1
Q
GI medications
A
- Laxatives and cathartics
- Antidiarrheals
- Antiemetics
- Emetics
- Gastritis and PUD medications
2
Q
Laxatives and cathartics
A
- Bulk-producing agents
- Stool softeners / Surfactants
- Lubricants / Emollients
- Hydrating agents/ Osmotic agents
- Hyperosmotic agents
- Stimulants / Irritants
3
Q
4 main actions of laxatives/cathartics
A
Increase pressure within the colon (bulk-producing agents)
Lubricate lining of colon (stool softeners and lubricants)
Increase fluid in colon (osmotic agents and hyper-osmotic agents)
Stimulate smooth muscle of colon (stimulant – irritants)
4
Q
obstruction
A
Rectal administration of laxatives is preferred over oral administration if there is any question of intestinal obstruction.
• Agents which stimulate peristalsis should always be avoided whenever obstruction is a possibility.
5
Q
Insoluble fiber
A
- Insoluble dietary fiber possesses passive water attracting properties that help to increase bulk, soften the stool and shorten transit time through the intestinal tract.
- Sources of insoluble fiber include: whole grain foods, bran, nuts, seeds, vegetables such as green beans, cauliflower, zucchini, celery, and tomato skins.
6
Q
Soluble fiber
A
- Soluble fiber undergoes metabolic processing via fermentation, yielding end- products that can improve bowel health..
- Soluble fiber sources include: legumes, oats, rye, barley, fruits (particularly apples and bananas), berries, vegetables, such as broccoli and carrots, and root vegetables, such as potatoes and yams.
7
Q
Psyllium/ Metamucil
A
- Category: Fiber laxative
- Indication: Constipation, irritable bowel, reduction of colon cancer risk, reduction of cholesterol levels and heart disease risk.
- MOA: Made from ground psyllium seed husks that contains both soluble and insoluble fiber. Adds bulk to stool and well as absorbing fluid into the feces to soften the stool.
Char: PO. Powder, capsules and wafers. May take several days before therapeutic effect is achieved. Increased oral intake of water may hasten effects.
• Side effects: Usually well tolerated. May cause diarrhea. Avoid use if any suspicion of intestinal obstruction. wafers contain gluten.
8
Q
Docusate/ Colace
A
- Category: Stool softener
- Indication: Constipation, hemorrhoids. Prophylaxis in patients who should not strain during bowel movement (i.e. after anorectal surgery, M.I.)
- MOA: Anionic surfactant
- Char: Capsule, Liquid, rectal suppository. The effect on stools is usually seen in 1 to 3 days after the first dose.
Side effects: Usually well tolerated. Flatulence, bloating, abdominal cramping May cause diarrhea. Avoid oral use if any suspicion of intestinal obstruction.
9
Q
Magnesium Hydroxide/ Milk of Magnesia
A
- Category: Osmotic laxative, antacid
- MOA: Magnesium salts are poorly absorbed by the GI tract and thus act as osmotic agents to draw water into the lumen of the GI tract.
- Indication: Constipation, indigestion
- Char: PO. Chewable tablets, capsules, liquid. Generally takes 6 hours for therapeutic effects.
Side effects: Diarrhea, cramping, abdominal pain. May precipitate or exacerbate electrolyte imbalances. Patients with severe chronic kidney disease are at greater risk for possible hypermagnesemia. Avoid use if any suspicion of intestinal obstruction.
10
Q
Bisacodyl/ Dulcolax

A
- Category: Stimulant laxative
- MOA: Increases intestinal motility.
- Indication: Constipation
- Char: PO. Generally takes 2 to 6 hours to work.
- Side effects: Diarrhea, abdominal cramping, sweating. Possible laxative dependence with prolonged use. Definitely avoid use if any suspicion of intestinal obstruction.
11
Q
Anti-diarrheal medications
A
- An anti-diarrheal drug is any medication which provides symptomatic relief for diarrhea.
- Opiates slow intestinal transit time, but Loperamide and Diphenoxylate with Atropine are most commonly used, since they do not have the usual side effects associated with narcotic use.
12
Q
Loperamide/ Imodium
A
- Category: Antidiarrheal – analog of Meperidine.
- MOA: Diminished peristalsis due to activation of opiate receptors in GI tract. Loperamide is an opioid receptor agonist and acts on the μ-opioid receptors in the myenteric plexus within the large intestines. It does not affect the central nervous system like other opioids.
Diminished activity of the myenteric plexus decreases the motility of the circular and longitudinal smooth muscles of the intestinal wall. This increases the amount of time substances stay in the intestine, allowing for more water to be absorbed out of the fecal matter.
• Indication: Acute diarrhea and the management of chronic diarrhea in patients with inflammatory bowel disease.
13
Q
Loperamide/Imodium char, SE
A
Char: PO. Generally well tolerated. No inherent analgesic properties.
• Side effects: Dizziness, headache. Generally, not to be used in parasitic or bacterial infections accompanied by fever.
***Not to be used in severe colitis due to risk of toxic megacolon.
14
Q
Diphenoxylate with Atropine/ Lomotil
A
- Category: Antidiarrheal
- MOA: Combination of morphine analog and acetylcholine inhibitor results in diminished peristalsis.
- Indication: Acute diarrhea
- Char: PO. Generally not indicated beyond 48 hours without consulting a physician. Although an analog of Meperidine, there are no inherent pain relieving effects.
15
Q
Diphenoxylate with Atropine/ Lomotil SE
A
• Side effects: Dry mouth is quite common, urinary retention, abdominal pain, constipation, (atropine effects).
Not to be used in diarrhea due to bacterial or parasitic infections/ Fever.
*** Contraindicated in patients with severe colitis due to risk of toxic megacolon.

16
Q
Other anti-diarrheal agents
A
• Bismuth subsalicylate (Pepto-Bismol)
• Bismuth subsalicylate (Kaopectate)*
• Opiates and synthetic opiates
* Please note that the original formulation of Kaopectate was kaolin clay (kaolinite) and pectin. The active ingredient of Kaopectate is now bismuth subsalicylate, the same active found in Pepto-Bismol.
17
Q
Emesis
A
vomiting center in the medulla is activated by stimuli such as vertigo and the gag reflex.
- Two sites in the brain stem have key roles in the vomiting reflex pathway: the chemoreceptor trigger zone (CRTZ) and the vomiting center (VC), which coordinates the motor mechanisms involved in vomiting.
- Both the CRTZ and the VC have multiple receptors, including histamine, dopamine type 2 (DA2) and serotonin type 3 (5-HT3) and serotonin type 4 (5-HTP4).
18
Q
Anti-emetics
A
- Different anti-emetic agents may be utilized depending on the severity of nausea or vomiting.
- Mild nausea and vomiting may respond to antihistamines.
- Moderate to severe N/V may require more potent agents that block the 5-HT3 receptor sites.
19
Q
Meclizine/ Antivert
A
- Category: Antiemetic
- MOA: H1 Histamine blocker
- Indication: Mild to moderate nausea such as in motion sickness or vertigo.
- Char: PO. Sedating antihistamine
- Side effects: Drowsiness, dizziness, dry mouth, urinary retention.
20
Q
Metoclopramide/ Reglan
A
- Category: Antiemetic/ pro-kinetic
- MOA: Dopamine 2 blocker and mixed serotonin 3 antagonist/serotonin 4 agonist
- Indication: Mild to moderate nausea, gastric stasis (i.e. after gastric surgery or diabetic gastroparesis. Also used in gastroesophageal reflux disease (GERD).
anti-emetic action of Metoclopramide is largely due to its antagonist activity at D2 receptors in the chemoreceptor trigger zone (CTZ). In more severe nausea and vomiting such as N/V associated with cancer chemotherapy, it has been superseded by the more effective 5-HT3 antagonists i.e. Ondansetron.
21
Q
Metoclopramide/ Reglan car, SE
A
- Char: Metoclopramide increases peristalsis of the jejunum and duodenum, increases tone and amplitude of gastric contractions, and relaxes the pyloric sphincter tone.
- Side effects: Drowsiness, dizziness and headache. It should be used with caution in Parkinson’s disease since, as a dopamine antagonist, it may worsen symptoms.
Contraindicated in patients with suspected bowel obstruction.

22
Q
Ondansetron/ Zofran
A
- Category: Antiemetic
- MOA: Blockade of serotonin (5HT3) receptor sites results in signifigant anti- nausea effect.
- Indication: Severe nausea
- Char: PO, IV. Effective agent for the severe nausea due to various chemotherapeutic agents. Given approximately 30 minutes or so prior to chemotherapeutic agent.
- Side effects: Dizziness, headache. Generally well tolerated.
23
Q
Other antiemetic drugs
A
• Corticosteroids such as Decadron may also be used for chemotherapy induced nausea. The exact mechanism of action for the antiemetic effects of a corticosteroid is not known.
• Marijuana derivatives or cannabinoids such as dronabinol (Marinol) are effective for mild to moderate nausea but can cause vertigo, disorientation and dysphoria.

24
Q
Emetic/ Syrup of Ipecac
A
- Category: Emetic
- MOA: Stimulation of medullary chemoreceptor trigger zone and local irritant of GI tract
- Indication: Induction of vomiting for drug overdose and certain poisonings.
- Char: PO. Effective orally, may produce emesis in 10 to 30 minutes. Give with large doses of water.
derived from the dried rhizome and roots of the Ipecacuanha plant,
25
Syrup of Ipecac SE
* Do not administer an emetic to any person with a diminished level of consciousness or to anyone who is unconscious.
* Do not use an emetic for caustic poisoning.
* Syrup of Ipecac is not generally given with charcoal, which will absorb the drug.
* Side effects: Abdominal muscle spasm (often lasting hours after stomach contents are emptied), dizziness and dehydration.
26
Gastritis
* Gastritis is inflammation of the gastric mucosa.
* Depending on the cause, gastritis may develop acutely or may persist chronically.
* There are multiple potential causes for gastritis including: bacterial infection (most often by H. pylori), aspirin and NSAID use, fungal infections (most often associated with immunodeficiency states), parasitic infections, viral infections, bile reflux, tobacco use, excessive alcohol consumption, certainconsumption, stress...
27
Peptic ulcer disease
* The majority of cases of PUD are caused by the bacterium, Helicobacter pylori.
* The other prominent cause of PUD is local irritation of the gastric mucosa by aspirin and NSAIDS such as ibuprofen.
* Severe stress such as that experienced by burn patients or trauma patients may also result in gastritis and PUD.
28
Gastric acid production
* Gastric acid is produced by the parietal cells of the gastric mucosa upon stimuli from multiple transmitters such as acetylcholine, histamine and gastrin.
* Receptor site binding of acetylcholine, histamine or gastrin results in the activation of the H+/K+-ATPase proton pump that secrets hydrochloric acid into the lumen of the stomach.
29
Gastritis, PUD and GERD drugs
```
• Commonly used drugs include:
• Antacids
• H2 Histamine blockers
• Proton pump blockers
• Triple therapy for H. pylori
• Misc. agents for gastritis and P.U.D. include Sucralfate, a drug that binds to disrupted G.I. mucosa and Misoprostol, a prostaglandin analogue.

```
30
Calcium carbonate/ Tums
• Category: Antacid
• MOA: Neutralization of stomach acid,
reducing mucosal irritation.
• Indication: Symptomatic relief of gastric
acid irritation.
• Char: PO. Pain relief precedes mucosal
healing. Potentially constipating. (Whereas aluminum containing antacids may cause diarrhea.)
Remember that the calcium containing antacids can cause constipation while the aluminum containing antacids can cause diarrhea.
31
Calcium carbonate/ Tums SE

• Side effects: Constipation. Drugs which alter the stomach or duodenal pH can alter the absorption of nutrients as well as the absorption other oral drugs. Increased pH may also inhibit protection against digested pathogens.
32
Ranitidine/ Zantac
• Category: H2 Histamine receptor antagonist • MOA: Blocks the action of histamine on
parietal cells in the stomach, decreasing acid
production by these cells.
• Indication: Gastritis, PUD, GERD
• Char: PO, IV. Now OTC. Fewer side effects
such as dizziness or altered mental status then noted with Tagamet. Side effect profile is greater when IV form is used.
Histamine stimulates the parietal cells of the stomach to produce gastric acid. H2 receptor antagonists can be used as primary therapy to heal ulcers that are not associated with H pylori infection.
33
Ranitidine/ Zantac SE

• Side effects: Generally well tolerated. Greater side effect profile when given I.V. Headache, confusion, dizziness, rash. Drugs which alter the stomach or duodenal pH can alter the absorption of nutrients as well as the absorption other oral drugs. Increased pH may also inhibit protection against digested pathogens.
Patients who are taking nonsteroidal anti-inflammatories (NSAIDs) may also be prescribed a prostaglandin analogue (Misoprostol) in order to help prevent peptic ulcers, which may be a side-effect of the NSAIDs.
34
Omeprazole/ Prilosec
• Category: Proton pump inhibitor
• MOA: Inhibits H+/K+ ATPase pump of parietal cells thus reducing acid secretion.
• Indication: Gastritis, PUD, GERD
• Char: PO. Generally used for 2 to 8 weeks for GERD and 1-2 weeks for PUD. Available as an OTC drug in a 5 mg dose whereas prescription doses are 10 mg, 20 mg and
40 mg.

35
Omeprazole/prilosec dosage
Omeprazole is now available in a 5 mg dose as an over the counter drug. Prescriptions for Omeprazole are available in 10 mg, 20 mg and 40 mg doses. Lansoprazole (Prevacid), Rabeprazole (Aciphex), Pantoprazole (Protonix), and Esomeprazole (Nexium) are other proton pump inhibitors (PPI). Esomeprazole/ Nexium is the ad famous purple pill, a drug that you can color coordinate with.
36
Omeprazole/ Prilosec SE
• Side effects: Headaches, dizziness, diarrhea. Drugs which alter the stomach or duodenal pH can alter the absorption of nutrients as well as the absorption other oral drugs. Increased pH may also inhibit protection against digested pathogens.
37
Esomeprazole/ Nexium
* Faced with the loss of patent protection and competition from generic manufacturers, AstraZeneca developed, launched, and heavily marketed Esomeprazole (Nexium), a single enantiomer form of Omeprazole.
* Thus, we now have a pill for which you are able to color coordinate.
38
Triple therapy for P.U.D.
* Triple therapy for 7 to 14 days is considered the treatment of choice for P.U.D. due to H pylori infection.
* Two forms of triple therapy are available: proton pump inhibitor based triple therapy and bismuth based triple therapy.
* Proton pump inhibitor based triple therapy is a PPI and 2 antibiotics for 1-2 weeks.
* Bismuth based triple therapy is bismuth subsalicylate and 2 antibiotics for 1-2 weeks.
39
Triple therapy for P.U.D. cont
* Bismuth may be used because it has been shown to damage the cell wall of H. pylori and other bacteria as well as reducing the bacterial adherence to mucosal cells.
* In order to promote mucosal healing, H2 histamine blockers may be used to block acid production although the proton pump inhibitors are generally used instead.
40
Non-endoscopic or noninvasive tests for H. Pylori
include serum H pylori antibody detection, fecal antigen tests, and urea breath tests.
► IgG antibodies to H pylori can be measured in serum, plasma, or whole blood. Results obtained from finger sticks are less reliable.
► Urea breath tests detect active H pylori infection by testing for the enzymatic activity of bacterial urease. In the presence of urease produced by H pylori, labeled carbon dioxide is produced in the stomach, absorbed into the bloodstream, diffused into the lungs, and exhaled.
► Fecal antigen testing identifies active H pylori infection by detecting the presence of H. pylori antigens in stools. This test is more accurate than antibody testing and less expensive than urea breath tests.
41
Triple therapy for P.U.D. abx
• Antibiotic options include Amoxicillin, Erythromycin, Clarithromycin (Biaxin), Tetracycline or Metronidazole (Flagyl).
• Although the growth of H. pylori is readily suppressed by a single antibiotic, antimicrobial monotherapy is discouraged because it does not eradicate the organism and leads to increased risk for the selection of resistant strains.

42
Triple therapy for P.U.D. regimen
• A typical prescription regimen for the treatment of H. pylori related P.U.D. would be as follows:
* Omeprazole (Prilosec) 20 mg bid plus
* Amoxicillin (Amoxil) 1 gm bid plus
* Clarithromycin (Biaxin) 500 mg daily
• Taken for 7 to 14 days, with appropriate lab tests for H. pylori to follow.

43
crohns vs UC
Crohn's disease can affect any part of the gastrointestinal tract from mouth to anus (with characteristic “skip lesions”) although the majority of cases start in the terminal ileum.
• Bowel involvement in ulcerative colitis is limited to the colon and the rectum.
• Microscopically, ulcerative colitis is
restricted to the mucosa (epithelial lining) of the bowel wall while Crohn's disease affects the bowel wall in it’s entirety.
44
sx and dx of crohsn and UC
abdominal pain, vomiting, diarrhea, hematochezia (bright red blood in stools), weight loss and various associated complaints or diseases like arthritis, erythema nodosum, pyoderma gangrenosum, and primary sclerosing cholangitis.
• Diagnosis of IBD is generally by colonoscopy and biopsy of pathologic lesions.
45
Categories of medications for inflammatory bowel disease
* Aminosalicylates
* Antibiotics
* Corticosteroids
* Immunomodulatory agents
* Probiotics
46
Aminosalicylates
* The active moiety of all of the aminosalicylates used to treat inflammatory bowel disease is 5-aminosalicylic acid (5-ASA), also called Mesalamine.
* Mesalamine is an anti-inflammatory drug used to treat inflammation of the digestive tract in U.C. and mild to moderate Crohn's disease.
* Mesalamine is a bowel-specific aminosalicylate drug that acts locally in the gut thereby having few systemic side effects.
47
5-ASA MOA
5 ASA produces an anti-inflammatory effect at least partly through modulation of the endocannabinoid system by means of elevating anandamide levels in the gut.
also an antioxidant that traps free radicals which are the potentially tissue damaging by-products of metabolism.
48
5 ASA forms , action
Oral Mesalamine comes in many forms including Sulfasalazine (Azulfadine).
• All forms of oral Mesalamine are mostly absorbed in the small intestine and do not reach the distal colon.
49
5-ASA/ Mesalamine overview
• Class: Aminosalicylates
• Indications: IBD
• MOA: Inhibition of leukotriene production, anti-prostaglandin and anti- oxidant effects.
• Char: PO, IM, IV and PR as suppository or enema (PR esp. in distal ulcerative colitis).
• Side effects: nausea, vomiting, diarrhea, and abdominal pain. Nephrotoxicity can occur

50
Pro-drug forms of Mesalamine

* There are several pro-drug forms of Mesalamine that release the drug at the ileum or beyond.
* Asarco tablets are coated with a ph- sensitive film which delays release of the medication until the higher pH of the terminal ileum and proximal colon are reached.
* Sulfasalazine (Azulfadine) has component which allows for drug release when exposed to bacteria localized to the colon.
51
Antibiotics
* Antibiotics are commonly given to assess for possible remission
* !!Patients with Crohn's disease seem to benefit more from antibiotics than do UC patients.
Improvement of colitis may occur as a result of treating small bowel bacterial overgrowth.

52
Antibiotics
* Metronidazole (Flagyl) and Ciprofloxacin (Ciprofloxin) are two of the most commonly utilized antibiotics for treating Crohn's' disease.
* You should recall that Metronidazole can cause nausea and vomiting and should not be taken by a patient consuming alcohol.
• Ciprofloxin is notable for its affinity to calcium and for the increased risk for the occurrence of tendon rupture in patients taking this drug.

53
Rifaximin/ Ixifaxin
* Rifaximin is a semi-synthetic drug based on the structure of Rifampin.
* It is currently approved by the FDA for the treatment of traveler's diarrhea and hepatic encephalopathy.
* Multiple trials are underway investigating the efficacy of Rifaximin for treating small bowel overgrowth syndrome, irritable bowel syndrome and inflammatory bowel disease.
54
Prednisone
* Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant and affects virtually all cells of the immune system.
* Prednisone is usually taken orally but can be delivered by I.M. or I.V. routes
• Prednisone is a pro-drug that is converted by the liver into prednisolone which is the most active form of the drug--glucocorticoid effect

55
Prednisone success for IBD
* Several studies suggest that prednisone or other similar corticosteroids will provide full remission to only 35 – 50% of all patients with either Crohn's or ulcerative colitis.
* Maintenance therapy is often needed to prevent a relapse in patients with both Crohn’s and ulcerative colitis.
56
Prednisone/ Deltasone overview
* Class: Glucocorticoid/ corticosteroid
* Indications: Preferred drug for reactive airways disease or moderate to severe allergic reaction. Important drug for leukemia reaction.
* MOA: Affects gene transcription to either stimulate or repress protein production.
* Char: PO, IM, IV and PR as suppository or enema. Prednisone has an intermediate duration of action (12-18 hours).
57
Prednisone/ Deltasone SE
• Side effects include reduced resistance to infections, hypertension, hyperglycemia and possible diabetes mellitus, severe bone loss, avascular necrosis, cataracts, myopathy, thinning of skin, diminished wound healing, easy bruising, insomnia and mental status changes and possible adrenal suppression.
• Increased appetite is a commonly reported side effect as is weight gain from salt and water retention.

58
Budenoside/ Entocort
* Budenoside is a synthetic glucocorticoid that is used to treat mild to moderate Crohn’s disease.
* The formulation of Entocort delays the release of the drug until it reaches the ileum and ascending colon.
• It has proven more effective than prednisone is a sub-set of Crohn's patients but less so for many patients with Crohn's.

59
Immunomodulatory drugs
* Immunomodulatory drugs including ASA and corticosteroids but the drugs not belonging to those groups are generally referred to as immunomodulators.
* Drugs in this class include Azthiopine, Mercaptopurine, Methotrexate, Cyclosporine and TNF inhibitors.
• These drugs are often used to allow for weaning from prednisone and to maintain the length of remission.

60
Azthioprine/ Immuran overview
• Class: Immunomodulator
• Indications: IBD, rheumatoid arthritis and
other auto-immune conditions, post- transplant cases (anti-rejection agent) and cancer chemotherapy.
• MOA: Pro-drug. Inhibits purine synthesis, resulting in an anti-proliferative effect and induction of apoptosis of T-cells.
• Char: PO, IM, IV. Azathioprine is a pro-drug which is converted in the body to its active form called mercaptopurine (Purinethol).
61
Azthioprine/ Immuran SE
* Side effects include nausea, fatigue, hair loss, and rash. Because Azthioprine suppresses the bone marrow, patients will be more susceptible to infection.
* Under FDA rules, patients taking Azthioprine, or other immunomodulators in its class, are excluded from eligibility for blood donation.
--more intense surveillance for signs of infection! also prednisone, advil!
62
Infliximib/ Remicade
• Class: Immunomodulator – TNF alpha inhibitor
• Indications: IBD, rheumatoid arthritis,
psoriasis and other auto-immune
conditions
• MOA: Inhibits the pro-inflammatory
cytokine, TNF-alpha.
• Char: A human-murine monocolonel
antibody
• IM or SQ dosing either every 2 weeks or
every 4 weeks.
watch for signs of infection!!!
63
Infliximib/ Remicade SE
• Side effects: Marked susceptibility to infection and sepsis, potential reactivation of hepatitis B, potential reactivation of tuberculosis, T-cell lymphoma and drug induced lupus
carry card saying you're on this drug!!
64
Inflammatory bowel disease tx goals
* The goal of treatment of both Crohn’s and UC is toward achieving remission, after which the patient is usually switched to a regimen of fewer drugs, with the hope fewer potential side effects.
* The time between flare-ups may be anywhere from weeks to years and varies wildly between patients.
65
Inflammatory bowel disease other tx
* Prebiotics and probiotics are showing increasing promise as treatments for IBD and in some studies have proven to be as effective as prescription drugs.
* Prebiotics are non-digestible food ingredients that stimulate the growth and/or activity of bacteria in the digestive system.
* Probiotics are live microorganisms
66
Inflammatory bowel disease and cannabis
* Research has also been focused on the effect of marijuana on the endothelial lining of the GI tract.
* Research trials have shown that many Crohn’s or UC patients show both subjective pain relief and decreased tissue inflammation when treated with cannabis.
* It is believed that in a healthy gut, natural endogenous cannabinoids are released from endothelial cells in response to injury.
