GI: Prokinetics and Antidiarrheal Flashcards
Outer longitudinal muscle
Peristalsis (aboral movement, unidirectional)
Myenteric plexus (Cholinergic affects)
Peptide hormone (motilin)
Inner circular muscle
Segmentation contraction (narrowed lumen and mixing)
Submucosa plexus
Cholinergic and adrenergic effects
Risk of diarrhea
Peristalsis > segmentation contraction
Risk of constipation
Segmentation contraction > peristalsis
Drugs regulating peristalsis
Cholinergics
Dopamine antagonists (Ach sensitizer)
Miscellaneous
Contrain: GI obstruction!!
Cholinergics
Bethanechol, Neostigmine
Ranitidine, nizadidine
Cisapride
Bethanechol (urecholine) MOA
Cholinergic agonist
Binds to muscarinic receptors and initiates smooth muscle contraction
Bethanechol uses
Gastric emptying in horses
↑ Ileocolic contraction in cattle
↑ bladder smooth muscle contraction
Bethanechol adverse effects
Non-specific binding (pleotrophic)
Profound sid effects
Diarrhea
Neostigmine (prostigmin) MOA
Acetylcholinesterase inhibitor
Inhibits degradation of Ach (stimulating cholinergic receptors)
Neostigmine uses
Myasthenia gravis
Large colon motility (equine)
Ranitidine and Nizatidine MOA
H2 blockers and inhibits AcholE
Cisapride MOA
Enhances Ach release
Agonist for 5-HT4 receptor
Dopamine antagonists (Ach sensitizer)
Metoclopramide (reglan), doperidone
Metoclopramide MOA
Antagonist: dopamine and 5HT3 centrally
Agonist: 5HT4
↑ release of Ach
Metoclopramide uses
Stimulates upper motility after surgery
Poster operative ileus
Domperidone MOA
Dopamine antagonist
Doesn’t cross BBB (↓ CNS effects compared to metoclopramide)
Domperidone uses
Not used in small animals
Treats fescue toxicity and agalactia in mare
Miscellaneous peristalsis regulators
Erythromycin
Lidocaine
Erythromycin
Macrolide antimicrobial
Lose dose: nonspecific GI motility by ↑activation of motilin receptor
Side effects: diarrhea (horses)
Lidocaine
Local anesthetic
Reduces postoperative ileus in horses
Lidocaine MOA
Suppress transmission of sympathetic tone
Prevent sympathetic reflexive SC
Produce direct excitatory effects on smooth muscle of the intestine
Suppress centrally mediated hyperalgesia
Motility Modifiers: Anticholinergics
Opioids
Anticholinergics
Mucosal protectants
Adsorbants
Opioids _______ segmental contractions
Increase
antidiarrheal → constipation
Anticholinergic drugs ________ both segmental contractions and peristalsis
Decrease
Opioids
Diphynoxylate (Lomotil): not used
Loperamide (Imodium): OTC
Opioid MOA
↑ segmentation and tone of GI sphincter
↓ propulsive contractions
Inhibits Ca2+ influx and ↓ calmodulin activity
Stimulates absorption of fluid, electrolytes and glucose
Anticholinergics
Atropine, Scopolamine, Isopropamide
N- Butylscopolammonium bromide
Colic treatment in horses
Severe forms of diarrhea
Absence of segmentation movement
Anticholinergics MOA
↓ GI motility (and intestinal secretions)
Contraindications for anticholinergics
Gastritis, vomiting, infectious diarrhea
Bismuth subsalicylate (pepto bismol)
Mucosal protectant and adsorbent
Systemic treatment for acute diarrhea
Adsorb bacterial enterotoxins
Gastric/ intestinal protective effect
Anti-inflammatory
Bismuth subsalicylate contraindication
Care in admin to cats
Deficient in glucuronyl transferase → toxic metabolic formation
Prokinetics
Enhance GI transit via interaction with receptors involved in regulation of motility
Prokinetics
Mosapride
Misoprostol
Colchicine
Mosapride
Potent 5HT4 receptor agonist
Experimental in horses
Useful for treatment of chronic constipation
Mu- opioid receptor antagonists
Peripherally acting (can’t cross BBB) on GI secretion and motility
Methylnaltrexone bromide and alvimopan (more potent)
Methylnaltrexone bromide
Limited use in horses
Inhibits morphine-induced intestinal effects
Alvimopan causes increased incidence of …
Myocardial infarction
