GI DRUGS

Osmotic Laxatives

Polyethylene glycol (Miralax), Lactulose, Magnesium hydroxide (milk of magnesia, aka "laxative salts")

1.MOA: draws water into intestinal lumen via poorly absorbed salts; fecal mass softens and swells, wall stretches, and peristalsis is stimulated

2. Low doses: Produces soft or semisoft stool in 6-12 hrs pending dosage

3. High doses: Produces soft or semisoft stool in 2-6 hrs pending dosage

4. SE: dehydration, abdominal bloating, cramping, flatulence, avoid MOM in patients with kidney disease; Sodium retention: can worsen heart failure, hypertension, edema

Stimulant Laxatives

Bisacodyl (Dulcolax), Senna (Senokot, Ex-Lax)

1. MOA: Stimulate intestinal motility Increase amount of water & electrolytes within the intestinal lumen by increasing secretion of water and ions into the intestine and reducing water and electrolyte absorption

2. Works within 6-12 hrs to produce a semifluid stool

3. Popular uses: treat opioid induced constipation and treat of constipation resulting from slow intestinal motility

3.SE: ABUSED, long term use discouraged

Bulk Forming Laxatives

Methylcellulose (Citrucel), Psyllium (Metamucil)

1. Consist of natural or semi-synthetic polysaccharides and celluloses which swell in water (similar to fiber)

2. Intestinal transit time is slowed as the fecal mass stretches the intestinal wall peristalsis

3. Produce a soft, formed stool after 1-3 days of use

4. SE: RARE, need to take with a full glass of juice or water

Surfactant Laxatives

Docusate sodium (Colace)

MOA: Alter stool consistency by lowering surface tension, Inhibit fluid absorption, stimulate secretion of water and electrolytes into intestinal lumen

Other Laxatives

Lubiprostone (Amitiza) - selective chloride channel activator Promotes secretion of chloride-rich fluid into the intestine

Mineral Oil - Enhances motility in the small intestine and colon: lubrication AE: anal leakage, and deposition of mineral oil in the liver.

Glycerin Suppository - often and lubricates hardened, impacted feces Evacuation occurs about 30 minutes after suppository insertion

1. Uses: IBS, opioid-induced constipation in chronic non-cancer patients

Serotonin Receptor Antagonists

Odansetron (Zofran) - Highly effective

1. MOA. Blocks 5HT3-receptors located in the CTZ and on afferent vagal neurons in the upper GI tract

2. Route: PO or IV

3. SE. HA, diarrhea, dizziness, QT prolongation

Dopamine Receptor Antagonists

Prochlorperazine (Phenergan), Metoclopramide (Reglan)

1. MOA. Suppresses nausea through blockade of dopamine receptors in the CTZ

2. SE. hypotension, sedation, respiratory depression

3. Route. IV, IM, PO

Substance P/neurokinin1 Receptor Antagonists

Aprepitant (Emend)

1. MOA. Blocks neurokinin -type receptors in the CTZ Prevents postoperative nausea/vomiting and CINV

2. SE. Generally well tolerated

Cannabinoid Agonists

Dronabinol/Marinol and nabilone/Cesamet

1. MOA. Unclear, but activates cannabinoid receptors in CTZ and/or vagal afferents

2. SE. Potential for abuse and psychotomimetic effects - CINV

3. Anorexia/wasting in AIDS

Antibiotics

Clarithromycin, Amoxicillin, Metronidazole (Flagyl)

1. MOA. kill H. pylori

2. 2 week course of 2 antibiotics + PPI is standard therapy

3. Side effects: nausea, diarrhea, $$$ therapy

Antisecretory Agents

H2 receptor antagonists Famotidine (Pepcid), Ranitidine (Zantac)

MOA: suppress acid secretion by blocking H2 receptors on parietal cells

Proton pump inhibitors - Esomeprazole (Nexium), Lansoprazole (Prevacid), Pantoprazole (Protonix)

1. MOA: suppress acid secretion by inhibiting H+, K+, ATP-ase (enzyme that makes gastric acid)

2. Can increase the risk of serious adverse events, including fracture, pneumonia, acid rebound, and possibly intestinal infection with C.diff

Mucosal Protectant

Sucralfate (Carafate)

MOA. Forms a barrier up to 6 hours over the ulcer crater that protects against acid and pepsin

AE: Constipation

Anti-secretory Agent (that enhances mucosal defenses)

Misoprostol (Cytotec)

1. MOA. Protects against NSAID-induced ulcers by stimulating secretion of mucous and bicarbonate, maintaining submucosal blood flow & suppression of gastric acid secretion

2.AE: Diarrhea and abdominal pain

3. AVOID in pregnancy, can stimulate uterine contraction

Antacids

Aluminum hydroxide, Calcium Carbonate

1. MOA. React with gastric acid to form neutral salts of low acidity, decrease destruction of gut wall; May also enhance mucosal protection by stimulating production of prostaglandins

Except for sodium bicarbonate, antacids do not alter systemic pH

2.Primarily used for peptic ulcer treatment Use with caution in patients with renal impairment - Can cause hypophosphatemia

3. AEs: Constipation or diarrhea.

IBS Drugs

Non-specific Antispasmodics, bulk-forming agents, antidiarrheals

No good evidence that these work any better than placebos

1.Tricyclic Antidepressants - Shown to reduce abdominal pain

IBS-specific drugs Alosetron (IBS-D) 5-HT3 antagonist decreasing motility Ondansetron (Zofran) Lubiprostone (IBS-C) Increases chloride-rich fluid secretion, softening stool, increasing motility

5-Aminosalicylates

Sulfasalazine (Azulfidine) - Used to treat IBD

1. Reduces inflammation; it also suppresses prostaglandin synthesis and migration of inflammatory cells into affected region

2.Most effective against acute episodes of mild to moderate ulcerative colitis

3. SE. nausea, fever, rash, arthalgias (joint pain)

Glucocorticoids

Dexamethasone Anti-inflammatory effects

1. Approved for mild to moderate Crohn's disease that involves the ileum and ascending colon

2. SE. adrenal suppression, osteoporosis, increased susceptibility to infection

Immunosuppressants

Azathioprine + Mercaptopurine, Cyclosporine, Methotrexate

1. Used for long-term therapy in UC and Crohn

2. Drugs can take 6 months to take effect

3. AEs: pancreatitis and neutropenia

Immunomodulators

Infliximab [Remicade]: Antibody

1. against Tumor Necrosis Factor-alpha (TNF-α)

2. Indicated for Moderate to severe Crohn's and UC to induce remission

3. Serious side effects: infections, infusion reactions

Antibiotics

Metronidazole [Flagyl], ciprofloxacin [Cipro], Rifamixin, (non absorbable rifamycin)

1. Crohn's disease: Can help control symptoms and achieve & maintain remission

2. Ulcerative colitis: Antibiotics largely ineffective, might reduce symptoms

3. AEs: peripheral neuropathy