GI drugs 2 Flashcards
categories of prokinetics
- Dopamine Antagonists
- Metoclopramide
- Domperidone - Serotonin Receptor Modulators
- Cisapride - Miscellaneous agents
- H2-receptor antagonists
- Cholinergics
types of dopamine antagonists used as prokinetics?
- Metoclopramide (Maxeran®)
- Domperidone (Motilium®)
how does metoclopramide work as a prokinetic? mechanism of action? where does it act?
- Acts peripherally as a prokinetic to increase ACh
> activates prejunctional 5-HT4 (serotonin) receptors on enteric cholinergic nerves
> blocks inhibitory dopamine (D2) receptors on enteric cholinergic nerves - Effects are limited to upper GI tract; however, not well-established
> Increase lower esophageal sphincter and promote gastric emptying; less effect on the distal bowel
what animals is metoclopramide used in? what animal should we exhibit caution with and why?
- Used in horses; dogs and cats
- Caution: horses–behavioural (excitement) changes
what forms does metoclopramide come in?
Tablets, oral solution, injectable
difference between domperidone and metoclopramide?
Domperidone is similar to metoclopramide; does not cross BBB as readily;
Serotonin Receptor Modulator used as a prokinetic
Cisapride
how does Cisapride work? availability and adverse effects? what applications and species is it used for?
- Acts peripherally to stimulate 5-HT4 receptors on presynaptic enteric neurons promoting the release of ACh
- Withdrawn from market due to adverse cardiac effects in humans
> Can be obtained as a compounded product from pharmacies - Broadest spectrum prokinetic
> Gastric reflux, gastroparesis (delayed emptying)
> Ileus; dog, cat, horse
> Constipation and megacolon in cats
How do H2-receptor antagonists work as prokinetics?
Nizatidine (Axid®) and Ranitidine (Zantac®)
- Appear to inhibit acetylcholinesterase which increases ACh levels promoting GI motility throughout the stomach, SI and colon
- Reduction in HCl production also stimulates stomach motility promoting emptying
what are two H2-receptor antagonists that are used as prokinetics
Nizatidine (Axid®) and Ranitidine (Zantac®)
what cholinergic is used as a prokinetic? is it commonly used and why?
- Bethanechol (Urecholine®, generic, compounded)
- Use is limited by adverse effects
> Salivation, abd cramps, diarrhea, bradycardia
adverse effects of bethanechol
Salivation, abd cramps, diarrhea, bradycardia
how does bethanechol work as a prokinetic?
Promotes contractility throughout GI tract
species and possible application for bethanechol use as a prokinetic?
- Cats, dogs, cattle? horses?
- May be of benefit in canine idiopathic megaesophagus
Diarrhea can result from an imbalance with:
- motility (hyper or hypo)
- water and electrolyte secretion
most treatments for diarreah use what strategy?
Most treatment is symptomatic and does not address the underlying problem
- replace fluids
- replace electrolytes and maintain acid/base balance
- provide relief
how can diarreah be a defence mechanism?
- eliminate pathogens
- eliminate toxins
categories of antidiarrheals
- Adsorbents
- Antimotility
- Antisecretory
how do adsorbents work?
Adsorbents bind chemicals, toxins preventing their absorption
- bound agents are eliminated in feces
- adsorbents can bind other drugs interactions
- many adsorbents also have protectant effects
> bind and coat mucosal surface
adsorbents used as antidiarrheals
- Bismuth Subsalicylate (Pepto-Bismol®)
- Kaolin/Pectin (Kaopectate®)
when is Bismuth Subsalicylate (Pepto-Bismol®) used? how does it work? adverse effects?
- used in acute diarrheas; may darken stool !
- chronic use can yield constipation
- bismuth, like sucralfate, acts as a protectant and coats the mucosa
- salicylate component inhibits PG’s yielding an anti-inflammatory effect
> caution due to salicylate component, which is absorbed in dogs and cats; unlikely in standard dosages to produce toxicity
> however, use in cats probably should be cautious or avoided
how do Kaolin/Pectin (Kaopectate®) work as antidiarrheals? efficacy? should be careful with what formulations? what product versions are available?
- adsorbents
- Kaolin (attapulgite or aluminum silicate) and pectin (carbohydrate)
- Supposedly binds toxins, bacteria….and other drugs
> Efficacy is questionable for binding toxins
Does not appear to reduce electrolyte and fluid loss
- Careful with salicylate containing formulations
- Veterinary products can be kaolin and pectin only, or contain other anti-
diarrhea drugs and compounds
Antimotility & Antisecretory drug categories for antidiarrheals
- Opioids
- Anticholinergics
types of opioids that are used as antidiarrheals
- Loperamide (Imodium®)
- Diphenoxylate (Lomotil®)
increased gut motility is usually accompanied by what in diarrheic animals?
Increased motility is usually accompanied by increased fluid and electrolyte secretion in diarrheic animals
opioids mechanism of action as an antidiarrheal? issue with prolonged use?
- Inhibit release of ACh by cholinergic nerves
- decreased propulsive activity but increase non-propulsive activity (segmentation)
> Allows for more time for reabsorption of fecal fluid - decrease intestinal secretion and increase tone in sphincters
- increase fluid, electrolyte, glucose uptake
- Causes constipation and ileus with prolonged use
loperamide vs diphenoxylate; which opiate has less side effects and why? which is used more commonly?
Loperamide
> Does not cross the BBB—less side effects
> Used more commonly than diphenoxylate
Diphenoxylate; what is it derived from? combined with what?
Meperidine derivative; formulated combined with atropine to reduce abuse
potential; atropine may help with diarrhea
how do anticholinergics work as antidiarrheals? when are they useful and what are their effects? what are their limitations?
Diminish motility/secretions in hypermotile hypersecretory
intestinal tract
- “antispasmodics” or “spasmolytics”
- main benefit in diarrhea may be reduced intestinal secretions
- may decrease urgency associated with some forms of diarrhea
- may decrease abdominal discomfort
- use in infectious diarrhea should be avoided as should impactions or ileus
- adverse effects limits their use
adverse effects of anticholinergics
constipation, urinary retention, blurred vision, CNS stimulation and tachycardia and dry mouth (xerostomia)
types of anticholinergics used as antidiarrheals
- Belladonna alkaloids (atropine, hyoscine butylbromide)
- Synthetic anticholinergics (propantheline)
what are the uses of belladonna alkaloids for diarrhea? what are some examples?
-Antimotility & Antisecretory
Belladonna alkaloids (atropine, hyoscine butylbromide)
- hyoscine butylbromide (Buscopan®)
- approved in horses for colic relief; injectable (slow IV)
- can be used to relax the large bowel and facilitate rectal examination and
colonoscopy
- atropine is present in many calf scour preparations along with kaolin, pectin and neomycin
- these alkaloids can cross BBB—more side effects
benefits and uses of synthetic anticholinergics for diarrhea treatment
-Antimotility & Antisecretory
v less likely to cross BBB
v used in dogs and cats as antidiarrheic; tablets
v has been used in horses: facilitate rectal exam & colonic spasms
Normal gastrointestinal transit is a function of
motility and mucosal absorption/secretion
Laxatives and cathartics promote defecation of a stool by:
v increasing frequency of defecation
v increasing fecal volume and consistency
v laxatives promote elimination of a soft-formed stool, while cathartics produce a more fluid evacuation
Excessive or continuous use of cathartics
may result in
diarrhea, colic, dehydration and shock
General uses for laxatives/cathartics include:
v chronic constipation and reduce impactions
v empty bowel for radiography, surgery, proctoscopy
v ease straining
