pharmacology: GI drugs

the pharmacology lecture on the conventional drugs used to treat various GI disorders. the first category we covered was laxatives, of which there are several different types. psyllium / metamucil is a laxative that is made of crushed psyllium husks, which contain both soluble and insoluble fiber-- allowing for more bulk, and softer stool. docusate / colase is a stool softener laxative that acts as an anionic surfactant, effectively making the intestinal lining more slippery. it is also used to dissolve earwax in cases of a blocked ear canal. magnesium hydroxide is an osmotic laxative, causing water to come out into the intestinal lumen. finally, dulcolax is an agent that decreases constipation by increasing intestinal motility.

on the other hand, there are agents designed to stop diarrhea, in cases of acute diarrhea or chronic diarrhea related to IBS. these are all generally contraindicated in cases of diarrhea with fever, due to parasitic or bacterial infections, and in cases of severe colitis to avoid toxic megacolon. loperamide is a morphine analog acts to stimulate the µ-opiod receptors in the myenteric plexus, effectively slowing down peristalsis. diphenoxylate is another morphine analog which is often combined with atropine for its inhibitory effects on acetylcholine, and commonly causes dry mouth as a side effect.

the analogous drugs for suppressing / inducing outflow on the top part of the GI tube: anti-emetics and emetics. both classes work on the two brainstem centers that are involved in the vomiting response-- chemoreceptor trigger zone and the vomiting center (responsible for the motor mechanisms involved). both centers have receptors for various neurotransmitters, especially histamine, dopamine, and serotonin (type 3 and 4, known as 5HT3 and 5HTP4, respectively).

antiemetics are drugs that block one of these receptor types. patients with mild nausea / vomiting symptoms are better off taking anti-histamines such as benadryl, whereas severe symptoms are best treated with 5HT3 blockers (serotonin receptor type 3 blockers). another example of an anti-histamine used to treat nausea is meclizine / antivert, which has the unfortunate side effect of urinary retention due to bladder neck spasm. metaclopramide is an anti-emetic that is especially indicated in gastric stasis following surgery, and ondansetron is a serotonin receptor blocker that is indicated for nausea concurrent with chemotherapy. on the other end of the spectrum, ipecac is used to trigger emesis by stimulating the same medullary centers that the anti-emetics suppress. it is administered with large amounts of water and can start working in 10-30 minutes. side effects might include dizziness, dehydration, and abdominal spasm, even on an empty stomach.

some drugs designed to alleviate symptoms of gastritis: TUMS is the trade name for calcium carbonate, which raises gastric pH and therefore temporarily lessens mucosal irritation. zantac / ranitidine blocks the H2 receptors for histamine, one of the substances that trigger acid release (the others being gastrin and acetylcholine). omeprazole / prilosec is a proton pump inhibitor which leads to less acid production by parietal cells and therefore can alleviate symptoms but may also lead to malabsorption as well as decreased defenses against certain pathogens. to treat peptic ulcer disease specifically, a "triple therapy" can be given for 7-14 days, which consists of a proton pump inhibitor and two antibiotics (two to prevent resistance). alternatively, bismuth subsalicylate or a histamine blocker can be used instead of the proton pump inhibitor to damage the h. pylori's cell wall or decrease gastric acidity, respectively.

drugs used to treat IBD fall into several categories. an aminosalicylate drug like mesalamine works to decrease inflammation by inhibiting leukotriene production as well as acting as an antioxidant- but may also cause nephrotoxicity. it is absorbed in the small intestine, but can be found in pro-drug forms such as asacol or sulfalazine which are absorbed in the large intestine via pH or colonic bacteria mechanisms. antibiotics are also used to treat IBD- most commonly a combination of metronidazole and cipro. another category used for IBD is the corticosteroid class, such as prednisone, used to suppress inflammation and the immune system on many fronts. some things to keep in mind with prednisone are the potential for addisonian crisis and avascular necrosis. immunomodulator drugs are also used, such as azthioprine / immuran, which inhibits purine synthesis, and infliximib / remicade, which inhibits TNF-alpha (but may cause t-cell lymphoma and drug induced lupus).

questions
1. agents which stimulate peristalsis should be used with caution in cases of...√√
2. what method of administration is preferred in such cases?√√
3. insoluble fiber's effect on GI?√√
4. sources of insoluble fiber?X†
5. sources of soluble fiber?XX
6. compare the physiological benefits of soluble vs. insoluble fiber.√

metamucil...
7. made from...√√
8. indicated in...†√
9. might help reduce...X†
10. mechanism of action?√√
11. timeframe of action?†√
12. which form of metamucil is not gluten free?√√

docusate...
13. category?√X√
14. mechanism?XX√
15. effect on stools is seen how long after first dose?XXX
16. avoid oral use if what is suspected?√√
17. also used for...X√√

magnesium hydroxide...
18. two mechanisms?√
19. how long until effects are felt?X
20. may precipitate or exacerbate...X
21. people with chronic kidney disease at a greater risk for...X

bisacodyl / dulcolax...
22. mechanism of action?†X
23. onset of action?X
24. especially indicated in...†
25. side effects?X

loperamide...
26. analog of...X√
27. mechanism?√X
28. unlike other opioids, loperamide...√√
29. two indications?X√
30. contraindicated in...X√

diphenoxylate plus atropine...
31. mechanism?†X
32. common side effect?√√
33. contraindicated in...X√

anti-emetics intro
34. two brain centers involved in vomiting reflex?
35. both centers have what types of receptors?
36. mild symptoms are best addressed by which type of anti emetic?
37. moderate / severe symptoms are best addressed by which type of anti emetic?

meclizine / antivert...
38. mechanism of action...†
39. side effects?†
40. last side effect due to...√

metoclopramide / reglan...
41. why is reglan considered a "pro kinetic"?√
42. indications? (3)X
43. side effects?
44. contraindicated in which two disorders?

ondansetron / zofran and others...
45. mechanism?
46. indication?√
47. given when in relation to the second indication in [46]?†
48. another drug that can be used for nausea induced by chemotherapy?X
49. marijuana derivative anti-emetic?X

ipecac...
50. mechanism of action?√√
51. onset of action?√
52. given with large doses of...
53. side effects?

gastritis, calcium carbonate...
54. three substances that trigger gastric acid release?√
55. why might drinking milk to alleviate ulcer pain be counterproductive?√
56. mechanism of TUMS?√
57. potential GI effect?√
58. long term use might cause...√

ranitidine / zantac...
59. mechanism of action?√
60. indications?X
61. when would zantac be administered IV?X
62. which method of administration has more side effects?X

omeprazole / prilosec...
63. mechanism?√
64. how long is it used for GERD and PID?√
65. side effects?†
66. esomeprazole is...√

triple therapy...
67. what are the two forms of triple therapy?
68. what substance might be added to the therapy to inhibit h. pylori reproduction?
69. how long is triple therapy generally administered?

5-ASA / mesalamine...
70. mechanism of action? (3)
71. indications?
72. side effects?
73. absorption in the GI tract?
74. pro-drug forms of mesalamine?
75. different mechanisms of [74]?

antibiotics...
76. which form of IBD shows more benefit from antibiotics?
77. two of the most commonly prescribed antibiotics for IBD?
78. hallmarks / warnings for [77]?

prednisone...
79. provides full remission to approximately what percent of IBD patients?
80. side effect on bone?
81. pro-drug form?

azthioprine / immuran...
82. class?
83. indications?
84. mechanism of action?
85. side effect on bone?

infliximib / remicade...
86. mechanism?
87. dosing schedule?
88. complications?

answers
1. suspected bowel obstruction.
2. rectal administration.
3. increase bulk, shorten transit time, softens stool.
4. whole grain foods
nuts
seeds
bran
green beans
cauliflower
zucchini
celery
tomato skins
5. legumes
oats
barley
6. insoluble: adds bulk and softens stool. soluble: fermentation yields products that are beneficial to enterocytes.

7. ground psyllium husks.
8. constipation, IBS.
9. cholesterol, colon cancer risk, heart disease.
10. contains both soluble and insoluble fiber, adds bulk and softens stool.
11. may take several days.
12. metamucil wafers contain wheat flour.

13. stool softener.
14. anionic surfactant-- makes bowel wall more slippery.
15. 1-3 days.
16. intestinal obstruction.
17. clearing out earwax.

18. acts as an osmotic agent in intestines, drawing more water out into the lumen. also acts as antacid, raising gastric secretion pH.
19. around 6 hours.
20. electrolyte imbalances such as hypokalemia.
21. hypermagnesemia.

22. irritant laxative-- increases intestinal motility.
23. 2 to 6 hours.
24. constipation due to severe back pain, which decreases intestinal motility due to edema.
25. diarrhea, cramping, sweating, dependence.

26. morphine.
27. activation of µ-opiate receptors in myenteric plexus within GI tract slows peristalsis.
28. doesn't affect CNS opiate receptors.
29. acute diarrhea and chronic diarrhea in IBS patients.
30. parasitic or bacterial infections accompanied by fever.

31. morphine analog plus acetylcholine inhibitor leads to decreased peristalsis.
32. dry mouth.
33. diarrhea with fever, diarrhea due to parasites or bacterial infection.

34. both in brain stem: chemoreceptor trigger zone and vomiting center (responsible for the motor mechanisms).
35. histamine, dopamine type 2, serotonin type 3 and 4.
36. anti-histamines.
37. serotonin type 3 receptor blockers.

38. H1 receptor blocker.
39. drowsiness, dizziness, dry mouth, urinary retention.
40. bladder neck spasm.

41. because it moves the bolus from the stomach to the intestines.
42. moderate N/V
gastric stasis due to surgery or diabetic gastroparesis.
GERD
43. drowsiness, dizziness, headache.
44. parkinson's, bowel obstruction.

45. 5HT3 blocker.
46. severe nausea, patients on chemotherapy.
47. 30 mins before chemotherapy.
48. decadron.
49. dronobinol.

50. stimulates the same medullary centers that zofran and dronabinol suppress.
51. 10-30 mins.
52. water.
53. abdominal muscle spasm
dizziness
dehydration.

54. acetylcholine, histamine, gastrin.
55. because calcium stimulates chief cells to produce more acid.
56. neutralizing stomach acid.
57. potentially constipating.
58. osteoporosis.

59. H2 receptor blocker.
60. PUD, gastritis, GERD.
61. burn victim.
62. IV.

63. inhibits hydrogen/potassium ATPase pump of parietal cells.
64. GERD: 2-8 weeks. PID: 1-2 weeks.
65. increased pH can cause malabsorption of nutrients and minerals as well as lowering defenses against certain pathogens.
66. an enantiomer of omeprazole.

67. proton pump inhibitor, bismuth based.
68. lactoferrin.
69. 7-14 days.

70. inhibit leukotriene production, anti-prostaglandin, anti-oxidant.
71. IBD.
72. N/V, diarrhea, abdominal pain, nephrotoxicity.
73. small intestine, doesn't reach colon.
74. asacol and sulfasalazine.
75. asacol based on higher pH in colon and sulfasalazine based on bacterial in colon.

76. crohn's.
77. metronidazole and ciprofloxin.
78. metro-- N/V, do not drink alcohol while taking. cipro-- tendon rupture, affinity for calcium.

79. 35-50%.
80. avascular necrosis, especially femur and humerus.
81. budenoside / enterocort.

82. immunomodulator.
83. IBD, RA, post-transplant.
84. inhibiting purine synthesis leads to an anti-proliferative effect and induction of t-cell apoptosis.
85. suppresses bone marrow, increasing susceptibility to infection.

86. inhibits TNF-alpha
87. IM or SQ dosing every 2 or 4 weeks.
88. t-cell lymphoma, drug induced lupus.