GI: Prokinetics and Antidiarrheal

Question 1

Outer longitudinal muscle

Answer 1

Peristalsis (aboral movement, unidirectional)
Myenteric plexus (Cholinergic affects)
Peptide hormone (motilin)

Question 2

Inner circular muscle

Answer 2

Segmentation contraction (narrowed lumen and mixing)
Submucosa plexus
Cholinergic and adrenergic effects

Question 3

Risk of diarrhea

Answer 3

Peristalsis > segmentation contraction

Question 4

Risk of constipation

Answer 4

Segmentation contraction > peristalsis

Question 5

Drugs regulating peristalsis

Answer 5

Cholinergics
Dopamine antagonists (Ach sensitizer)
Miscellaneous
Contrain: GI obstruction!!

Question 6

Cholinergics

Answer 6

Bethanechol, Neostigmine
Ranitidine, nizadidine
Cisapride

Question 7

Bethanechol (urecholine) MOA

Answer 7

Cholinergic agonist
Binds to muscarinic receptors and initiates smooth muscle contraction

Question 8

Bethanechol uses

Answer 8

Gastric emptying in horses
↑ Ileocolic contraction in cattle
↑ bladder smooth muscle contraction

Question 9

Bethanechol adverse effects

Answer 9

Non-specific binding (pleotrophic)
Profound sid effects
Diarrhea

Question 10

Neostigmine (prostigmin) MOA

Answer 10

Acetylcholinesterase inhibitor
Inhibits degradation of Ach (stimulating cholinergic receptors)

Question 11

Neostigmine uses

Answer 11

Myasthenia gravis
Large colon motility (equine)

Question 12

Ranitidine and Nizatidine MOA

Answer 12

H2 blockers and inhibits AcholE

Question 13

Cisapride MOA

Answer 13

Enhances Ach release
Agonist for 5-HT4 receptor

Question 14

Dopamine antagonists (Ach sensitizer)

Answer 14

Metoclopramide (reglan), doperidone

Question 15

Metoclopramide MOA

Answer 15

Antagonist: dopamine and 5HT3 centrally
Agonist: 5HT4
↑ release of Ach

Question 16

Metoclopramide uses

Answer 16

Stimulates upper motility after surgery
Poster operative ileus

Question 17

Domperidone MOA

Answer 17

Dopamine antagonist
Doesn’t cross BBB (↓ CNS effects compared to metoclopramide)

Question 18

Domperidone uses

Answer 18

Not used in small animals
Treats fescue toxicity and agalactia in mare

Question 19

Miscellaneous peristalsis regulators

Answer 19

Erythromycin
Lidocaine

Question 20

Erythromycin

Answer 20

Macrolide antimicrobial
Lose dose: nonspecific GI motility by ↑activation of motilin receptor
Side effects: diarrhea (horses)

Question 21

Lidocaine

Answer 21

Local anesthetic
Reduces postoperative ileus in horses

Question 22

Lidocaine MOA

Answer 22

Suppress transmission of sympathetic tone
Prevent sympathetic reflexive SC
Produce direct excitatory effects on smooth muscle of the intestine
Suppress centrally mediated hyperalgesia

Question 23

Motility Modifiers: Anticholinergics

Answer 23

Opioids
Anticholinergics
Mucosal protectants
Adsorbants

Question 24

Opioids _______ segmental contractions

Answer 24

Increase
antidiarrheal → constipation

Question 25

Anticholinergic drugs ________ both segmental contractions and peristalsis

Answer 25

Decrease

Question 26

Opioids

Answer 26

Diphynoxylate (Lomotil): not used Loperamide (Imodium): OTC

Question 27

Opioid MOA

Answer 27

↑ segmentation and tone of GI sphincter ↓ propulsive contractions Inhibits Ca2+ influx and ↓ calmodulin activity Stimulates absorption of fluid, electrolytes and glucose

Question 28

Anticholinergics

Answer 28

Atropine, Scopolamine, Isopropamide

Question 29

N- Butylscopolammonium bromide

Answer 29

Colic treatment in horses Severe forms of diarrhea Absence of segmentation movement

Question 30

Anticholinergics MOA

Answer 30

↓ GI motility (and intestinal secretions)

Question 31

Contraindications for anticholinergics

Answer 31

Gastritis, vomiting, infectious diarrhea

Question 32

Bismuth subsalicylate (pepto bismol)

Answer 32

Mucosal protectant and adsorbent Systemic treatment for acute diarrhea Adsorb bacterial enterotoxins Gastric/ intestinal protective effect Anti-inflammatory

Question 33

Bismuth subsalicylate contraindication

Answer 33

Care in admin to cats Deficient in glucuronyl transferase → toxic metabolic formation

Question 34

Prokinetics

Answer 34

Enhance GI transit via interaction with receptors involved in regulation of motility

Question 35

Prokinetics

Answer 35

Mosapride Misoprostol Colchicine

Question 36

Mosapride

Answer 36

Potent 5HT4 receptor agonist Experimental in horses Useful for treatment of chronic constipation

Question 37

Mu- opioid receptor antagonists

Answer 37

Peripherally acting (can't cross BBB) on GI secretion and motility Methylnaltrexone bromide and alvimopan (more potent)

Question 38

Methylnaltrexone bromide

Answer 38

Limited use in horses Inhibits morphine-induced intestinal effects

Question 39

Alvimopan causes increased incidence of ...

Answer 39

Myocardial infarction