Wk4 antidiarrheals/laxatives/IBS drugs

Question 1

Cisapride

Answer 1

Prokinetic –> increased motility

5HT4 agonist (and 5H3 ANtagonist)

Tx: diabetic gastroparesis

**restricted use dt cardiac toxicity

Question 2

Domperidone

Answer 2

D2 receptor antagonist

increase GI motility throughout the entire GI tract

Question 3

Macrolides (erythromycin)

Answer 3

stimulate motilin receptors directly on GI smooth muscle → initiation of migrating motor complex

Question 4

Metoclopramide

Answer 4

D2 receptor antagonist

increase GI motility throughout the entire GI tract

Question 5

Diphenoxylate

Answer 5

Opiate

most effective antidiarrheal

Crosses BBB so abuse potential and needs Rx

mixed with atropine to discourage abuse

Question 6

Loperamide

Answer 6

opiate

most effective antidiarrheal

doesn’t cross BBB so available OTC

Question 7

Cholestyramine

Answer 7

Binds bile salts

Question 8

Colestipol

Answer 8

Binds bile salts

Question 9

Kaolin/Pectin

Answer 9

Absorbant

Question 10

Bismuth Subsalicylate

MOA as antidiarrheal?

Answer 10

inhibits prostaglandin and chloride secretion in the large intestine

Question 11

Crofelmer use?

MOA?

Answer 11

HIV diarrhea

blocks CFTR –> decreases Cl- secretion

Question 12

Octreotide MOA?

Effects at different doses?

Answer 12

Somatostatin analogue

low dose stimulates motility

high dose inhibits motility

overall decrease in secretion

Question 13

Docusate class?

MOA?

Answer 13

Stool softener

surfactant –> softens stool by allowing mixing of aqueous and fatty substances

Question 14

Mineral Oil Class?

MOA?

Answer 14

Stool softener

lubricates feces –> decreased water absorption from stool

Question 15

Dietary fiber

Answer 15

increase mass of stool → distension → enteric reflexes → increased GI motility → decreased transit time through the colon

“stool stabilizers” – also less diarrhea

Question 16

Anthraquinone

Answer 16

Contact cathartic

Stimulates peristalsis

large intestine

less potent

Question 17

Bisacodyl

Answer 17

Contact cathartic

Stimulates peristalsis

large intestine

less potent

is given as a prodrug → 6 hour latency

Question 18

Castor oil

Answer 18

Contact cathartic

Stimulates peristalsis

large AND small intestine

VERY potent

**uterine contractions

dehydration

Question 19

Linaclotide

Answer 19

activates guanylyl cyclase-C on the luminal surface of intestinal epithelial cells

increased intra- and extra-cellular cGMP activates (CFTR) → increased Cl- secretion

Tx: constipation IBS

not in pregnancy or for peds

Question 20

Lubiprostone

Answer 20

activation of chloride channel ClC-2 → more Cl- secretion → increased water content in stool

constipation IBS

NOT in PREGNANCY

Question 21

Alvimopan

Answer 21

selective μ receptor antagonists that do not cross the BBB (won’t antagonize central analgesic effects of opiate medications)

used to shorten period of postoperative ileus following small or large bowel resection (short term)

**cardiotoxicity

Question 22

Methylnaltrexone

Answer 22

selective μ receptor antagonists that do not cross the BBB (won’t antagonize central analgesic effects of opiate medications)

patients receiving palliative care for advanced illness (long term)

Question 23

Lactulose

Answer 23

Osmotic cathartic (purgative)

reduces plasma NH4 conc; tx for hepatic encephalopathy

Question 24

Magnesium hydroxide

Answer 24

Osmotic cathartic (purgative)

MOA???

Question 25

Sodium Phosphate

Answer 25

Osmotic cathartic (purgative) MOA: increased electrolytes in colon

Question 26

Polyethylene glycol

Answer 26

Osmotic cathartic (purgative) used for whole bowel irrigation prior to colonoscopy/endoscopy

Question 27

TCA's Amitriptyline, Desipramine

Answer 27

blocking NE reptake into postganglionic sympathetic neurons results in increased NE concentrations in the synapse → increased NE actions on the α2 receptor → decreased ACh release blocking DA reuptake into enteric interneurons → increased DA concentrations in the synapse → increased D2-mediated inhibition of cholinergic smooth muscle motoneurons Diarrhea IBS tx

Question 28

SSRIs Fluoxetine, Paroxetine, Sertraline

Answer 28

Increased peristalsis more 5HT in synapse --> afferent activation Tx: constipation IBS

Question 29

Alosterone

Answer 29

Antidiarrheal 5HT3 antagonist Tx: diarrheal IBD **last resort, bad constipation

Question 30

Tegaserod

Answer 30

Prokinetic selective 5HT4 agonist Tx: constipation IBS **last resort, big Cardiac side fx

Question 31

cause a characteristic, harmless, brown pigmentation of the colonic mucosa

Answer 31

anthraquinones

Question 32

D2 receptor antagonist does not cross BBB compassionate use only not available in USA

Answer 32

Domperidone

Question 33

D2 receptor antagonist crosses BBB parkisonism pituitary effects (impotence, galactorhea, menstruation disorders)

Answer 33

Metaclopramide

Question 34

Secondary MOA or tegaserod and cisapride:

Answer 34

activate cAMP-dependent chloride secretion form the colon