GI Drugs II

Question 1

Bulk Forming Laxatives

Answer 1

• Psyllium, Methylcellulose, Polycarbophil
• Undigestible, hydrophilic colloids that absorb water forming a bulky emolient gel to distend the colon and promote peristalsis
• Bacterial digestion of plant fibers causes bloating and flatus

Question 2

Stool Softeners

Answer 2

• Soften stool by allowing water and liquids to penetrate
• Docusate (colace)- oral
• Glycerin suppository
• Mineral oil (slows water abs form stool)

Question 3

Osmotic Laxatives

Answer 3

• Mg(OH)2, Sorbitol, Lactulose, Polyethylene Glycol (PEG)

- Soluble but non-absorbable, increase stool liquidity

Question 4

Stimulant Laxatives

Answer 4

• Bisacodyl (Dulcolax), Senna, Aloe Vera
• Induce BM by ENS stimulation and stimulation of colonic electrolytes and fluid
• BM in 6-12 hrs orally; 1/2-2 hrs rectally
• Biscodyl + PEG = cleanse before colonoscopy

Question 5

Opioid Agonists

Answer 5

• Diphenoxylate + Loperamide
• Anti-Diarrheals– activate mu-opioid receptors in ENS to increase colonic transit time and increase fecal water absorption
• Diphenoxylate has potential for CNS effect at high doses and prolonged use can lead to dependence
• Loperamide doesn’t cross BBB

Question 6

Octreotide

Answer 6

• Somatostatin Analog, Anti-Diarrheal
• Inhibits secretion of multiple hormones and NT- gastrin, secretin, VIP, histamine
• Decreases intestinal fluid secretion and pancreatic secretion
• Slows GI motility and inhibits GB ctrxn
  Tx: Secretory diarhhea (NET), diarrhea due to vagotomy, dumping syndrome, short bowel syndrome
  Adv Effects: N/V, abd pain, flatulence
• Impaired pancreatic secretion
• Gallstones & hypothyroid w/ long-term use

Question 7

IBS Drugs

Answer 7

Constipation Predominant: Cl- Channel activators- lubiprostone, linaclotide

Pain + Severe IBS: Amytriptyline, Desipramine (tricyclic antidepressants), inhibit 5HT3 rec. which inhibit visceral afferent pain

Question 8

Alosetron

Answer 8

• 5 HT3 receptor antagonist
• Tx of severe diarrhea predominant IBS
• Rare but severe tox- severe constipation, ischemic colitis
• Restricted to women w/ severe diarrhea predominant IBS who haven’t responded to traditional treatments

Question 9

5- Aminosalicylates

Answer 9

• Mesalamine (Sulfasalazine, olsalazine, balasalazide)
• 1st line tx for mild-moderate UC and chron’s involving the colon or distal ileum (not proven)
• Sulfasalazine has more side effects- GI, arthralgias, mylalgias, BM suppression

Question 10

Glucocorticoids

Answer 10

• Tx for moderate-severe IBD
• Predisone- most common, oral
• Hydrocortisone enemas- minimize systemic abs. w/ max. effect
• Budesonide- control release oral formula releases drug at the distal ileum and colon where its absorbed, 10% bioavailable b/c of rapid 1st pass metab.
  Budesonide = 1st line tx for mild-moderate Chron’s involving the ileum and proximal colon

Question 11

Azathioprine and 6-MP

Answer 11

• Purine Antimetabolites for moderate IBD
  -Immunosuppresive properties
• Induction and remission of UC and Chron’s
• 50-60% of pt. w/ active disease achieve remission after 3-6 mo. and help maintain remission in up to 80% pt.
  Adv. Effects: - Hepatotoxicity
• Mucositis, GI upset
• BM Suppression

Question 12

Methotrexate

Answer 12

• Anti-folate for moderate IBD
• Maintains remission in Chron’s, efficacy unclear in UC
  Adv Effects: - BM suppression
• GI upset, mucositis

Question 13

Anti- TNF Therapy

Answer 13

• Infliximab, adalidumab, certolizumab
• mABs vs. TNF
• Tx for moderate to severe Chron’s w/ inadequate response to traditional therapy
• Infliximab: tx of acute/chronic UC w/ inadequate response to mesalamine or CSC
• Induction therapy allows symptomatic improvement in 60% and disease improvement in 30% of pt w/ moderate-severe Chron’s
  Adv Effects: Opportunistic infections b/c of TH1 suppression
• TB, Fungal, listerosis, bacterial sepsis

Question 14

Natalizumab

Answer 14

• Anti Integrin Therapy
• Humanized mAB vs. integrin alpha-4 subunit– blocks several integrins on circulating inflammatory cells (prevent leukocytes from adhering to vascular endothelium)
• Tx for moderate-severe chron’s who have failed other tx through a restricted program
• 50% respond to initial tx, 60% maintain long term response, 40% end up in remission
  Adverse Effects: RARE PML

Question 15

Serotonin 5HT3 Antagonists

Answer 15

• Odansetron (zofran), Granisetron, Dolasetron, Palonosetron
• Primary tx for chemo-induced B/V
• Enhanced efficacy w/ combo of CSC (dexamethasone) + NK1 rec. antagonist (aprepitant)
• Not useful for motion sickness

Question 16

Neurokinin (NK1) Rec Antagonists

Answer 16

• Aprepitant, Fosaprepitant
• Anti-emetics used in combo w/ 5HT3 rec. antagonists and CSC for prevention of acute and delayed N/V from chemo
• Fosaprepitant converted to aprepitant 30 min after infusion

Question 17

H1 Anti-Histamines

Answer 17

• Diphenydramine, Dimethyhydrimate, Meclizine
• Weakly anti-emetic but good for motion sickness
• Anticholinergic– sedative
• Meclizine- less sedating than others