Pharm of Drugs in Lower GI

Question 1

2 classes of drugs that stimulate the ENS (for constipation)

Answer 1

Laxatives (bulk, osmotic, stimulant)

Opioid receptor antagonists

Question 2

Bulk Laxatives

Answer 2

Introduction of indigestible, water absorbing molecules
Intestinal distention leading to ENS stimulation of peristalsis
Through dietary fiber or supplemental intake (methycellulose, psyllium husk)

Question 3

Osmotic laxatives

Answer 3

Poorly absorbed salts that retain and/or draw water back into the colon via osmosis
Increased stimulation of peristalsis
Some may have additional effectiveness as stool softeners
Ex: salts and sugars, polyethelene glycol (know this name)

Question 4

Side effects of osmotic laxatives

Answer 4

Electrolyte imbalance (salts only)
Bloating and/or flatulence
Abdominal cramps and/or diarrhea

Question 5

Stimulant/Contact laxatives

Answer 5

Direct stimulation of myenteric plexus in ENS
Increases smooth muscle motility and evacuation of contents
Ex: sennosides, diphenylmethane

Question 6

Side effects of Stimulant/Contact laxatives

Answer 6

Cramping and/or diarrhea
Pigmentation in colon (thought to be benign)
Should not take castor oil during pregnancy

Question 7

Stool softeners

Answer 7

Increases surface lubrication of feces (possible penetration of liquid as well)
Soften fecal matter to reduce effort of excretion
Also known as emollients
Ex: glycerin, docusate

Question 8

Opioid Receptor Antagonists

Answer 8

Selective competitive block of mu-opioid receptors
Prevent opioid-mediated stimulation of GI tract
Used for opioid-induced constipation
Ex: methylnaltrexone
Subcutaneous administration
Do not cross the BBB (peripherally selective effective) - no analgesic effect

Question 9

Contraindications and side effects of opioid-receptor antagonists

Answer 9

Contraindicated in: Known or suspected GI blockage

Side effects: abdominal pain/cramping, diarrhea and/or flatulence, nausea

Question 10

Opioid induced constipation line of therapies

Answer 10

Laxatives and stool softeners as first line

Progress to opioid receptor antagonists and/or Cl channel activators (lubiprostone)

Question 11

Antimotility agents for diarrhea

Answer 11

Ex: loperamide (selective mu opioid receptor agonist)
Inhibition of ENS activity leading to increased colonic transport time and water absorption
Does not readily cross BBB (peripherally selective)
Does not appear to produce tolerance

Question 12

Loperamide

Answer 12

Selective mu opioid receptor agonist
Used for acute non-infectious diarrhea or chronic diarrhea
Inhibition of ENS activity leading to increased colonic transport time and water absorption

Question 13

Bismuth subsalicylate

Answer 13

Antisecretory effects
Reduction of intestinal prostaglandin production (reduced motility) and reduced Cl secretion (reduced liquidity)
Antimicrobial effects

Question 14

Theory of treatment for IBS

Answer 14

Manage symptoms

Constipation, diarrhea, pain, bloating, cramping

Question 15

Aminosalicylates

Answer 15

5-aminosalicylate
Anti-inflammatory through a variety of possible mechanisms:
NSAID-like inhibition of prostaglandins
Interfere with cytokine porduction
Reduced leukocyte activity

Question 16

5-aminosalicylic acid

Answer 16

Acts topically at the site of diseased mucosa (systemic absorption and distribution not required)
A lot is absorbed, so there are formulations designed to increase drug exposure to distal small and the large intestine
For UC (induction and maintenance of remission)
Contraindications similar to aspirin (allergies, children under 2)

Question 17

Mesalamine

Answer 17

Collective term for delayed release 5-ASA formulations

Question 18

Side effects of 5-ASA

Answer 18

Nausea and/or GI upset
Headaches
Impaired folate absorption
Hypersensitivity (rare)
Inflammation of kidney (rare)

Question 19

Glucocorticoids

Answer 19

For induction of remission in IBD
Ex: prednisone, prednisolone, or budesonide
Anti-inflammation through inhibition of chemokine/cytokine production, and inhibit transcription of several pro-inflammatory mediators

Question 20

Side effects of glucocorticoids

Answer 20

PUD
Adrenal suppression
Fewer side effects with budesonide

Question 21

Purine analogues

Answer 21

Immunosuppressants
Ex: azathioprine
Converted to guanine analogue that halts DNA/RNA synthesis
Somewhat selective for cells dividing rapidly, such as immune cells
For UC and Crohn’s

Question 22

Methotrexate

Answer 22

Immunosuppressant
Inhibition of a key enzyme required for nucleotide synthesis (folate cant be produced)
Inhibition of cell proliferation unlikely at doses used in IBD treatment
For Crohn’s

Question 23

Anti-TNFa therapy

Answer 23

Ex: infliximab
Monoclonal antibody against TNF
Prevents receptor activation that leads to inflammatory response
IV administration
Used for induction and maintenance of moderate to severe Crohns/UC, and the ones that are unresponsive to previous therapies

Question 24

Side effects of Anti-TNFa therapy

Answer 24

Opportunistic infections
Hypersensitivity
Increased lymphoma risk

Question 25

Anti-integrin therapy

Answer 25

Ex: Vedolizumab
Prevent leukocyte adhesion to endothelium via integrin antagonism
Somewhat selective for gut endothelial cell adhesion molecules
For moderate-severe UC and Crohn’s