesion is (different drugs are coated to go further in the colon).
What are some ADRs of aminosalicylates?
- adverse effects of sulfonamides (allergy, rash, hemolytic anemia; interference with folic acid absorption).
*** What are the TNF antagonists?
- indicated for acute/chronic Crohn’s disease in moderate to severe conditions.
- infliximab or adalimbumab for ulcerative colitis
- work by preventing TNF from binding to receptors to inhibit pro-inflammatory cytokine expression.
When are TNF antagonists used?
- remission/maintenance in pts with inadequate response to mesalamine/steroids
What are some anti-integrin therapies?
Natalizumab= monoclonal antibody against alpha-4 subunit of integrin on the surface of leukocytes. Prevents leukocyte binding to vascular endothelium (p-selectins and ICAM-1).
When are anti-integrin therapies used?
- when pts are refractory to TNF antagonists
What is an ADR of anti-integrin therapy (natalizumab)?
multi-focal leukoenceophalopathy= degeneration of white matter in the brain
*** How do you treat ulcerative colitis (IBD) that is less than 40 cm?
budesonide= newer corticosteroid formulated to release steroid in intestines to minimize systemic steroidal ADRs.
*coticosteroids inhibit production of inflammatory cytokines (TNF-a, IL-1, IL-8) and cell adhesion molecules.
How do you treat ulcerative colitis (IBD) that is greater than 40 cm?
- mild= oral mesalamine or sulfasalazine
- moderate= steroids
- severe= mercaptopurine or azathioprine
How do you treat Crohn’s disease (IBD)?
- mild= mesalamine or budesonide
- moderate= steroids
- severe= IV steroids, azathioprine, mercaptopurine, or anti-TNF drugs for longer term use for refractory cases to conventional therapy.
