GIS W4 Colon Pharmacology

Question 1

What critical metabolites produced during fermentation of fiber promote intestinal gluconeogenesis?

Answer 1

Proprionate and butyrate

Question 2

What critical metabolite produced during fermentation of fiber induces Treg cells to dampen inflammation?

Answer 2

Acetate

Question 3

In the small intestine, what cells on the villi absorb fluid?
What is the process driven by?

Answer 3

Cells at the tips of villi, Na+

Question 4

In the small intestine, what cells on the villi secrete fluid? What is the process driven by?

Answer 4

Cells in the crypts, CL-

Question 5

Na+, K+ and Cl- are brought across the basolateral membrane via the _______ symporter

Answer 5

NKCC1

Question 6

Cations are transported back across the basolateral membrane via ______________________.

Answer 6

Na+/K+ ATPase and K+ channels

Question 7

Cl- is moved across the apical membrane by _____.

d) Na+ and H2O follow via the ______________.

Answer 7

CFTR

paracellular route

Question 8

13) Short Bowel Syndrome Treatment

b) Glucagon-like peptide 2 (GLP-2) analogue

Answer 8

TEDUGLUTIDE

binds to enteric neurons and endocrine cells  release of trophic hormones that increase mucosal epithelial growth  enhance fluid and nutrient absorption

Question 9

a) In the absence of nutrient absorption, Na+ enters colonocytes via a ________________

Answer 9

sodium channel (ENaC)

Question 10

________ is a peptide hormone (released by goblet cells) that activates guanylyl cyclase C (GC-C) which increases cGMP

c) Increases in cGMP or cAMP increase flow through CFTR

Answer 10

GUANYLIN

Question 11

This Diarrhea causes excess secretion of chloride and/or inhibition of NaCl transport across apical membrane
ii) Causes: infection, inflammation

Answer 11

a) Secretory diarrhea

Question 12

This diarrhea changes in luminal contents result in water being pulled from bloodstream
ii) Causes: Incomplete absorption

Answer 12

b) Osmotic diarrhea

Question 13

This drug affects chloride secretion

a) Activator of CIC-2

Answer 13

LUBIPROSTONE

Question 14

LINACLOTIDE MOA

Answer 14

This drug is an activator of GC-C

i) Activates guanylyl cyclase C  increase cGMP  activation of CFTR  increase Cl- secretion  retention of H2O in lumen  looser stool

Question 15

CROFELEMER MOA

Answer 15

This drug is an inhibitor of CFTR

i) Voltage-independent inhibition of CFTR (and one other chloride channel)  decrease Cl- secretion  increase absorption of H2O from lumen  firmer stool

Question 16

OCTREOTIDE MOA

Answer 16

This drug is a Somatostatin analogue

ii) Multiple effects on GI tract:
(1) 1) decreases 5HT-stimulated, cGMP-dependent Cl- secretion
(2) 2) decreased NT/hormone release (esp. 5-HT) 3) low doses increase motility, high doses decrease motility

Question 17

BISMUTH SUBSALICYLATE MOA

Answer 17

Cox inhibitor

i) Salicylate  decreased prostaglandin synthesis  decreased cAMP  decreased Cl- secretion  increased absorption of H2O from lumen  firmer stool

Question 18

LUBIPROSTONE MOA

Answer 18

i) Increased Cl- secretion –> retention of H2O in lumen –> looser stool

Question 19

LACTULOSE, MAGNESIUM HYDROXIDE, SODIUM PHOSPHATE, POLYETHYLENE GLYCOL

MOA

Answer 19

b) Osmotic cathartics

i) Not absorbed  increased retention of H2O in lumen due to osmosis  looser stool

Question 20

specifically decreases plasma ammonia concentrations –> used to treat portal systemic encephalopathy

Answer 20

ii) LACTULOSE

Question 21

i) CHOLESTYRAMINE, COLESTIPOL

MOA

Answer 21

Bile acid binding resins

(1) decrease reabsorption of bile salts (Crohn’s disease, resection of terminal ileum)  secretory diarrhea

Question 22

These SSRIs are effective treatments for constipation-predominant IBS

Answer 22

FLUOXETINE, PAROXETINE, SERTALINE

ii) decrease reuptake 5-HT into ECL cells  increased 5-HT in the synapse
 increase primary afferent activity  increase peristalsis

Question 23

Bulk laxatives MOA

Answer 23

increase the stimulation of mechanoreceptors

ii) Attract water and increase stool mass

Question 24

DIETARY FIBER, METHYLCELLULOSE, PSYLLIUM are classified as…

Answer 24

BULK LAXATIVES:

Question 25

f) Contact cathartics MOA

Answer 25

are thought to stimulate the peristaltic reflex

Question 26

ANTHRAQUINONE DERIVATIVES, BISACODYL, and CASTOR OIL are classified as…

Answer 26

CONTACT (IRRITANT) CATHARTICS

Question 27

___________is a prodrug; must be converted to ricinoleic acid
(1) Acts on both the small and large intestine  shorter latency and more significant side effects

Answer 27

CASTOR OIL

Question 28

This 5-HT3 antagonist decreases gastric motility

Answer 28

ALOSETRON

Question 29

TEGASEROD and CISAPRIDE MOA

Answer 29

5-HT4 agonists increase gastric motility

Activation of presynaptic receptors  increases NT release from myenteric neurons  increases peristalsis

Question 30

DOMPERIDONE and METOCLOPRAMIDE MOA

Answer 30

D2 receptor antagonists

Inhibition of dopamine inhibition  increase actions of ACh in gut (i.e., they are cholinomimetics)  increase motility in entire gut (i.e., they are prokinetic)

Question 31

DIPHENOXYLATE and LOPERAMIDE MOA

Answer 31

Opiates: decrease motility and secretion

Question 32

ALVIMOPAN and METHYLNALOXONE MOA

Answer 32

μ receptor antagonists

Selective antagonists that don’t cross the BBB  increase gastric motility

Question 33

Drugs directly affecting cholinergic function are NOT used to treat diarrhea or constipation, but what are TWO EXCEPTIONS

Answer 33

i) TRICYCLIC ANTIDEPRESSANTS (AMITRIPTYLINE, DESIPRAMINE)

and

ii) ATROPINE

Question 34

Prokinetics

Answer 34

(1) D2 receptor antagonists: DOMPERIDONE (restricted use), METOCLOPRAMIDE
(2) Macrolides: ERYTHROMYCIN
(3) 5HT4 Agonists: CISAPRIDE (restricted use)

Question 35

Antidiarrheals

Answer 35

ii) Opiates: LOPERAMIDE, DIPHENOXYLATE+ATROPINE
(1) Multiple uses including traveler’s diarrhea
iii) BABRs: CHOLESTYRAMINE, COLESTIPOL
(1) Malabsorption of bile salts (Crohn’s disease, resection of terminal ileum
iv) OCTREOTIDE: severe diarrhea due to dumping syndrome, short bowel syndrome, vagotomy, AIDS
v) BISMUTH SUBSALYCILATE: traveller’s diarrhea
vi) CREFELEMER: diarrhea due to AIDS